A whole stand basal area projection model for Appalachian hardwoods

Treesearch

John R. Brooks; Lichun Jiang; Matthew Perkowski; Benktesh Sharma

2008-01-01

Two whole-stand basal area projection models were developed for Appalachian hardwood stands. The proposed equations are an algebraic difference projection form based on existing basal area and the change in age, trees per acre, and/or dominant height. Average equation error was less than 10 square feet per acre and residuals exhibited no irregular trends.

Thermal history regulates methylbutenol basal emission rate in Pinus ponderosa.

PubMed

Gray, Dennis W; Goldstein, Allen H; Lerdau, Manuel T

2006-07-01

Methylbutenol (MBO) is a 5-carbon alcohol that is emitted by many pines in western North America, which may have important impacts on the tropospheric chemistry of this region. In this study, we document seasonal changes in basal MBO emission rates and test several models predicting these changes based on thermal history. These models represent extensions of the ISO G93 model that add a correction factor C(basal), allowing MBO basal emission rates to change as a function of thermal history. These models also allow the calculation of a new emission parameter E(standard30), which represents the inherent capacity of a plant to produce MBO, independent of current or past environmental conditions. Most single-component models exhibited large departures in early and late season, and predicted day-to-day changes in basal emission rate with temporal offsets of up to 3 d relative to measured basal emission rates. Adding a second variable describing thermal history at a longer time scale improved early and late season model performance while retaining the day-to-day performance of the parent single-component model. Out of the models tested, the T(amb),T(max7) model exhibited the best combination of day-to-day and seasonal predictions of basal MBO emission rates.

Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy.

PubMed

Welter, M-L; Burbaud, P; Fernandez-Vidal, S; Bardinet, E; Coste, J; Piallat, B; Borg, M; Besnard, S; Sauleau, P; Devaux, B; Pidoux, B; Chaynes, P; Tézenas du Montcel, S; Bastian, A; Langbour, N; Teillant, A; Haynes, W; Yelnik, J; Karachi, C; Mallet, L

2011-05-03

Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

Temperature, energy metabolism, and adaptive divergence in two oyster subspecies.

PubMed

Li, Ao; Li, Li; Song, Kai; Wang, Wei; Zhang, Guofan

2017-08-01

Comparisons of related species that have diverse spatial distributions provide an efficient way to investigate adaptive evolution in face of increasing global warming. The oyster subjected to high environmental selections is a model species as sessile marine invertebrate. This study aimed to detect the adaptive divergence of energy metabolism in two oyster subspecies from the genus Crassostrea - C. gigas gigas and C. gigas angulata -which are broadly distributed along the northern and southern coasts of China, respectively. We examined the effects of acute thermal stress on energy metabolism in two oyster subspecies after being common gardened for one generation in identical conditions. Thermal responses were assessed by incorporating physiological, molecular, and genomic approaches. Southern oysters exhibited higher fluctuations in metabolic rate, activities of key energetic enzymes, and levels of thermally induced gene expression than northern oysters. For genes involved in energy metabolism, the former displayed higher basal levels of gene expression and a more pronounced downregulation of thermally induced expression, while the later exhibited lower basal levels and a less pronounced downregulation of gene expression. Contrary expression pattern was observed in oxidative stress gene. Besides, energy metabolic tradeoffs were detected in both subspecies. Furthermore, the genetic divergence of a nonsynonymous SNP ( SOD-132 ) and five synonymous SNPs in other genes was identified and validated in these two subspecies, which possibly affects downstream functions and explains the aforementioned phenotypic variations. Our study demonstrates that differentiations in energy metabolism underlie the plasticity of adaptive divergence in two oyster subspecies and suggest C. gigas angulata with moderate phenotypic plasticity has higher adaptive potential to cope with exacerbated global warming.

Farmers develop more aggressive histologic subtypes of basal cell carcinoma. Experience from a Tertiary Hospital in Northern Greece.

PubMed

Apalla, Z; Lallas, A; Sotiriou, E; Lazaridou, E; Vakirlis, E; Trakatelli, M; Kyrgidis, A; Ioannides, D

2016-04-01

Ultraviolet radiation plays an important role in the pathogenesis of non-melanoma skin cancer. Outdoor workers, including farmers, experience higher exposure levels compared to the general population. Available literature data suggest that occupational ultraviolet exposure represents an independent risk factor for squamous cell carcinoma; whereas for basal cell carcinoma (BCC) this association still remains unclarified. To analyse the epidemiological, clinical and histological data of patients diagnosed with BCC, and correlate them with outdoor occupation in farmers. Individuals with histologically diagnosed BCCs, between September 2013 and September 2015, were included in the study. Their medical data, including epidemiological, clinical and histological characteristics, were recorded and analysed in conjunction with the occupation. Farmers were identified based on their specific public health insurance. Three hundred and forty patients, with 542 BCCs were included in the study. One hundred and twenty (35.3%) were farmers. Mean age of farmers was lower than non-farmers (66.0 ± 9.1 years vs. 75 ± 6.6 years, Mann-Whitney U-test, P < 0.001). Farmers had a sixfold higher probability for exhibiting photodamaged skin (OR = 6.02, 95% CI: 3.66-9.90, P < 0.001). Farmer workers were more likely to exhibit infiltrative or morpheaform BCC, but less likely to develop superficial BCC. Our results indicate a higher risk of earlier development of more aggressive histological subtypes of BCCs in farmers. Photodamage was also more common in this group. Primary and secondary prevention strategies focusing on outdoor workers, including farmers, are mandatory. © 2016 European Academy of Dermatology and Venereology.

Interplay between metabolic rate and diet quality in the South American fox, Pseudalopex culpaeus.

PubMed

Silva, Sergio I; Jaksic, Fabian M; Bozinovic, Francisco

2004-01-01

We studied the metabolic costs associated with the ingestion of peppertree fruits (Schinus molle) in the culpeo fox, Pseudalopex culpaeus, the second largest canid in South America. Throughout its range of distribution, this fox feeds on rodents and other small vertebrates, and also on peppertree fruits, which represent 98% of total fruits consumed in semiarid Chile. Peppertree contains a high diversity of phytochemicals. Foxes feeding on diets containing rats and peppertree fruits (mixed diets) exhibited a 98.9% increase in basal rate of metabolism when compared to rat-acclimated foxes. Thus, acute ingestion of chemically defended fruits has an energetic cost for the fox, reflected in higher values of basal metabolism. Increased metabolic rates may be associated with increased protein synthesis for detoxification and for tissue repair, including the production of biotransformation enzymes.

Identifying enhanced cortico-basal ganglia loops associated with prolonged dance training

PubMed Central

Li, Gujing; He, Hui; Huang, Mengting; Zhang, Xingxing; Lu, Jing; Lai, Yongxiu; Luo, Cheng; Yao, Dezhong

2015-01-01

Studies have revealed that prolonged, specialized training combined with higher cognitive conditioning induces enhanced brain alternation. In particular, dancers with long-term dance experience exhibit superior motor control and integration with their sensorimotor networks. However, little is known about the functional connectivity patterns of spontaneous intrinsic activities in the sensorimotor network of dancers. Our study examined the functional connectivity density (FCD) of dancers with a mean period of over 10 years of dance training in contrast with a matched non-dancer group without formal dance training using resting-state fMRI scans. FCD was mapped and analyzed, and the functional connectivity (FC) analyses were then performed based on the difference of FCD. Compared to the non-dancers, the dancers exhibited significantly increased FCD in the precentral gyri, postcentral gyri and bilateral putamen. Furthermore, the results of the FC analysis revealed enhanced connections between the middle cingulate cortex and the bilateral putamen and between the precentral and the postcentral gyri. All findings indicated an enhanced functional integration in the cortico-basal ganglia loops that govern motor control and integration in dancers. These findings might reflect improved sensorimotor function for the dancers consequent to long-term dance training. PMID:26035693

MoS2 monolayer catalyst doped with isolated Co atoms for the hydrodeoxygenation reaction.

PubMed

Liu, Guoliang; Robertson, Alex W; Li, Molly Meng-Jung; Kuo, Winson C H; Darby, Matthew T; Muhieddine, Mohamad H; Lin, Yung-Chang; Suenaga, Kazu; Stamatakis, Michail; Warner, Jamie H; Tsang, Shik Chi Edman

2017-08-01

The conversion of oxygen-rich biomass into hydrocarbon fuels requires efficient hydrodeoxygenation catalysts during the upgrading process. However, traditionally prepared CoMoS 2 catalysts, although efficient for hydrodesulfurization, are not appropriate due to their poor activity, sulfur loss and rapid deactivation at elevated temperature. Here, we report the synthesis of MoS 2 monolayer sheets decorated with isolated Co atoms that bond covalently to sulfur vacancies on the basal planes that, when compared with conventionally prepared samples, exhibit superior activity, selectivity and stability for the hydrodeoxygenation of 4-methylphenol to toluene. This higher activity allows the reaction temperature to be reduced from the typically used 300 °C to 180 °C and thus allows the catalysis to proceed without sulfur loss and deactivation. Experimental analysis and density functional theory calculations reveal a large number of sites at the interface between the Co and Mo atoms on the MoS 2 basal surface and we ascribe the higher activity to the presence of sulfur vacancies that are created local to the observed Co-S-Mo interfacial sites.

MoS2 monolayer catalyst doped with isolated Co atoms for the hydrodeoxygenation reaction

NASA Astrophysics Data System (ADS)

Liu, Guoliang; Robertson, Alex W.; Li, Molly Meng-Jung; Kuo, Winson C. H.; Darby, Matthew T.; Muhieddine, Mohamad H.; Lin, Yung-Chang; Suenaga, Kazu; Stamatakis, Michail; Warner, Jamie H.; Tsang, Shik Chi Edman

2017-08-01

The conversion of oxygen-rich biomass into hydrocarbon fuels requires efficient hydrodeoxygenation catalysts during the upgrading process. However, traditionally prepared CoMoS2 catalysts, although efficient for hydrodesulfurization, are not appropriate due to their poor activity, sulfur loss and rapid deactivation at elevated temperature. Here, we report the synthesis of MoS2 monolayer sheets decorated with isolated Co atoms that bond covalently to sulfur vacancies on the basal planes that, when compared with conventionally prepared samples, exhibit superior activity, selectivity and stability for the hydrodeoxygenation of 4-methylphenol to toluene. This higher activity allows the reaction temperature to be reduced from the typically used 300 °C to 180 °C and thus allows the catalysis to proceed without sulfur loss and deactivation. Experimental analysis and density functional theory calculations reveal a large number of sites at the interface between the Co and Mo atoms on the MoS2 basal surface and we ascribe the higher activity to the presence of sulfur vacancies that are created local to the observed Co-S-Mo interfacial sites.

Growth Performance, Mineral Digestibility, and Blood Characteristics of Ostriches Receiving Drinking Water Supplemented with Varying Levels of Chelated Trace Mineral Complex.

PubMed

Seyfori, Hossein; Ghasemi, Hossein Ali; Hajkhodadadi, Iman; Nazaran, Mohammad Hassan; Hafizi, Maryam

2018-05-01

The effects of water supplementation of chelated trace minerals (CTM, which is named Bonzaplex designed with chelate compounds technology) on growth performance, apparent total tract digestibility (ATTD) of minerals, and some blood metabolites, TM, and antioxidant enzyme values in African ostriches were investigated from 8 to 12 months of age. A total of 20 8-month-old ostriches (five birds in five replicate pens) was randomly allocated into one of the following four treatments: (1) control (basal diet + tap water), (2) low CTM (basal diet +100 mg/bird/day CTM powder in tap water), (3) medium CTM (basal diet +1 g/bird/day CTM powder in tap water), and (4) high CTM (basal diet +2 g/bird/day CTM powder in tap water). Compared with control, medium CTM improved (P < 0.05) daily weight gain and ATTD of phosphorous, zinc, and copper in 12-month-old ostriches. Furthermore, the feed conversion ratio was lower, and ATTD of magnesium was higher in the medium- and high-CTM groups than that in the control group (P < 0.05). At the end of the trial, ostriches receiving high-CTM treatment exhibited the lower (P < 0.05) serum triglyceride and very low-density lipoprotein cholesterol concentrations and higher copper levels compared to those of the control treatment. Supplementation of higher amounts of CTM (medium and high CTM) also increased the activity of serum superoxide dismutase (P < 0.05). No differences were detected for other blood parameters including glucose, total protein, albumin, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, iron, magnesium, and glutathione peroxidase values. In conclusion, supplementation of CTM at the level of 1 g/bird/day to the drinking water can be recommended for improving growth performance, mineral absorption, and antioxidant status of ostriches fed diets containing the recommended levels of inorganic TM.

Genetic differences in NMDA and D1 receptor levels, and operant responding for food and morphine in Lewis and Fischer 344 rats.

PubMed

Martín, Sonsoles; Lyupina, Yulia; Crespo, José Antonio; González, Begoña; García-Lecumberri, Carmen; Ambrosio, Emilio

2003-05-30

Previously, we have shown that Lewis (LEW) rats acquire faster than Fischer 344 (F344) rats operant food- and morphine-reinforced tasks under fixed-ratio schedules of reinforcement. The first purpose of the present work has been to study if differences in operant responding behavior may participate in the reported differences in morphine self-administration behavior between both inbred rat strains. To this end, we have analyzed the microstructure of responding obtained under a variable-interval (VI) of food reinforcement by calculating the inter-response time (IRT) for each rat strain. LEW rats exhibited shorter IRTs than F344 rats, suggesting that LEW rats may have an inherent high or compulsive operant responding activity. When subjects of both inbred rat strains were submitted to a schedule of morphine reinforcement of high responding requirements such as progressive ratio schedules, LEW rats also reached significantly higher breaking points and final response ratio than F344 rats for i.v. morphine self-administration. Given that there are neurochemical differences between both rat strains and that glutamatergic N-methyl-D-aspartate (NMDA) and dopaminergic D(1) receptors have been involved in operant responding behavior, a second purpose of this work has been to measure basal NMDA and D(1) receptor levels in these rat strains by quantitative receptor autoradiography. Compared to F344 rats, LEW rats showed higher basal NMDA receptor levels in frontal and cingulate cortex, caudate putamen, central amygdaloid nuclei, and intermediate white layer of superior colliculus, and higher basal D(1) receptor levels in several areas of hippocampus and thalamus, and substantia nigra pars reticulata. Taken together, these results suggest that an inherent high operant responding activity of LEW rats may have a role in the previous reported faster acquisition of opiate-reinforced behavior in operant self-administration paradigms under fixed-ratio schedules of reinforcement. In addition, a basal higher NMDA and D(1) receptor levels of LEW rats compared to F344 rats may participate in the neurochemical background that mediates the behavioral differences between both inbred rat strains.

Effects of Dietary Xanthophylls, Canthaxanthin and Astaxanthin on N-Methyl-N-nitrosourea-induced Rat Mammary Carcinogenesis.

PubMed

Yuri, Takashi; Yoshizawa, Katsuhiko; Emoto, Yuko; Kinoshita, Yuichi; Yuki, Michiko; Tsubura, Airo

Natural xanthophylls, canthaxanthin and astaxanthin are known to exhibit anticancer activity. However, the dietary effects of canthaxanthin and astaxanthin on N-methyl-N-nitrosourea (MNU)-induced mammary cancer remain controversial, and their mechanisms of action have not been clearly identified. Three-week-old female Sprague-Dawley rats were fed a xanthophyll-free (basal diet) diet or experimental diets containing canthaxanthin or astaxanthin (0.04% and 0.4%) for 5 weeks (until 8 weeks of age), after which all rats were provided the basal diet (n=15 each). Rats were administered MNU at 6 weeks of age, and the incidence of mammary tumors at 20 weeks of age was compared. The expression of adiponectin in mammary adipose tissues taken at 7 weeks of age was also compared. Compared to the basal diet group, the 0.4% (but not the 0.04%) astaxanthin diet significantly reduced the incidence of palpable mammary carcinoma (92% vs. 42%; p<0.05), while the low and high canthaxanthin diets produced no significant inhibition. Adiponectin immunoblotting showed significantly higher expression in the 0.4% astaxanthin diet group, while the other groups were similar to the basal diet group. High concentrations of astaxanthin suppress MNU-induced mammary carcinoma. Changes in adiponectin may be involved in the mechanism of action. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Basal cell adenocarcinoma in the gland of the third eyelid of a brown bear (Ursus arctos)

PubMed Central

SAKAI, Hiroki; GOTO, Minami; KOMATSU, Takeshi

2017-01-01

The right third eyelid of an adult female brown bear (c) was swollen and removed. Histopathology revealed a tumor exhibiting proliferation with mild infiltration, consisting of multi-stratified glandular structures of the innermost laminal neoplastic cells and the basaloid neoplastic cells, and with eosinophilic thick basal lamina material around the glandular structures. Both types of neoplastic cells exhibited moderate anisokaryosis, and mitotic figures were observed in the basaloid neoplastic cells. The laminal neoplastic cells were cytokeratin (CK) 8/18-positive. In contrast, the basaloid neoplastic cells were CK14- and p63-positive, but α-smooth muscle actin- and calponin-negative. The case described herein is the first report of basal cell adenocarcinoma in the gland of the third eyelid of a bear. PMID:28637946

Singing-related neural activity distinguishes two putative pallidal cell types in the songbird basal ganglia: comparison to the primate internal and external pallidal segments

PubMed Central

Goldberg, Jesse H.; Adler, Avital; Bergman, Hagai; Fee, Michale S.

2010-01-01

The songbird area X is a basal ganglia homologue that contains two pallidal cell types—local neurons that project within the basal ganglia and output neurons that project to the thalamus. Based on these projections, it has been proposed that these classes are structurally homologous to the primate external (GPe) and internal (GPi) pallidal segments. To test the hypothesis that the two area X pallidal types are functionally homologous to GPe and GPi neurons, we recorded from neurons in area X of singing juvenile male zebra finches, and directly compare their firing patterns to neurons recorded in the primate pallidus. In area X, we find two cell classes that exhibited high firing (HF) rates (>60Hz) characteristic of pallidal neurons. HF-1 neurons, like most GPe neurons we examined, exhibited large firing rate modulations, including bursts and long pauses. In contrast, HF-2 neurons, like GPi neurons, discharged continuously without bursts or long pauses. To test if HF-2 neurons were the output neurons that project to the thalamus, we next recorded directly from pallidal axon terminals in thalamic nucleus DLM, and found that all terminals exhibited singing-related firing patterns indistinguishable from HF-2 neurons. Our data show that singing-related neural activity distinguishes two putative pallidal cell types in area X: thalamus-projecting neurons that exhibit activity similar to the primate GPi, and non-thalamus-projecting neurons that exhibit activity similar to the primate GPe. These results suggest that song learning in birds and motor learning in mammals employ conserved basal ganglia signaling strategies. PMID:20484651

Preterm infants who are prone to distress: differential effects of parenting on 36-month behavioral and cognitive outcomes.

PubMed

Poehlmann, Julie; Hane, Amanda; Burnson, Cynthia; Maleck, Sarah; Hamburger, Elizabeth; Shah, Prachi E

2012-10-01

The differential susceptibility (DS) model suggests that temperamentally prone-to-distress infants may exhibit adverse outcomes in negative environments but optimal outcomes in positive environments. This study explored temperament, parenting, and 36-month cognition and behavior in preterm infants using the DS model. We hypothesized that temperamentally prone to distress preterm infants would exhibit more optimal cognition and fewer behavior problems when early parenting was positive; and less optimal cognition and more behavior problems when early parenting was less positive. Participants included 109 preterm infants (gestation <37 weeks) and their mothers. We assessed neonatal risk and basal vagal tone in the neonatal intensive care unit; infant temperament and parenting interactions at 9 months post-term; and child behavior and cognitive skills at 36 months post-term. Hierarchical regression analyses tested study hypotheses. Temperamentally prone-to-distress infants exhibited more externalizing problems if they experienced more critical parenting at 9 months (β = -.20, p < 0.05) but fewer externalizing problems with more positive parenting. Similarly, variations in maternal positive affect (β = .25, p < .01) and intrusive behaviors (β = .23, p < .05) at 9 months predicted 36-month cognition at high but not at low levels of infant temperamental distress. Higher basal vagal tone predicted fewer externalizing problems (β = -.19, p < .05). Early parenting behaviors relate to later behavior and development in preterm infants who are temperamentally prone to distress, and neonatal basal vagal tone predicts subsequent externalizing behaviors. These findings suggest that both biological reactivity and quality of caregiving are important predictors for later outcomes in preterm infants and may be considered as foci for developmental surveillance and interventions. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Effects of dietary supplementation of selenium and iodine on growth performance, carcass characteristics and histology of thyroid gland in goats.

PubMed

Aghwan, Zeiad Amjad; Sazili, Awis Qurni; Kadhim, Khalid Kamil; Alimon, Abdul Razak; Goh, Yong Meng; Adeyemi, Kazeem Dauda

2016-05-01

This study assessed the effects of dietary selenium (Se), iodine (I) and a combination of both on growth performance, thyroid gland activity, carcass characteristics and the concentration of iodine and selenium in Longissimus lumborum (LL) muscle in goats. Twenty-four bucks were randomly assigned to four dietary treatments: control (CON), basal diet without supplementation, basal diet + 0.6 mg Se/kg dry matter (DM) (SS), 0.6 mg I/kg DM (IP), or combination of 0.6 mg/kg DM Se and 0.6 mg/kg DM I (SSIP) and fed for 100 days. Animals fed diet SSIP exhibited higher (P < 0.05) body weight and better feed conversion ratio (FCR) than those fed other diets. Dressing percentage of goats fed the supplemented diets was higher (P < 0.05) than that of the control. Carcasses from the IP group had higher (P < 0.05) total fat proportion than the SSIP group. The levels of both elements were significantly elevated (P < 0.05) in LL muscle in supplemented goats. Thyroid follicular epithelial cells of IP and SSIP animals were significantly higher than those of CON and SS groups. The study demonstrated that the combined Se and I dietary supplementation improves growth performance, carcass dressing percentage and increases the retention of Se and I in goat meat. © 2015 Japanese Society of Animal Science.

Sex-reversed correlation between stress levels and dominance rank in a captive non-breeder flock of crows.

PubMed

Ode, Minami; Asaba, Akari; Miyazawa, Eri; Mogi, Kazutaka; Kikusui, Takefumi; Izawa, Ei-Ichi

2015-07-01

Group living has both benefits and costs to individuals; benefits include efficient acquisition of resources, and costs include stress from social conflicts among group members. Such social challenges result in hierarchical dominance ranking among group members as a solution to avoid escalating conflict that causes different levels of basal stress between individuals at different ranks. Stress-associated glucocorticoid (corticosterone in rodents and birds; CORT) levels are known to correlate with dominance rank in diverse taxa and to covary with various social factors, such as sex and dominance maintenance styles. Although there is much evidence for sex differences in the basal levels of CORT in various species, the correlation of sex differences in basal CORT with dominance rank is poorly understood. We investigated the correlation between CORT metabolites (CM) in the droppings and social factors, including rank and sex, in a captive non-breeder group of crows. In this group, all the single males dominated all the single females, and dominance ranks were stable among single males but relatively unstable among single females. CM levels and rank were significantly correlated in a sex-reversed fashion: males at higher rank (i.e., more dominant) had higher CM, whereas females at higher rank exhibited lower CM. This is the first evidence of sex-reversed patterns of CM-rank correlation in birds. The results suggest that different mechanisms of stress-dominance relationships operate on the sexes in non-breeder crow aggregations; in males, stress is associated with the cost of aggressive displays, whereas females experience subordination stress due to males' overt aggression. Copyright © 2015 Elsevier Inc. All rights reserved.

Feline mammary basal-like adenocarcinomas: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype.

PubMed

Wiese, David A; Thaiwong, Tuddow; Yuzbasiyan-Gurkan, Vilma; Kiupel, Matti

2013-09-03

Breast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer susceptibility) mutations. Feline mammary adenocarcinomas (FMAs) are highly malignant and share a similar basal-like subtype. The purpose of this study was to classify FMAs according to the current human classification of breast cancer that includes evaluation of ER, PR and HER2 status and expression of basal CK 5/6 and EGFR. Furthermore, we selected triple negative, basal-like FMAs to screen for BRCA mutations similar to those described in human TNBC. Twenty four FMAs were classified according to the current human histologic breast cancer classification including immunohistochemistry (IHC) for ER, PR HER2, CK5/6 and EGFR. Genetic alteration and loss of heterozygosity of BRCA1 and BRCA2 genes were analyzed in triple negative, basal-like FMAs. IHC for ER, PR and HER2 identified 14 of the 24 (58%) FMAs as a triple negative. Furthermore, 11 of these 14 (79%) triple negative FMAs had a basal-like subtype. However, no genetic abnormalities were detected in BRCA1 and BRCA2 by direct sequencing and loss of heterozygosity analysis. FMAs are highly aggressive neoplasms that are commonly triple negative and exhibit a basal-like morphology. This is similar to human TNBC that are also commonly classified as a basal-like subtype. While sequencing of a select number of triple negative, basal-like FMAs and testing for loss of heterozygosity of BRCA1 and BRCA2 did not identify mutations similar to those described in human TNBC, further in-depth evaluation is required to elucidate a potential role of BRCA in the tumorigenesis of triple negative, basal-like FMAs. The strong similarities in clinical behavior, morphology and IHC phenotype suggest that triple negative, basal-like FMAs may be a suitable spontaneous animal model for studying novel therapeutic approaches against human basal-like TNBC.

Reduced nocturnal hypoglycaemia with basal insulin peglispro compared with insulin glargine: pooled analyses of five randomized controlled trials.

PubMed

Rosenstock, Julio; Marre, Michel; Qu, Yongming; Zhang, Shuyu; Bastyr, Edward J; Prince, Melvin J; Chang, Annette M

2016-11-01

Basal insulin peglispro (BIL) is a novel basal insulin with hepato-preferential action, resulting from reduced peripheral effects. This report summarizes hypoglycaemia data from five BIL phase III studies with insulin glargine as the comparator, including three double-blind trials. Prespecified pooled analyses (n = 4927) included: patients with type 2 diabetes (T2D) receiving basal insulin only, those with T2D on basal-bolus therapy, and those with type 1 diabetes (T1D). BIL treatment resulted in a 36-45% lower nocturnal hypoglycaemia rate compared with glargine, despite greater reduction in glycated haemoglobin (HbA1c) and higher basal insulin dosing. The total hypoglycaemia rate was similar in patients with T2D on basal treatment only, trended towards being higher (10%) in patients with T2D on basal-bolus treatment (p = .053), and was 15% higher (p < .001) with BIL versus glargine in patients with T1D, with more daytime hypoglycaemia in the T1D and T2D groups who were receiving basal-bolus therapy. In T1D, during the maintenance treatment period (26-52 weeks), the total hypoglycaemia rate was not significantly different. There were no differences in severe hypoglycaemia in the T1D or T2D pooled analyses. BIL versus glargine treatment resulted in greater HbA1c reduction with less nocturnal hypoglycaemia in all patient populations, higher daytime hypoglycaemia with basal-bolus therapy in the T1D and T2D groups, and an associated increase in total hypoglycaemia in the patients with T1D. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

A new long-necked ‘sauropod-mimic’ stegosaur and the evolution of the plated dinosaurs

PubMed Central

Mateus, Octávio; Maidment, Susannah C.R.; Christiansen, Nicolai A.

2009-01-01

Stegosaurian dinosaurs have a quadrupedal stance, short forelimbs, short necks, and are generally considered to be low browsers. A new stegosaur, Miragaia longicollum gen. et sp. nov., from the Late Jurassic of Portugal, has a neck comprising at least 17 cervical vertebrae. This is eight additional cervical vertebrae when compared with the ancestral condition seen in basal ornithischians such as Scutellosaurus. Miragaia has a higher cervical count than most of the iconically long-necked sauropod dinosaurs. Long neck length has been achieved by ‘cervicalization’ of anterior dorsal vertebrae and probable lengthening of centra. All these anatomical features are evolutionarily convergent with those exhibited in the necks of sauropod dinosaurs. Miragaia longicollum is based upon a partial articulated skeleton, and includes the only known cranial remains from any European stegosaur. A well-resolved phylogeny supports a new clade that unites Miragaia and Dacentrurus as the sister group to Stegosaurus; this new topology challenges the common view of Dacentrurus as a basal stegosaur. PMID:19324778

Sex-specific effects of prenatal chronic mild stress on adult spatial learning capacity and regional glutamate receptor expression profiles.

PubMed

Wang, Yan; Ma, Yuchao; Hu, Jingmin; Zhang, Xinxin; Cheng, Wenwen; Jiang, Han; Li, Min; Ren, Jintao; Zhang, Xiaosong; Liu, Mengxi; Sun, Anji; Wang, Qi; Li, Xiaobai

2016-07-01

Both animal experiments and clinical studies have demonstrated that prenatal stress can cause cognitive disorders in offspring. To explore the scope of these deficits and identify potential underlying mechanisms, we examined the spatial learning and memory performance and glutamate receptor (GluR) expression patterns of adult rats exposed to prenatal chronic mild stress (PCMS). Principal component analysis (PCA) was employed to reveal the interrelationships among spatial learning indices and GluR expression changes. Female PCMS-exposed offspring exhibited markedly impaired spatial learning and memory in the Morris water maze (MWM) task compared to control females, while PCMS-exposed males showed better initial spatial learning in the MWM compared to control males. PCMS also altered basal and post-MWM glutamate receptor expression patterns, but these effects differed markedly between sexes. Male PCMS-exposed offspring exhibited elevated basal expression of NR1, mGluR5, and mGluR2/3 in the prefrontal cortex (PFC), whereas females showed no basal expression changes. Following MWM training, PCMS-exposed males expressed higher NR1 in the PFC and mammillary body (MB), higher mGluR2/3 in PFC, and lower NR2B in the hippocampus (HIP), PFC, and MB compared to unstressed MWM-trained males. Female PCMS-exposed offspring showed strongly reduced NR1 in MB and NR2B in the HIP, PFC, and MB, and increased mGluR2/3 in PFC compared to unstressed MWM-trained females. This is the first report suggesting that NMDA subunits in the MB are involved in spatial learning. Additionally, PCA further suggests that the NR1-NR2B form is the most important for spatial memory formation. These results reveal long-term sex-specific effects of PCMS on spatial learning and memory performance in adulthood and implicate GluR expression changes within HIP, PFC, and MB as possible molecular mechanisms underlying cognitive dysfunction in offspring exposed to prenatal stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells.

PubMed

Chan, S A; Smith, C

2001-12-15

1. Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was measured by oxidative amperometry and cell membrane turnover was measured by voltage clamp cell capacitance measurements. 2. The sAPs evoked inward Na(+) and Ca(2+) currents that were statistically identical to those evoked by native action potential waveforms. On average, a single secretory granule underwent fusion following sAP stimulation. An equivalent amount of membrane was then quickly internalised (tau = 560 ms). 3. Stimulation with sAP trains revealed a biphasic relationship between cell firing rate and endocytic activity. At basal stimulus frequencies (single to 0.5 Hz) cells exhibited a robust membrane internalisation that then diminished as firing increased to intermediate levels (1.9 and 6 Hz). However at the higher stimulation rates (10 and 16 Hz) endocytic activity rebounded and was again able to effectively maintain cell surface near pre-stimulus levels. 4. Treatment with cyclosporin A and FK506, inhibitors of the phosphatase calcineurin, left endocytosis characteristics unaltered at the lower basal stimulus levels, but blocked the resurgence in endocytosis seen in control cells at higher sAP frequencies. 5. Based on these findings we propose that, under physiological electrical stimulation, chromaffin cells internalise membrane via two distinct pathways that are separable. One is prevalent at basal stimulus frequencies, is lessened with increased firing, and is insensitive to cyclosporin A and FK506. A second endocytic form is activated by increased firing frequencies, and is selectively blocked by cyclosporin A and FK506.

Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells

PubMed Central

Chan, Shyue-An; Smith, Corey

2001-01-01

Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was measured by oxidative amperometry and cell membrane turnover was measured by voltage clamp cell capacitance measurements. The sAPs evoked inward Na+ and Ca2+ currents that were statistically identical to those evoked by native action potential waveforms. On average, a single secretory granule underwent fusion following sAP stimulation. An equivalent amount of membrane was then quickly internalised (τ = 560 ms). Stimulation with sAP trains revealed a biphasic relationship between cell firing rate and endocytic activity. At basal stimulus frequencies (single to 0.5 Hz) cells exhibited a robust membrane internalisation that then diminished as firing increased to intermediate levels (1.9 and 6 Hz). However at the higher stimulation rates (10 and 16 Hz) endocytic activity rebounded and was again able to effectively maintain cell surface near pre-stimulus levels. Treatment with cyclosporin A and FK506, inhibitors of the phosphatase calcineurin, left endocytosis characteristics unaltered at the lower basal stimulus levels, but blocked the resurgence in endocytosis seen in control cells at higher sAP frequencies. Based on these findings we propose that, under physiological electrical stimulation, chromaffin cells internalise membrane via two distinct pathways that are separable. One is prevalent at basal stimulus frequencies, is lessened with increased firing, and is insensitive to cyclosporin A and FK506. A second endocytic form is activated by increased firing frequencies, and is selectively blocked by cyclosporin A and FK506. PMID:11744761

Cross-Country Differences in Basal and Stress-Induced Cortisol Secretion in Older Adults

PubMed Central

Lupien, Sonia J.; Fiocco, Alexandra; Suchecki, Deborah

2014-01-01

Objective Several studies have emphasized the association between socioeconomic status (SES) and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries. Methods Salivary cortisol of 260 older adults from Canada and Brazil were nalyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST) in both populations. Results Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants. Conclusion These findings suggest that country context may modulate cortisol secretion and could impact the population health. PMID:25153322

Cross-country differences in basal and stress-induced cortisol secretion in older adults.

PubMed

Souza-Talarico, Juliana N; Plusquellec, Pierrich; Lupien, Sonia J; Fiocco, Alexandra; Suchecki, Deborah

2014-01-01

Several studies have emphasized the association between socioeconomic status (SES) and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries. Salivary cortisol of 260 older adults from Canada and Brazil were analyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST) in both populations. Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants. These findings suggest that country context may modulate cortisol secretion and could impact the population health.

Effect of Extrusion Temperature on the Plastic Deformation of an Mg-Y-Zn Alloy Containing LPSO Phase Using In Situ Neutron Diffraction

NASA Astrophysics Data System (ADS)

Garces, G.; Perez, P.; Cabeza, S.; Kabra, S.; Gan, W.; Adeva, P.

2017-11-01

The evolution of the internal strains during in situ tension and compression tests has been measured in an MgY2Zn1 alloy containing long-period stacking ordered (LPSO) phase using neutron diffraction. The alloy was extruded at two different temperatures to study the influence of the microstructure and texture of the magnesium and the LPSO phases on the deformation mechanisms. The alloy extruded at 623 K (350 °C) exhibits a strong fiber texture with the basal plane parallel to the extrusion direction due to the presence of areas of coarse non-recrystallised grains. However, at 723 K (450 °C), the magnesium phase is fully recrystallised with grains randomly oriented. On the other hand, at the two extrusion temperatures, the LPSO phase orients their basal plane parallel to the extrusion direction. Yield stress is always slightly higher in compression than in tension. Independently on the stress sign and the extrusion temperature, the beginning of plasticity is controlled by the activation of the basal slip system in the dynamic recrystallized grains. Therefore, the elongated fiber-shaped LPSO phase which behaves as the reinforcement in a metal matrix composite is responsible for this tension-compression asymmetry.

Microbial biomass and basal respiration of selected Sub-Antarctic and Antarctic soils in the areas of some Russian polar stations

NASA Astrophysics Data System (ADS)

Abakumov, E.; Mukhametova, N.

2014-07-01

Antarctica is a unique place for soil, biological, and ecological investigations. Soils of Antarctica have been studied intensively during the last century, when different national Antarctic expeditions visited the sixth continent with the aim of investigating nature and the environment. Antarctic investigations are comprised of field surveys mainly in the terrestrial landscapes, where the polar stations of different countries are situated. That is why the main and most detailed soil surveys were conducted in the McMurdo Valleys, Transantarctic Mountains, South Shetland Islands, Larsemann Hills and the Schirmacher Oasis. Our investigations were conducted during the 53rd and 55th Russian Antarctic expeditions in the base of soil pits, and samples were collected in Sub-Antarctic and Antarctic regions. Sub-Antarctic or maritime landscapes are considered to be very different from Antarctic landscapes due to differing climatic and geogenic conditions. Soils of diverse zonal landscapes were studied with the aim of assessing the microbial biomass level, basal respiration rates and metabolic activity of microbial communities. This investigation shows that Antarctic soils are quite diverse in profile organization and carbon content. In general, Sub-Antarctic soils are characterized by more developed humus (sod) organo-mineral horizons as well as by an upper organic layer. The most developed organic layers were revealed in peat soils of King George Island, where its thickness reach, in some cases, was 80 cm. These soils as well as soils formed under guano are characterized by the highest amount of total organic carbon (TOC), between 7.22 and 33.70%. Coastal and continental Antarctic soils exhibit less developed Leptosols, Gleysols, Regolith and rare Ornhitosol, with TOC levels between 0.37 and 4.67%. The metabolic ratios and basal respiration were higher in Sub-Antarctic soils than in Antarctic ones, which can be interpreted as a result of higher amounts of fresh organic remnants in organic and organo-mineral horizons. The soils of King George Island also have higher portions of microbial biomass (max 1.54 mg g-1) compared to coastal (max 0.26 mg g-1) and continental (max 0.22 mg g-1) Antarctic soils. Sub-Antarctic soils differ from Antarctic ones mainly by having increased organic layer thickness and total organic carbon content, higher microbial biomass carbon content, basal respiration, and metabolic activity levels.

Neuroimaging abnormalities in adults with sickle cell anemia

PubMed Central

Insel, Philip; Truran, Diana; Vichinsky, Elliot P.; Neumayr, Lynne D.; Armstrong, F.D.; Gold, Jeffrey I.; Kesler, Karen; Brewer, Joseph; Weiner, Michael W.

2014-01-01

Objective: This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA). Methods: Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition). Results: After adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = −2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = −3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures. Conclusions: Our findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA. PMID:24523480

Pristine Basal- and Edge-Plane-Oriented Molybdenite MoS2 Exhibiting Highly Anisotropic Properties.

PubMed

Tan, Shu Min; Ambrosi, Adriano; Sofer, Zdenĕk; Huber, Štěpán; Sedmidubský, David; Pumera, Martin

2015-05-04

The layered structure of molybdenum disulfide (MoS2 ) is structurally similar to that of graphite, with individual sheets strongly covalently bonded within but held together through weak van der Waals interactions. This results in two distinct surfaces of MoS2 : basal and edge planes. The edge plane was theoretically predicted to be more electroactive than the basal plane, but evidence from direct experimental comparison is elusive. Herein, the first study comparing the two surfaces of MoS2 by using macroscopic crystals is presented. A careful investigation of the electrochemical properties of macroscopic MoS2 pristine crystals with precise control over the exposure of one plane surface, that is, basal plane or edge plane, was performed. These crystals were characterized thoroughly by AFM, Raman spectroscopy, X-ray photoelectron spectroscopy, voltammetry, digital simulation, and DFT calculations. In the Raman spectra, the basal and edge planes show anisotropy in the preferred excitation of E2g and A1g phonon modes, respectively. The edge plane exhibits a much larger heterogeneous electron transfer rate constant k(0) of 4.96×10(-5) and 1.1×10(-3)  cm s(-1) for [Fe(CN)6 ](3-/4-) and [Ru(NH3 )6 ](3+/2+) redox probes, respectively, compared to the basal plane, which yielded k(0) tending towards zero for [Fe(CN)6 ](3-/4-) and about 9.3×10(-4)  cm s(-1) for [Ru(NH3 )6 ](3+/2+) . The industrially important hydrogen evolution reaction follows the trend observed for [Fe(CN)6 ](3-/4-) in that the basal plane is basically inactive. The experimental comparison of the edge and basal planes of MoS2 crystals is supported by DFT calculations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Environment, Migratory Tendency, Phylogeny and Basal Metabolic Rate in Birds

PubMed Central

Jetz, Walter; Freckleton, Robert P.; McKechnie, Andrew E.

2008-01-01

Basal metabolic rate (BMR) represents the minimum maintenance energy requirement of an endotherm and has far-reaching consequences for interactions between animals and their environments. Avian BMR exhibits considerable variation that is independent of body mass. Some long-distance migrants have been found to exhibit particularly high BMR, traditionally interpreted as being related to the energetic demands of long-distance migration. Here we use a global dataset to evaluate differences in BMR between migrants and non-migrants, and to examine the effects of environmental variables. The BMR of migrant species is significantly higher than that of non-migrants. Intriguingly, while the elevated BMR of migrants on their breeding grounds may reflect the metabolic machinery required for long-distance movements, an alternative (and statistically stronger) explanation is their occupation of predominantly cold high-latitude breeding areas. Among several environmental predictors, average annual temperature has the strongest effect on BMR, with a 50% reduction associated with a 20°C gradient. The negative effects of temperature variables on BMR hold separately for migrants and non-migrants and are not due their different climatic associations. BMR in migrants shows a much lower degree of phylogenetic inertia. Our findings indicate that migratory tendency need not necessarily be invoked to explain the higher BMR of migrants. A weaker phylogenetic signal observed in migrants supports the notion of strong phenotypic flexibility in this group which facilitates migration-related BMR adjustments that occur above and beyond environmental conditions. In contrast to the findings of previous analyses of mammalian BMR, primary productivity, aridity or precipitation variability do not appear to be important environmental correlates of avian BMR. The strong effects of temperature-related variables and varying phylogenetic effects reiterate the importance of addressing both broad-scale and individual-scale variation for understanding the determinants of BMR. PMID:18810267

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

PubMed Central

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

2016-01-01

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

PubMed

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

2016-02-29

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

Effect of LPSO and SFs on microstructure evolution and mechanical properties of Mg-Gd-Y-Zn-Zr alloy

NASA Astrophysics Data System (ADS)

Xu, Chao; Nakata, Taiki; Qiao, Xiaoguang; Zheng, Mingyi; Wu, Kun; Kamado, Shigeharu

2017-01-01

High performance Mg-8.2Gd-3.8Y-1.0Zn-0.4Zr alloy with high strength and excellent ductility has been successfully developed by hot extrusion. The effect of plate-shaped long period stacking ordered (LPSO) phases and solute-segregated stacking faults (SFs) on the dynamically recrystallization (DRX) behavior was analyzed. The plate-shaped LPSO phases stimulate the DRX by particle stimulated nucleation mechanism, leading to higher DRX ratio and weaker basal texture. While for the alloy with dense fine SFs inside the original grains, discontinuous DRX initially occurs at the original grain boundaries, and the DRX is obviously restricted. Consequently, alloy containing dense SFs exhibits higher strength but lower ductility compared with alloy with plated-shaped LPSO phases.

Effect of LPSO and SFs on microstructure evolution and mechanical properties of Mg-Gd-Y-Zn-Zr alloy

PubMed Central

Xu, Chao; Nakata, Taiki; Qiao, Xiaoguang; Zheng, Mingyi; Wu, Kun; Kamado, Shigeharu

2017-01-01

High performance Mg-8.2Gd-3.8Y-1.0Zn-0.4Zr alloy with high strength and excellent ductility has been successfully developed by hot extrusion. The effect of plate-shaped long period stacking ordered (LPSO) phases and solute-segregated stacking faults (SFs) on the dynamically recrystallization (DRX) behavior was analyzed. The plate-shaped LPSO phases stimulate the DRX by particle stimulated nucleation mechanism, leading to higher DRX ratio and weaker basal texture. While for the alloy with dense fine SFs inside the original grains, discontinuous DRX initially occurs at the original grain boundaries, and the DRX is obviously restricted. Consequently, alloy containing dense SFs exhibits higher strength but lower ductility compared with alloy with plated-shaped LPSO phases. PMID:28134297

1,1-Bis(3'-indolyl)-1-(p-biphenyl)methane inhibits basal-like breast cancer growth in athymic nude mice

PubMed Central

Su, Yunpeng; Vanderlaag, Kathryn; Ireland, Courtney; Ortiz, Janelle; Grage, Henry; Safe, Stephen; Frankel, Arthur E

2007-01-01

Introduction 1,1-Bis (3'-indolyl)-1-(p-biphenyl) methane (CDIM9) has been identified as a new peroxisome proliferator-activated receptor (PPAR)-γ agonist that exhibits both receptor dependent and independent antitumor activities. CDIM9 has not previously been studied with respect to its effects against basal-like breast cancer. Our goal in the present study was to investigate the anti-basal-like breast tumor activity of CDIM9 in vitro and in vivo. Methods The effects of CDIM9 on cell protein and DNA syntheses were determined in basal-like breast cancer MDA-MB231 and BT549 cells in vitro. Maximum tolerated dose and dose-limited toxicity were determined in BalB/c mice, and antitumor growth activities were assessed in MDA-MB231 basal-like breast tumor xenografts in athymic nude mice. Results CDIM9 exhibited selective cell cytotoxicity and anti-proliferation effects on basal-like breast cancer lines. In MDA-MB231 cell, CDIM9 induced caveolin-1 and p27 expression, which was significantly downregulated by co-treatment with the PPAR-γ antagonist GW9662. Nonsteroidal anti-inflammatory drug-activated gene-1 and activating transcription factor-3 were upregulated by CDIM9 through a PPAR-γ independent pathway. CDIM9 (40 mg/kg daily, intraperitoneally, for 35 days) inhibited the growth of subcutaneous MDA-MB231 tumor xenografts by 87%, and produced a corresponding decrease in proliferation index. Nearly half of the treated mice (46%) had complete durable remissions, confirmed by histology. The growth of an established tumor was inhibited by CDIM9 treatment (64 mg/kg daily, intraperitoneally, for 10 days), with a mean tumor growth inhibition of 67% as compared with controls. CDIM9 induced increases in tumor caveolin-1 and p27 in vivo, which may contribute to its antitumor activity in basal-like breast cancer. Conclusion CDIM9 showed potent antiproliferative effects on basal-like breast cancer cell in tissue culture and dramatic growth inhibition in animal models at safe doses. These findings justify further development of this drug for treatment of basal-like breast cancer. PMID:17764562

Choline acetyltransferase expression during periods of behavioral activity and across natural sleep-wake states in the basal forebrain.

PubMed

Greco, M A; McCarley, R W; Shiromani, P J

1999-01-01

The present study examined whether the expression of the messenger RNA encoding the protein responsible for acetylcholine synthesis is associated with sleep-wakefulness. Choline acetyltransferase messenger RNA levels were analysed using a semi-quantitative assay in which reverse transcription was coupled to complementary DNA amplification using the polymerase chain reaction. To examine the relationship between steady-state messenger RNA and behavioral activity, rats were killed during the day (4.00 p.m.) or night (4.00 a.m.), and tissue from the vertical and horizontal limbs of the diagonal bands of Broca was analysed. Choline acetyltransferase messenger RNA levels were higher during the day than during the night. The second study examined more closely the association between choline acetyltransferase messenger RNA levels and individual bouts of wakefulness, slow-wave sleep or rapid eye movement sleep. Choline acetyltransferase messenger RNA levels were low during wakefulness, intermediate in slow-wave sleep and high during rapid eye movement sleep. In contrast, protein activity, measured at a projection site of cholinergic neurons of the basal forebrain, was higher during wakefulness than during sleep. These findings suggest that choline acetyltransferase protein and messenger RNA levels exhibit an inverse relationship during sleep and wakefulness. The increased messenger RNA expression during sleep is consistent with a restorative function of sleep.

Variability of Basal Rate Profiles in Insulin Pump Therapy and Association with Complications in Type 1 Diabetes Mellitus.

PubMed

Laimer, Markus; Melmer, Andreas; Mader, Julia K; Schütz-Fuhrmann, Ingrid; Engels, Heide-Rose; Götz, Gabriele; Pfeifer, Martin; Hermann, Julia M; Stettler, Christoph; Holl, Reinhard W

2016-01-01

Traditionally, basal rate profiles in continuous subcutaneous insulin infusion therapy are individually adapted to cover expected insulin requirements. However, whether this approach is indeed superior to a more constant BR profile has not been assessed so far. This study analysed the associations between variability of BR profiles and acute and chronic complications in adult type 1 diabetes mellitus. BR profiles of 3118 female and 2427 male patients from the "Diabetes-Patienten-Verlaufsdokumentation" registry from Germany and Austria were analysed. Acute and chronic complications were recorded 6 months prior and after the most recently documented basal rate. The "variability index" was calculated as variation of basal rate intervals in percent and describes the excursions of the basal rate intervals from the median basal rate. The variability Index correlated positively with severe hypoglycemia (r = .06; p<0.001), hypoglycemic coma (r = .05; p = 0.002), and microalbuminuria (r = 0.05; p = 0.006). In addition, a higher variability index was associated with higher frequency of diabetic ketoacidosis (r = .04; p = 0.029) in male adult patients. Logistic regression analysis adjusted for age, gender, duration of disease and total basal insulin confirmed significant correlations of the variability index with severe hypoglycemia (β = 0.013; p<0.001) and diabetic ketoacidosis (β = 0.012; p = 0.017). Basal rate profiles with higher variability are associated with an increased frequency of acute complications in adults with type 1 diabetes.

Pyronin Y (basic xanthene dye)-bentonite composite: A spectroscopic study

NASA Astrophysics Data System (ADS)

Tabak, A.; Kaya, M.; Yilmaz, N.; Meral, K.; Onganer, Y.; Caglar, B.; Sungur, O.

2014-02-01

The expansion by 1.43 Angstrom of basal spacing and the shift to higher frequencies of in-plane ring vibrations of the Pyronin Y molecule at 1603 and 1527 cm-1 on the formation of Pyronin Y-bentonite composite exhibited that the dye cations might be oriented as a monolayer form in the interlamellar spacing with aromatic rings parallel to clay layers. Thermal analysis results of this composite compared to those of raw bentonite signified the different outer sphere water entities associated with the replacement of inorganic cations with organic dye cations and the gradual decomposition of the organic molecule in the interlamellar spacing. Thermo-Infrared spectra of Pyronin Y-bentonite sample up to high temperatures showed the thermal stability of the dye-clay composite as a result of the presence of π interactions. The pore structure characteristics of Pyronin Y-bentonite composite exhibited the increase in the number of mesopores during formation of the composite.

Elevated basal progesterone levels are associated with increased preovulatory progesterone rise but not with higher pregnancy rates in ICSI cycles with GnRH antagonists.

PubMed

Mutlu, Mehmet Firat; Erdem, Mehmet; Mutlu, Ilknur; Bulut, Berk; Erdem, Ahmet

2017-09-01

To ascertain the association between basal progesterone (P) levels and the occurrence of preovulatory progesterone rise (PPR) and clinical pregnancy rates (CPRs) in ICSI cycles with GnRH antagonists. Serum P levels of 464 patients were measured on day 2 and day of hCG of cycles. Cycles with basal P levels>1.6ng/mL were cancelled. All embryos were cryopreserved in cycles with P levels≥2ng/mL on the day of hCG. The primary outcome measures were the incidence of PPR (P>1.5ng/mL) and CPR with regard to basal P. Basal P levels were significantly higher in cycles with PPR than in those without PPR (0.63±0.31 vs. 0.48±0.28ng/mL). Area under the curve for basal P according to ROC analysis to discriminate between elevated and normal P levels on the day of hCG was 0.65 (0.58-0.71 95% CI, p<0.01). The cut-off value for basal P levels that best discriminates between cycles with and without PPR was 0.65ng/mL. Cycles with basal P levels above 0.65ng/mL had a significantly higher incidence of PPR (30.9% vs. 13.5%) but similar clinical and cumulative pregnancy rates (38.8% vs. 31.1% and 41.7% vs. 32.6%, respectively) in comparison to cycles with basal P levels below 0.65ng/mL. In multivariate regression analysis, basal P levels, LH level on the first day of antagonist administration, and estradiol levels on the day of hCG trigger were the variables that predicted PPR. Basal P levels were associated with increased incidence of PPR but not with CPR. Copyright © 2017 Elsevier B.V. All rights reserved.

Abnormal Ion Permeation through Cystic Fibrosis Respiratory Epithelium

NASA Astrophysics Data System (ADS)

Knowles, M. R.; Stutts, M. J.; Spock, A.; Fischer, N.; Gatzy, J. T.; Boucher, R. C.

1983-09-01

The epithelium of nasal tissue excised from subjects with cystic fibrosis exhibited higher voltage and lower conductance than tissue from control subjects. Basal sodium ion absorption by cystic fibrosis and normal nasal epithelia equaled the short-circuit current and was amiloride-sensitive. Amiloride induced chloride ion secretion in normal but not cystic fibrosis tissue and consequently was more effective in inhibiting the short-circuit current in cystic fibrosis epithelia. Chloride ion-free solution induced a smaller hyperpolarization of cystic fibrosis tissue. The increased voltage and amiloride efficacy in cystic fibrosis reflect absorption of sodium ions across an epithelium that is relatively impermeable to chloride ions.

Neonatal nociception elevated baseline blood pressure and attenuated cardiovascular responsiveness to noxious stress in adult rats.

PubMed

Chu, Ya-Chun; Yang, Cheryl C H; Lin, Ho-Tien; Chen, Pin-Tarng; Chang, Kuang-Yi; Yang, Shun-Chin; Kuo, Terry B J

2012-10-01

Neonatal nociception has significant long-term effects on sensory perception in adult animals. Although neonatal adverse experience affect future responsiveness to stressors is documented, little is known about the involvement of early nociceptive experiences in the susceptibility to subsequent nociceptive stress exposure during adulthood. The aim of this study is to explore the developmental change in cardiovascular regulating activity in adult rats that had been subjected to neonatal nociceptive insults. To address this question, we treated neonatal rats with an intraplantar injection of saline (control) or carrageenan at postnatal day 1. The carrageenan-treated rats exhibited generalized hypoalgesia at basal state, and localized hyperalgesia after re-nociceptive challenge induced by intraplantar injections of complete Freund's adjuvant (CFA) as adults. Then we recorded baseline cardiovascular variables and 24-h responsiveness to an injection of CFA in the free-moving adult rats with telemetric technique. The carrageenan-treated rats showed significantly higher basal blood pressures (110.3±3.16 vs. control 97.0±4.28 mmHg). In control animals, baroreceptor reflex sensitivity (BRS) decreased, sympathetic vasomotor activity increased, and parasympathetic activity was inhibited after CFA injection. Blood pressure elevation was evident (107.0±2.75 vs. pre-injection 97.0±4.28 mmHg). Comparatively, the carrageenan-treated rats showed a higher BRS (BrrLF 1.03±0.09 vs. control 0.70±0.06 ms/mmHg) and higher parasympathetic activity [0.93±0.17 vs. control 0.32±0.02 ln(ms²)] after CFA injection. The change in blood pressure is negligible (111.9±4.05 vs. pre-injection 110.3±3.16 mmHg). Our research has shown that neonatal nociception alters future pain sensation, raises basal blood pressure level, and attenuates cardiovascular responsiveness to nociceptive stress in adult rats. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Glucose, Lactate and Glutamine but not Glutamate Support Depolarization-Induced Increased Respiration in Isolated Nerve Terminals.

PubMed

Hohnholt, Michaela C; Andersen, Vibe H; Bak, Lasse K; Waagepetersen, Helle S

2017-01-01

Synaptosomes prepared from various aged and gene modified experimental animals constitute a valuable model system to study pre-synaptic mechanisms. Synaptosomes were isolated from whole brain and the XFe96 extracellular flux analyzer (Seahorse Bioscience) was used to study mitochondrial respiration and glycolytic rate in presence of different substrates. Mitochondrial function was tested by sequentially exposure of the synaptosomes to the ATP synthase inhibitor, oligomycin, the uncoupler FCCP (carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone) and the electron transport chain inhibitors rotenone and antimycin A. The synaptosomes exhibited intense respiratory activity using glucose as substrate. The FCCP-dependent respiration was significantly higher with 10 mM glucose compared to 1 mM glucose. Synaptosomes also readily used pyruvate as substrate, which elevated basal respiration, activity-dependent respiration induced by veratridine and the respiratory response to uncoupling compared to that obtained with glucose as substrate. Also lactate was used as substrate by synaptosomes but in contrast to pyruvate, mitochondrial lactate mediated respiration was comparable to respiration using glucose as substrate. Synaptosomal respiration using glutamate and glutamine as substrates was significantly higher compared to basal respiration, whereas oligomycin-dependent and FCCP-induced respiration was lower compared to the responses obtained in the presence of glucose as substrate. We provide evidence that synaptosomes are able to use besides glucose and pyruvate also the substrates lactate, glutamate and glutamine to support their basal respiration. Veratridine was found to increase respiration supported by glucose, pyruvate, lactate and glutamine and FCCP was found to increase respiration supported by glucose, pyruvate and lactate. This was not the case when glutamate was the only energy substrate.

Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction.

PubMed

Browne, Caroline A; Hanke, Joachim; Rose, Claudia; Walsh, Irene; Foley, Tara; Clarke, Gerard; Schwegler, Herbert; Cryan, John F; Yilmazer-Hanke, Deniz

2014-12-01

Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites 3,4-dihydroxyphenyacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 min after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or post-traumatic stress disorder.

Effect of Acute Swim Stress on Plasma Corticosterone and Brain Monoamine Levels in Bidirectionally Selected DxH Recombinant Inbred Mouse Strains Differing in Fear Recall and Extinction

PubMed Central

Browne, Caroline A.; Hanke, Joachim; Rose, Claudia; Walsh, Irene; Foley, Tara; Clarke, Gerard; Schwegler, Herbert; Cryan, John F.; Yilmazer-Hanke, Deniz

2015-01-01

Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus, and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 minutes after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or posttraumatic stress disorder. PMID:25117886

Characterization of basal gene expression trends over a diurnal cycle in Xiphophorus maculatus skin, brain and liver.

PubMed

Lu, Yuan; Reyes, Jose; Walter, Sean; Gonzalez, Trevor; Medrano, Geraldo; Boswell, Mikki; Boswell, William; Savage, Markita; Walter, Ronald

2018-06-01

Evolutionarily conserved diurnal circadian mechanisms maintain oscillating patterns of gene expression based on the day-night cycle. Xiphophorus fish have been used to evaluate transcriptional responses after exposure to various light sources and it was determined that each source incites distinct genetic responses in skin tissue. However, basal expression levels of genes that show oscillating expression patterns in day-night cycle, may affect the outcomes of such experiments, since basal gene expression levels at each point in the circadian path may influence the profile of identified light responsive genes. Lack of knowledge regarding diurnal fluctuations in basal gene expression patterns may confound the understanding of genetic responses to external stimuli (e.g., light) since the dynamic nature of gene expression implies animals subjected to stimuli at different times may be at very different stages within the continuum of genetic homeostasis. We assessed basal gene expression changes over a 24-hour period in 200 select Xiphophorus gene targets known to transcriptionally respond to various types of light exposure. We identified 22 genes in skin, 36 genes in brain and 28 genes in liver that exhibit basal oscillation of expression patterns. These genes, including known circadian regulators, produced the expected expression patterns over a 24-hour cycle when compared to circadian regulatory genes identified in other species, especially human and other vertebrate animal models. Our results suggest the regulatory network governing diurnal oscillating gene expression is similar between Xiphophorus and other vertebrates for the three Xiphophorus organs tested. In addition, we were able to categorize light responsive gene sets in Xiphophorus that do, and do not, exhibit circadian based oscillating expression patterns. Copyright © 2017 Elsevier Inc. All rights reserved.

Texture Development in a Friction Stir Lap-Welded AZ31B Magnesium Alloy

NASA Astrophysics Data System (ADS)

Naik, B. S.; Chen, D. L.; Cao, X.; Wanjara, P.

2014-09-01

The present study was aimed at characterizing the microstructure, texture, hardness, and tensile properties of an AZ31B-H24 Mg alloy that was friction stir lap welded (FSLWed) at varying tool rotational rates and welding speeds. Friction stir lap welding (FSLW) resulted in the presence of recrystallized grains and an associated hardness drop in the stir zone (SZ). Microstructural investigation showed that both the AZ31B-H24 Mg base metal (BM) and SZ contained β-Mg17Al12 and Al8Mn5 second phase particles. The AZ31B-H24 BM contained a type of basal texture (0001)<110> with the (0001) plane nearly parallel to the rolled sheet surface and <110> directions aligned in the rolling direction. FSLW resulted in the formation of another type of basal texture (0001)<100> in the SZ, where the basal planes (0001) became slightly tilted toward the transverse direction, and the prismatic planes (100) and pyramidal planes (101) exhibited a 30 deg + ( n - 1) × 60 deg rotation ( n = 1, 2, 3, …) with respect to the rolled sheet normal direction, due to the shear plastic flow near the pin surface that occurred from the intense local stirring. With increasing tool rotational rate and decreasing welding speed, the maximum intensity of the basal poles (0001) in the SZ decreased due to a higher degree of dynamic recrystallization that led to a weaker or more random texture. The tool rotational rate and welding speed had a strong effect on the failure load of FSLWed joints. A combination of relatively high welding speed (20 mm/s) and low tool rotational rate (1000 rpm) was observed to be capable of achieving a high failure load. This was attributed to the relatively small recrystallized grains and high intensity of the basal poles in the SZ arising from the low heat input as well as the presence of a small hooking defect.

Tens of micron-sized unilamellar nanosheets of Y/Eu layered rare-earth hydroxide: efficient exfoliation via fast anion exchange and their self-assembly into oriented oxide film with enhanced photoluminescence

NASA Astrophysics Data System (ADS)

Zhu, Qi; Li, Ji-Guang; Li, Xiaodong; Sun, Xudong; Qi, Yang; Zhu, Miaoyong; Sakka, Yoshio

2014-02-01

Layered rare-earth hydroxide (LRH) crystals of (Y0.95Eu0.05)2(OH)5NO3·nH2O with a lateral size of ˜ 300 μm and a thickness of ˜ 9 μm have been synthesized via a hydrothermal reaction of mixed nitrate solutions in the presence of mineralizer NH4NO3 at 200 °C for 24 h. LRH exhibits the ability to undergo intercalation and anion exchange with DS- (C12H25OSO3-) via hydrothermal treatment. Compared with traditional anion exchange at room temperature, hydrothermal processing not only shortens the anion exchange time from 720 to 24 h but also increases the basal spacing. The arrangements of DS- in the interlayer of LRH are significantly affected by the DS- concentration and reaction temperature, and the basal spacing of the LRH-DS sample in the crystal edge is assumed to be larger than that in the crystal center. A higher DS- concentration and reaction temperature both induce more intercalation of DS- anions into the interlayer gallery, thus yielding a larger basal spacing. Unilamellar nanosheets with a lateral size of ⩾60 μm and a thickness of ˜ 1.6 nm can be obtained by delaminating LRH-DS in formamide. The resultant unilamellar nanosheets are single crystalline. Transparent (Y0.95Eu0.05)2O3 phosphor films with a uniform [111] orientation and a layer thickness of ˜ 90 nm were constructed with the nanosheets as building blocks via spin-coating, followed by proper annealing. The oriented oxide film exhibits a strong red emission at 614 nm (the 5D0-7F2 transition of Eu3+), whose intensity is ˜ 2 times that of the powder form owing to the significant exposure of the (222) facets.

Metastatic giant basal cell carcinoma: a case report.

PubMed

Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

2016-01-01

Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

Deformation Mechanisms and Formability Window for As-Cast Mg-6Al-2Ca-1Sn-0.3Sr Alloy (MRI 230D)

NASA Astrophysics Data System (ADS)

Suresh, Kalidass; Pitcheswara Rao, Kamineni; Chalasani, Dharmendra; Yellapregada Venkata Rama Krishna, Prasad; Hort, Norbert; Dieringa, Hajo

2018-03-01

The hot deformation characteristics of MRI 230D alloy have been evaluated in the temperature range 260-500 °C and strain rate range 0.0003-10 s-1, on the basis of processing map. The processing map exhibited two domains in the ranges: (1) 300-370 °C and 0.0003-0.001 s-1 and (2) 370-480 °C and 0.0003-0.1 s-1. Dynamic recrystallization occurs in the both domains with basal slip dominating in the first domain along with climb as recovery process and second-order pyramidal slip dominating in the second with the recovery by cross-slip. In Domains (1) and (2), the apparent activation energy values estimated using the kinetic rate equation are 143 and 206 kJ/mole, respectively, the first one being close to that for lattice self-diffusion confirming climb. It is recommended that the alloy is best processed at 450 °C and strain rates less than 0.1 s-1, where non-basal slip and cross-slip occur extensively to impart excellent workability. The alloy exhibits flow instability in the form of adiabatic shear band formation and flow localization at lower temperatures and higher strain rates. Forging of a cup-shaped component was performed under various conditions, and the results validated the predictions of the processing map on the workability domains as well as the instability regimes.

The Acyl Desaturase CER17 Is Involved in Producing Wax Unsaturated Primary Alcohols and Cutin Monomers1[OPEN

PubMed Central

Yang, Xianpeng; Zhao, Huayan; Kosma, Dylan K.; Dyer, John M.; Li, Rongjun; Liu, Xiulin; Wang, Zhouya; Jenks, Matthew A.

2017-01-01

We report n-6 monounsaturated primary alcohols (C26:1, C28:1, and C30:1 homologs) in the cuticular waxes of Arabidopsis (Arabidopsis thaliana) inflorescence stem, a class of wax not previously reported in Arabidopsis. The Arabidopsis cer17 mutant was completely deficient in these monounsaturated alcohols, and CER17 was found to encode a predicted ACYL-COENZYME A DESATURASE LIKE4 (ADS4). Studies of the Arabidopsis cer4 mutant and yeast variously expressing CER4 (a predicted fatty acyl-CoA reductase) with CER17/ADS4, demonstrated CER4’s principal role in synthesis of these monounsaturated alcohols. Besides unsaturated alcohol deficiency, cer17 mutants exhibited a thickened and irregular cuticle ultrastructure and increased amounts of cutin monomers. Although unsaturated alcohols were absent throughout the cer17 stem, the mutation’s effects on cutin monomers and cuticle ultrastructure were much more severe in distal than basal stems, consistent with observations that the CER17/ADS4 transcript was much more abundant in distal than basal stems. Furthermore, distal but not basal stems of a double mutant deficient for both CER17/ADS4 and LONG-CHAIN ACYL-COA SYNTHETASE1 produced even more cutin monomers and a thicker and more disorganized cuticle ultrastructure and higher cuticle permeability than observed for wild type or either mutant parent, indicating a dramatic genetic interaction on conversion of very long chain acyl-CoA precursors. These results provide evidence that CER17/ADS4 performs n-6 desaturation of very long chain acyl-CoAs in both distal and basal stems and has a major function associated with governing cutin monomer amounts primarily in the distal segments of the inflorescence stem. PMID:28069670

The Acyl Desaturase CER17 Is Involved in Producing Wax Unsaturated Primary Alcohols and Cutin Monomers.

PubMed

Yang, Xianpeng; Zhao, Huayan; Kosma, Dylan K; Tomasi, Pernell; Dyer, John M; Li, Rongjun; Liu, Xiulin; Wang, Zhouya; Parsons, Eugene P; Jenks, Matthew A; Lü, Shiyou

2017-02-01

We report n-6 monounsaturated primary alcohols (C 26:1 , C 28:1 , and C 30:1 homologs) in the cuticular waxes of Arabidopsis (Arabidopsis thaliana) inflorescence stem, a class of wax not previously reported in Arabidopsis. The Arabidopsis cer17 mutant was completely deficient in these monounsaturated alcohols, and CER17 was found to encode a predicted ACYL-COENZYME A DESATURASE LIKE4 (ADS4). Studies of the Arabidopsis cer4 mutant and yeast variously expressing CER4 (a predicted fatty acyl-CoA reductase) with CER17/ADS4, demonstrated CER4's principal role in synthesis of these monounsaturated alcohols. Besides unsaturated alcohol deficiency, cer17 mutants exhibited a thickened and irregular cuticle ultrastructure and increased amounts of cutin monomers. Although unsaturated alcohols were absent throughout the cer17 stem, the mutation's effects on cutin monomers and cuticle ultrastructure were much more severe in distal than basal stems, consistent with observations that the CER17/ADS4 transcript was much more abundant in distal than basal stems. Furthermore, distal but not basal stems of a double mutant deficient for both CER17/ADS4 and LONG-CHAIN ACYL-COA SYNTHETASE1 produced even more cutin monomers and a thicker and more disorganized cuticle ultrastructure and higher cuticle permeability than observed for wild type or either mutant parent, indicating a dramatic genetic interaction on conversion of very long chain acyl-CoA precursors. These results provide evidence that CER17/ADS4 performs n-6 desaturation of very long chain acyl-CoAs in both distal and basal stems and has a major function associated with governing cutin monomer amounts primarily in the distal segments of the inflorescence stem. © 2017 American Society of Plant Biologists. All Rights Reserved.

Simulating Ice Dynamics in the Amundsen Sea Sector

NASA Astrophysics Data System (ADS)

Schwans, E.; Parizek, B. R.; Morlighem, M.; Alley, R. B.; Pollard, D.; Walker, R. T.; Lin, P.; St-Laurent, P.; LaBirt, T.; Seroussi, H. L.

2017-12-01

Thwaites and Pine Island Glaciers (TG; PIG) exhibit patterns of dynamic retreat forced from their floating margins, and could act as gateways for destabilization of deep marine basins in the West Antarctic Ice Sheet (WAIS). Poorly constrained basal conditions can cause model predictions to diverge. Thus, there is a need for efficient simulations that account for shearing within the ice column, and include adequate basal sliding and ice-shelf melting parameterizations. To this end, UCI/NASA JPL's Ice Sheet System Model (ISSM) with coupled SSA/higher-order physics is used in the Amundsen Sea Embayment (ASE) to examine threshold behavior of TG and PIG, highlighting areas particularly vulnerable to retreat from oceanic warming and ice-shelf removal. These moving-front experiments will aid in targeting critical areas for additional data collection in ASE as well as for weighting accuracy in further melt parameterization development. Furthermore, a sub-shelf melt parameterization, resulting from Regional Ocean Modeling System (ROMS; St-Laurent et al., 2015) and coupled ISSM-Massachusetts Institute of Technology general circulation model (MITgcm; Seroussi et al., 2017) output, is incorporated and initially tested in ISSM. Data-guided experiments include variable basal conditions and ice hardness, and are also forced with constant modern climate in ISSM, providing valuable insight into i) effects of different basal friction parameterizations on ice dynamics, illustrating the importance of constraining the variable bed character beneath TG and PIG; ii) the impact of including vertical shear in ice flow models of outlet glaciers, confirming its role in capturing complex feedbacks proximal to the grounding zone; and iii) ASE's sensitivity to sub-shelf melt and ice-front retreat, possible thresholds, and how these affect ice-flow evolution.

Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species.

PubMed

Chen, Qianqian; Heston, Jonathan B; Burkett, Zachary D; White, Stephanie A

2013-10-01

Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song.

Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species

PubMed Central

Chen, Qianqian; Heston, Jonathan B.; Burkett, Zachary D.; White, Stephanie A.

2013-01-01

SUMMARY Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song. PMID:24006346

Emergence of context-dependent variability across a basal ganglia network.

PubMed

Woolley, Sarah C; Rajan, Raghav; Joshua, Mati; Doupe, Allison J

2014-04-02

Context dependence is a key feature of cortical-basal ganglia circuit activity, and in songbirds the cortical outflow of a basal ganglia circuit specialized for song, LMAN, shows striking increases in trial-by-trial variability and bursting when birds sing alone rather than to females. To reveal where this variability and its social regulation emerge, we recorded stepwise from corticostriatal (HVC) neurons and their target spiny and pallidal neurons in Area X. We find that corticostriatal and spiny neurons both show precise singing-related firing across both social settings. Pallidal neurons, in contrast, exhibit markedly increased trial-by-trial variation when birds sing alone, created by highly variable pauses in firing. This variability persists even when recurrent inputs from LMAN are ablated. These data indicate that variability and its context sensitivity emerge within the basal ganglia network, suggest a network mechanism for this emergence, and highlight variability generation and regulation as basal ganglia functions. Copyright © 2014 Elsevier Inc. All rights reserved.

Emergence of context-dependent variability across a basal ganglia network

PubMed Central

Woolley, Sarah C.; Rajan, Raghav; Joshua, Mati; Doupe, Allison J.

2014-01-01

Summary Context-dependence is a key feature of cortical-basal ganglia circuit activity, and in songbirds, the cortical outflow of a basal ganglia circuit specialized for song, LMAN, shows striking increases in trial-by-trial variability and bursting when birds sing alone rather than to females. To reveal where this variability and its social regulation emerge, we recorded stepwise from cortico-striatal (HVC) neurons and their target spiny and pallidal neurons in Area X. We find that cortico-striatal and spiny neurons both show precise singing-related firing across both social settings. Pallidal neurons, in contrast, exhibit markedly increased trial-by-trial variation when birds sing alone, created by highly variable pauses in firing. This variability persists even when recurrent inputs from LMAN are ablated. These data indicate that variability and its context-sensitivity emerge within the basal ganglia network, suggest a network mechanism for this emergence, and highlight variability generation and regulation as basal ganglia functions. PMID:24698276

Site, gender and age variation in normal skin colour on the back and the forearm: tristimulus colorimeter measurements.

PubMed

Fullerton, A; Serup, J

1997-02-01

To study whether anatomical location and age and gender of subjects had any influence on the objective skin colour measurements. Baseline colour in prone position was measured with the Minolta ChromaMeter® in the upper, middle and lower level of the upper back and on the forearm of 168 volunteers. These two sites are commonly used in skin testing. Higher basal a* and lower basal L* levels were found on the upper scapular region compared to the lower scapular region and the subscapular region. The basal b* level showed no variation relative to site. The basal a* and the basal b* levels were lower on the forearm compared to the upper back while the basal L* level was higher. Females above 65 years showed a less coloured skin with lower values as compared to those of younger age. Females were found to have a generally lower basal a* level than males both on the upper back and forearm skin. These relatively major differences and sources of variation have to be considered when planning irritancy studies where colour differences between erythema and normal skin is used.

Developing Higher Order Reading Comprehension Skills in the Learning Disabled Student: A Non-Basal Approach.

ERIC Educational Resources Information Center

Solomon, Sheila

This practicum study evaluated a non-basal, multidisciplinary, multisensory approach to teaching higher order reading comprehension skills to eight fifth-grade learning-disabled students from low socioeconomic minority group backgrounds. The four comprehension skills were: (1) identifying the main idea; (2) determining cause and effect; (3) making…

Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy (BBIT) for glycemic control, body weight stability, and treatment satisfaction in patients treated using BBIT for type 2 diabetes without severe insulin deficiency: A randomized prospective pilot study.

PubMed

Yamamoto, Saki; Hayashi, Toshiyuki; Ohara, Makoto; Goto, Satoshi; Sato, Jun; Nagaike, Hiroe; Fukase, Ayako; Sato, Nobuko; Hiromura, Munenori; Tomoyasu, Masako; Nakanishi, Noriko; Lee, Soushou; Osamura, Anna; Yamamoto, Takeshi; Fukui, Tomoyasu; Hirano, Tsutomu

2018-03-26

We examined whether 0.9 mg/day liraglutide plus basal insulin (Lira-basal) is superior to basal-bolus insulin therapy (BBIT) for type 2 diabetes (T2DM) without severe insulin deficiency as determined by glucagon stimulation. Fifty patients receiving BBIT were enrolled in this 24-week, prospective, randomized, open-labeled study. After excluding subjects with fasting C-peptide immunoreactivity (CPR) < 1.0 ng/mL and CPR increase < 1.0 ng/mL at 6 min post glucagon injection, 25 were randomly allocated to receive Lira-basal (n = 12) or continued BBIT (n = 13). Primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight (BW), 7-point self-monitored blood glucose (SMBG), and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores. The Lira-basal group demonstrated reduced HbA1c, whereas the BBIT group showed no change. BW was reduced in the Lira-basal group but increased in the BBIT group. The Lira-basal group also exhibited significantly reduced pre-breakfast and pre-lunch SMBG. DTSQs scores improved in the Lira-basal group but not the BBIT group. Plasma lipids, liver function, and kidney function were not significantly changed in either group. Lira-basal therapy is superior to BBIT for T2DM without severe insulin deficiency. This study was registered with UMIN Clinical Trials Registry (UMIN000028313). Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Primary squamous cell carcinoma of the breast with unusual basal-HER2 phenotype.

PubMed

Shui, Ruohong; Li, Anqi; Yang, Fei; Zhou, Xiaoyan; Yu, Baohua; Xu, Xiaoli; Yang, Wentao

2014-01-01

To report three cases of primary squamous cell carcinoma of the breast with an unusual "basal-HER2" phenotype. Clinical data were analyzed. Morphological features were observed. Immunohistochemical study for ER, PR, HER2, Ki-67, CK 5/6, CK10/13, CK14, EGFR, P63 and FISH detection of HER2 gene amplification were performed. Three patients were all female with 26, 57 and 66 years old. The tumors were 3 cm, 4 cm and 5 cm in size respectively. Morphologically, all three tumors were pure squamous cell carcinoma and entirely composed metaplastic squamous cells. Two tumors were moderately differentiated and one was poorly differentiated. All three patients were positive for P63 or CK10/13. All three tumors exhibited basal-HER2 phenotype: negative for ER and PR, positive for HER2 protein and HER2 gene amplification, and positive for at least two basal markers. SCC with basal-HER2 phenotype is an extremely rare subset of breast carcinoma. Since it may have worse prognosis than typical basal-like SCC, recognization of this unusual SCC in routine work may have obvious clinical significance.

The incidence of satellite cysts in keratocystic odontogenic tumors.

PubMed

Pavelić, Boiidar; Katunarić, Marina; Segović, Sanja; Karadole, Maja Cimas; Katanec, Davor; Saban, Aida; Puhar, Ivan

2014-03-01

Renaming of the Odontogenic Keratocyst as the Keratocystic Odontogenic Tumor by the World Health Organization (WHO) is based on the aggressive nature of this lesion. Satellite cysts founded in the walls of the original cysts may give rise to a new lesion formation. The aim of this retrospecitve study was to identify the existence of specific features according incidence of satellite cysts and the pallisading of the basal layer of the epithelium and to establish their mutual correlation. The histopathologic data of Keratocystic Odontogenic Tumor on the basis of new WHO's classification (2005) were analized. Prominent palisade basal cell layer was found in 415 (94.75%) and partially absent palisade basal cell layer in 23 (5.25%) cases. Satellite cysts were presented in prominent palisade basal cell layer in 85 specimens (20.5%) and in cases with partial absent of the palisade basal layer in 3 spicemens (13%). The higher the frequency of pallisading was the higher the frequency of satellite cysts was (p > 0.05).

Distribution and ultrastructural characteristics of dark cells in squamous metaplasias of the respiratory tract epithelium.

PubMed Central

Klein-Szanto, A. J.; Nettesheim, P.; Pine, A.; Martin, D.

1981-01-01

Dark epithelial basal cells were found in both carcinogen-induced and non-carcinogen-induced squamous metaplasias of the tracheal epithelium. Formaldehyde-induced squamous metaplasias exhibited 4% dark cells in the basal layer. Metaplasias induced by vitamin A deficiency and those induced by dimethylbenz(alpha)anthracene (DMBA) without atypia showed 18--20% basal dark cells. DMBA-induced metaplasias with moderate to severe atypia exhibited 50% basal dark cells. The labeling index of basal cells in metaplastic epithelia, regardless of the inducing agent, was 16--18%, ie, the same as that of the normal esophageal stratified squamous epithelium. The percentage of labeled dark basal cells per total dark cell population was approximately 19% in the non-carcinogen-induced metaplasias and in the DMBA-induced metaplasias without atypia. In the atypical metaplasias induced by DMA this percentage increased to 26. On the basis of ultrastructural observations, five types of dark epithelial cells could be distinguished in the metaplastic epithelia: Type I (ovoid or fusiform dark cell with abundant cytoplasmic filaments, desmosomes, and free ribosomes--dark keratinocyte type); Type II (ovoid or spherical small cell with scant cytoplasm with few organelles--basal respiratory type); Type III (irregular or ovoid, few cytoplasmic filaments and organelles and desmosomes, extremely abundant free ribosomes--dedifferentiated type); Type IV (fusiform or ovoid, large mitochondria, prominent ergastoplasm, secretion droplets--mucous cell type); and type V (irregular shape, organelle remnants, vacuoles, pyknotic nuclei--involutional-cell type). Type I was the predominant cell type in formaldehyde-induced metaplasias and was also commonly seen in DMBA-induced metaplasias without atypia. Type II predominated in metaplasias induced by vitamin A deficiency. Type III was seen in DMBA-induced metaplasias and was the predominant cell type in the atypical epithelial alterations. Type IV cells occurred only in the latter, and Type V cells were occasionally seen in formaldehyde- as well as in DMBA-induced atypical metaplasias. Each type of squamous metaplasia could thus be recognized by a determined numerical distribution of dark cells in the basal layer and a specific pattern of distribution of the ultrastructurally defined dark cell categories. Images Figure 3 Figure 4 Figure 5 Figure 1 Figure 2 Figure 6 Figure 7 PMID:6786102

Mechanical Properties of Mg-Gd and Mg-Y Solid Solutions

NASA Astrophysics Data System (ADS)

Kula, Anna; Jia, Xiaohui; Mishra, Raj K.; Niewczas, Marek

2016-12-01

The mechanical properties of Mg-Gd and Mg-Y solid solutions have been studied under uniaxial tension and compression between 4 K and 298 K (-269 °C and 25 °C). The results reveal that Mg-Gd alloys exhibit higher strength and ductility under tension and compression attributed to the more effective solid solution strengthening and grain-boundary strengthening effects. Profuse twinning has been observed under compression, resulting in a material texture with strong dominance of basal component parallel to compression axis. Under tension, twining is less active and the texture evolution is controlled mostly by slip. The alloys exhibit pronounced yield stress asymmetry and significantly different work-hardening behavior under tension and compression. Increasing of Gd and/or Y concentration leads to the reduction of the tension-compression asymmetry due to the weakening of the recrystallization texture and more balanced twinning and slip activity during plastic deformation. The results suggest that under compression of Mg-Y alloys slip is more active than twinning in comparison to Mg-Gd alloys.

Solute softening and defect generation during prismatic slip in magnesium alloys

NASA Astrophysics Data System (ADS)

Yi, Peng; Cammarata, Robert C.; Falk, Michael L.

2017-12-01

Temperature and solute effects on prismatic slip of 〈a〉 dislocations in Mg are studied using molecular dynamics simulation. Prismatic slip is controlled by the low mobility screw dislocation. The screw dislocation glides on the prismatic plane through alternating cross-slip between the basal plane and the prismatic plane. In doing so, it exhibits a locking-unlocking mechanism at low temperatures and a more continuous wavy propagation at high temperatures. The dislocation dissociates into partials on the basal plane and the constriction formation of the partials is identified to be the rate-limiting process for unlocking. In addition, the diffusion of partials on the basal plane enables the formation of jogs and superjogs for prismatic slip, which lead to the generation of vacancies and dislocation loops. Solute softening in Mg alloys was observed in the presence of both Al and Y solute. The softening in prismatic slip is found to be due to solute pinning on the basal plane, instead of the relative energy change of the screw dislocation on the basal and prismatic planes, as has been hypothesized.

A time- and matrix-dependent TGFBR3–JUND–KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies

PubMed Central

Wang, Chun-Chao; Bajikar, Sameer S.; Jamal, Leen; Atkins, Kristen A.; Janes, Kevin A.

2014-01-01

Basal-like breast carcinoma is characterized by poor prognosis and high intratumor heterogeneity. In an immortalized basal-like breast epithelial cell line, we identified two anti-correlated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic 3D culture. The first contains multiple TGFβ-related genes including TGFBR3, whereas the second contains JUND and the basal-like marker, KRT5. TGFBR3 and JUND interconnect through four negative-feedback loops to form a circuit that exhibits spontaneous damped oscillations in 3D culture. The TGFBR3–JUND circuit appears conserved in some premalignant lesions that heterogeneously express KRT5. The circuit depends on ECM engagement, as detachment causes a rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine tenascin C, which is critical for intraductal colonization of basal-like breast cancer cells in vivo. Intratumor heterogeneity need not stem from partial differentiation and could instead reflect dynamic toggling of cells between expression states that are not cell autonomous. PMID:24658685

In-situ analysis of the slip activity during tensile deformation of cast and extruded Mg-10Gd-3Y-0.5Zr (wt.%) at 250 °C

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, H.; The State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240; Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI 48824

The slip activity and slip interaction in tensile deformation of peak-aged cast and extruded Mg-10Gd-3Y-0.5Zr (wt.%) at 250 °C was investigated using in-situ scanning electron microscopy. Basal slip was the most likely system to be activated during the tensile deformation, while prismatic < a > and pyramidal < c + a > slip also contributed to the deformation. No twinning was observed. The number of non-basal slip systems accounted for ~ 36% of the total active slip systems for the cast alloy, while non-basal slip accounted for 12–17% of the total deformation observations in the extruded alloy. Multiple-slip was observedmore » within grains, and the basal/prismatic pairing type dominated the multiple-slip observations. Slip transfer occurred across grain boundaries and most of the slip transfer observations showed basal-basal type. The involved slip systems of slip transfer pairs were always associated with the same < a > direction. The slip transfer occurred more easily at low angle boundaries (LABs) and boundaries with misorientations greater than 75°. - Highlights: • Slip deformation of a Mg-RE alloy at 250 °C was investigated using in-situ SEM. • The extruded-T5 GW103 alloy did not exhibit a high anisotropic behavior. • Multiple-slip was observed within grains, and basal/prismatic type dominated. • Slip transfer occurred and most of the observations showed basal-basal type. • Slip transfer occurred more easily at LABs and boundaries with misorientations > 75°.« less

Cholinergic basal forebrain structures are not essential for mediation of the arousing action of glutamate.

PubMed

Lelkes, Zoltán; Abdurakhmanova, Shamsiiat; Porkka-Heiskanen, Tarja

2017-09-18

The cholinergic basal forebrain contributes to cortical activation and receives rich innervations from the ascending activating system. It is involved in the mediation of the arousing actions of noradrenaline and histamine. Glutamatergic stimulation in the basal forebrain results in cortical acetylcholine release and suppression of sleep. However, it is not known to what extent the cholinergic versus non-cholinergic basal forebrain projection neurones contribute to the arousing action of glutamate. To clarify this question, we administered N-methyl-D-aspartate (NMDA), a glutamate agonist, into the basal forebrain in intact rats and after destruction of the cholinergic cells in the basal forebrain with 192 immunoglobulin (Ig)G-saporin. In eight Han-Wistar rats with implanted electroencephalogram/electromyogram (EEG/EMG) electrodes and guide cannulas for microdialysis probes, 0.23 μg 192 IgG-saporin was administered into the basal forebrain, while the eight control animals received artificial cerebrospinal fluid. Two weeks later, a microdialysis probe targeted into the basal forebrain was perfused with cerebrospinal fluid on the baseline day and for 3 h with 0.3 mmNMDA on the subsequent day. Sleep-wake activity was recorded for 24 h on both days. NMDA exhibited a robust arousing effect in both the intact and the lesioned rats. Wakefulness was increased and both non-REM and REM sleep were decreased significantly during the 3-h NMDA perfusion. Destruction of the basal forebrain cholinergic neurones did not abolish the wake-enhancing action of NMDA. Thus, the cholinergic basal forebrain structures are not essential for the mediation of the arousing action of glutamate. © 2017 European Sleep Research Society.

Occult pneumothoraces in Chinese patients with significant blunt chest trauma: radiological classification and proposed clinical significance.

PubMed

Lee, Ryan K L; Graham, Colin A; Yeung, Janice H H; Ahuja, Anil T; Rainer, Timothy H

2012-12-01

An occult pneumothorax (OP) is a pneumothorax not seen on a supine chest X-ray (CXR) but detected on abdominal or thoracic computed tomography (CT) scanning. With the increasing use of CT in the management of significantly injured trauma patients, more OPs are being detected. The aim of this study was to classify OPs diagnosed on thoracic CT (TCT) and correlate them with their clinical significance. Retrospective analysis of prospectively collected trauma registry data. Total 36 (N=36) consecutive significantly injured trauma patients admitted through the emergency department (ED) who sustained blunt chest trauma and underwent TCT between 1 January 2007 and 31 December 2008 were included. OP was defined as the identification (by a consultant radiologist) of a pneumothorax on TCT that had not been detected on supine CXR. OPs were classified by laterality (unilateral/bilateral) and location (apical, basal, non apical/basal). The size of pneumothoraces, severity of injury [including number of associated thoracic injuries and injury severity score (ISS)], length of hospital stay and mortality were compared between groups. The need for tube thoracostomy and clinical outcome were also analysed. Patients with bilateral OPs (N=8) had significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 23, p=0.02) and longer hospital stay (median: 20 days vs. 11 days, p=0.01) than those with a unilateral OP (N=28). Basal OPs (N=7) were significantly larger than apical (N=10) and non-apical/basal Ops (N=11). Basal OPs were associated with significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 17 days, p=0.02) than apical Ops, which had higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 15 days, p=0.02) than non-apical/basal OPs. Non-apical/basal OPs were associated with more related injuries (median: 2 vs. 1, p=0.02) than apical OPs. All apical and non-apical/basal OPs were successfully managed expectantly without associated mortality. This TCT classification of OP is proposed to help clinicians to decide on subsequent management of the OP. Basal OPs are significantly larger in size, and both basal and bilateral OPs are associated with higher severity of injury and longer hospital stay. These groups of patient may benefit from prophylactic tube thoracostomy instead of conservative treatment. On the other hand, apical and non-apical/basal groups is smaller in size, less severely injured and thus can be successfully managed expectantly. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations

PubMed Central

Vinciati, Federica

2017-01-01

Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical–basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on “direct pathway” SPNs (dSPNs) and “indirect pathway” SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (∼1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15–30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, and SPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits. SIGNIFICANCE STATEMENT Chronic depletion of dopamine from the striatum, a part of the basal ganglia, causes some symptoms of Parkinson's disease. Here, we elucidate how dopamine depletion alters striatal neuron firing in vivo, with an emphasis on defining whether and how spiny projection neurons (SPNs) engage in the synchronized beta-frequency (15–30 Hz) oscillations that become pathologically exaggerated throughout basal ganglia circuits in parkinsonism. We discovered that a select population of so-called “indirect pathway” SPNs not only fire at abnormally high rates, but are also particularly prone to being recruited to exaggerated beta oscillations. Our results provide an important link between two complementary theories that explain the presentation of disease symptoms on the basis of changes in firing rate or firing synchronization/rhythmicity. PMID:28847810

Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease.

PubMed

Frejo, Lidia; Gallego-Martinez, Alvaro; Requena, Teresa; Martin-Sanz, Eduardo; Amor-Dorado, Juan Carlos; Soto-Varela, Andres; Santos-Perez, Sofia; Espinosa-Sanchez, Juan Manuel; Batuecas-Caletrio, Angel; Aran, Ismael; Fraile, Jesus; Rossi-Izquierdo, Marcos; Lopez-Escamez, Jose Antonio

2018-04-13

Epidemiological studies have found a higher prevalence of allergic symptoms and positive prick tests in patients with Meniere's disease (MD); however the effect of allergenic extracts in MD has not been established. Thus, this study aims to determine the effect of Aspergillus and Penicillium stimulation in cytokine release and gene expression profile in MD. Patients with MD showed higher basal levels of IL-1β, IL-1RA, IL-6 and TNF-α when compared to healthy controls. We observed that IL-1β levels had a bimodal distribution suggesting two different subgroups of patients, with low and high basal levels of cytokines. Gene expression profile in peripheral blood mononuclear cells (PBMC) showed significant differences in patients with high and low basal levels of IL-1β. We found that both mold extracts triggered a significant release of TNF-α in MD patients, which were not found in controls. Moreover, after mold stimulation, MD patients showed a different gene expression profile in PBMC, according to the basal levels of IL-1β. The results indicate that a subset of MD patients have higher basal levels of proinflammatory cytokines and the exposure to Aspergillus and Penicillium extracts may trigger additional TNF-α release and contribute to exacerbate inflammation.

Impact of early developmental fluoride exposure on the peripheral pain sensitivity in mice.

PubMed

Ma, Jing; Liu, Fei; Liu, Peng; Dong, Ying-Ying; Chu, Zheng; Hou, Tie-Zhou; Dang, Yong-Hui

2015-12-01

Consumption of high concentration of fluoride in the drinking water would cause the fluorosis and chronic pain. Similar pain syndrome appeared in the patients in fluoride therapy of osteoporotic. The aim of the current study was to examine whether exposing immature mice to fluoride would modify the peripheral pain sensitivity or even cause a pain syndrome. We gave developmental fluoride exposure to mice in different concentration (0mg/L, 50mg/L and 100mg/L) and evaluated their basal pain threshold. Von Frey hair test, hot plate test and formalin test were conducted to examine the mechanical, thermal nociceptive threshold and inflammatory pain, respectively. In addition, the expression of hippocampal brain-derived neurotrophic factor (BDNF) was also evaluated by Western blotting. Hyperalgesia in fluoride exposure mice was exhibited in the Von Frey hair test, hot plate test and formalin test. Meanwhile, the expression of BDNF was significantly higher than that of control group. The results suggest that early developmental fluoride exposure may lower the basal pain threshold and be associated with the increasing of BDNF expression in hippocampus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Strengthening Effect of Extruded Mg-8Sn-2Zn-2Al Alloy: Influence of Micro and Nano-Size Mg2Sn Precipitates

PubMed Central

Cheng, Weili; Bai, Yang; Wang, Lifei; Wang, Hongxia; Bian, Liping; Yu, Hui

2017-01-01

In this study, Mg-8Sn-2Zn-2Al (TZA822) alloys with varying Mg2Sn contents prior to extrusion were obtained by different pre-treatments (without and with T4), and the strengthening response related to micro and nano-size Mg2Sn precipitates in the extruded TZA822 alloys was reported. The results showed that the morphology of nano-size Mg2Sn precipitates exhibits a significant change in basal plane from rod-like to spherical, owing to the decrement in the fraction of micro-size particles before extrusion. Meanwhile, the spherical Mg2Sn precipitates provided a much stronger strengthening effect than did the rod-like ones, which was ascribed to uniform dispersion and refinement of spherical precipitates to effectively hinder basal dislocation slip. As a consequence, the extruded TZA822 alloy with T4 showed a higher tensile yield strength (TYS) of 245 MPa, ultimate tensile strength (UTS) of 320 MPa and elongation (EL) of 26.5%, as well as a lower degree of yield asymmetry than their counterpart without T4. Detailed reasons for the strengthening effect were given and analyzed. PMID:28773180

Strengthening Effect of Extruded Mg-8Sn-2Zn-2Al Alloy: Influence of Micro and Nano-Size Mg₂Sn Precipitates.

PubMed

Cheng, Weili; Bai, Yang; Wang, Lifei; Wang, Hongxia; Bian, Liping; Yu, Hui

2017-07-18

In this study, Mg-8Sn-2Zn-2Al (TZA822) alloys with varying Mg₂Sn contents prior to extrusion were obtained by different pre-treatments (without and with T4), and the strengthening response related to micro and nano-size Mg₂Sn precipitates in the extruded TZA822 alloys was reported. The results showed that the morphology of nano-size Mg₂Sn precipitates exhibits a significant change in basal plane from rod-like to spherical, owing to the decrement in the fraction of micro-size particles before extrusion. Meanwhile, the spherical Mg₂Sn precipitates provided a much stronger strengthening effect than did the rod-like ones, which was ascribed to uniform dispersion and refinement of spherical precipitates to effectively hinder basal dislocation slip. As a consequence, the extruded TZA822 alloy with T4 showed a higher tensile yield strength (TYS) of 245 MPa, ultimate tensile strength (UTS) of 320 MPa and elongation (EL) of 26.5%, as well as a lower degree of yield asymmetry than their counterpart without T4. Detailed reasons for the strengthening effect were given and analyzed.

The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice

PubMed Central

Ju, Xiang-Chun; Hou, Qiong-Qiong; Sheng, Ai-Li; Wu, Kong-Yan; Zhou, Yang; Jin, Ying; Wen, Tieqiao; Yang, Zhengang; Wang, Xiaoqun; Luo, Zhen-Ge

2016-01-01

Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding. DOI: http://dx.doi.org/10.7554/eLife.18197.001 PMID:27504805

Effect of Extrusion Parameters on Texture and Microstructure Evolution of Extruded Mg-1 pctMn and Mg-1 pctMn-Sr Alloys

NASA Astrophysics Data System (ADS)

Borkar, Hemant; Pekguleryuz, Mihriban

2015-01-01

Three Mg alloys Mg-1 pctMn (M1), Mg-1 pctMn-1.3 pctSr, and Mg-1 pctMn-2.1 pctSr were subjected to two different extrusion temperatures and two different extrusion speeds in lab-scale extrusion. The extrusion temperatures of 573 K and 673 K (300 °C and 400 °C) and two ram speeds of 4 and 8 mm/s were used at constant extrusion ratio of 7. M1 exhibited strong basal texture after extrusion at 673 K (400 °C) at higher speed. At 573 K (300 °C), recrystallization in all alloys takes place completely or partially by continuous dynamic recrystallization mechanism, while particle stimulated nucleation (PSN) occurs in all M1-Sr alloys at both extrusion temperatures and speeds. At 673 K (400 °C), grain boundary bulging is the only recrystallization mechanism in alloy M1, while it occurs in combination with PSN in M1-Sr alloys. The effect of texture weakening by PSN is more significant in M1-Sr alloys extruded at 573 K (400 °C). The plant extrusion trials were carried out on Mg-1 pctMn, Mg-1 pctMn-0.3 pctSr, and Mg-1 pctMn-2.1 pctSr at 623 K (350 °C) with different speeds than in lab-scale extrusion. M1 alloy exhibited strong basal texture at both speeds, while Sr additions of 0.3 and 2.1 pct promoted similar amount of texture weakening.

Thermoelectric materials and devices

NASA Technical Reports Server (NTRS)

Park, Yeonjoon (Inventor); Choi, Sang H. (Inventor); King, Glen C. (Inventor); Elliott, James R. (Inventor); Talcott, Noel A. (Inventor)

2011-01-01

New thermoelectric materials comprise highly [111]-oriented twinned group IV alloys on the basal plane of trigonal substrates, which exhibit a high thermoelectric figure of merit and good material performance, and devices made with these materials.

Differential sensitivities of pulmonary and coronary arteries to hemoglobin-based oxygen carriers and nitrovasodilators: study in a bovine ex vivo model of vascular strips.

PubMed

Fonseca, Vera; Avizinis, Jessica; Moon-Massat, Paula; Freilich, Daniel; Kim, Hae Won; Hai, Chi-Ming

2010-01-01

Vasoconstriction is a major adverse effect of first and second generation hemoglobin-based oxygen carriers (HBOCs) that hinders their development as blood substitute. However, intravenous infusion of HBOC-201 (second generation) to patients induces significant pulmonary hypertension without significant coronary vasoconstriction. We compared contractile responses of isolated bovine pulmonary and coronary arterial strips to HBOC-201 and HBOC-205LL.LT.MW600 (third generation), polymerized bovine hemoglobins of different molecular weight, and their attenuation by nitroglycerin, sodium nitroprusside (SNP), and sodium nitrite. Pulmonary arteries developed negligible basal tone, but exhibited HBOC-dependent amplification of phenylephrine-induced contractions. In contrast, coronary arteries developed significant basal tone, and exhibited HBOC-dependent constant force increment to serotonin-induced contractions. Therefore, relative to basal tone, HBOC-induced contractions were greater in pulmonary than coronary arteries. Furthermore, HBOC-205LL.LT.MW600 appeared to be less vasoactive than HBOC-201. Unexpectedly, pulmonary and coronary arteries exhibited differential sensitivities to nitrovasodilators in parallel with their differential sensitivities to HBOC. However, SNP and sodium nitrite induced significant methemoglobin formation from HBOC, whereas nitroglycerin did not. These results suggest that phenotypic differences between pulmonary and coronary vascular smooth muscle cells could explain the differential hypertensive effects of HBOC on pulmonary and coronary circulation in patients. Among the three nitrovasodilators investigated, nitroglycerin appears to be the most promising candidate for attenuating HBOC-induced pulmonary hypertension in older HBOCs.

Lipid metabolism and body composition in Gclm(-/-) mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kendig, Eric L.; Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267; Chen, Ying

2011-12-15

In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipidmore » for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial oxygen consumption. Black-Right-Pointing-Pointer Expression of lipid metabolizing genes is extremely low in Gclm(-/-) mice.« less

Taking a Closer Look--Continuous Glucose Monitoring in Non-Critically Ill Hospitalized Patients with Type 2 Diabetes Mellitus Under Basal-Bolus Insulin Therapy.

PubMed

Schaupp, Lukas; Donsa, Klaus; Neubauer, Katharina M; Mader, Julia K; Aberer, Felix; Höll, Bernhard; Spat, Stephan; Augustin, Thomas; Beck, Peter; Pieber, Thomas R; Plank, Johannes

2015-09-01

Inpatient glucose management is based on four daily capillary blood glucose (BG) measurements. The aim was to test the capability of continuous glucose monitoring (CGM) for assessing the clinical impact and safety of basal-bolus insulin therapy in non-critically ill hospitalized patients with type 2 diabetes mellitus (T2DM). Eighty-four patients with T2DM (age, 68±10 years; glycosylated hemoglobin, 72±28 mmol/mol; body mass index, 31±7 kg/m(2)) were treated with basal-bolus insulin. CGM was performed with the iPro(®)2 system (Medtronic MiniMed, Northridge, CA) and calibrated retrospectively. A remarkable consistency between CGM and BG measurements and therapy improvement was shown over the study period of 501 patient-days. The number of CGM and BG measurements (CGM/BG) in the range from 3.9-10 mmol/L increased from 67.7%/67.2% (on Day 1) to 77.5%/78.6% (on the last day) (P<0.04). The number of low glycemic episodes (3.3 to <3.9 mmol/L) during nighttime detected by CGM was 15-fold higher, and the number of episodes >13.9 mmol/L detected by CGM during night was 12.5-fold higher than the values from the BG measurements. Ninety-nine percent of data points were in the clinically accurate or acceptable Clarke Error Grid Zones A+B, and the relative numbers of correctly identified episodes of <3.9 and >13.9 mmol/L detected by CGM (sensitivity) were 47.3% and 81.5%, respectively. Our data exhibit a good agreement between overall CGM and BG measurements, but there were a high number of missed hypo- and hyperglycemic episodes with BG measurements, particularly during nighttime. Overall assessment of glycemic control using CGM is feasible, whereas the use of CGM for individualized therapy decisions needs further improvement.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calabrese, Gabriele, E-mail: calabrese@pdi-berlin.de; Corfdir, Pierre; Gao, Guanhui

We demonstrate the self-assembled growth of vertically aligned GaN nanowire ensembles on a flexible Ti foil by plasma-assisted molecular beam epitaxy. The analysis of single nanowires by transmission electron microscopy reveals that they are single crystalline. Low-temperature photoluminescence spectroscopy demonstrates that in comparison to standard GaN nanowires grown on Si, the nanowires prepared on the Ti foil exhibit an equivalent crystalline perfection, a higher density of basal-plane stacking faults, but a reduced density of inversion domain boundaries. The room-temperature photoluminescence spectrum of the nanowire ensemble is not influenced or degraded by the bending of the substrate. The present results pavemore » the way for the fabrication of flexible optoelectronic devices based on GaN nanowires on metal foils.« less

The G protein Gi1 exhibits basal coupling but not preassembly with G protein-coupled receptors.

PubMed

Bondar, Alexey; Lazar, Josef

2017-06-09

The G i/o protein family transduces signals from a diverse group of G protein-coupled receptors (GPCRs). The observed specificity of G i/o -GPCR coupling and the high rate of G i/o signal transduction have been hypothesized to be enabled by the existence of stable associates between G i/o proteins and their cognate GPCRs in the inactive state (G i/o -GPCR preassembly). To test this hypothesis, we applied the recently developed technique of two-photon polarization microscopy (2PPM) to Gα i1 subunits labeled with fluorescent proteins and four GPCRs: the α 2A -adrenergic receptor, GABA B , cannabinoid receptor type 1 (CB 1 R), and dopamine receptor type 2. Our experiments with non-dissociating mutants of fluorescently labeled Gα i1 subunits (exhibiting impaired dissociation from activated GPCRs) showed that 2PPM is capable of detecting GPCR-G protein interactions. 2PPM experiments with non-mutated fluorescently labeled Gα i1 subunits and α 2A -adrenergic receptor, GABA B , or dopamine receptor type 2 receptors did not reveal any interaction between the G i1 protein and the non-stimulated GPCRs. In contrast, non-stimulated CB 1 R exhibited an interaction with the G i1 protein. Further experiments revealed that this interaction is caused solely by CB 1 R basal activity; no preassembly between CB 1 R and the G i1 protein could be observed. Our results demonstrate that four diverse GPCRs do not preassemble with non-active G i1 However, we also show that basal GPCR activity allows interactions between non-stimulated GPCRs and G i1 (basal coupling). These findings suggest that G i1 interacts only with active GPCRs and that the well known high speed of GPCR signal transduction does not require preassembly between G proteins and GPCRs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of Anti-diarrhoeal Herbs on Growth Performance, Nutrient Digestibility, and Meat Quality in Pigs

PubMed Central

Cho, J. H.; Zhang, S.; Kim, I. H.

2012-01-01

Two studies were conducted to investigate the effects of anti-diarrhoeal herbs on growth performance, nutrient digestibility, and meat quality in pigs. In Exp 1, 150 weanling-growing piglets (average BW = 7.5±0.24 kg, average age = 27±1 d) were allotted into one of the five dietary treatments, including: i) CON, basal diet, ii) DP, basal diet+1 g/kg date pits, iii) JH, basal diet+0.5 g/kg Japanese-honeysuckle, iv) HCT, basal diet+1 g/kg houttuynia cordata thunb, and v) LE, basal diet+1 g/kg laquer tree extract. From wk 0 to 5, the JH, HCT and LE groups presented higher (p<0.05) ADFI, ADG and gain/feed ratio (G/F) than CON and DP groups. During wk 5 to 10, Pigs fed JH, HCT and LE diets indicated higher (p<0.05) ADG and ADFI than the pigs fed CON and DP diets. During the entire experimental period, a significant increase of ADG appeared in JH, HCT and LE (p<0.05). Pigs fed JH, HCT and LE diets got a higher (p<0.05) ADFI than the pigs fed CON and DP diets. Pigs fed diets with supplementations of herb additives revealled lower (p<0.05) score of diarrhea pigs during d 2 to d 6 compared with pigs fed CON diet. In Exp 2, 60 growing-finishing barrows and gilts (average BW = 54.10±1.20 kg, average age = 54±3 d) were allotted to three treatments: i) CON, basal diet; ii) YG, basal diet+1 g/kg yellow ginger and iii) HR, basal dietary+1 g/kg hoantchy root, respectively. From wk 0 to 5, Dietary supplementation of YG and HR enhanced (p<0.05) ADG. No difference was found between YG and HR treatments. During, wk 5 to 10, ADG also was observed higher in YG and HR treatments than CON group (p<0.05). Additional, YG had the highest ADG (p<0.05) among treatments. There was always an increase of ADG in YG and HR (p<0.05) through all periods. HR treatment showed a lower (p<0.05) score of diarrhoeal pigs on d 1and d 2 compared with CON treatment. Pigs fed YG and HR diets had a higher (p<0.05) longissimus muscle area (LMA) than pigs fed CON diet. In conclusion, anti-diarrhoeal herbs can improve growth performance, and prevent diarrhea incidence in pigs, it can also increase LMA in finishing pigs. PMID:25049522

Qualitative evaluation of the iris and ciliary body by ultrasound biomicroscopy in subjects with angle closure.

PubMed

Ku, Judy Y; Nongpiur, Monisha E; Park, Judy; Narayanaswamy, Arun K; Perera, Shamira A; Tun, Tin A; Kumar, Rajesh S; Baskaran, Mani; Aung, Tin

2014-12-01

To qualitatively analyze anterior chamber structures imaged by ultrasound biomicroscopy (UBM) in primary angle-closure patients. Subjects diagnosed as primary angle-closure suspect (PACS), primary angle-closure glaucoma (PACG), and previous acute primary angle closure (APAC) were recruited prospectively along with a group of normal controls. UBM was performed under standardized dark room conditions and qualitative assessment was carried out using a set of reference photographs of standard UBM images to categorize the various anatomic features related to angle configuration. These included overall and basal iris thicknesses, iris convexity, iris angulation, ciliary body size, and ciliary sulcus. A total of 60 PACS, 114 PACG, 41 APAC, and 33 normal controls were included. Patients were predominantly older Chinese females. After controlling the confounding effect of age and sex, eyes with overall thicker irides [medium odds ratio (OR) 3.58, thick OR 2.84] when compared with thin irides have a significantly higher likelihood of having PACS/PACG/APAC versus controls. Thicker basal iris component (medium OR 4.13, thick OR 3.39) also have higher likelihood of having angle closure when compared with thin basal iris thickness. Subjects with basal iris insertion, mild iris angulation, and large ciliary body have a higher OR of having angle closure. In contrast, the presence/absence of a ciliary sulcus did not influence the likelihood of angle closure. Eyes with thicker overall and basal iris thicknesses are more likely to have angle closure than controls. Other features that increase the likelihood of angle closure include basal iris insertion, mild iris angulation, and large ciliary body.

Sequential development of apical-basal and planar polarities in aggregating epitheliomuscular cells of Hydra.

PubMed

Seybold, Anna; Salvenmoser, Willi; Hobmayer, Bert

2016-04-01

Apical-basal and planar cell polarities are hallmarks of metazoan epithelia required to separate internal and external environments and to regulate trans- and intracellular transport, cytoskeletal organization, and morphogenesis. Mechanisms of cell polarization have been intensively studied in bilaterian model organisms, particularly in early embryos and cultured cells, while cell polarity in pre-bilaterian tissues is poorly understood. Here, we have studied apical-basal and planar polarization in regenerating (aggregating) clusters of epitheliomuscular cells of Hydra, a simple representative of the ancestral, pre-bilaterian phylum Cnidaria. Immediately after dissociation, single epitheliomuscular cells do not exhibit cellular polarity, but they polarize de novo during aggregation. Reestablishment of the Hydra-specific epithelial bilayer is a result of short-range cell sorting. In the early phase of aggregation, apical-basal polarization starts with an enlargement of the epithelial apical-basal diameter and by the development of belt-like apical septate junctions. Specification of the basal pole of epithelial cells occurs shortly later and is linked to synthesis of mesoglea, development of hemidesmosome-like junctions, and formation of desmosome-like junctions connecting the basal myonemes of neighbouring cells. Planar polarization starts, while apical-basal polarization is already ongoing. It is executed gradually starting with cell-autonomous formation, parallelization, and condensation of myonemes at the basal end of each epithelial cell and continuing with a final planar alignment of epitheliomuscular cells at the tissue level. Our findings reveal that epithelial polarization in Hydra aggregates occurs in defined steps well accessible by histological and ultrastructural techniques and they will provide a basis for future molecular studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhancement of the coercivity in Co-Ni layered double hydroxides by increasing basal spacing.

PubMed

Zhang, Cuijuan; Tsuboi, Tomoya; Namba, Hiroaki; Einaga, Yasuaki; Yamamoto, Takashi

2016-09-14

The magnetic properties of layered double hydroxides (LDH) containing transition metal ions can still develop, compared with layered metal hydroxide salts which exhibit structure-dependent magnetism. In this article, we report the preparation of a hybrid magnet composed of Co-Ni LDH and n-alkylsulfonate anions (Co-Ni-CnSO3 LDH). As Co-Ni LDH is anion-exchangeable, we can systematically control the interlayer spacing by intercalating n-alkylsulfonates with different carbon numbers. The magnetic properties were examined with temperature- and field-dependent magnetization measurements. As a result, we have revealed that the coercive field depends on the basal spacing. It is suggested that increasing the basal spacing varies the competition between the in-plane superexchange interactions and long-range out-of-plane dipolar interactions. Moreover, a jump in the coercive field at around 20 Å of the basal spacing is assumed to be the modification of the magnetic ordering in Co-Ni-CnSO3 LDH.

Homeostatic maintenance of ponderosa pine gas exchange in response to stand density changes.

PubMed

McDowell, Nate G; Adams, Henry D; Bailey, John D; Hess, Marcey; Kolb, Thomas E

2006-06-01

Homeostatic maintenance of gas exchange optimizes carbon gain per water loss. Homeostasis is regulated by short-term physiological and long-term structural mechanisms, both of which may respond to changes in resource availability associated with competition. Therefore, stand density regulation via silvicultural manipulations may facilitate growth and survival through mechanisms operating at both short and long timescales. We investigated the responses of ponderosa pine (Pinus ponderosa) to stand basal area manipulations in Arizona, USA. Stand basal area was manipulated to seven replicated levels in 1962 and was maintained for four decades by decadal thinning. We measured basal area increment (BAI) to assess the response and sustainability of wood growth, carbon isotope discrimination (A) inferred from annual rings to assess the response of crown gas exchange, and ratios of leaf area to sapwood area (A(l):A(s)) to assess longer term structural acclimation. Basal area treatments increased soil water potential (r2 = 0.99) but did not affect photosynthetic capacity. BAI increased within two years of thinning, and the 40-year mean BAI was negatively correlated with stand basal area (r2 = 0.98). delta was negatively correlated with stand basal area for years 5 through 12 after thinning (r2 = 0.90). However, delta was relatively invariant with basal area for the period 13-40 years after initial thinning despite maintenance of treatment basal areas via repeated decadal thinnings. Independent gas exchange measurements verified that the ratio of photosynthesis to stomatal conductance was invariant with basal area, but absolute values of both were elevated at lower basal areas. A(l):A(s) was negatively correlated with basal area (r2 = 0.93). We hypothesize that increased A(l):A(s) is a homeostatic response to increased water availability that maximizes water-use efficiency and whole-tree carbon uptake. Elevated A(l):A(s) of trees at low basal areas was associated with greater resilience to climate, i.e., greater absolute BAI during drought; however, trees with high A(l):A(s) in low basal area stands also exhibited the greatest sensitivity to drought, i.e., greater relative decline in BAI.

Landscape heterogeneity modulates forest sensitivity to climate

NASA Astrophysics Data System (ADS)

Jencso, Kelsey; Hu, Jia; Hoylman, Zachary

2015-04-01

Elevation dependent snowmelt magnitude and timing strongly influences net ecosystem productivity in forested mountain watersheds. However, previous work has provided little insight into how internal watershed topography and organization may modulate plant available water and forest growth across elevation gradients. We collected 800 tree cores from four coniferous tree species across a range of elevation, topographic positions and aspects in the Lubrecht Experimental Forest, Montana, USA. We compared the annual basal area increment growth rate to precipitation and temperature from a 60-year SNOTEL data record, groundwater and soil moisture data in sideslope and hollow positions, and topographic indices derived from a LiDAR digital elevation model. At the watershed scale, we evaluated the relationships between topographic indices, LiDAR derived estimates of basal area and seasonal patterns of the Landsat derived Enhanced Vegetation Index. Preliminary results indicate strong relationships between the rates of annual basal growth and the topographic wetness index (TWI), with differing slopes dependent on tree species (P. menziesii R2 = 0.66-0.71, P. ponderosa R2 = 0.87, L. occidentalis R2 = 0.71) and elevation. Generally, trees located in wetter landscape positions (higher TWI) exhibited greater annual growth per unit of precipitation relative to trees located in drier landscape positions (lower TWI). Similarly, watershed scale analysis of LiDAR derived biomass and seasonal greenness indicates differential growth response due to local convergence and divergence across elevation and insolation gradients. These observations suggest that topographically driven water redistribution patterns may modulate the effects of large scale gradients in precipitation and temperature, thereby creating hotspots for conifer productivity in semiarid watersheds.

Landscape Heterogeneity Modulates Forest Sensitivity to Climate

NASA Astrophysics Data System (ADS)

Hoylman, Z. H.; Jencso, K. G.; Hu, J.; Running, S. W.

2014-12-01

Elevation dependent snowmelt magnitude and timing strongly influences net ecosystem productivity in forested mountain watersheds. However, previous work has provided little insight into how internal watershed topography and organization may modulate plant available water and forest growth across elevation gradients. We collected 800 tree cores from five coniferous tree species across a range of elevations, topographic positions and aspects in the Lubrecht Experimental Forest, Montana, USA. We compared the annual basal area increment growth rate to precipitation and temperature from a 60-year SNOTEL data record, groundwater and soil moisture data in sideslope and hollow positions, and topographic indices derived from a LiDAR digital elevation model. At the watershed scale, we evaluated the relationships between topographic indices, LiDAR derived estimates of basal area and seasonal patterns of the Landsat derived Enhanced Vegetation Index. Preliminary results indicate strong relationships between the rates of annual basal growth and the topographic wetness index (TWI) , with differing slopes dependent on tree species (P. menziesii R2 = 0.66-0.71, P. ponderosa R2 = 0.87, L. occidentalis R2 = 0.71) and elevation. Generally, trees located in wetter landscape positions (higher TWI) exhibited greater annual growth per unit of precipitation relative to trees located in drier landscape positions (lower TWI). Watershed scale analysis of LiDAR derived biomass and seasonal greenness indicates differential growth response due to elevation gradients, irradiance and local convergence and divergence. These preliminary observations suggest that topographically driven water redistribution patterns may modulate the effects of large scale gradients in precipitation and temperature, thereby creating hotspots for conifer productivity in semiarid watersheds.

Signaling via the Trichoderma atroviride mitogen-activated protein kinase Tmk 1 differentially affects mycoparasitism and plant protection.

PubMed

Reithner, Barbara; Schuhmacher, Rainer; Stoppacher, Norbert; Pucher, Marion; Brunner, Kurt; Zeilinger, Susanne

2007-11-01

Trichoderma atroviride is a mycoparasite of a number of plant pathogenic fungi thereby employing morphological changes and secretion of cell wall degrading enzymes and antibiotics. The function of the tmk 1 gene encoding a mitogen-activated protein kinase (MAPK) during fungal growth, mycoparasitic interaction, and biocontrol was examined in T. atroviride. Deltatmk 1 mutants exhibited altered radial growth and conidiation, and displayed de-regulated infection structure formation in the absence of a host-derived signal. In confrontation assays, tmk 1 deletion caused reduced mycoparasitic activity although attachment to Rhizoctonia solani and Botrytis cinerea hyphae was comparable to the parental strain. Under chitinase-inducing conditions, nag 1 and ech 42 transcript levels and extracellular chitinase activities were elevated in a Deltatmk 1 mutant, whereas upon direct confrontation with R. solani or B. cinerea a host-specific regulation of ech 42 transcription was found and nag 1 gene transcription was no more inducible over an elevated basal level. Deltatmk 1 mutants exhibited higher antifungal activity caused by low molecular weight substances, which was reflected by an over-production of 6-pentyl-alpha-pyrone and peptaibol antibiotics. In biocontrol assays, a Deltatmk 1 mutant displayed a higher ability to protect bean plants against R. solani.

Signaling via the Trichoderma atroviride mitogen-activated protein kinase Tmk1 differentially affects mycoparasitism and plant protection

PubMed Central

Reithner, Barbara; Schuhmacher, Rainer; Stoppacher, Norbert; Pucher, Marion; Brunner, Kurt; Zeilinger, Susanne

2015-01-01

Trichoderma atroviride is a mycoparasite of a number of plant pathogenic fungi thereby employing morphological changes and secretion of cell wall degrading enzymes and antibiotics. The function of the tmk1 gene encoding a mitogen-activated protein kinase (MAPK) during fungal growth, mycoparasitic interaction, and biocontrol was examined in T. atroviride. Δtmk1 mutants exhibited altered radial growth and conidiation, and displayed de-regulated infection structure formation in the absence of a host-derived signal. In confrontation assays, tmk1 deletion caused reduced mycoparasitic activity although attachment to Rhizoctonia solani and Botrytis cinerea hyphae was comparable to the parental strain. Under chitinase-inducing conditions, nag1 and ech42 transcript levels and extracellular chitinase activities were elevated in a Δtmk1 mutant, whereas upon direct confrontation with R. solani or B. cinerea a host-specific regulation of ech42 transcription was found and nag1 gene transcription was no more inducible over an elevated basal level. Δtmk1 mutants exhibited higher antifungal activity caused by low molecular weight substances, which was reflected by an over-production of 6-pentyl-α-pyrone and peptaibol antibiotics. In biocontrol assays, a Δtmk1 mutant displayed a higher ability to protect bean plants against R. solani. PMID:17509915

Glycemic control and maternal and fetal outcomes in pregnant women with type 1 diabetes according to the type of basal insulin.

PubMed

Chico, A; Herranz, L; Corcoy, R; Ramírez, O; Goya, M M; Bellart, J; González-Romero, S; Codina, M; Sánchez, P; Cortázar, A; Acosta, D; Picón, M J; Rubio, J A; Megía, A; Sancho, M A; Balsells, M; Solá, E; González, N L; López-López, J

2016-11-01

To examine the potential role of the type of basal insulin on glycemic control and maternal and foetal outcomes in pregnant women with type 1 diabetes (T1DM). Retrospective cohort study of pregnancies attended at 18 Spanish tertiary hospitals. T1DM, singleton pregnancies, delivery between 2002-2010, and use of the same basal and prandial insulin from before pregnancy until delivery. A total of 1534 pregnancies were included. The basal insulin most commonly used was Neutral Protamine Hagedorn (NPH) (51.7%), followed by glargine (23.2%) and continuous subcutaneous insulin infusion (CSII) (21.1%). CSII users had longer diabetes duration. Multiple logistic regression analysis showed that CSII was independently associated with lower doses of insulin, higher glycated haemoglobin (HbA 1c ) in all trimesters, and higher rates of miscarriage, preterm birth and neonatal hypoglycemia. Glargine was related to a higher risk of preterm birth and a small-for-gestational age infant (SGA). The odds ratios (OR) of the associations between insulin type and clinical outcomes (from 0.642 to 4.894) have a relevant magnitude. In this observational study of pregnant women with T1DM, the type of basal insulin was independently associated with metabolic variables and foetal outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A young woman with visual hallucinations, delusions of persecution and a history of performing arson with possible three-generation Fahr disease.

PubMed

Shirahama, M; Akiyoshi, J; Ishitobi, Y; Tanaka, Y; Tsuru, J; Matsushita, H; Hanada, H; Kodama, K

2010-01-01

Fahr disease (FD) is a rare neurological and psychiatric disorder. The disease is classified by intracranial calcification of the basal ganglia with the globus pallidus region being particularly affected. We examined a young woman with visual hallucinations, delusions of persecution and a history of performing arson with possible third-generation FD. Case report of third-generation FD. A 23-year-old woman was arrested for two arsons: i) The patient exhibited progressive psychotic symptoms, including visual hallucinations, delusion of injury, irritability, lability of mood, mental retardation and visual disorders and ii) Computed tomography (CT) imaging demonstrated bilateral calcifications of the basal ganglia (globus pallidus) in the patient, her mother and her grandmother. We found a family with a three-generation history of FD who exhibited calcification in the brain and mental retardation. Compared to her mother, the patient described here displayed anticipation of disease onset.

Impact of oral and waterborne administration of rhamnolipids on the susceptibility of channel catfish (Ictalurus punctatus) to Flavobacterium columnare infection.

PubMed

Zhang, Dongdong; Beck, Benjamin H; Lange, Miles; Zhao, Honggang; Thongda, Wilawan; Ye, Zhi; Li, Chao; Peatman, Eric

2017-01-01

Flavobacterium columnare is the causative agent of columnaris disease and causes tremendous morbidity and mortality of farmed fish globally. Previously, we identified a potential lectin-mediator (a rhamnose-binding lectin; RBL1a) of F. columnare adhesion and showed higher RBL1a expression in susceptible channel catfish under basal conditions and following infection. Exposure of challenged fish to the carbohydrate ligand l-rhamnose just prior to a challenge substantially decreased columnaris mortality and pathogen adherence via the down-regulation of RBL1a. While highly effective in protecting fish from columnaris, l-rhamnose is prohibitively expensive, underscoring the need for alternative cost-effective sources of rhamnose for disease control. One such alternative may be microbially produced glycolipid compounds termed rhamnolipids (RLs), which feature abundant l-rhamnose moieties and are readily available from commercial sources. In the present study, we examined whether commercially available RLs (administered either by immersion or via feed) would function similarly to l-rhamnose in affording host protection against F. columnare. A four-week feeding trial with basal and RL top-coated diets (basal diet + RLs) was conducted in channel catfish fingerlings. Surprisingly, columnaris challenges revealed significantly lower survival following the 10 d challenge period in RL diet fed fish when compared with the basal treatment group (p < 0.001). In fish fed RLs, we observed a rapid and large-scale upregulation of RBL1a immediately after challenge combined with a suppression of mucin and lysozyme transcripts. Similarly, fish that were briefly pre-exposed to RLs by immersion and then challenged exhibited lower survival as compared to unexposed fish during a 4 d trial. In conclusion, RLs do not represent an alternative to rhamnose as an experimental treatment for protecting catfish from columnaris mortality. Further research is needed to find other affordable and efficacious alternative sources of l-rhamnose. Copyright © 2016 Elsevier Ltd. All rights reserved.

Correlation Between Personality Traits and Testosterone Concentrations in Healthy Population.

PubMed

Tajima-Pozo, Kazuhiro; Bayón, Camila; Díaz-Marsá, Marina; Carrasco, Jose Luis

2015-01-01

High plasma testosterone levels have been associated with aggression, sexual behaviour and social status. The aim of this paper was to study the correlation between basal plasma testosterone levels and personality variables in healthy participants. Fifty-four participants were randomly enrolled into this study. Basal plasma testosterone levels were measured between 8:30 am and 10 am. After 24 hours of blood drawing, each subject completed personality questionnaires. Positive correlation between basal plasma testosterone levels and anti-social personality traits in both genders was observed (r = 0.336 and P < 0.018). Also, a positive correlation was observed between basal plasmatestosterone levels and criminal thinking traits (r = 0. 376, P < 0.05) and Millon compulsive (r = 0.386, P < 0.010) in both genders. In female participants, a positive correlation between basal plasmatestosterone levels and psychoticism (r = 0. 25, P < 0.019) and Cloninger AUTO TCI (r = 0.507, P < 0.004) was observed. In males participants positive correlation between baseline plasmatic Testosterone levels and Millon Antisocial trait (r = 0. 544, P < 0.19) and Millon Hypomania trait (r = 0. 485, P < 0.41) and Millon Drug Abuse trait (r = 0.632, P < 0.05) was reported. Our results suggest gender differences in clinical and personality variables related with basal plasma testosterone level. In men, high plasma testosterone levels were associated with clinical traits, substance abuse and hypomania. Women with higher basal testosterone levels showed higher scores on personality self-direction traits.

The Human Airway Epithelial Basal Cell Transcriptome

PubMed Central

Wang, Rui; Zwick, Rachel K.; Ferris, Barbara; Witover, Bradley; Salit, Jacqueline; Crystal, Ronald G.

2011-01-01

Background The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. Methodology/Principal Findings Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the “human airway basal cell signature” as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. Conclusion/Significance The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium. PMID:21572528

Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study.

PubMed

O'Brien, Katie M; Cole, Stephen R; Tse, Chiu-Kit; Perou, Charles M; Carey, Lisa A; Foulkes, William D; Dressler, Lynn G; Geradts, Joseph; Millikan, Robert C

2010-12-15

Previous research identified differences in breast cancer-specific mortality across 4 intrinsic tumor subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2(+)/ER(-)). We used immunohistochemical markers to subtype 1,149 invasive breast cancer patients (518 African American, 631 white) in the Carolina Breast Cancer Study, a population-based study of women diagnosed with breast cancer. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9 years. Cancer subtypes luminal A, luminal B, basal-like, and HER2(+)/ER(-) were distributed as 64%, 11%, 11%, and 5% for whites, and 48%, 8%, 22%, and 7% for African Americans, respectively. Breast cancer mortality was higher for participants with HER2(+)/ER(-) and basal-like breast cancer compared with luminal A and B. African Americans had higher breast cancer-specific mortality than whites, but the effect of race was statistically significant only among women with luminal A breast cancer. However, when compared with the luminal A subtype within racial categories, mortality for participants with basal-like breast cancer was higher among whites (HR = 2.0, 95% CI: 1.2-3.4) than African Americans (HR = 1.5, 95% CI: 1.0-2.4), with the strongest effect seen in postmenopausal white women (HR = 3.9, 95% CI: 1.5-10.0). Our results confirm the association of basal-like breast cancer with poor prognosis and suggest that basal-like breast cancer is not an inherently more aggressive disease in African American women compared with whites. Additional analyses are needed in populations with known treatment profiles to understand the role of tumor subtypes and race in breast cancer mortality, and in particular our finding that among women with luminal A breast cancer, African Americans have higher mortality than whites. ©2010 AACR.

Thalamic and extrathalamic mechanisms of consciousness after severe brain injury.

PubMed

Lutkenhoff, Evan S; Chiang, Jeffrey; Tshibanda, Luaba; Kamau, Evelyn; Kirsch, Murielle; Pickard, John D; Laureys, Steven; Owen, Adrian M; Monti, Martin M

2015-07-01

What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development. Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology. Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy. These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal. © 2015 American Neurological Association.

Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines

PubMed Central

2010-01-01

Introduction Normal and neoplastic breast tissues are comprised of heterogeneous populations of epithelial cells exhibiting various degrees of maturation and differentiation. While cultured cell lines have been derived from both normal and malignant tissues, it remains unclear to what extent they retain similar levels of differentiation and heterogeneity as that found within breast tissues. Methods We used 12 reduction mammoplasty tissues, 15 primary breast cancer tissues, and 20 human breast epithelial cell lines (16 cancer lines, 4 normal lines) to perform flow cytometry for CD44, CD24, epithelial cell adhesion molecule (EpCAM), and CD49f expression, as well as immunohistochemistry, and in vivo tumor xenograft formation studies to extensively analyze the molecular and cellular characteristics of breast epithelial cell lineages. Results Human breast tissues contain four distinguishable epithelial differentiation states (two luminal phenotypes and two basal phenotypes) that differ on the basis of CD24, EpCAM and CD49f expression. Primary human breast cancer tissues also contain these four cellular states, but in altered proportions compared to normal tissues. In contrast, cultured cancer cell lines are enriched for rare basal and mesenchymal epithelial phenotypes, which are normally present in small numbers within human tissues. Similarly, cultured normal human mammary epithelial cell lines are enriched for rare basal and mesenchymal phenotypes that represent a minor fraction of cells within reduction mammoplasty tissues. Furthermore, although normal human mammary epithelial cell lines exhibit features of bi-potent progenitor cells they are unable to differentiate into mature luminal breast epithelial cells under standard culture conditions. Conclusions As a group breast cancer cell lines represent the heterogeneity of human breast tumors, but individually they exhibit increased lineage-restricted profiles that fall short of truly representing the intratumoral heterogeneity of individual breast tumors. Additionally, normal human mammary epithelial cell lines fail to retain much of the cellular diversity found in human breast tissues and are enriched for differentiation states that are a minority in breast tissues, although they do exhibit features of bi-potent basal progenitor cells. These findings suggest that collections of cell lines representing multiple cell types can be used to model the cellular heterogeneity of tissues. PMID:20964822

Proteomics and immunohistochemistry define some of the steps involved in the squamous differentiation of the bladder transitional epithelium: a novel strategy for identifying metaplastic lesions.

PubMed

Celis, J E; Celis, P; Ostergaard, M; Basse, B; Lauridsen, J B; Ratz, G; Rasmussen, H H; Orntoft, T F; Hein, B; Wolf, H; Celis, A

1999-06-15

Here, we present a novel strategy for dissecting some of the steps involved in the squamous differentiation of the bladder urothelium leading to squamous cell carcinomas (SCCs). First, we used proteomic technologies and databases (http://biobase.dk/cgi-bin/celis) to reveal proteins that were expressed specifically by fresh normal urothelium and three SCCs showing no urothelial components. Thereafter, antibodies against some of the differentially expressed proteins as well as a few known keratinocyte markers were used to stain serial cryostat sections (immunowalking) of biopsies obtained from bladder cystectomies of two of the SCC-bearing patients (884-1 and 864-1). Because bladder cancer is a field disease, we surmised that the urothelium of these patients may exhibit a spectrum of abnormalities ranging from early metaplastic stages to invasive disease. Immunohistochemical analysis revealed three types of non-keratinizing metaplastic lesions (types 1-3) that did not express keratins 7, 8, 18, and 20 (expressed by normal urothelium) and could be distinguished based on their staining with keratin 19 antibodies. Type 1 lesions showed staining of all cell layers in the epithelium (with differences in the staining intensity of the basal compartment), whereas type 2 lesions exhibited mainly basal cell staining. Type 3 lesions did not stain with keratin 19 antibodies. In cystectomy 884-1, type 3 lesions exhibited the same immunophenotype as the SCC and may be regarded as precursors to the tumor. Basal cells in these lesions did not express keratin 13, suggesting that the tumor, which was also keratin 13 negative, may have arisen from the expansion of these cells. Similar results were observed with cystectomy 864-1, which showed carcinoma in situ of the SCC type. SCC 864-1 exhibited both keratin 19-negative and -positive cells, implying that the tumor arose from the expansion of the basal cell compartment of type 2 and 3 lesions. Besides providing with a novel strategy for revealing metaplastic lesions, our studies have shown that it is feasible to apply powerful proteomic technologies to the analysis of complex biological samples under conditions that are as close as possible to the in vivo situation.

Differences in Fine-Root Biomass of Trees and Understory Vegetation among Stand Types in Subtropical Forests

PubMed Central

Fu, Xiaoli; Wang, Jianlei; Di, Yuebao; Wang, Huimin

2015-01-01

Variation of total fine-root biomass among types of tree stands has previously been attributed to the characteristics of the stand layers. The effects of the understory vegetation on total fine-root biomass are less well studied. We examined the variation of total fine-root biomass in subtropical tree stands at two sites of Datian and Huitong in China. The two sites have similar humid monsoon climate but different soil organic carbon. One examination compared two categories of basal areas (high vs. low basal area) in stands of single species. A second examination compared single-species and mixed stands with comparable basal areas. Low basal area did not correlate with low total fine-root biomass in the single-species stands. The increase in seedling density but decrease in stem density for the low basal area stands at Datian and the quite similar stand structures for the basal-area contrast at Huitong helped in the lack of association between basal area and total fine-root biomass at the two sites, respectively. The mixed stands also did not yield higher total fine-root biomasses. In addition to the lack of niche complementarity between tree species, the differences in stem and seedling densities and the belowground competition between the tree and non-tree species also contributed to the similarity of the total fine-root biomasses in the mixed and single-species stands. Across stand types, the more fertile site Datian yielded higher tree, non-tree and total fine-root biomasses than Huitong. However, the contribution of non-tree fine-root biomass to the total fine-root biomass was higher at Huitong (29.4%) than that at Datian (16.7%). This study suggests that the variation of total fine-root biomass across stand types not only was associated with the characteristics of trees, but also may be highly dependent on the understory layer. PMID:26047358

Differences in Fine-Root Biomass of Trees and Understory Vegetation among Stand Types in Subtropical Forests.

PubMed

Fu, Xiaoli; Wang, Jianlei; Di, Yuebao; Wang, Huimin

2015-01-01

Variation of total fine-root biomass among types of tree stands has previously been attributed to the characteristics of the stand layers. The effects of the understory vegetation on total fine-root biomass are less well studied. We examined the variation of total fine-root biomass in subtropical tree stands at two sites of Datian and Huitong in China. The two sites have similar humid monsoon climate but different soil organic carbon. One examination compared two categories of basal areas (high vs. low basal area) in stands of single species. A second examination compared single-species and mixed stands with comparable basal areas. Low basal area did not correlate with low total fine-root biomass in the single-species stands. The increase in seedling density but decrease in stem density for the low basal area stands at Datian and the quite similar stand structures for the basal-area contrast at Huitong helped in the lack of association between basal area and total fine-root biomass at the two sites, respectively. The mixed stands also did not yield higher total fine-root biomasses. In addition to the lack of niche complementarity between tree species, the differences in stem and seedling densities and the belowground competition between the tree and non-tree species also contributed to the similarity of the total fine-root biomasses in the mixed and single-species stands. Across stand types, the more fertile site Datian yielded higher tree, non-tree and total fine-root biomasses than Huitong. However, the contribution of non-tree fine-root biomass to the total fine-root biomass was higher at Huitong (29.4%) than that at Datian (16.7%). This study suggests that the variation of total fine-root biomass across stand types not only was associated with the characteristics of trees, but also may be highly dependent on the understory layer.

50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

PubMed

Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

2016-02-01

The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated glutamate increase was related to elevation in basal interictal glutamate, suggesting a common mechanism, possibly impaired glutamate metabolism. Divergent mechanisms may exist for seizure induction and increased glutamate in patients with epilepsy. These data highlight the potential risk of 50 Hz stimulation in patients with epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

A comparison of basal and eye-flush tears for the analysis of cat tear proteins.

PubMed

Petznick, Andrea; Evans, Margaret D M; Madigan, Michele C; Markoulli, Maria; Garrett, Qian; Sweeney, Deborah F

2011-02-01

To identify a rapid and effective tear collection method providing sufficient tear volume and total protein content (TPC) for analysis of individual proteins in cats. Domestic adult short-haired cats (12-37 months; 2.7-6.6 kg) were used in the study. Basal tears without stimulation and eye-flush tears after instillation of saline (10 μl) were collected using microcapillary tubes from animal eyes either unwounded control or wounded with 9-mm central epithelial debridement giving four groups with n = 3. Tear comparisons were based on total time and rate for tear collection, TPC using micro bicinchoninic acid (BCA), tear immunoglobulin A (IgA), total matrix-metalloproteinase (MMP)-9 concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and MMP-9 activity. Eye-flush tears were collected significantly faster than basal tears in wounded eyes with higher rates for tear collection in unwounded control and wounded eyes. TPC was significantly lower in eye-flush tears compared to basal tears. The relative proportion of tear IgA normalized to TPC (% IgA of TPC) was not significantly different between basal and eye-flush tears. In unwounded control eyes, MMP-9 was slightly higher in eye-flush than in basal tears; activity of MMP-9 in both tear types was similar. In wounded eyes, eye-flush tears showed highest MMP-9 levels and activity on Day 1, which subsequently decreased to Day 7. MMP-9 activity in basal tears from wounded eyes did not display changes in expression. Eye-flush tears can be collected rapidly providing sufficient tear volume and TPC. This study also indicates that eye-flush tears may be more suitable than basal tears for the analysis of MMPs following corneal wounding. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Dynamics of Nampt/visfatin and high molecular weight adiponectin in response to oral glucose load in obese and lean women.

PubMed

Unlütürk, Uğur; Harmanci, Ayla; Yildiz, Bülent Okan; Bayraktar, Miyase

2010-04-01

High molecular weight adiponectin (HMWA) is the active circulating form of adiponectin. Nampt/visfatin is the enzyme secreted from adipocytes in an active form and is one of the putative regulators of insulin secretion. To investigate the dynamics of total adiponectin (TA), HMWA and Nampt/visfatin in obese and lean women during oral glucose tolerance test (OGTT). We studied normal glucose-tolerant (NGT), age-matched, 30 obese and 30 lean women. All subjects underwent a standard 75 g, 2-h OGTT, and area under the curve (AUC) during OGTT for glucose, insulin, Nampt/visfatin, TA and HMWA was calculated. Body fat mass was assessed by bioimpedance analysis. Results Obese women had significantly higher basal and AUC values for insulin and Nampt/visfatin, whereas basal and AUC-HMWA were significantly lower in this group. Alternatively, obese and lean groups had similar basal and AUC values for glucose and TA. Basal insulin levels were negatively correlated with HMWA levels, but not with basal Nampt/visfatin. AUC-insulin was correlated positively with AUC-visfatin, and negatively with AUC-HMWA. Total and truncal body fat mass showed positive correlation with basal and AUC-visfatin, and negative correlation with basal and AUC-HMWA. In the NGT state, obese women have higher Nampt/visfatin and lower HMWA levels, both basally and in response to oral glucose challenge. The dynamics of Nampt/visfatin and HMWA during OGTT appear to be linked with insulin and adiposity. Counter-regulatory adaptations in HMWA and Nampt/visfatin might have an impact on suggested adipoinsular axis, contributing to maintenance of normal glucose tolerance.

Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate and porcine origin

PubMed Central

Mueller, Kate R; Balamurugan, A.N.; Cline, Gary W; Pongratz, Rebecca L; Hooper, Rebecca L; Weegman, Bradley P; Kitzmann, Jennifer P; Taylor, Michael J; Graham, Melanie L; Schuurman, Henk-Jan; Papas, Klearchos K

2014-01-01

Background Porcine islet xenotransplantation is considered a potential cell-based therapy for type 1 diabetes. It is currently being evaluated in diabetic nonhuman primates (NHP) to assess safety and efficacy of the islet product. However, due to a variety of distinct differences between the respective species, including the insulin secretory characteristics of islets, the suitability and predictive value of the preclinical model in the extrapolation to the clinical setting remains a critical issue. Methods Islets isolated from human (n=3), NHP (n=2), adult pig (AP, n=3) and juvenile pig (JP, n=3) pancreata were perifused with medium at basal glucose (2.5mM) followed by high glucose (16.7mM) concentrations. The total glucose-stimulated insulin secretion (GSIS) was calculated from generated insulin secretion profiles. Results NHP islets exhibited GSIS 3-fold higher than human islets, while AP and JP islets exhibited GSIS 1/3 and 1/16 of human islets, respectively. The insulin content of NHP and AP islets was similar to that of human islets, whereas that of JP islets was 1/3 of human islets. Conclusion Despite the fact that human, NHP, and AP islets contain similar amounts of insulin, the much higher GSIS for NHP islets than for human, AP and JP islets suggests the need for increased dosing of islets from JP and AP in pig-to-NHP transplantation which may be substantially higher than that required for humans. Finally, porcine islet xenotransplantation to humans may require significantly higher dosing given the lower GSIS of AP islets compared to human islets. PMID:23384163

Dopamine and noradrenaline efflux in the prefrontal cortex in the light and dark period: effects of novelty and handling and comparison to the nucleus accumbens.

PubMed

Feenstra, M G; Botterblom, M H; Mastenbroek, S

2000-01-01

We used on-line microdialysis measurements of dopamine and noradrenaline extracellular concentrations in the medial prefrontal cortex of awake, freely moving rats during the dark and the light period of the day to study whether (i) basal efflux would be higher in the active, dark period than in the inactive, light period; (ii) the activation induced by environmental stimuli would be dependent on these conditions. When determined one day after cannula placement, noradrenaline and dopamine levels were higher during the dark. Maximal relative increases induced by novelty and handling were 150% and 175-200%, respectively, and were very similar in the light and the dark, but the net increases were higher in the dark. Separate groups were tested one week after cannula placement to ensure recovery of possibly disturbed circadian rhythms. While basal levels in the dark were now approximately twice those in the light, the maximal relative and net increases after both novelty and handling were very similar. Basal levels of dopamine in the nucleus accumbens (one day after cannula placement) were not different in the light or dark, but were increased by novelty and handling to about 130% only in the light period, not in the dark. Thus, in the prefrontal cortex, dopamine strongly resembles noradrenaline, in that basal efflux was state dependent, whereas activation by stimuli was not. In the nucleus accumbens, basal dopamine efflux was not state dependent, but activation by stimuli was. These results suggest that there are differential effects of circadian phase on basal activity and responsiveness of the mesolimbic vs the mesocortical dopamine system.

Tapanuli Organoclay Addition Into Linear Low Density Polyethylene-Pineapple Fiber Composites

NASA Astrophysics Data System (ADS)

Adawiyah, Robiatul; Juwono, Ariadne L.; Roseno, Seto

2010-12-01

Linear low density polyethylene-Tapanuli organoclay-pineapple fiber composites were succesfully synthesized by a melt intercalation method. The clay was modified as an organoclay by a cation exchange reaction using hexadecyl trimethyl ammonium bromide (HDTMABr) surfactant. The X-ray diffraction results of the organoclay exhibited a higher basal spacing of 1.87 nm compared to the unmodified clay of 1.46 nm. The composite tensile strength was enhanced up to 46.4% with the 1 wt% organoclay addition. Both tensile and flexural moduli increased up to 150.6% and 43% with the 3 wt% organoclay addition to the composites. However, the flexural strength of the composites was not improved with the organoclay addition. The addition of organoclay has also decreased the heat deflection temperature of the composites.

Effect of partial supplementation of sun-dried Azolla as a protein source on the immunity and antioxidant status of commercial broilers.

PubMed

Chichilichi, Biswal; Mohanty, G P; Mishra, S K; Pradhan, C R; Behura, N C; Das, A; Behera, K

2015-09-01

The present study was conducted to evaluate the effect of partial supplementation of sun-dried Azolla as a protein source on the immunity of commercial broilers in coastal Odisha. A 180 day-old broiler chicks were distributed in six dietary treatments viz. C1: Basal diet, C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet + 5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4: Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc hypersensitivity (CBH) and humoral immunity response were determined at the 38(th) day of age. At 42(nd) day, the weight of lymphoid organs, an antioxidant enzyme, and lipid peroxidation activity were determined. The CBH response did not differ significantly among the treated groups, but the sheep red blood cells response was significantly higher in T4. The weight of lymphoid organs or immune organs of all the treated groups did not differ significantly (p>0.05). The erythrocyte catalase level of T4 group was found to be significantly higher than rest of the treated groups except T3. It may be concluded that supplementation of Azolla at 10% of dietary protein requirement along with enzyme supplementation in an isonitrogenous diet showed a better immune response in broilers.

Effect of partial supplementation of sun-dried Azolla as a protein source on the immunity and antioxidant status of commercial broilers

PubMed Central

Chichilichi, Biswal; Mohanty, G. P.; Mishra, S. K.; Pradhan, C. R.; Behura, N. C.; Das, A.; Behera, K.

2015-01-01

Aim: The present study was conducted to evaluate the effect of partial supplementation of sun-dried Azolla as a protein source on the immunity of commercial broilers in coastal Odisha. Materials and Methods: A 180 day-old broiler chicks were distributed in six dietary treatments viz. C1: Basal diet, C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet + 5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4: Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc hypersensitivity (CBH) and humoral immunity response were determined at the 38th day of age. At 42nd day, the weight of lymphoid organs, an antioxidant enzyme, and lipid peroxidation activity were determined. Results: The CBH response did not differ significantly among the treated groups, but the sheep red blood cells response was significantly higher in T4. The weight of lymphoid organs or immune organs of all the treated groups did not differ significantly (p>0.05). The erythrocyte catalase level of T4 group was found to be significantly higher than rest of the treated groups except T3. Conclusion: It may be concluded that supplementation of Azolla at 10% of dietary protein requirement along with enzyme supplementation in an isonitrogenous diet showed a better immune response in broilers. PMID:27047208

The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex

PubMed Central

Yao, Xiao Jie; Vélez Ruiz, Gisselle; Whorton, Matthew R.; Rasmussen, Søren G. F.; DeVree, Brian T.; Deupi, Xavier; Sunahara, Roger K.; Kobilka, Brian

2009-01-01

G protein-coupled receptors (GPCRs) mediate the majority of physiologic responses to hormones and neurotransmitters. However, many GPCRs exhibit varying degrees of agonist-independent G protein activation. This phenomenon is referred to as basal or constitutive activity. For many of these GPCRs, drugs classified as inverse agonists can suppress basal activity. There is a growing body of evidence that basal activity is physiologically relevant, and the ability of a drug to inhibit basal activity may influence its therapeutic properties. However, the molecular mechanism for basal activation and inhibition of basal activity by inverse agonists is poorly understood and difficult to study, because the basally active state is short-lived and represents a minor fraction of receptor conformations. Here, we investigate basal activation of the G protein Gs by the β2 adrenergic receptor (β2AR) by using purified receptor reconstituted into recombinant HDL particles with a stoichiometric excess of Gs. The β2AR is site-specifically labeled with a small, environmentally sensitive fluorophore enabling direct monitoring of agonist- and Gs-induced conformational changes. In the absence of an agonist, the β2AR and Gs can be trapped in a complex by enzymatic depletion of guanine nucleotides. Formation of the complex is enhanced by the agonist isoproterenol, and it rapidly dissociates on exposure to concentrations of GTP and GDP found in the cytoplasm. The inverse agonist ICI prevents formation of the β2AR-Gs complex, but has little effect on preformed complexes. These results provide insights into G protein-induced conformational changes in the β2AR and the structural basis for ligand efficacy. PMID:19470481

Brain angiogenic gene-expression in congenital heart disease.

PubMed

Sánchez, Olga; Ruiz-Romero, Aina; Domínguez, Carmen; Ferrer, Queralt; Ribera, Irene; Rodríguez-Sureda, Víctor; Alijotas, Jaume; Arévalo, Sílvia; Carreras, Elena; Cabero, Lluís; Llurba, Elisa

2017-12-05

To analyze potential differences in the expression of antiangiogenic and angiogenic factors and of genes associated with chronic hypoxia in cerebral tissue from euploid fetuses with congenital heart disease (CHD) and control fetuses. Cerebral tissue was obtained from 15 fetuses with CHD and 12 control fetuses undergoing termination of pregnancy. Expression profiles of the antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1), the angiogenic vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF), and genes associated with chronic hypoxia were determined by real-time PCR in tissue from the frontal cortex and from basal ganglia-hypothalamus. sFlt-1 expression was 48% higher in the frontal cortex (p=0.0431) and 72% higher in the basal ganglia-hypothalamus (p=0.0369) of CHD fetuses than controls. VEGF-A expression was 60% higher in the basal ganglia-hypothalamus (p=0.0432) of CHD fetuses. The expression of hypoxia-inducible factor-2α (HIF-2α) in the basal ganglia-hypothalamus was 98% higher in CHD fetuses (p=0.0456). An overall dysregulation of angiogenesis with a net balance towards an antiangiogenic environment was observed in the cerebral tissue from fetuses with CHD, suggesting that these fetuses may have an intrinsic angiogenic impairment that could contribute to impaired brain perfusion and abnormal neurological development later in life. This article is protected by copyright. All rights reserved.

Perilipin overexpression in mice protects against diet-induced obesity

USDA-ARS?s Scientific Manuscript database

Perilipin A is the most abundant phosphoprotein on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Perilipin null mice exhibit diminished adipose tissue, elevated basal lipolysis, reduced catecholamine-stimulated lipolysis, and increased insulin resistance. To understand t...

High-field study of UCo2Si2: Magnetostriction at metamagnetic transition and influence of Fe substitution

NASA Astrophysics Data System (ADS)

Andreev, A. V.; Skourski, Y.; Gorbunov, D. I.; Prokeš, K.

2018-05-01

UCo2Si2 (tetragonal crystal structure) is antiferromagnet below TN = 83 K with ferromagnetic basal-plane layers of U magnetic moments oriented parallel to the c axis. The layers are coupled in +-+- sequence along this axis. In fields of 45 T applied along the c axis, UCo2Si2 exhibits very sharp metamagnetic transition to ++- uncompensated antiferromagnetic state. The transition is accompanied by pronounced magnetostriction effects. The crystal expands along the c axis by 1 * 10-4 and shrinks in the basal plane by 0.5 * 10-4 (at 1.5 K) resulting in negligible volume effect. Between 20 K and 40 K the transition changes from the first- to the second-order type. The Fe doping in UCo2Si2 reduces TN from 83 K to 80 K at x = 0.2 in U(Co1-xFex)2Si2. Metamagnetic transition shifts to higher fields (from 45 T at x = 0-56 T for x = 0.2). Magnetization jump over the transition remains practically the same which is in agreement with uranium magnetic moment determined by neutron diffraction on crystal with x = 0.1 as 1.29 μB, i.e. only slightly lower than that in UCo2Si2.

Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition.

PubMed

McCairn, Kevin W; Iriki, Atsushi; Isoda, Masaki

2013-01-09

Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.

Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue.

PubMed Central

Nagle, R. B.; Hao, J.; Knox, J. D.; Dalkin, B. L.; Clark, V.; Cress, A. E.

1995-01-01

The progression of prostate carcinoma may be influenced by the biochemical nature of the basal lamina surrounding the primary carcinoma cells. As a first step toward understanding this process, the composition and structure of the basal lamina in normal prostate, prostatic intraepithelial neoplasia, and human carcinoma were determined. In addition, a comparison was made between the attachments of the normal basal cell to its underlying basal lamina and those made by primary prostate carcinoma. The normal basal cells form both focal adhesions and hemidesmosomal-like structures as observed by transmission electron microscopy. The normal basal cells exhibited a polarized distribution of hemidesmosomal associated proteins including BP180, BP230, HD1, plectin, laminin-gamma 2(B2t), collagen VII, and the corresponding integrin laminin receptors alpha 6 beta 1 and alpha 6 beta 4. The expression and distribution pattern of these proteins were retained in the prostate intraepithelial neoplasia lesions. In contrast, the carcinoma cells uniformly lacked hemidesmosomal structures, the integrin alpha 6 beta 4, BP180, laminin-gamma 2 (B2t), and collagen VII but did express BP230 (30%), plectin, HD1 (15%), and the integrin laminin receptors alpha 3 beta 1 and alpha 6 beta 1. These results suggest that, although a detectable basal lamina structure is present in carcinoma, its composition and cellular attachments are abnormal. The loss of critical cellular attachments may play a role in influencing the progression potential of prostate carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7778688

Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome

PubMed Central

Powers, Brian E.; Velazquez, Ramon; Kelley, Christy M.; Ash, Jessica A.; Strawderman, Myla S.; Alldred, Melissa J.; Ginsberg, Stephen D.; Mufson, Elliott J.

2016-01-01

Individuals with Down syndrome (DS) exhibit intellectual disability and develop Alzheimer's disease-like neuropathology during the third decade of life. The Ts65Dn mouse model of DS exhibits key features of both disorders, including impairments in learning, attention and memory, as well as atrophy of basal forebrain cholinergic neurons (BFCNs). The present study evaluated attentional function in relation to BFCN morphology in young (3 months) and middle-aged (12 months) Ts65Dn mice and disomic (2N) controls. Ts65Dn mice exhibited attentional dysfunction at both ages, with greater impairment in older trisomics. Density of BFCNs was significantly lower for Ts65Dn mice independent of age, which may contribute to attentional dysfunction since BFCN density was positively associated with performance on an attention task. BFCN volume decreased with age in 2N but not Ts65Dn mice. Paradoxically, BFCN volume was greater in older trisomic mice, suggestive of a compensatory response. In sum, attentional dysfunction occurred in both young and middle-aged Ts65Dn mice, which may in part reflect reduced density and/or phenotypic alterations in BFCNs. PMID:26719290

Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome.

PubMed

Powers, Brian E; Velazquez, Ramon; Kelley, Christy M; Ash, Jessica A; Strawderman, Myla S; Alldred, Melissa J; Ginsberg, Stephen D; Mufson, Elliott J; Strupp, Barbara J

2016-12-01

Individuals with Down syndrome (DS) exhibit intellectual disability and develop Alzheimer's disease-like neuropathology during the third decade of life. The Ts65Dn mouse model of DS exhibits key features of both disorders, including impairments in learning, attention and memory, as well as atrophy of basal forebrain cholinergic neurons (BFCNs). The present study evaluated attentional function in relation to BFCN morphology in young (3 months) and middle-aged (12 months) Ts65Dn mice and disomic (2N) controls. Ts65Dn mice exhibited attentional dysfunction at both ages, with greater impairment in older trisomics. Density of BFCNs was significantly lower for Ts65Dn mice independent of age, which may contribute to attentional dysfunction since BFCN density was positively associated with performance on an attention task. BFCN volume decreased with age in 2N but not Ts65Dn mice. Paradoxically, BFCN volume was greater in older trisomic mice, suggestive of a compensatory response. In sum, attentional dysfunction occurred in both young and middle-aged Ts65Dn mice, which may in part reflect reduced density and/or phenotypic alterations in BFCNs.

Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice.

PubMed

Boucherie, C; Boutin, C; Jossin, Y; Schakman, O; Goffinet, A M; Ris, L; Gailly, P; Tissir, F

2018-03-01

The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex.

Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice

PubMed Central

Boucherie, C; Boutin, C; Jossin, Y; Schakman, O; Goffinet, A M; Ris, L; Gailly, P; Tissir, F

2018-01-01

The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compartment of aNPC is key to this communication process. We found that Celsr1, a cadherin of the adhesion G protein coupled receptor family, controls branching of aNPC basal processes abutting the meninges and thereby regulates retinoic acid (RA)-dependent neurogenesis. Loss-of-function of Celsr1 results in a decreased number of endfeet, modifies RA-dependent transcriptional activity and biases aNPC commitment toward self-renewal at the expense of basal progenitor and neuron production. The mutant cortex has a reduced number of neurons, and Celsr1 mutant mice exhibit microcephaly and behavioral abnormalities. Our results uncover an important role for Celsr1 protein and for the basal compartment of neural progenitor cells in fate decision during the development of the cerebral cortex. PMID:29257130

Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy.

PubMed

Nandi, Nilay; Tyra, Lauren K; Stenesen, Drew; Krämer, Helmut

2014-10-27

How cellular stresses up-regulate autophagy is not fully understood. One potential regulator is the Drosophila melanogaster protein Acinus (Acn), which is necessary for autophagy induction and triggers excess autophagy when overexpressed. We show that cell type-specific regulation of Acn depends on proteolysis by the caspase Dcp-1. Basal Dcp-1 activity in developing photoreceptors is sufficient for this cleavage without a need for apoptosis to elevate caspase activity. On the other hand, Acn was stabilized by loss of Dcp-1 function or by the presence of a mutation in Acn that eliminates its conserved caspase cleavage site. Acn stability also was regulated by AKT1-mediated phosphorylation. Flies that expressed stabilized forms of Acn, either the phosphomimetic Acn(S641,731D) or the caspase-resistant Acn(D527A), exhibited enhanced basal autophagy. Physiologically, these flies showed improvements in processes known to be autophagy dependent, including increased starvation resistance, reduced Huntingtin-induced neurodegeneration, and prolonged life span. These data indicate that AKT1 and caspase-dependent regulation of Acn stability adjusts basal autophagy levels. © 2014 Nandi et al.

The molecular basis of the genesis of basal tone in internal anal sphincter

PubMed Central

Zhang, Cheng-Hai; Wang, Pei; Liu, Dong-Hai; Chen, Cai-Ping; Zhao, Wei; Chen, Xin; Chen, Chen; He, Wei-Qi; Qiao, Yan-Ning; Tao, Tao; Sun, Jie; Peng, Ya-Jing; Lu, Ping; Zheng, Kaizhi; Craige, Siobhan M.; Lifshitz, Lawrence M.; Keaney Jr, John F.; Fogarty, Kevin E.; ZhuGe, Ronghua; Zhu, Min-Sheng

2016-01-01

Smooth muscle sphincters exhibit basal tone and control passage of contents through organs such as the gastrointestinal tract; loss of this tone leads to disorders such as faecal incontinence. However, the molecular mechanisms underlying this tone remain unknown. Here, we show that deletion of myosin light-chain kinases (MLCK) in the smooth muscle cells from internal anal sphincter (IAS-SMCs) abolishes basal tone, impairing defecation. Pharmacological regulation of ryanodine receptors (RyRs), L-type voltage-dependent Ca2+ channels (VDCCs) or TMEM16A Ca2+-activated Cl− channels significantly changes global cytosolic Ca2+ concentration ([Ca2+]i) and the tone. TMEM16A deletion in IAS-SMCs abolishes the effects of modulators for TMEM16A or VDCCs on a RyR-mediated rise in global [Ca2+]i and impairs the tone and defecation. Hence, MLCK activation in IAS-SMCs caused by a global rise in [Ca2+]i via a RyR-TMEM16A-VDCC signalling module sets the basal tone. Targeting this module may lead to new treatments for diseases like faecal incontinence. PMID:27101932

Epiplasmins and epiplasm in paramecium: the building of a submembraneous cytoskeleton.

PubMed

Aubusson-Fleury, Anne; Bricheux, Geneviève; Damaj, Raghida; Lemullois, Michel; Coffe, Gérard; Donnadieu, Florence; Koll, France; Viguès, Bernard; Bouchard, Philippe

2013-07-01

In ciliates, basal bodies and associated appendages are bound to a submembrane cytoskeleton. In Paramecium, this cytoskeleton takes the form of a thin dense layer, the epiplasm, segmented into regular territories, the units where basal bodies are inserted. Epiplasmins, the main component of the epiplasm, constitute a large family of 51 proteins distributed in 5 phylogenetic groups, each characterized by a specific molecular design. By GFP-tagging, we analyzed their differential localisation and role in epiplasm building and demonstrated that: 1) The epiplasmins display a low turnover, in agreement with the maintenance of an epiplasm layer throughout the cell cycle; 2) Regionalisation of proteins from different groups allows us to define rim, core, ring and basal body epiplasmins in the interphase cell; 3) Their dynamics allows definition of early and late epiplasmins, detected early versus late in the duplication process of the units. Epiplasmins from each group exhibit a specific combination of properties. Core and rim epiplasmins are required to build a unit; ring and basal body epiplasmins seem more dispensable, suggesting that they are not required for basal body docking. We propose a model of epiplasm unit assembly highlighting its implication in structural heredity in agreement with the evolutionary history of epiplasmins. Copyright © 2013 Elsevier GmbH. All rights reserved.

Basal melt rates of Filchner Ice Shelf, Antarctica

NASA Astrophysics Data System (ADS)

Humbert, A.; Nicholls, K. W.; Corr, H. F. J.; Steinhage, D.; Stewart, C.; Zeising, O.

2017-12-01

Thinning of ice shelves around Antarctica has been found to be partly driven by an increase in basal melt as a result of warmer waters entering the sub-ice shelf cavity. In-situ observations of basal melt rate are, however, sparse. A new robust and efficient phase sensitive radio echo sounder (pRES) allows to measure change in ice thickness and vertical strain at high accuracy, so that the contribution of basal melt to the change in thickness can be estimated. As modeling studies suggest that the cavity beneath Filchner Ice Shelf, Antarctica, might be prone to intrusion of warm water pulses within this century, we wished to derive a baseline dataset and an understanding of its present day spatial variability. Here we present results from pRES measurements over two field seasons, 2015/16-16/17, comprising 86 datasets over the southern Filchner Ice Shelf, covering an area of about 6500km2. The maximum melt rate is only slightly more than 1m/a, but the spatial distribution exhibits a complex pattern. For the purpose of testing variability of basal melt rates on small spatial scales, we performed 26 measurements over distances of about 1km, and show that the melt rates do not vary by more than 0.25m/a.

Enhanced systemic immune reactivity to a Basal cell carcinoma associated antigen following photodynamic therapy.

PubMed

Kabingu, Edith; Oseroff, Allan R; Wilding, Gregory E; Gollnick, Sandra O

2009-07-01

Numerous preclinical studies have shown that local photodynamic therapy (PDT) of tumors enhances systemic antitumor immunity. However, other than single-case and anecdotal reports, this phenomenon has not been examined following clinical PDT. To determine whether PDT in a clinical setting enhances systemic recognition of tumor cells, we examined whether PDT of basal cell carcinoma resulted in an increased systemic immune response to Hip1, a tumor antigen associated with basal cell carcinoma. Basal cell carcinoma lesions were either treated with PDT or surgically removed. Blood was collected from patients immediately before or 7 to 10 days following treatment. Peripheral blood leukocytes were isolated from HLA-A2-expressing patients and reactivity to a HLA-A2-restricted Hip1 peptide was measured by INF-gamma ELISpot assay. Immune recognition of Hip1 increased in patients whose basal cell carcinoma lesions were treated with PDT. This increase in reactivity was significantly greater than reactivity observed in patients whose lesions were surgically removed. Patients with superficial lesions exhibited greater enhancement of reactivity compared with patients with nodular lesions. Immune reactivity following PDT was inversely correlated with treatment area and light dose. These findings show for the first time that local tumor PDT can enhance systemic immune responses to tumors in patients, and validate previous preclinical findings.

Alterations in soil microbial community composition and biomass following agricultural land use change.

PubMed

Zhang, Qian; Wu, Junjun; Yang, Fan; Lei, Yao; Zhang, Quanfa; Cheng, Xiaoli

2016-11-04

The effect of agricultural land use change on soil microbial community composition and biomass remains a widely debated topic. Here, we investigated soil microbial community composition and biomass [e.g., bacteria (B), fungi (F), Arbuscular mycorrhizal fungi (AMF) and Actinomycete (ACT)] using phospholipid fatty acids (PLFAs) analysis, and basal microbial respiration in afforested, cropland and adjacent uncultivated soils in central China. We also investigated soil organic carbon and nitrogen (SOC and SON), labile carbon and nitrogen (LC and LN), recalcitrant carbon and nitrogen (RC and RN), pH, moisture, and temperature. Afforestation averaged higher microbial PLFA biomass compared with cropland and uncultivated soils with higher values in top soils than deep soils. The microbial PLFA biomass was strongly correlated with SON and LC. Higher SOC, SON, LC, LN, moisture and lower pH in afforested soils could be explained approximately 87.3% of total variation of higher total PLFAs. Afforestation also enhanced the F: B ratios compared with cropland. The basal microbial respiration was higher while the basal microbial respiration on a per-unit-PLFA basis was lower in afforested land than adjacent cropland and uncultivated land, suggesting afforestation may increase soil C utilization efficiency and decrease respiration loss in afforested soils.

Alterations in soil microbial community composition and biomass following agricultural land use change

NASA Astrophysics Data System (ADS)

Zhang, Qian; Wu, Junjun; Yang, Fan; Lei, Yao; Zhang, Quanfa; Cheng, Xiaoli

2016-11-01

The effect of agricultural land use change on soil microbial community composition and biomass remains a widely debated topic. Here, we investigated soil microbial community composition and biomass [e.g., bacteria (B), fungi (F), Arbuscular mycorrhizal fungi (AMF) and Actinomycete (ACT)] using phospholipid fatty acids (PLFAs) analysis, and basal microbial respiration in afforested, cropland and adjacent uncultivated soils in central China. We also investigated soil organic carbon and nitrogen (SOC and SON), labile carbon and nitrogen (LC and LN), recalcitrant carbon and nitrogen (RC and RN), pH, moisture, and temperature. Afforestation averaged higher microbial PLFA biomass compared with cropland and uncultivated soils with higher values in top soils than deep soils. The microbial PLFA biomass was strongly correlated with SON and LC. Higher SOC, SON, LC, LN, moisture and lower pH in afforested soils could be explained approximately 87.3% of total variation of higher total PLFAs. Afforestation also enhanced the F: B ratios compared with cropland. The basal microbial respiration was higher while the basal microbial respiration on a per-unit-PLFA basis was lower in afforested land than adjacent cropland and uncultivated land, suggesting afforestation may increase soil C utilization efficiency and decrease respiration loss in afforested soils.

Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet.

PubMed

Xu, Li; Huang, Danping; Hu, Qiaolin; Wu, Jing; Wang, Yizhen; Feng, Jie

2015-06-28

To assess the effects of betaine on hepatic lipid accumulation and investigate the underlying mechanism, thirty-two male Sprague-Dawley rats weighing 100 (sd 2·50) g were divided into four groups, and started on one of four treatments: basal diet, basal diet with betaine administration, high-fat diet and high-fat diet with betaine administration. The results showed that no significant difference of body weight was found among experimental groups. Compared with high-fat diet-fed rats, a betaine supplementation decreased (P< 0·05) hepatic TAG accumulation induced by high-fat diet, which was also supported by hepatic histology results. Additionally, hepatic betaine-homocysteine methyltransferase concentration [corrected] as well as its mRNA abundance and lecithin level were found increased (P< 0·05) by betaine supplementation in both basal diet-fed rats and high-fat diet-fed rats. Betaine administration in high-fat diet-fed rats exhibited a higher (P< 0·05) concentration [corrected] of hepatic carnitine palmitoyltransferase 1 (CPT1) compared with high-fat diet-fed rats. High-fat diet inhibited (P< 0·05) the gene expression of hepatic PPARα and CPT1. However, betaine administration in high-fat diet-fed rats elevated (P< 0·05) the gene expression of PPARα and CPT1. Moreover, concentration, gene and protein expressions of hepatic fibroblast growth factor 21 (FGF21) were increased (P< 0·05) in response to betaine administration in high-fat diet group; meanwhile the gene expression of hepatic AMP-activated protein kinase was increased (P< 0·05) as well. The results suggest that betaine administration enhanced hepatic lipid export and fatty acid oxidation in high-fat diet-fed rats, thus effectively alleviating fat accumulation in the liver.

Fecal endocrine profiles and ejaculate traits in black-footed cats (Felis nigripes) and sand cats (Felis margarita).

PubMed

Herrick, J R; Bond, J B; Campbell, M; Levens, G; Moore, T; Benson, K; D'Agostino, J; West, G; Okeson, D M; Coke, R; Portacio, S C; Leiske, K; Kreider, C; Polumbo, P J; Swanson, W F

2010-01-15

Information regarding the reproductive biology of black-footed cats (BFC) and sand cats (SC) is extremely limited. Our objectives were to: (1) validate fecal hormone analysis (estrogens, E; progestagens, P; androgens, T) for noninvasive monitoring of gonadal activity; (2) characterize estrous cyclicity, ovulatory mechanisms, gestation, and seasonality; and (3) evaluate male reproductive activity via fecal androgen metabolites and ejaculate traits. In both species, the estrous cycle averaged 11-12 days. In BFC (n=8), estrus lasted 2.2+/-0.2 days with peak concentrations of E (2962.8+/-166.3 ng/g feces) increasing 2.7-fold above basal concentrations. In SC (n=6), peak concentrations of E (1669.9+/-83.5 ng/g feces) during estrus (2.9+/-0.2 days) were 4.0-fold higher than basal concentrations. Nonpregnant luteal phases occurred in 26.5% (26 of 98) of BFC estrous cycles, but were not observed in SC (0 of 109 cycles). In both species, P concentrations during pregnancy were elevated (32.3+/-3.0 microg/g feces BFC; 8.5+/-0.7 microg/g feces SC) approximately 10-fold above basal concentrations. Fecal T concentrations in males averaged 3.1+/-0.1 microg/g feces in BFC and 2.3+/-0.0 microg/g feces in SC. Following electroejaculation, 200 to 250 microl of semen was collected containing 29.9 (BFC) to 36.5 (SC)x10(6) spermatozoa with 40.4 (SC) to 46.8 (BFC)% normal morphology. All females exhibited estrous cycles during the study and spermatozoa were recovered from all males on every collection attempt, suggesting poor reproductive success in these species may not be due to physiological infertility.

Protracted effects of chronic stress on serotonin-dependent thermoregulation.

PubMed

Natarajan, Reka; Northrop, Nicole A; Yamamoto, Bryan K

2015-01-01

Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. The body temperature is controlled in part, by the medial preoptic area (mPOA) of the hypothalamus. To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress (CUS) paradigm produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 d of CUS. Four days after the last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10 °C were recorded. The CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that the CUS induced changes to the 5HTergic system alter mPOA function in thermoregulation. These findings help us to explain the mechanisms underlying chronic stress-induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed.

Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus.

PubMed

Chang, Yu-Hung; Hwu, Der-Wei; Chang, Dao-Ming; An, Ling-Wang; Hsieh, Chang-Hsun; Lee, Yau-Jiunn

2017-06-01

Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included. A total of 1002 patients were enrolled (pioglitazone: 559, detemir: 264, glargine: 179). After propensity score matching, there were 105 patients with matchable baseline characteristics in each group. After a mean of 3.5 years of follow-up, the pioglitazone group showed a greater HbA1c reduction than the detemir group and the glargine group. Despite patients in all three groups exhibiting significant body weight gain, those in the pioglitazone group and the glargine group showed greater body weight increases than the patients in the detemir group (2.1, 1.6 and 0.8 kg, respectively, p < 0.05). Interestingly, Cox regression analysis indicated that patients under detemir or glargine treatment had a higher probability of CKD progression as compared with the pioglitazone group, with hazard ratios of 2.63 (95% CI 1.79-3.88) and 3.13 (95% CI 2.01-4.87), respectively. Our study first showed that treatment with both pioglitazone and basal insulin improved glycemic control, while only pioglitazone treatment was observed to be advantageous in terms of preserving renal function when used as an add-on therapy for patients with type 2 DM in whom sulfonylurea and metformin regimens failed.

Protracted effects of chronic stress on serotonin dependent thermoregulation

PubMed Central

Natarajan, Reka; Northrop, Nicole A.; Yamamoto, Bryan K.

2016-01-01

Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. Body temperature is controlled in part, by the medial preoptic area of the hypothalamus (mPOA). To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress paradigm (CUS) produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 days of CUS. Four days after last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10°C were recorded. CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that CUS induced changes to the 5HTergic system alters mPOA function in thermoregulation. These findings help explain mechanisms underlying chronic stress induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed. PMID:26414686

Soil Microbial Biomass, Basal Respiration and Enzyme Activity of Main Forest Types in the Qinling Mountains

PubMed Central

Cheng, Fei; Peng, Xiaobang; Zhao, Peng; Yuan, Jie; Zhong, Chonggao; Cheng, Yalong; Cui, Cui; Zhang, Shuoxin

2013-01-01

Different forest types exert essential impacts on soil physical-chemical characteristics by dominant tree species producing diverse litters and root exudates, thereby further regulating size and activity of soil microbial communities. However, the study accuracy is usually restricted by differences in climate, soil type and forest age. Our objective is to precisely quantify soil microbial biomass, basal respiration and enzyme activity of five natural secondary forest (NSF) types with the same stand age and soil type in a small climate region and to evaluate relationship between soil microbial and physical-chemical characters. We determined soil physical-chemical indices and used the chloroform fumigation-extraction method, alkali absorption method and titration or colorimetry to obtain the microbial data. Our results showed that soil physical-chemical characters remarkably differed among the NSFs. Microbial biomass carbon (Cmic) was the highest in wilson spruce soils, while microbial biomass nitrogen (Nmic) was the highest in sharptooth oak soils. Moreover, the highest basal respiration was found in the spruce soils, but mixed, Chinese pine and spruce stands exhibited a higher soil qCO2. The spruce soils had the highest Cmic/Nmic ratio, the greatest Nmic/TN and Cmic/Corg ratios were found in the oak soils. Additionally, the spruce soils had the maximum invertase activity and the minimum urease and catalase activities, but the maximum urease and catalase activities were found in the mixed stand. The Pearson correlation and principle component analyses revealed that the soils of spruce and oak stands obviously discriminated from other NSFs, whereas the others were similar. This suggested that the forest types affected soil microbial properties significantly due to differences in soil physical-chemical features. PMID:23840671

Egg components and hatchling lipid reserves: parental investment in kinosternid turtles from the southeastern United States.

PubMed

Nagle, R D; Burke, V J; Congdon, J D

1998-05-01

We measured egg components and pre-ovulatory parental investment in kinosternid turtles (Kinosternon baurii, Kinosternon subrubrum, Sternotherus minor, and Sternotherus odoratus) from the southeastern USA. Allocation patterns were determined by comparing lipid content of eggs and hatchlings, to determine whether females of species with hatchlings that exhibit a delayed nest-emergence strategy: (1) allocate higher proportions of energy storage lipids to eggs, (2) produce hatchlings with higher levels of storage lipids, and (3) have higher levels of pre-ovulatory parental investment in comparison to species whose hatchlings exhibit immediate emergence. Whereas total non-polar lipid (NPL) proportions by dry mass of eggs varied significantly among species, NPL proportions of hatchlings were not significantly different. Pre-ovulatory parental investment in care (proportion of hatchling NPL to egg NPL) was 40, 50, and 55% for K. subrubrum, S. minor, and S. odoratus, respectively. Lipid class composition of eggs and hatchlings was studied to distinguish lipids allocated for energy storage from those allocated to other functions. For both eggs and hatchlings, individual lipid classes (triacylglycerol, triacylglycerol fatty acid, cholesterol, cholesterol ester, and phospholipid) as proportions of total lipid, were similar among species. The major lipid class component of eggs and hatchlings of all species was triacylglycerol (> 83%), an energy storage lipid. Substantial changes in lipid classes during embryogenesis were similar among species and included: (1) depletion of triacylglycerol, (2) increase in cholesterol esters, and (3) changes in phospholipid composition. Incubation time varied significantly among species, and appeared to be responsible for differential energy utilization during embryogenesis. Our results are inconsistent with the previously observed pattern that hatchlings exhibiting a delayed nest-emergence strategy are allocated higher proportions of energy storage lipids than those that exhibit immediate emergence. However, because the species that overwinters in the nest (K. subrubrum) hatches approximately 40 days later than the species that typically does not (S. odoratus), hatchling K. subrubrum may contain higher non-polar lipid proportions than hatchling S. odoratus during similar winter time periods. Kinosternid hatchlings contain enough stored lipids to support basal maintenance costs for substantial time periods. We suggest that such reserves may be critical to hatchling survival during a period of negative energy balance, regardless of nest emergence strategy.

The Importance of Large-Diameter Trees to Forest Structural Heterogeneity

PubMed Central

Lutz, James A.; Larson, Andrew J.; Freund, James A.; Swanson, Mark E.; Bible, Kenneth J.

2013-01-01

Large-diameter trees dominate the structure, dynamics and function of many temperate and tropical forests. However, their attendant contributions to forest heterogeneity are rarely addressed. We established the Wind River Forest Dynamics Plot, a 25.6 ha permanent plot within which we tagged and mapped all 30,973 woody stems ≥1 cm dbh, all 1,966 snags ≥10 cm dbh, and all shrub patches ≥2 m2. Basal area of the 26 woody species was 62.18 m2/ha, of which 61.60 m2/ha was trees and 0.58 m2/ha was tall shrubs. Large-diameter trees (≥100 cm dbh) comprised 1.5% of stems, 31.8% of basal area, and 17.6% of the heterogeneity of basal area, with basal area dominated by Tsuga heterophylla and Pseudotsuga menziesii. Small-diameter subpopulations of Pseudotsuga menziesii, Tsuga heterophylla and Thuja plicata, as well as all tree species combined, exhibited significant aggregation relative to the null model of complete spatial randomness (CSR) up to 9 m (P≤0.001). Patterns of large-diameter trees were either not different from CSR (Tsuga heterophylla), or exhibited slight aggregation (Pseudotsuga menziesii and Thuja plicata). Significant spatial repulsion between large-diameter and small-diameter Tsuga heterophylla suggests that large-diameter Tsuga heterophylla function as organizers of tree demography over decadal timescales through competitive interactions. Comparison among two forest dynamics plots suggests that forest structural diversity responds to intermediate-scale environmental heterogeneity and disturbances, similar to hypotheses about patterns of species richness, and richness- ecosystem function. Large mapped plots with detailed within-plot environmental spatial covariates will be required to test these hypotheses. PMID:24376579

The importance of large-diameter trees to forest structural heterogeneity.

PubMed

Lutz, James A; Larson, Andrew J; Freund, James A; Swanson, Mark E; Bible, Kenneth J

2013-01-01

Large-diameter trees dominate the structure, dynamics and function of many temperate and tropical forests. However, their attendant contributions to forest heterogeneity are rarely addressed. We established the Wind River Forest Dynamics Plot, a 25.6 ha permanent plot within which we tagged and mapped all 30,973 woody stems ≥ 1 cm dbh, all 1,966 snags ≥ 10 cm dbh, and all shrub patches ≥ 2 m(2). Basal area of the 26 woody species was 62.18 m(2)/ha, of which 61.60 m(2)/ha was trees and 0.58 m(2)/ha was tall shrubs. Large-diameter trees (≥ 100 cm dbh) comprised 1.5% of stems, 31.8% of basal area, and 17.6% of the heterogeneity of basal area, with basal area dominated by Tsuga heterophylla and Pseudotsuga menziesii. Small-diameter subpopulations of Pseudotsuga menziesii, Tsuga heterophylla and Thuja plicata, as well as all tree species combined, exhibited significant aggregation relative to the null model of complete spatial randomness (CSR) up to 9 m (P ≤ 0.001). Patterns of large-diameter trees were either not different from CSR (Tsuga heterophylla), or exhibited slight aggregation (Pseudotsuga menziesii and Thuja plicata). Significant spatial repulsion between large-diameter and small-diameter Tsuga heterophylla suggests that large-diameter Tsuga heterophylla function as organizers of tree demography over decadal timescales through competitive interactions. Comparison among two forest dynamics plots suggests that forest structural diversity responds to intermediate-scale environmental heterogeneity and disturbances, similar to hypotheses about patterns of species richness, and richness- ecosystem function. Large mapped plots with detailed within-plot environmental spatial covariates will be required to test these hypotheses.

Cerebrovascular regulation in men and women: stimulus-specific role of cyclooxygenase

PubMed Central

Peltonen, Garrett L; Harrell, John W; Rousseau, Cameron L; Ernst, Brady S; Marino, Mariah L; Crain, Meghan K; Schrage, William G

2015-01-01

Greater cerebral artery vasodilation mediated by cyclooxygenase (COX) in female animals is unexplored in humans. We hypothesized that young, healthy women would exhibit greater basal cerebral blood flow (CBF) and greater vasodilation during hypoxia or hypercapnia compared to men, mediated by a larger contribution of COX. We measured middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) in 42 adults (24 women, 18 men; 24 ± 1 years) during two visits, in a double-blind, placebo-controlled design (COX inhibition, 100 mg oral indomethacin, Indo). Women were studied early in the follicular phase of the menstrual cycle (days 1–5). Two levels of isocapnic hypoxia (SPO2 = 90% and 80%) were induced for 5-min each. Separately, hypercapnia was induced by increasing end-tidal carbon dioxide (PETCO2) 10 mmHg above baseline. A positive change in MCAv (ΔMCAv) reflected vasodilation. Basal MCAv was greater in women compared to men (P < 0.01) across all conditions. Indo decreased baseline MCAv (P < 0.01) similarly between sexes. Hypoxia increased MCAv (P < 0.01), but ΔMCAv was not different between sexes. Indo did not alter hypoxic vasodilation in either sex. Hypercapnia increased MCAv (P < 0.01), but ΔMCAv was not different between sexes. Indo elicited a large decrease in hypercapnic vasodilation (P < 0.01) that was similar between sexes. During the early follicular phase, women exhibit greater basal CBF than men, but similar vasodilatory responses to hypoxia and hypercapnia. Moreover, COX is not obligatory for hypoxic vasodilation, but plays a vital and similar role in the regulation of basal CBF (∼30%) and hypercapnic response (∼55%) between sexes. PMID:26149282

Distinct Neurochemical Adaptations Within the Nucleus Accumbens Produced by a History of Self-Administered vs Non-Contingently Administered Intravenous Methamphetamine

PubMed Central

Lominac, Kevin D; Sacramento, Arianne D; Szumlinski, Karen K; Kippin, Tod E

2012-01-01

Methamphetamine is a highly addictive psychomotor stimulant yet the neurobiological consequences of methamphetamine self-administration remain under-characterized. Thus, we employed microdialysis in rats trained to self-administer intravenous (IV) infusions of methamphetamine (METH-SA) or saline (SAL) and a group of rats receiving non-contingent IV infusions of methamphetamine (METH-NC) at 1 or 21 days withdrawal to determine the dopamine and glutamate responses in the nucleus accumbens (NAC) to a 2 mg/kg methamphetamine intraperitoneal challenge. Furthermore, basal NAC extracellular glutamate content was assessed employing no net-flux procedures in these three groups at both time points. At both 1- and 21-day withdrawal points, methamphetamine elicited a rise in extracellular dopamine in SAL animals and this effect was sensitized in METH-NC rats. However, METH-SA animals showed a much greater sensitized dopamine response to the drug challenge compared with the other groups. Additionally, acute methamphetamine decreased extracellular glutamate in both SAL and METH-NC animals at both time-points. In contrast, METH-SA rats exhibited a modest and delayed rise in glutamate at 1-day withdrawal and this rise was sensitized at 21 days withdrawal. Finally, no net-flux microdialysis revealed elevated basal glutamate and increased extraction fraction at both withdrawal time-points in METH-SA rats. Although METH-NC rats exhibited no change in the glutamate extraction fraction, they exhibited a time-dependent elevation in basal glutamate levels. These data illustrate for the first time that a history of methamphetamine self-administration produces enduring changes in NAC neurotransmission and that non-pharmacological factors have a critical role in the expression of these methamphetamine-induced neurochemical adaptations. PMID:22030712

Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia.

PubMed

Ratnadurai-Giridharan, Shivakeshavan; Cheung, Chung C; Rubchinsky, Leonid L

2017-11-01

Conventional deep brain stimulation of basal ganglia uses high-frequency regular electrical pulses to treat Parkinsonian motor symptoms but has a series of limitations. Relatively new and not yet clinically tested, optogenetic stimulation is an effective experimental stimulation technique to affect pathological network dynamics. We compared the effects of electrical and optogenetic stimulation of the basal gangliaon the pathologicalParkinsonian rhythmic neural activity. We studied the network response to electrical stimulation and excitatory and inhibitory optogenetic stimulations. Different stimulations exhibit different interactions with pathological activity in the network. We studied these interactions for different network and stimulation parameter values. Optogenetic stimulation was found to be more efficient than electrical stimulation in suppressing pathological rhythmicity. Our findings indicate that optogenetic control of neural synchrony may be more efficacious than electrical control because of the different ways of how stimulations interact with network dynamics.

Sudden death in Leigh syndrome: an autopsy case.

PubMed

Ventura, Francesco; Rocca, Gabriele; Gentile, Raffaella; De Stefano, Francesco

2012-09-01

The present report describes the sudden death of a 3-year-old female child who had been clinically diagnosed with Leigh syndrome.Leigh syndrome is a heterogeneous progressive neurodegenerative disorder, which is characterized by focal or bilateral lesions in the thalamus, basal ganglia, brainstem, cerebellum, and spinal cord. Affected patients exhibit a variable clinical picture that frequently includes psychomotor retardation or regression, recurrent episodes of vomiting, failure to thrive, and signs of brainstem and basal ganglia dysfunction.The child was found dead in bed. Autopsy described the presence of symmetrical, necrotizing lesions scattered within the basal ganglia, thalamus, diencephalon, brainstem, and spinal-cord gray matter and revealed the presence of gastric contents in the upper and lower airways. We report the results of genetic investigations and describe the histological and immunohistochemical features that confirmed the diagnosis. These findings suggest that Leigh syndrome should be regarded as predisposing children to sudden death, especially by asphyxia secondary to the neurological disorder.

Morphological elucidation of basal ganglia circuits contributing reward prediction

PubMed Central

Fujiyama, Fumino; Takahashi, Susumu; Karube, Fuyuki

2015-01-01

Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor–critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:25698913

Adenoid cystic carcinoma of breast: Recent advances

PubMed Central

Miyai, Kosuke; Schwartz, Mary R; Divatia, Mukul K; Anton, Rose C; Park, Yong Wook; Ayala, Alberto G; Ro, Jae Y

2014-01-01

Adenoid cystic carcinoma (ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features (i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with the ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features. PMID:25516849

Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.

PubMed

Humphries, Mark D; Gurney, Kevin

2012-07-01

Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Tree species diversity and its relationship to stand parameters and geomorphology features in the eastern Black Sea region forests of Turkey.

PubMed

Ozcelik, Ramazan; Gul, Altay Ugur; Merganic, Jan; Merganicova, Katarina

2008-05-01

We studied the effects of stand parameters (crown closure, basal area, stand volume, age, mean stand diameter number of trees, and heterogeneity index) and geomorphology features (elevation, aspect and slope) on tree species diversity in an example of untreated natural mixed forest stands in the eastern Black Sea region of Turkey. Tree species diversity and basal area heterogeneity in forest ecosystems are quantified using the Shannon-Weaver and Simpson indices. The relationship between tree species diversity basal area heterogeneity stand parameters and geomorphology features are examined using regression analysis. Our work revealed that the relationship between tree species diversity and stand parameters is loose with a correlation coefficient between 0.02 and 0.70. The correlation of basal area heterogeneity with stand parameters fluctuated between 0.004 and 0.77 (R2). According to our results, stands with higher tree species diversity are characterised by higher mean stand diameter number of diameter classes, basal area and lower homogeneity index value. Considering the effect of geomorphology features on tree species or basal area heterogeneity we found that all investigated relationships are loose with R < or = 0.24. A significant correlation was detected only between tree species diversity and aspect. Future work is required to verify the detected trends in behaviour of tree species diversity if it is to estimate from the usual forest stand parameters and topography characteristics.

Assessment of urban tree growth from structure, nutrients and composition data derived from airborne lidar and imaging spectroscopy

NASA Astrophysics Data System (ADS)

Gu, H.; Townsend, P. A.; Singh, A.

2014-12-01

Urban forests provide important ecosystem services related to climate, nutrients, runoff and aesthetics. Assessment of variations in urban forest growth is critical to urban management and planning, as well as to identify responses to climate and other environmental changes. We estimated annual relative basal area increment by tree rings from 37 plots in Madison, Wisconsin and neighboring municipalities. We related relative basal area growth to variables of vegetation traits derived from remote sensing, including structure (aboveground biomass, diameter, height, basal area, crown width and crown length) from discrete-return airborne lidar, and biochemical variables (foliar nitrogen, carbon, lignin, cellulose, fiber and LMA), spectral indices (NDVI, NDWI, PRI, NDII etc.) and species composition from AVIRIS hyperspectral imagery. Variations in tree growth was mainly correlated with tree species composition (R2 = 0.29, RMSE = 0.004) with coniferous stands having a faster growth rate than broadleaf plots. Inclusion of stand basal area improved model prediction from R2 = 0.29 to 0.35, with RMSE = 0.003. Then, we assessed the growth by functional type, we found that foliar lignin concentration and the proportion of live coniferous trees explained 57% variance in the growth of conifer stands. In contrast, broadleaf forest growth was more strongly correlated with species composition and foliar carbon (R2 = 0.59, RMSE = 0.003). Finally, we compared the relative basal area growth by species. In our study area, red pine and white pine exhibited higher growth rates than other species, while white oak plots grew slowest. There is a significant negative relationship between tree height and the relative growth in red pine stands (r = -0.95), as well as a strong negative relationship between crown width and the relative growth in white pine stands (r = -0.87). Growth declines as trees grow taller and wider may partly be the result of reduced photosynthesis and water availability. We also found that canopy cellulose content was negatively correlated with growth in white oak (r = -0.59), which could be caused by trade off of carbon allocation from shoot storage to leaves. These results demonstrate the potential of lidar and hyperspectral imagery to characterize important traits associated with biomass accumulation in urban forests.

Distinct tumor protein p53 mutants in breast cancer subgroups.

PubMed

Dumay, Anne; Feugeas, Jean-Paul; Wittmer, Evelyne; Lehmann-Che, Jacqueline; Bertheau, Philippe; Espié, Marc; Plassa, Louis-François; Cottu, Paul; Marty, Michel; André, Fabrice; Sotiriou, Christos; Pusztai, Lajos; de Thé, Hugues

2013-03-01

Tumor protein p53 (TP53) is mutated in approximately 30% of breast cancers, but this frequency fluctuates widely between subclasses. We investigated the p53 mutation status in 572 breast tumors, classified into luminal, basal and molecular apocrine subgroups. As expected, the lowest mutation frequency was observed in luminal (26%), and the highest in basal (88%) tumors. Luminal tumors showed significantly higher frequency of substitutions (82 vs. 65%), notably A/T to G/C transitions (31 vs. 15%), whereas molecular apocrine and basal tumors presented much higher frequencies of complex mutations (deletions/insertions) (36 and 33%, respectively, vs. 18%). Accordingly, missense mutations were significantly more frequent in luminal tumors (75 vs. 54%), whereas basal tumors displayed significantly increased rates of TP53 truncations (43 vs. 25%), resulting in loss of function and/or expression. Interestingly, as basal tumors, molecular apocrine tumors presented with a high rate of complex mutations, but paradoxically, these were not associated with increased frequency of p53 truncation. As in luminal tumors, this could reflect a selective pressure for p53 gain of function, possibly through P63/P73 inactivation. Collectively, these observations point not only to different mechanisms of TP53 alterations, but also to different functional consequences in the different breast cancer subtypes. Copyright © 2012 UICC.

Serial hepatic gene expression profiling in Angus steers during feed restriction and realimentation

USDA-ARS?s Scientific Manuscript database

Growing ruminants maintained under dietary restriction for extended periods will exhibit compensatory growth when reverted to ad libitum feeding. This period of compensatory growth is associated with increased feed efficiency, lower basal energy requirements, and changes in circulating concentration...

Expression-Linked Patterns of Codon Usage, Amino Acid Frequency, and Protein Length in the Basally Branching Arthropod Parasteatoda tepidariorum

PubMed Central

Whittle, Carrie A.; Extavour, Cassandra G.

2016-01-01

Abstract Spiders belong to the Chelicerata, the most basally branching arthropod subphylum. The common house spider, Parasteatoda tepidariorum, is an emerging model and provides a valuable system to address key questions in molecular evolution in an arthropod system that is distinct from traditionally studied insects. Here, we provide evidence suggesting that codon usage, amino acid frequency, and protein lengths are each influenced by expression-mediated selection in P. tepidariorum. First, highly expressed genes exhibited preferential usage of T3 codons in this spider, suggestive of selection. Second, genes with elevated transcription favored amino acids with low or intermediate size/complexity (S/C) scores (glycine and alanine) and disfavored those with large S/C scores (such as cysteine), consistent with the minimization of biosynthesis costs of abundant proteins. Third, we observed a negative correlation between expression level and coding sequence length. Together, we conclude that protein-coding genes exhibit signals of expression-related selection in this emerging, noninsect, arthropod model. PMID:27017527

Transport and phosphorylation of choline in higher plant cells. Phosphorus-31 nuclear magnetic resonance studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bligny, R.; Foray, M.F.; Roby, C.

1989-03-25

When sycamore cells were suspended in basal medium containing choline, the latter was taken up by the cells very rapidly. A facilitated diffusion system appertained at low concentrations of choline and exhibited Michaelis-Menten kinetics. At higher choline concentrations simple diffusion appeared to be the principal mode of uptake. Addition of choline to the perfusate of compressed sycamore cells monitored by /sup 31/P NMR spectroscopy resulted in a dramatic accumulation of P-choline in the cytoplasmic compartment containing choline kinase and not in the vacuole. The total accumulation of P-choline over a 10-h period exhibited Michaelis-Menten kinetics. During this period, in themore » absence of Pi in the perfusion medium there was a marked depletion of glucose-6-P, and the cytoplasmic Pi resonance disappeared almost completely. When a threshold of cytoplasmic Pi was attained, the phosphorylation of choline was sustained by the continuous release of Pi from the vacuole although at a much lower rate. However, when 100 microM inorganic phosphate was present in the perfusion medium, externally added Pi was preferentially used to sustain P-choline synthesis. It is clear, therefore, that cytosolic choline kinase associated with a carrier-mediated transport system for choline uptake appeared as effective systems for continuously trapping cytoplasmic Pi including vacuolar Pi entering the cytoplasm.« less

Dietary Administration of Banana (Musa acuminata) Peel Flour Affects the Growth, Antioxidant Status, Cytokine Responses, and Disease Susceptibility of Rohu, Labeo rohita

PubMed Central

Giri, Sib Sankar; Jun, Jin Woo; Sukumaran, Venkatachalam; Park, Se Chang

2016-01-01

To explore the feasibility of Musa acuminata (banana) peels as a feed additive, effects of banana peel flour (BPF) on the growth and immune functions of Labeo rohita were evaluated. Diets containing five different concentrations of BPF (0% [basal diet], 1% [B1], 3% [B3], 5% [B5], and 7% [B7]) were fed to the fish (average weight: 15.3 g) for 60 days. The final weight gain and specific growth rate were higher (P < 0.05) in the B5 group. The most significant improvements in immune parameters such as lysozyme, alternative complement pathway, leukocyte phagocytic, superoxide dismutase, and catalase activities were observed in the B5 group. However, the B5 group exhibited the lowest malondialdehyde activity. IgM and glutathione peroxidise activities were significantly elevated in the treatment groups, except in B1, after only 30 days of feeding. Of the examined cytokine-related genes, IL-1β, TNF-α, and HSP70 were upregulated in the head kidney and hepatopancreas, and expressions were generally higher in the B3 and B5 groups. Moreover, B5 group challenged with Aeromonas hydrophila 60 days after feeding exhibited the highest survival rate (70%; P < 0.05). These results suggest that dietary BPF at 5% could promote growth performance and strengthen immunity in L. rohita. PMID:27294156

Dietary Administration of Banana (Musa acuminata) Peel Flour Affects the Growth, Antioxidant Status, Cytokine Responses, and Disease Susceptibility of Rohu, Labeo rohita.

PubMed

Giri, Sib Sankar; Jun, Jin Woo; Sukumaran, Venkatachalam; Park, Se Chang

2016-01-01

To explore the feasibility of Musa acuminata (banana) peels as a feed additive, effects of banana peel flour (BPF) on the growth and immune functions of Labeo rohita were evaluated. Diets containing five different concentrations of BPF (0% [basal diet], 1% [B1], 3% [B3], 5% [B5], and 7% [B7]) were fed to the fish (average weight: 15.3 g) for 60 days. The final weight gain and specific growth rate were higher (P < 0.05) in the B5 group. The most significant improvements in immune parameters such as lysozyme, alternative complement pathway, leukocyte phagocytic, superoxide dismutase, and catalase activities were observed in the B5 group. However, the B5 group exhibited the lowest malondialdehyde activity. IgM and glutathione peroxidise activities were significantly elevated in the treatment groups, except in B1, after only 30 days of feeding. Of the examined cytokine-related genes, IL-1β, TNF-α, and HSP70 were upregulated in the head kidney and hepatopancreas, and expressions were generally higher in the B3 and B5 groups. Moreover, B5 group challenged with Aeromonas hydrophila 60 days after feeding exhibited the highest survival rate (70%; P < 0.05). These results suggest that dietary BPF at 5% could promote growth performance and strengthen immunity in L. rohita.

More than a colour change: insect melanism, disease resistance and fecundity.

PubMed

Dubovskiy, I M; Whitten, M M A; Kryukov, V Y; Yaroslavtseva, O N; Grizanova, E V; Greig, C; Mukherjee, K; Vilcinskas, A; Mitkovets, P V; Glupov, V V; Butt, T M

2013-07-22

A 'dark morph' melanic strain of the greater wax moth, Galleria mellonella, was studied for its atypical, heightened resistance to infection with the entomopathogenic fungus, Beauveria bassiana. We show that these insects exhibit multiple intraspecific immunity and physiological traits that distinguish them from a non-melanic, fungus-susceptible morph. The melanic and non-melanic morphs were geographical variants that had evolved different, independent defence strategies. Melanic morphs exhibit a thickened cuticle, higher basal expression of immunity- and stress-management-related genes, higher numbers of circulating haemocytes, upregulated cuticle phenoloxidase (PO) activity concomitant with conidial invasion, and an enhanced capacity to encapsulate fungal particles. These insects prioritize specific augmentations to those frontline defences that are most likely to encounter invading pathogens or to sustain damage. Other immune responses that target late-stage infection, such as haemolymph lysozyme and PO activities, do not contribute to fungal tolerance. The net effect is increased larval survival times, retarded cuticular fungal penetration and a lower propensity to develop haemolymph infections when challenged naturally (topically) and by injection. In the absence of fungal infection, however, the heavy defence investments made by melanic insects result in a lower biomass, decreased longevity and lower fecundity in comparison with their non-melanic counterparts. Although melanism is clearly correlated with increased fungal resistance, the costly mechanisms enabling this protective trait constitute more than just a colour change.

Endocrine Secretory Reserve and Proinsulin Processing in Recipients of Islet of Langerhans Versus Whole Pancreas Transplants

PubMed Central

Elkhafif, Nabeel M.; Borot, Sophie; Morel, Philippe; Demuylder-Mischler, Sandrine; Giovannoni, Laurianne; Toso, Christian; Bosco, Domenico; Berney, Thierry

2013-01-01

OBJECTIVE β-Cells have demonstrated altered proinsulin processing after islet transplantation. We compare β-cell metabolic responses and proinsulin processing in pancreas and islet transplant recipients with respect to healthy control subjects. RESEARCH DESIGN AND METHODS We studied 15 islet and 32 pancreas transplant recipients. Islet subjects were subdivided into insulin-requiring (IR-ISL, n = 6) and insulin-independent (II-ISL, n = 9) groups. Ten healthy subjects served as control subjects. Subjects were administered an intravenous arginine stimulation test, and insulin, C-peptide, total proinsulin, intact proinsulin, and proinsulin fragment levels were determined from serum samples. Acute insulin response (AIR) and proinsulin processing rates were calculated. RESULTS We found that basal insulin and C-peptide levels were higher in the pancreas group than in all other groups. II-ISL patients had basal insulin and C-peptide levels similar to healthy control subjects. The IR-ISL group had significantly lower AIRs than all other groups. Basal processing rates were higher in the pancreas and II-ISL groups than in healthy control subjects and the IR-ISL group. After arginine stimulation, all groups had elevated processing rates, with the exception of the IR-ISL group. CONCLUSIONS Our data suggest that II-ISL transplant recipients can maintain basal metabolic parameters similar to healthy control subjects at the cost of a higher rate of proinsulin processing. IR-ISL transplant recipients, on the other hand, demonstrate both lower insulin response and lower basal rates of proinsulin processing even after arginine stimulation. PMID:24041681

Basal insulin persistence, associated factors, and outcomes after treatment initiation among people with type 2 diabetes mellitus in the US.

PubMed

Perez-Nieves, Magaly; Kabul, Samaneh; Desai, Urvi; Ivanova, Jasmina I; Kirson, Noam Y; Cummings, Alice Kate; Birnbaum, Howard G; Duan, Ran; Cao, Dachuang; Hadjiyianni, Irene

2016-01-01

To assess basal insulin persistence, associated factors, and economic outcomes for insulin-naïve people with type 2 diabetes mellitus (T2DM) in the US. People aged ≥18 years diagnosed with T2DM initiating basal insulin between April 2006 and March 2012 (index date), no prior insulin use, and continuous insurance coverage for 6 months before (baseline) and 24 months after index date (follow-up period) were selected using de-identified administrative claims data in the US. Based on whether there were ≥30 day gaps in basal insulin use in the first year post-index, patients were classified as continuers (no gap), interrupters (≥1 prescription after gap), and discontinuers (no prescription after gap). Factors associated with persistence - assessed using multinomial logistic regression model; annual healthcare resource use and costs during follow-up period - compared separately between continuers and interrupters, and continuers and discontinuers. Of the 19,110 people included in the sample (mean age: 59 years, ∼60% male), 20% continued to use basal insulin, 62% had ≥1 interruption, and 18% discontinued therapy in the year after initiation. Older age, multiple antihyperglycemic drug use, and injectable antihyperglycemic use during baseline were associated with significantly higher likelihoods of continuing basal insulin. Relative to interrupters and discontinuers, continuers had fewer emergency department visits, shorter hospital stays, and lower medical costs (continuers: $10,890, interrupters: $13,674, discontinuers: $13,021), but higher pharmacy costs (continuers: $7449, interrupters: $5239, discontinuers: $4857) in the first year post-index (p < 0.05 for all comparisons). Total healthcare costs were similar across the three cohorts. Findings for the second year post-index were similar. The majority of people in this study interrupted or discontinued basal insulin treatment in the year after initiation; and incurred higher medical resource use and costs than continuers. The findings are limited to the commercially insured population in the US. In addition, persistence patterns were assessed using administrative claims as opposed to actual medication-taking behavior and did not account for measures of glycemic control. Further research is needed to understand the reasons behind basal insulin persistence and the implications thereof, to help clinicians manage care for T2DM more effectively.

Structural and compositional controls on transpiration in 40- and 450-year-old riparian forests in western Oregon, USA.

PubMed

Moore, Georgianne W; Bond, Barbara J; Jones, Julia A; Phillips, Nathan; Meinzer, Federick C

2004-05-01

Large areas of forests in the Pacific Northwest are being transformed to younger forests, yet little is known about the impact this may have on hydrological cycles. Previous work suggests that old trees use less water per unit leaf area or sapwood area than young mature trees of the same species in similar environments. Do old forests, therefore, use less water than young mature forests in similar environments, or are there other structural or compositional components in the forests that compensate for tree-level differences? We investigated the impacts of tree age, species composition and sapwood basal area on stand-level transpiration in adjacent watersheds at the H.J. Andrews Forest in the western Cascades of Oregon, one containing a young, mature (about 40 years since disturbance) conifer forest and the other an old growth (about 450 years since disturbance) forest. Sap flow measurements were used to evaluate the degree to which differences in age and species composition affect water use. Stand sapwood basal area was evaluated based on a vegetation survey for species, basal area and sapwood basal area in the riparian area of two watersheds. A simple scaling exercise derived from estimated differences in water use as a result of differences in age, species composition and stand sapwood area was used to estimate transpiration from late June through October within the entire riparian area of these watersheds. Transpiration was higher in the young stand because of greater sap flux density (sap flow per unit sapwood area) by age class and species, and greater total stand sapwood area. During the measurement period, mean daily sap flux density was 2.30 times higher in young compared with old Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) trees. Sap flux density was 1.41 times higher in young red alder (Alnus rubra Bong.) compared with young P. menziesii trees, and was 1.45 times higher in old P. menziesii compared with old western hemlock (Tsuga heterophylla (Raf.) Sarg.) trees. Overall, sapwood basal area was 21% higher in the young stand than in the old stand. In the old forest, T. heterophylla is an important co-dominant, accounting for 58% of total sapwood basal area, whereas P. menziesii is the only dominant conifer in the young stand. Angiosperms accounted for 36% of total sapwood basal area in the young stand, but only 7% in the old stand. For all factors combined, we estimated 3.27 times more water use by vegetation in the riparian area of the young stand over the measurement period. Tree age had the greatest effect on stand differences in water use, followed by differences in sapwood basal area, and finally species composition. The large differences in transpiration provide further evidence that forest management alters site water balance via elevated transpiration in vigorous young stands.

Glutamate Delta-1 Receptor Regulates Metabotropic Glutamate Receptor 5 Signaling in the Hippocampus.

PubMed

Suryavanshi, Pratyush S; Gupta, Subhash C; Yadav, Roopali; Kesherwani, Varun; Liu, Jinxu; Dravid, Shashank M

2016-08-01

The delta family of ionotropic glutamate receptors consists of glutamate delta-1 (GluD1) and glutamate delta-2 receptors. We have previously shown that GluD1 knockout mice exhibit features of developmental delay, including impaired spine pruning and switch in the N-methyl-D-aspartate receptor subunit, which are relevant to autism and other neurodevelopmental disorders. Here, we identified a novel role of GluD1 in regulating metabotropic glutamate receptor 5 (mGlu5) signaling in the hippocampus. Immunohistochemical analysis demonstrated colocalization of mGlu5 with GluD1 punctas in the hippocampus. Additionally, GluD1 protein coimmunoprecipitated with mGlu5 in the hippocampal membrane fraction, as well as when overexpressed in human embryonic kidney 293 cells, demonstrating that GluD1 and mGlu5 may cooperate in a signaling complex. The interaction of mGlu5 with scaffold protein effector Homer, which regulates mechanistic target of rapamycin (mTOR) signaling, was abnormal both under basal conditions and in response to mGlu1/5 agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) in GluD1 knockout mice. The basal levels of phosphorylated mTOR and protein kinase B, the signaling proteins downstream of mGlu5 activation, were higher in GluD1 knockout mice, and no further increase was induced by DHPG. We also observed higher basal protein translation and an absence of DHPG-induced increase in GluD1 knockout mice. In accordance with a role of mGlu5-mediated mTOR signaling in synaptic plasticity, DHPG-induced internalization of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits was impaired in the GluD1 knockout mice. These results demonstrate that GluD1 interacts with mGlu5, and loss of GluD1 impairs normal mGlu5 signaling potentially by dysregulating coupling to its effector. These studies identify a novel role of the enigmatic GluD1 subunit in hippocampal function. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

The effect of dietary bacterial organic selenium on growth performance, antioxidant capacity, and Selenoproteins gene expression in broiler chickens.

PubMed

Dalia, A M; Loh, T C; Sazili, A Q; Jahromi, M F; Samsudin, A A

2017-08-18

Selenium (Se) is an essential trace mineral in broilers, which has several important roles in biological processes. Organic forms of Se are more efficient than inorganic forms and can be produced biologically via Se microbial reduction. Hence, the possibility of using Se-enriched bacteria as feed supplement may provide an interesting source of organic Se, and benefit broiler antioxidant system and other biological processes. The objective of this study was to examine the impacts of inorganic Se and different bacterial organic Se sources on the performance, serum and tissues Se status, antioxidant capacity, and liver mRNA expression of selenoproteins in broilers. Results indicated that different Se sources did not significantly (P ≤ 0.05) affect broiler growth performance. However, bacterial organic Se of T5 (basal diet +0.3 mg /kg feed ADS18 Se), T4 (basal diet +0.3 mg /kg feed ADS2 Se), and T3 (basal diet +0.3 mg /kg feed ADS1 Se) exhibited significantly (P ≤ 0.05) highest Se concentration in serum, liver, and kidney respectively. Dietary inorganic Se and bacterial organic Se were observed to significantly affect broiler serum ALT, AST, LDH activities and serum creatinine level. ADS18 supplemented Se of (Stenotrophomonas maltophilia) bacterial strain showed the highest GSH-Px activity with the lowest MDA content in serum, and the highest GSH-Px and catalase activity in the kidney, while bacterial Se of ADS2 (Klebsiella pneumoniae) resulted in a higher level of GSH-Px1 and catalase in liver. Moreover, our study showed that in comparison with sodium selenite, only ADS18 bacterial Se showed a significantly higher mRNA level in GSH-Px1, GSH-Px4, DIO1, and TXNDR1, while both ADS18 and ADS2 showed high level of mRNA of DIO2 compared to sodium selenite. The supplementation of bacterial organic Se in broiler chicken, improved tissue Se deposition, antioxidant status, and selenoproteins gene expression, and can be considered as an effective alternative source of Se in broiler chickens.

Phylogenetic evidence for an ancestral coevolution between a major clade of coccidian parasites and elasmobranch hosts.

PubMed

Xavier, Raquel; Santos, Joana L; Veríssimo, Ana

2018-05-01

Cartilaginous fishes are the oldest jawed vertebrates and are also reported to be the hosts of some of the most basal lineages of Cestoda and Aporocotylidae (Digenea) parasites. Recently a phylogenetic analysis of the coccidia (Apicomplexa) infecting marine vertebrates revealed that the lesser spotted dogfish harbours parasite lineages basal to Eimeria Schneider, 1875 and the group formed by Schellackia Reichenow, 1919, Lankesterella Ames, 1923, Caryospora Leger, 1904 and Isospora Schneider, 1881. In the present study we have found additional lineages of coccidian parasites infecting the cownose ray Rhinoptera bonasus Mitchill and the blue shark Prionace glauca Linnaeus. These lineages were also found as basal to species from the genera Lankesterella, Schellackia, Caryospora and Isospora infecting higher vertebrates. These results confirm previous phylogenetic assessments and suggest that these parasitic lineages first evolved in basal vertebrate hosts (i.e. Chondrichthyes), and that the more derived lineages infect higher vertebrates (e.g. birds and mammals) conforming to the evolution of their hosts. We hypothesise that elasmobranchs might host further ancestral parasite lineages harbouring unknown links of parasite evolution.

Laser Interferometer Measurements of the Viscoelastic Properties of Tectorial Membrane Mutants

NASA Astrophysics Data System (ADS)

Jones, Gareth; Russell, Ian; Lukashkin, Andrei

2011-11-01

The visco-elastic properties of the tectorial membrane (TM) can be determined by measuring the propagation velocity of travelling waves over a range of frequencies. This study presents a new method using laser interferometry and compares the TM's material properties (sheer storage modulus, G' and viscosity, η) at basal and apical locations in wild-type mice and basal locations of three mutant groups (TectaY1870C/+, Tectb-/- and Otoa-/-). The G' and η values calculated for the wild-type mice are similar to estimates derived using other methods whereas the mutant groups all exhibit slower wave propagation velocities and reduced longitudinal coupling.

Changes of poststimulatory plasma renin activity in women with hyperthyroidism or hypothyroidism in relation to therapy.

PubMed

Marcisz, Czeslaw; Kucharz, Eugene J; Marcisz-Orzel, Magdalena; Poręba, Ryszard; Orzel, Arkadiusz; Sioma-Markowska, Urszula

2011-01-01

The influence of thyroid hormones upon renin-angiotensin-aldosterone system is poorly understood. Under basal conditions, individuals belong to normal, low or high plasma renin activity (PRA) subjects. The study was designed to evaluate basal and poststimulatory PRA and serum aldosterone (Aldo) level in patients with hyperthyroidism or hypothyroidism during therapy. We examined 73 women with hyperthyroidism, 27 women with hypothyroidism and 36 healthy controls. The patients were investigated before initiation of therapy and after attainment of euthyroid state. All subjects were investigated under basal conditions (normal-sodium diet) and after application of a low-sodium diet for three days and upright position for 3 hr. PRA, serum Aldo level, blood pressure, serum sodium, potassium and thyroid hormone levels were determined in all subjects. The subjects were classified as low PRA (<1.0 ng/ml/h), normal PRA (1.0-4.0 ng/ml/h) and high PRA (>4.0 ng/ml/h) individuals according to results obtained under basal conditions. Relatively higher poststimulatory enhancement in PRA was found in patients with hyperthyroidism, especially those with low basal PRA, than in those with hypothyroidism. In women with thyroid dysfunctions poststimulatory increase in Aldo were relative lower than poststimulatory enhancement of PRA. After therapy these difference disappeared. The poststimulatory changes in PRA depended on the basal PRA. Poststimulatory PRA is higher in hyperthyroid women, especially those with low basal PRA. In women with hypothyroidism, basal and poststimulatory PRA is low. Blood pressure and severity of thyroid dysfunction was found to be similar in the patients with low, normal or high basic PRA. In women with thyroid dysfunctions, serum Aldo level and its relative poststimulatory increments are inadequate to changes of PRA; it is suggested that the dissociation in the renin-angiotensin-aldosterone system occurs in hyperthyroid and hypothyroid women.

Endurance exercise training induces fat depot-specific differences in basal autophagic activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, Goki; Kato, Hisashi; Izawa, Tetsuya, E-mail: tizawa@mail.doshisha.ac.jp

The purpose of this study was to uncover the effect of exercise training on the expression of autophagy marker proteins in epididymal white adipose tissue (eWAT), inguinal WAT (iWAT), and the stromal vascular fraction (SVF) collected from eWAT. Male Wistar rats aged 4–5 weeks were randomly divided into two groups, sedentary control (n = 7) and exercise-trained (n = 7). Rats in the exercise-trained group were exercised on a treadmill set at a 5° incline 5 days/week for 9 weeks. We determined that the expression levels of an autophagosome-associating form of microtubule-associated protein 1 light chain 3 (LC3)-II and of p62 were significantly highermore » in eWAT from exercise-trained than from control rats, while those of adipose-specific deletion of autophagy-related protein (ATG7) and lysosomal-associated membrane protein type 2A (LAMP2a) showed no difference between groups. However, in iWAT, the expression levels of LC3-II and ATG7 were significantly higher in exercise-trained than in control rats. The expression of p62 was highly correlated with that of peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and lipid metabolism, in both WAT types (eWAT, r = 0.856, P < 0.05; iWAT, r = 0.762, P < 0.05), whereas LC3-II and PPARγ levels were highly correlated in eWAT (r = 0.765, P < 0.05) but not in iWAT (r = −0.306, ns). In SVF, the expression levels of LC3II, ATG7, and LAMP2a were significantly higher in exercise-trained than in control rats. These results suggest that exercise training suppresses basal autophagy activity in eWAT, but that this activity is enhanced in iWAT and SVF collected from eWAT. Thus, the adaptation of basal autophagic activity following exercise training exhibits fat depot-specific differences. - Highlights: • Autophagy has been associated with obesity and associated diseases. • We examined exercise-associated rat white adipose tissue (WAT) autophagy markers. • Exercise increased autophagosome associated LC3-II in WAT. • Exercise-induced changes in p62 and ATG7 were WAT-type specific. • Exercise-induced basal autophagic activity shows fat depot-specific differences.« less

GLUTAMATE NEUROTOXICITY IN THE DEVELOPING RAT COCHLEA: PHYSIOLOGICAL AND MORPHOLOGICAL APPROACHES

EPA Science Inventory

The neurotoxic effects of exogenous glutamate were studied in the rat cochlea. lutamate-treated rats (4g/kg/day ip, postnatal days 2 through 9) exhibited electrophysiologically-measured elevations in high frequency thresholds usually associated with hair cell loss in the basal re...

A Mechanistic Study of Proapoptotic Daxx-Par4 Axis in Prostate Cancer

DTIC Science & Technology

2011-01-01

markers of autophagy: Beclin-1, LC3 , and p62 . In culture, Daxx K/D cells also exhibited increased basal and inducible (rapamycin; nutrient...deprivation) autophagy. We observed changes in autophagy markers in Daxx K/D cells in culture, including an increase in the LC3 -II:LC3-I ratio, decreased p62 ...tumors exhibited elevated levels of DAPK1 protein, and also an increase in the autophagy markers Beclin-1 and LC3 , as determined via IHC (Fig. 1B). In

Treatment persistence in the use of basal insulins in Poland and Germany
.

PubMed

Rathmann, Wolfgang; Czech, Marcin; Franek, Edward; Kostev, Karel

2017-02-01

To compare short-term basal insulin therapy persistence and its predictors in Poland and Germany. Persistence was defined as proportions of patients remaining on the initial basal insulin (analogs: Poland: n = 6,889, Germany: n = 454,067; neutral protamine Hagedorn (NPH) insulins: Poland: n = 50,761, Germany: n = 226,064) over 2 years based on nationwide prescription databases (LRx; IMS Health) in Poland and Germany from 2013 to 2015. Persistence was evaluated by Kaplan-Meier curves (log-rank tests). Risk of discontinuation of initial basal insulin was investigated using Cox regression models adjusting for age, sex, comedication with other glucose-lowering agents and baseline or comedication with antihypertensives, lipid-lowering drugs, antidepressants, and antiepileptics. In Poland, 2-year persistence was 83.0% in analog insulin and 73.3% in NPH users (p < 0.001). In Germany, persistence was also higher in patients with analog insulins (92.6% vs. 79.0%; p < 0.001). Analog insulin users were less likely to discontinue basal insulin compared with NPH users (adjusted hazard ratio (95%CI): Poland: 0.73 (0.67 - 0.79); Germany: 0.27 (0.27 - 0.28)). Higher age (> 75 vs. ≤ 60 years: Poland: 1.24 (1.16 - 1.33), Germany: 1.09 (1.07 - 1.11)) and GLP-1 receptor agonist use (Poland: 2.76 (1.38 - 5.53), Germany: 1.21 (1.16 - 1.26)) were related to higher risk of discontinuation. Male sex, metformin, sulfonylurea, thiazolidinedione, and short-acting insulin prescriptions as well as antihypertensive, anti-epileptic, and lipid-lowering drug use were associated with lower risk of discontinuation in both countries (all p < 0.05). This real-world study shows that both in Poland and Germany treatment persistence of newly-prescribed basal insulin is influenced by type of insulin (analog vs. NPH) and by glucose-lowering and other comedications.
.

Implicit perceptual-motor skill learning in mild cognitive impairment and Parkinson's disease.

PubMed

Gobel, Eric W; Blomeke, Kelsey; Zadikoff, Cindy; Simuni, Tanya; Weintraub, Sandra; Reber, Paul J

2013-05-01

Implicit skill learning is hypothesized to depend on nondeclarative memory that operates independent of the medial temporal lobe (MTL) memory system and instead depends on cortico striatal circuits between the basal ganglia and cortical areas supporting motor function and planning. Research with the Serial Reaction Time (SRT) task suggests that patients with memory disorders due to MTL damage exhibit normal implicit sequence learning. However, reports of intact learning rely on observations of no group differences, leading to speculation as to whether implicit sequence learning is fully intact in these patients. Patients with Parkinson's disease (PD) often exhibit impaired sequence learning, but this impairment is not universally observed. Implicit perceptual-motor sequence learning was examined using the Serial Interception Sequence Learning (SISL) task in patients with amnestic Mild Cognitive Impairment (MCI; n = 11) and patients with PD (n = 15). Sequence learning in SISL is resistant to explicit learning and individually adapted task difficulty controls for baseline performance differences. Patients with MCI exhibited robust sequence learning, equivalent to healthy older adults (n = 20), supporting the hypothesis that the MTL does not contribute to learning in this task. In contrast, the majority of patients with PD exhibited no sequence-specific learning in spite of matched overall task performance. Two patients with PD exhibited performance indicative of an explicit compensatory strategy suggesting that impaired implicit learning may lead to greater reliance on explicit memory in some individuals. The differences in learning between patient groups provides strong evidence in favor of implicit sequence learning depending solely on intact basal ganglia function with no contribution from the MTL memory system.

Cost-effectiveness analysis of IDegLira versus basal-bolus insulin for patients with type 2 diabetes in the Slovak health system

PubMed Central

Psota, Marek; Psenkova, Maria Bucek; Racekova, Natalia; Ramirez de Arellano, Antonio; Vandebrouck, Tom; Hunt, Barnaby

2017-01-01

Aims To investigate the cost-effectiveness of once-daily insulin degludec/liraglutide (IDegLira) versus basal-bolus therapy in patients with type 2 diabetes not meeting glycemic targets on basal insulin from a healthcare payer perspective in Slovakia. Methods Long-term clinical and economic outcomes for patients receiving IDegLira and basal-bolus therapy were estimated using the IMS CORE Diabetes Model based on a published pooled analysis of patient-level data. Results IDegLira was associated with an improvement in quality-adjusted life expectancy of 0.29 quality-adjusted life years (QALYs) compared with basal-bolus therapy. The average lifetime cost per patient in the IDegLira arm was EUR 2,449 higher than in the basal-bolus therapy arm. Increased treatment costs with IDegLira were partially offset by cost savings from avoided diabetes-related complications. IDegLira was highly cost-effective versus basal-bolus therapy with an incremental cost-effectiveness ratio of EUR 8,590 per QALY gained, which is well below the cost-effectiveness threshold set by the law in Slovakia. Conclusion IDegLira is cost-effective in Slovakia, providing a simple option for intensification of basal insulin therapy without increasing the risk of hypoglycemia or weight gain and with fewer daily injections than a basal-bolus regimen. PMID:29276398

Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

PubMed

Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

2018-02-14

The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

Survey of Basal Stem Rot Disease on Oil Palms (Elaeis guineensis Jacq.) in Kebun Bukit Kijang,North Sumatera, Indonesia

NASA Astrophysics Data System (ADS)

Lisnawita; Hanum, H.; Tantawi, A. R.

2016-08-01

Basal stem rot disease caused by Ganoderma sp. is a significant disease on oil palm plantations in Indonesia, especially in North Sumatera. Currently, the pathogen does not only attack the plants that have produced (old plants) but also attacks the plants that have not produced in the first generation yet. A survey of the distribution of the basal stem rot disease in the plantation of the community has been completed in order to illustrate the distribution and the incidence of the basal stem rot disease in 5 locations of the oil palm plantation of the community in Desa Bukit Kijang, Region of Asahan, North Sumatera, Indonesia. From the research, it is revealed that the basal stem rot disease has spread to all of the observed locations with the level of disease incidence between 0.71% in Kebun Bukit Kijang 3 to 50% in the 17 years old oil palm in Kebun Bukit Kijang 4 and Bukit Kijang 5. The observable symptoms of the basal stem rot disease are chlorotic leaves, the appearance of fruiting body, collapsed plants, and the existence of holes on the basal stem. The incidence of basal stem rot disease is higher on land due to a high sand content (>50%).

Two Parallel Olfactory Pathways for Processing General Odors in a Cockroach

PubMed Central

Watanabe, Hidehiro; Nishino, Hiroshi; Mizunami, Makoto; Yokohari, Fumio

2017-01-01

In animals, sensory processing via parallel pathways, including the olfactory system, is a common design. However, the mechanisms that parallel pathways use to encode highly complex and dynamic odor signals remain unclear. In the current study, we examined the anatomical and physiological features of parallel olfactory pathways in an evolutionally basal insect, the cockroach Periplaneta americana. In this insect, the entire system for processing general odors, from olfactory sensory neurons to higher brain centers, is anatomically segregated into two parallel pathways. Two separate populations of secondary olfactory neurons, type1 and type2 projection neurons (PNs), with dendrites in distinct glomerular groups relay olfactory signals to segregated areas of higher brain centers. We conducted intracellular recordings, revealing olfactory properties and temporal patterns of both types of PNs. Generally, type1 PNs exhibit higher odor-specificities to nine tested odorants than type2 PNs. Cluster analyses revealed that odor-evoked responses were temporally complex and varied in type1 PNs, while type2 PNs exhibited phasic on-responses with either early or late latencies to an effective odor. The late responses are 30–40 ms later than the early responses. Simultaneous intracellular recordings from two different PNs revealed that a given odor activated both types of PNs with different temporal patterns, and latencies of early and late responses in type2 PNs might be precisely controlled. Our results suggest that the cockroach is equipped with two anatomically and physiologically segregated parallel olfactory pathways, which might employ different neural strategies to encode odor information. PMID:28529476

Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin.

PubMed

Mueller, Kate R; Balamurugan, A N; Cline, Gary W; Pongratz, Rebecca L; Hooper, Rebecca L; Weegman, Bradley P; Kitzmann, Jennifer P; Taylor, Michael J; Graham, Melanie L; Schuurman, Henk-Jan; Papas, Klearchos K

2013-01-01

Porcine islet xenotransplantation is considered a potential cell-based therapy for type 1 diabetes. It is currently being evaluated in diabetic nonhuman primates (NHP) to assess safety and efficacy of the islet product. However, due to a variety of distinct differences between the respective species, including the insulin secretory characteristics of islets, the suitability and predictive value of the preclinical model in the extrapolation to the clinical setting remain a critical issue. Islets isolated from human (n = 3), NHP (n = 2), adult pig (AP, n = 3), and juvenile pig (JP, n = 4) pancreata were perifused with medium at basal glucose (2.5 mm) followed by high glucose (16.7 mm) concentrations. The total glucose-stimulated insulin secretion (GSIS) was calculated from generated insulin secretion profiles. Nonhuman primate islets exhibited GSIS 3-fold higher than AP islets, while AP and JP islets exhibited GSIS 1/3 and 1/30 of human islets, respectively. The insulin content of NHP and AP islets was similar to that of human islets, whereas that of JP islets was 1/5 of human islets. Despite the fact that human, NHP, and AP islets contain similar amounts of insulin, the much higher GSIS for NHP islets than for AP and JP islets suggests the need for increased dosing of islets from JP and AP in pig-to-NHP transplantation. Porcine islet xenotransplantation to humans may require significantly higher dosing given the lower GSIS of AP islets compared to human islets. © 2013 John Wiley & Sons A/S.

Insulin and C-peptide secretion in non-obese patients with polycystic ovarian disease.

PubMed

Mahabeer, S; Jialal, I; Norman, R J; Naidoo, C; Reddi, K; Joubert, S M

1989-09-01

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during an oral glucose tolerance test (oGTT) were assessed in 11 non-obese patients with polycystic ovarian disease (PCOD) and 11 reference subjects matched for age, height and weight. Also, 6 patients with PCOD and 6 normal women were subjected to intravenous glucose tolerance testing (ivGTT) On oGTT, all subjects exhibited normal glucose tolerance; however, PCOD patients had significantly higher mean plasma glucose levels at 30, 60, 90 and 120 min and higher mean incremental glucose areas. In addition the patients with polycystic ovaries showed higher mean basal IRI and C-peptide levels, higher mean glucose stimulated IRI and C-peptide levels and higher mean incremental IRI and C-peptide values. The molar ratios of C-peptide/IRI were significantly lower in the PCOD group at all time intervals after glucose stimulation when compared to the normal women. During ivGTT, there were significantly higher mean glucose levels at 5, 40, 50 and 60 min in the PCOD group when compared to the reference group. The IRI response to intravenous glucose in the PCOD women was similar to the reference group. The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.

Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: Relationship with spatial impairment

PubMed Central

Bañuelos, C.; LaSarge, C. L.; McQuail, J. A.; Hartman, J. J.; Gilbert, R. J.; Ormerod, B. K.; Bizon, J. L.

2013-01-01

Both cholinergic and GABAergic projections from the rostral basal forebrain have been implicated in hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in co-distributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase (ChAT) immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 (GAD67) immunopositive) neurons, and total (NeuN immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline. PMID:22817834

Evolving force balance at Columbia Glacier, Alaska, during its rapid retreat

USGS Publications Warehouse

O'Neel, S.; Pfeffer, W.T.; Krimmel, R.; Meier, M.

2005-01-01

Changes in driving and resistive stresses play an essential role in governing the buoyancy forces that are important controls on the speed and irreversibility of tidewater glacier retreats. We describe changes in geometry, velocity, and strain rate and present a top-down force balance analysis performed over the lower reach of Columbia Glacier. Our analysis uses new measurements and estimates of basal topography and photogrammetric surface velocity measurements made between 1977 and 2001, while assuming depth-independent strain. Sensitivity tests show that the method is robust and insensitive to small changes in the calculation parameters. Spatial distributions of ice speed show little correspondence with driving stress. Instead, spatial patterns of ice speed exhibit a nonlinear correspondence with basal drag. Primary resistance to flow comes from basal drag, but lateral drag becomes increasingly more important throughout the retreat, which may account for observed increases in speed. Maximum basal drag is always located in a prominent constriction located ~12 km upstream from the preretreat terminus. Once the terminus retreated into deep water off the terminal moraine marking the modern maximum extent, the upstream location of this maximum basal drag helped to promote thinning and decrease effective pressure in the lower region by limiting replenishing ice flow from upstream. An increase in both ice velocity and calving resulted, initiating what appears to be an irreversible retreat. Copyright 2005 by the American Geophysical Union.

Basal testosterone, leadership and dominance: A field study and meta-analysis.

PubMed

van der Meij, Leander; Schaveling, Jaap; van Vugt, Mark

2016-10-01

This article examines the role of basal testosterone as a potential biological marker of leadership and hierarchy in the workplace. First, we report the result of a study with a sample of male employees from different corporate organizations in the Netherlands (n=125). Results showed that employees with higher basal testosterone levels reported a more authoritarian leadership style, but this relationship was absent among those who currently held a real management position (i.e., they had at least one subordinate). Furthermore, basal testosterone levels were not different between managers and non-managers, and testosterone was not associated with various indicators of status and hierarchy such as number of subordinates, income, and position in the organizational hierarchy. In our meta-analysis (second study), we showed that basal testosterone levels were not associated with leadership in men nor in women (9 studies, n=1103). Taken together, our findings show that basal testosterone is not associated with having a leadership position in the corporate world or related to leadership styles in leaders. We suggest that basal testosterone could play a role in acquiring leadership positions through dominant and authoritarian behavior. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Alteration and mineralization of an oceanic forearc and the ophiolite-ocean crust analogy

USGS Publications Warehouse

Alt, J.C.; Teagle, D.A.H.; Brewer, T.; Shanks, Wayne C.; Halliday, A.

1998-01-01

Mineralogical, chemical, and isotopic (O, C, S, and Sr) analyses were performed on minerals and bulk rocks from a forearc basement section to understand alteration processes and compare with mid-ocean ridges (MOR) and ophiolites. Ocean Drilling Program Hole 786B in the Izu-Bonin forearc penetrates 103 m of sediment and 725 m into volcanic flows, breccias, and basal dikes. The rocks comprise boninites and andesites to rhyolites. Most of the section was affected by low-temperature (<100??C) seawater alteration, with temperatures increasing downward. The rocks are partly (5-25%) altered to smectite, Fe-oxyhydroxide, calcite, and phillipsite, and exhibit gains of K, Rb, and P, loss of Ca, variable changes in Si, Na, Mg, Fe, Sr, and Y, and elevated ??18O and 87Sr/86Sr. Higher temperatures (???150??C) in the basal dikes below 750 m led to more intense alteration and formation of chlorite-smectite, corrensite, albite, K-feldspar, and quartz (??chlorite). A 5 m thick hydrothermally altered and pyritized zone at 815 m in the basal dikes reacted with mixtures of seawater and hydrothermal fluids to Mg-chlorite, albite, and pyrite, and gained Mg and S and lost Si and Ca. Focused flow of hydrothermal fluids produced sericitization halos (Na-K sericite, quartz, pyrophyllite, K-feldspar, and pyrite) along quartz veins at temperatures of 200??-250??C. High 87Sr/86Sr ratios of chloritized (???0.7055) and sericitized (???0.7065) rocks indicate involvement of seawater via mixing with hydrothermal fluids. Low ??34S of sulfide (???2 to -5.5???) and sulfate (12.5???) are consistent with input of magmatic SO2 into hydrothermal fluids and disproportionation to sulfide and sulfate. Alteration processes were generally similar to those at MORs, but the arc section is more intensively altered, in part because of the presence of abundant glassy rocks and mafic phases. The increase in alteration grade below 750 m and the mineralization in the basal dikes are analogous to changes that occur near the base of the volcanic section in MOR and the Troodos ophiolite.

Ethanol attracts scolytid beetles to Phytophthora ramorum cankers on coast live oak

Treesearch

Rick G. Kelsey; Maia M. Beh; David C. Shaw; Daniel K. Manter

2013-01-01

Ethanol in sapwood was analyzed along vertical transects, through small spot cankers and larger basal cankers, of Phytophthora ramorum-infected stems of Quercus agrifolia at three sites in California. Trees with large basal cankers, known to attract scolytid beetles, had a 4.3 times higher ethanol level than trees with spot cankers...

Yield and size of oyster mushroom grown on rice/wheat straw basal substrate supplemented with cotton seed hull.

PubMed

Yang, Wenjie; Guo, Fengling; Wan, Zhengjie

2013-10-01

Oyster mushroom (Pleurotus ostreatus) was cultivated on rice straw basal substrate, wheat straw basal substrate, cotton seed hull basal substrate, and wheat straw or rice straw supplemented with different proportions (15%, 30%, and 45% in rice straw substrate, 20%, 30%, and 40% in wheat straw substrate) of cotton seed hull to find a cost effective substrate. The effect of autoclaved sterilized and non-sterilized substrate on growth and yield of oyster mushroom was also examined. Results indicated that for both sterilized substrate and non-sterilized substrate, oyster mushroom on rice straw and wheat basal substrate have faster mycelial growth rate, comparatively poor surface mycelial density, shorter total colonization period and days from bag opening to primordia formation, lower yield and biological efficiency, lower mushroom weight, longer stipe length and smaller cap diameter than that on cotton seed hull basal substrate. The addition of cotton seed hull to rice straw and wheat straw substrate slowed spawn running, primordial development and fruit body formation. However, increasing the amount of cotton seed hull can increase the uniformity and white of mycelium, yield and biological efficiency, and increase mushroom weight, enlarge cap diameter and shorten stipe length. Compared to the sterilized substrate, the non-sterilized substrate had comparatively higher mycelial growth rate, shorter total colonization period and days from bag opening to primordia formation. However, the non-sterilized substrate did not gave significantly higher mushroom yield and biological efficiency than the sterilized substrate, but some undesirable characteristics, i.e. smaller mushroom cap diameter and relatively long stipe length.

Enhanced mitochondrial complex gene function and reduced liver size may mediate improved feed efficiency of beef cattle during compensatory growth

USDA-ARS?s Scientific Manuscript database

Growing ruminants maintained under dietary restriction for extended periods will exhibit compensatory growth when reverted to ad libitum feeding. This period of compensatory growth is associated with increased feed efficiency, lower basal energy requirements, and changes in circulating concentration...

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress

PubMed Central

Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C.; van Wingen, Guido A.; Fernández, Guillén

2016-01-01

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus–pituitary–adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. PMID:26668010

Sulfur mustard-induced apoptosis in hairless guinea pig skin.

PubMed

Kan, Robert K; Pleva, Christina M; Hamilton, Tracey A; Anderson, Dana R; Petrali, John P

2003-01-01

The present study was aimed to examine whether apoptosis is involved in the pathogenesis of sulfur mustard (SM)-induced basal cell death. Skin sites of the hairless guinea pig exposed to SM vapor for 8 minutes were harvested at 3, 6, 12, 24, and 48 hours postexposure. Immunohistochemical detection of basal cell apoptosis was performed using the ApopTag in situ apoptosis labeling kit. Only occasional apoptotic basal cells (BC)were observed in nonexposed and perilesional control sites. At lesional sites, apoptosis of BC was not detected at 3 hours postexposure. However, at 6 hours and 12 hours postexposure, 18% and 59% of BC were apoptotic, respectively. At 24 and 48 hours postexposure, individual apoptotic basal cells were not clearly recognizable due to necrosis. At the ultrastructural level, degenerating BC exhibited typical apoptotic morphology including nuclear condensation and chromatin margination. The results suggest that apoptotic cell death is a cytotoxic mechanism with the number of BC undergoing apoptosis significantly increasing from 6 to 12 hours postexposure. In addition, because necrosis is preferential at 24 hours postexposure, we believe that SM-induced cell death involves early apoptosis and late necrosis, which temporally overlap to produce a single cell death pathway along an apoptotic-necrotic continuum.

Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function.

PubMed

Mastronardi, Claudio; Smiley, Gregory G; Raber, Jacob; Kusakabe, Takashi; Kawaguchi, Akio; Matagne, Valerie; Dietzel, Anja; Heger, Sabine; Mungenast, Alison E; Cabrera, Ricardo; Kimura, Shioko; Ojeda, Sergio R

2006-12-20

Thyroid transcription factor 1 (TTF1) [also known as Nkx2.1 (related to the NK-2 class of homeobox genes) and T/ebp (thyroid-specific enhancer-binding protein)], a homeodomain gene required for basal forebrain morphogenesis, remains expressed in the hypothalamus after birth, suggesting a role in neuroendocrine function. Here, we show an involvement of TTF1 in the control of mammalian puberty and adult reproductive function. Gene expression profiling of the nonhuman primate hypothalamus revealed that TTF1 expression increases at puberty. Mice in which the Ttf1 gene was ablated from differentiated neurons grew normally and had normal basal ganglia/hypothalamic morphology but exhibited delayed puberty, reduced reproductive capacity, and a short reproductive span. These defects were associated with reduced hypothalamic expression of genes required for sexual development and deregulation of a gene involved in restraining puberty. No extrapyramidal impairments associated with basal ganglia dysfunction were apparent. Thus, although TTF1 appears to fulfill only a morphogenic function in the ventral telencephalon, once this function is satisfied in the hypothalamus, TTF1 remains active as part of the transcriptional machinery controlling female sexual development.

Investigating the microstructural and neurochemical environment within the basal ganglia of current methamphetamine abusers.

PubMed

Lin, Joanne C; Jan, Reem K; Kydd, Rob R; Russell, Bruce R

2015-04-01

Methamphetamine is a highly addictive psychostimulant and the medical, social, and economic consequences associated with its use have become a major international problem. Current evidence has shown methamphetamine to be particularly neurotoxic to dopamine neurons and striatal structures within the basal ganglia. A previous study from our laboratory demonstrated larger putamen volumes in actively using methamphetamine-dependent participants. The purpose of this current study was to determine whether striatal structures in the same sample of participants also exhibit pathology on the microstructural and molecular level. Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were carried out in current methamphetamine users (n = 18) and healthy controls (n = 22) to investigate diffusion indices and neurometabolite levels in the basal ganglia. Contrary to findings from previous DTI and MRS studies, no significant differences in diffusion indices or metabolite levels were observed in the basal ganglia regions of current methamphetamine users. These findings differ from those reported in abstinent users and the absence of diffusion and neurochemical abnormalities may suggest that striatal enlargement in current methamphetamine use may be due to mechanisms other than edema and glial proliferation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Differential serotonergic innervation of the amygdala in bonobos and chimpanzees

PubMed Central

Barger, Nicole; Taglialatela, Jared P.; Gendron-Fitzpatrick, Annette; Hof, Patrick R.; Hopkins, William D.; Sherwood, Chet C.

2016-01-01

Humans’ closest living relatives are bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), yet these great ape species differ considerably from each other in terms of social behavior. Bonobos are more tolerant of conspecifics in competitive contexts and often use sexual behavior to mediate social interactions. Chimpanzees more frequently employ aggression during conflicts and actively patrol territories between communities. Regulation of emotional responses is facilitated by the amygdala, which also modulates social decision-making, memory and attention. Amygdala responsiveness is further regulated by the neurotransmitter serotonin. We hypothesized that the amygdala of bonobos and chimpanzees would differ in its neuroanatomical organization and serotonergic innervation. We measured volumes of regions and the length density of serotonin transporter-containing axons in the whole amygdala and its lateral, basal, accessory basal and central nuclei. Results showed that accessory basal nucleus volume was larger in chimpanzees than in bonobos. Of particular note, the amygdala of bonobos had more than twice the density of serotonergic axons than chimpanzees, with the most pronounced differences in the basal and central nuclei. These findings suggest that variation in serotonergic innervation of the amygdala may contribute to mediating the remarkable differences in social behavior exhibited by bonobos and chimpanzees. PMID:26475872

Comparison of dynamic change of egg selenium deposition after feeding sodium selenite or selenium-enriched yeast.

PubMed

Lu, J; Qu, L; Shen, M M; Hu, Y P; Guo, J; Dou, T C; Wang, K H

2018-05-19

The aim of this study was to compare the dynamic change of egg selenium (Se) deposition after sodium selenite (SS) or selenium-enriched yeast (SY) supplementation for 1, 3, 5, 7, 14, 21, 28, 56, and 84 d. A total of 576 32-wk-old Hy-Line Brown laying hens were randomly assigned to 3 groups (192 laying hens per group) with 6 replicates, and fed a basal diet (without Se supplementation) or basal diets with 0.3 mg/kg of Se from SS or 0.3 mg/kg of Se from SY, respectively. The results showed that the Se concentrations in the eggs from hens fed a SY-supplemented diet were significantly higher (P < 0.001) than those from hens fed a SS-supplemented diet or a basal diet after 3 d. And the Se concentrations in the eggs from hens fed a SS-supplemented diet were significantly higher (P < 0.001) than those from hens fed a basal diet after 14 d. There was a positive linear and quadratic correlation between Se concentrations in the eggs from hens fed a SY-supplemented diet (r2 = 0.782, P < 0.001; r2 = 0.837, P < 0.001) or SS-supplemented diet (r2 = 0.355, P < 0.001; r2 = 0.413, P < 0.001) and number of feeding days. The Se concentrations in the breasts from hens fed a SY-supplemented diet were 126.98% higher (P < 0.001) than those from hens fed a SS-supplemented diet, and were 299.44% higher (P < 0.001) than those from hens fed a basal diet after the 84-d feeding period. In conclusion, the dietary Se was gradually transferred into eggs with the extension of the experimental duration. The deposition rate of Se in the eggs from hens fed a SY-supplemented diet was much more rapid than that from hens fed a SS-supplemented diet, and the organic Se from SY had higher bioavailability as compared to inorganic Se from SS.

Ablation of cdk4 and cdk6 affects proliferation of basal progenitor cells in the developing dorsal and ventral forebrain.

PubMed

Grison, Alice; Gaiser, Carine; Bieder, Andrea; Baranek, Constanze; Atanasoski, Suzana

2018-03-23

Little is known about the molecular players driving proliferation of neural progenitor cells (NPCs) during embryonic mouse development. Here, we demonstrate that proliferation of NPCs in the developing forebrain depends on a particular combination of cell cycle regulators. We have analyzed the requirements for members of the cyclin-dependent kinase (cdk) family using cdk-deficient mice. In the absence of either cdk4 or cdk6, which are both regulators of the G1 phase of the cell cycle, we found no significant effects on the proliferation rate of cortical progenitor cells. However, concomitant loss of cdk4 and cdk6 led to a drastic decrease in the proliferation rate of NPCs, specifically the basal progenitor cells of both the dorsal and ventral forebrain at embryonic day 13.5 (E13.5). Moreover, basal progenitors in the forebrain of Cdk4;Cdk6 double mutant mice exhibited altered cell cycle characteristics. Cdk4;cdk6 deficiency led to an increase in cell cycle length and cell cycle exit of mutant basal progenitor cells in comparison to controls. In contrast, concomitant ablation of cdk2 and cdk6 had no effect on the proliferation of NCPs. Together, our data demonstrate that the expansion of the basal progenitor pool in the developing telencephalon is dependent on the presence of distinct combinations of cdk molecules. Our results provide further evidence for differences in the regulation of proliferation between apical and basal progenitors during cortical development. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.

Mammary Tumors Initiated by Constitutive Cdk2 Activation Contain an Invasive Basal-like Component1

PubMed Central

Corsino, Patrick E; Davis, Bradley J; Nörgaard, Peter H; Teoh Parker, Nicole N; Law, Mary; Dunn, William; Law, Brian K

2008-01-01

The basal-like subtype of breast cancer is associated with invasiveness, high rates of postsurgical recurrence, and poor prognosis. Aside from inactivation of the BRCA1 tumor-suppressor gene, little is known concerning the mechanisms that cause basal breast cancer or the mechanisms responsible for its invasiveness. Here, we show that the heterogeneous mouse mammary tumor virus-cyclin D1-Cdk2 (MMTV-D1K2) transgenic mouse mammary tumors contain regions of spindle-shaped cells expressing both luminal and myoepithelial markers. Cell lines cultured from these tumors exhibit the same luminal/myoepithelial mixed-lineage phenotype that is associated with human basal-like breast cancer and express a number of myoepithelial markers including cytokeratin 14, P-cadherin, α smooth muscle actin, and nestin. The MMTV-D1K2 tumor-derived cell lines form highly invasive tumors when injected into mouse mammary glands. Invasion is associated with E-cadherin localization to the cytoplasm or loss of E-cadherin expression. Cytoplasmic E-cadherin correlates with lack of colony formation in vitro and β-catenin and p120ctn localization to the cytoplasm. The data suggest that the invasiveness of these cell lines results from a combination of factors including mislocalization of E-cadherin, β-catenin, and p120ctn to the cytoplasm. Nestin expression and E-cadherin mislocalization were also observed in human basal-like breast cancer cell lines, suggesting that these results are relevant to human tumors. Together, these results suggest that abnormal Cdk2 activation may contribute to the formation of basal-like breast cancers. PMID:18953433

Correlates of elemental-isotopic composition of stream fishes: the importance of land-use, species identity and body size.

PubMed

Montaña, C G; Schalk, C M

2018-04-01

The isotopic (δ 13 C and δ 15 N) and stoichiometric (C:N:P) compositions of four fish species (Family Centrarchidae: Lepomis auritus, Lepomis cyanellus; Family Cyprinidae: Nocomis leptocephalus, Semotilus atromaculatus) were examined across four North Carolina Piedmont streams arrayed along an urbanization gradient. Both isotopic and stoichiometric composition of fishes appeared to track changes occurring in basal resource availability. Values of δ 13 C of basal resources and consumers were more enriched at the most urbanized streams. Similarly, basal resources and consumers were δ 15 N-enriched at more urbanized streams. Basal resource stoichiometry varied across streams, with periphyton being the most variable. Primary consumers stoichiometry also differed across streams. Intraspecific variation in fish stoichiometry correlated with the degree of urbanization, as the two cyprinids had higher N content and L. cyanellus had higher P content in more urbanized streams, probably due to enrichment of basal resources. Intrinsic factors, specifically species identity and body size also affected stoichiometric variation. Phosphorus (P) content increased significantly with body size in centrarchids, but not in cyprinids. These results suggest that although species identity and body size are important predictors of elemental stoichiometry, the complex nature of altered urban streams may yield imbalances in the elemental composition of consumers via their food resources. © 2018 The Fisheries Society of the British Isles.

Tyrosine Phosphorylation of the Human Serotonin Transporter: A Role in the Transporter Stability and Function

PubMed Central

Annamalai, Balasubramaniam; Mannangatti, Padmanabhan; Arapulisamy, Obulakshmi; Shippenberg, Toni S.; Jayanthi, Lankupalle D.

2012-01-01

The serotonin (5-HT) transporter (SERT) regulates serotoninergic neurotransmission by clearing 5-HT released into the synaptic space. Phosphorylation of SERT on serine and threonine mediates SERT regulation. Whether tyrosine phosphorylation regulates SERT is unknown. Here, we tested the hypothesis that tyrosine-phosphorylation of SERT regulates 5-HT transport. In support of this, alkali-resistant 32P-labeled SERT was found in rat platelets, and Src-tyrosine kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4,d]pyrimidine (PP2) decreased platelet SERT function and expression. In human placental trophoblast cells expressing SERT, PP2 reduced transporter function, expression, and stability. Although siRNA silencing of Src expression decreased SERT function and expression, coexpression of Src resulted in PP2-sensitive increases in SERT function and expression. PP2 treatment markedly decreased SERT protein stability. Compared with WT-SERT, SERT tyrosine mutants Y47F and Y142F exhibited reduced 5-HT transport despite their higher total and cell surface expression levels. Moreover, Src-coexpression increased total and cell surface expression of Y47F and Y142F SERT mutants without affecting their 5-HT transport capacity. It is noteworthy that Y47F and Y142F mutants exhibited higher protein stability compared with WT-SERT. However, similar to WT-SERT, PP2 treatment decreased the stability of Y47F and Y142F mutants. Furthermore, compared with WT-SERT, Y47F and Y142F mutants exhibited lower basal tyrosine phosphorylation and no further enhancement of tyrosine phosphorylation in response to Src coexpression. These results provide the first evidence that SERT tyrosine phosphorylation supports transporter protein stability and 5HT transport. PMID:21992875

Impact of Basal Conditions on Grounding-Line Retreat

NASA Astrophysics Data System (ADS)

Koellner, S. J.; Parizek, B. R.; Alley, R. B.; Muto, A.; Holschuh, N.; Nowicki, S.

2017-12-01

An often-made assumption included in ice-sheet models used for sea-level projections is that basal rheology is constant throughout the domain of the simulation. The justification in support of this assumption is that physical data for determining basal rheology is limited and a constant basal flow law can adequately approximate current as well as past behavior of an ice-sheet. Prior studies indicate that beneath Thwaites Glacier (TG) there is a ridge-and-valley bedrock structure which likely promotes deformation of soft tills within the troughs and sliding, more akin to creep, over the harder peaks; giving rise to a spatially variable basal flow law. Furthermore, it has been shown that the stability of an outlet glacier varies with the assumed basal rheology, so accurate projections almost certainly need to account for basal conditions. To test the impact of basal conditions on grounding-line evolution forced by ice-shelf perturbations, we modified the PSU 2-D flowline model to enable the inclusion of spatially variable basal rheology along an idealized bedrock profile akin to TG. Synthetic outlet glacier "data" were first generated under steady-state conditions assuming a constant basal flow law and a constant basal friction coefficient field on either a linear or bumpy sloping bed. In following standard procedures, a suite of models were then initialized by assuming different basal rheologies and then determining the basal friction coefficients that produce surface velocities matching those from the synthetic "data". After running each of these to steady state, the standard and full suite of models were forced by drastically reducing ice-shelf buttressing through side-shear and prescribed basal-melting perturbations. In agreement with previous findings, results suggest a more plastic basal flow law enhances stability in response to ice-shelf perturbations by flushing ice from farther upstream to sustain the grounding-zone mass balance required to prolong the current grounding-line position. Mixed rheology beds tend to mimic the retreat of the higher-exponent bed, a behavior enhanced over bumps as the stabilizing ridges tap into ice from local valleys. Thus, accounting for variable basal conditions in ice-sheet model projections is critical for improving both the timing and magnitude of retreat.

Periparturient dairy cows do not exhibit hepatic insulin resistance, yet adipose-specific insulin resistance occurs in cows prone to high weight loss.

PubMed

Zachut, M; Honig, H; Striem, S; Zick, Y; Boura-Halfon, S; Moallem, U

2013-09-01

The periparturient period in dairy cows is associated with alterations in insulin action in peripheral tissues; however, the molecular mechanism underlying this process is not completely understood. The objective was to examine the response to a glucose tolerance test (GTT) and to analyze insulin signaling in liver and adipose tissues in pre- and postpartum dairy cows. Liver and adipose tissue biopsies were taken before and after GTT, at 17d prepartum and again at 3 to 5d postpartum from 8 high-yielding Israeli Holstein dairy cows. Glucose clearance rate after GTT was similar pre- and postpartum. Basal insulin concentrations and the insulin response to GTT were approximately 4-fold higher prepartum than postpartum. In accordance, phosphorylation of the hepatic insulin receptor after GTT was higher prepartum than postpartum. Across periods, a positive correlation was observed between the basal and peak plasma insulin and phosphorylated insulin receptor after GTT in the liver. Hepatic phosphorylation of protein kinase B after GTT was elevated pre- and postpartum. Conversely, in adipose tissue, phosphorylation of protein kinase B after GTT pre- and postpartum was increased only in 4 out of 8 cows that lost less body weight postpartum. Our results demonstrate that hepatic insulin signaling is regulated by plasma insulin concentrations as part of the homeorhetic adjustments toward calving, and do not support a model of hepatic insulin resistance in periparturient cows. Nevertheless, we suggest that specific insulin resistance in adipose tissue occurs pre- and postpartum only in cows prone to high weight loss. The different responses among these cows imply that genetic background may affect insulin responsiveness in adipose tissue pre- and postpartum. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast.

PubMed

Bak, Ann Mosegaard; Møller, Andreas Buch; Vendelbo, Mikkel Holm; Nielsen, Thomas Svava; Viggers, Rikke; Rungby, Jørgen; Pedersen, Steen Bønløkke; Jørgensen, Jens Otto Lunde; Jessen, Niels; Møller, Niels

2016-07-01

Increased availability of lipids may conserve muscle protein during catabolic stress. Our study was designed to define 1) intracellular mechanisms leading to increased lipolysis and 2) whether this scenario is associated with decreased amino acid and urea fluxes, and decreased muscle amino acid release in obese subjects under basal and fasting conditions. We therefore studied nine lean and nine obese subjects twice, after 12 and 72 h of fasting, using measurements of mRNA and protein expression and phosphorylation of lipolytic and protein metabolic signaling molecules in fat and muscle together with whole body and forearm tracer techniques. Obese subjects displayed increased whole body lipolysis, decreased urea production rates, and decreased forearm muscle protein breakdown per 100 ml of forearm tissue, differences that persisted after 72 h of fasting. Lipolysis per fat mass unit was reduced in obese subjects and, correspondingly, adipose tissue hormone-sensitive lipase (HSL) phosphorylation and mRNA and protein levels of the adipose triglyceride lipase (ATGL) coactivator CGI58 were decreased. Fasting resulted in higher HSL phosphorylations and lower protein levels of the ATGL inhibitor G0S2. Muscle protein expressions of mammalian target of rapamycin (mTOR) and 4EBP1 were lower in obese subjects, and MuRf1 mRNA was higher with fasting in lean but not obese subjects. Phosphorylation and signaling of mTOR decreased with fasting in both groups, whereas ULK1 protein and mRNA levels increased. In summary, obese subjects exhibit increased lipolysis due to a large fat mass with blunted prolipolytic signaling, together with decreased urea and amino acid fluxes both in the basal and 72-h fasted state; this is compatible with preservation of muscle and whole body protein. Copyright © 2016 the American Physiological Society.

Evaluating the influence of stress on the dislocation creep flow law for quartz

NASA Astrophysics Data System (ADS)

Tokle, L.; Hirth, G.

2017-12-01

Due to the abundance of quartz in the continental crust, quartz rheology is fundamental to our understanding of many geodynamic processes. Microstructures in many naturally deformed quartzites deformed at ductile conditions, indicate that dislocation creep is a common deformation mechanism in quartz at crustal conditions. The dislocation creep flow laws for quartz were constructed based on deformation experiments on aggregates at temperatures from 900 to 1100°C and strain rates of 10-5-10-6 s-1. Hirth et al. (2001) point out that these flow laws underestimate sample strengths for experiments conducted below 900°C; yet samples deformed as low as 700°C exhibit dislocation creep microstructures. To address this discrepancy, we compared 14 different studies on experimentally deformed wet quartzite aggregates ranging in temperature from 700 to 1100°C. Our analysis shows that two clear trends develop, one with a power-law stress exponent of n = 4 and the other, at a higher stress, with a stress exponent of n = 3. This change suggests a transition in the rate-limiting process; further, the conditions where the transition in stress exponent occurs correlate well with changes in quartz c-axis fabrics in general shear experiments. At low stresses, quartz fabrics are defined by a Y-max, indicating prism slip, while at higher stresses quartz fabrics are defined by basal slip. Our interpretation is that the c-axis fabrics represent the easy slip system in quartz and hypothesize that basal slip is rate-limiting at low stresses while prism is rate-limiting at high stresses. A change in the stress exponent has significant consequences for our understanding of high stress tectonic environments, such as the brittle-ductile transition and sediment rheology in a subducting slab.

Temperature-induced physiological stress and reproductive characteristics of the migratory seahorse Hippocampus erectus during a thermal stress simulation.

PubMed

Qin, Geng; Johnson, Cara; Zhang, Yuan; Zhang, Huixian; Yin, Jianping; Miller, Glen; Turingan, Ralph G; Guisbert, Eric; Lin, Qiang

2018-05-15

Inshore-offshore migration occurs frequently in seahorse species either because of prey opportunities or because it is driven by reproduction, and variations in water temperature may dramatically change migratory seahorse behavior and physiology. The present study investigated the behavioral and physiological responses of the lined seahorse Hippocampus erectus under thermal stress and evaluated the potential effects of different temperatures on its reproduction. The results showed that the thermal tolerance of the seahorses was time dependent. Acute thermal stress (30°C, 2-10 hours) increased the basal metabolic rate (breathing rate) and the expression of stress response genes ( Hsp genes) significantly and further stimulated seahorse appetite. Chronic thermal treatment (30°C, 4 weeks) led to a persistently higher basal metabolic rate, higher stress response gene expression, and higher mortality, indicating that the seahorses could not acclimate to chronic thermal stress and might experience massive mortality due to excessive basal metabolic rates and stress damage. Additionally, no significant negative effects on gonad development or reproductive endocrine regulation genes were observed in response to chronic thermal stress, suggesting that seahorse reproductive behavior could adapt to higher-temperature conditions during migration and within seahorse breeding grounds. In conclusion, this simulation experiment indicated that temperature variations during inshore-offshore migration have no effect on reproduction but promote basal metabolic rates and stress responses significantly. Therefore, we suggest that the high observed tolerance of seahorse reproduction was in line with the inshore-offshore reproductive migration pattern of lined seahorse. © 2018. Published by The Company of Biologists Ltd.

The hidden dimensions of the competition effect: basal cortisol and basal testosterone jointly predict changes in salivary testosterone after social victory in men.

PubMed

Zilioli, Samuele; Watson, Neil V

2012-11-01

Dominance struggles appear to affect hormone concentrations in many mammalian species, such that higher concentrations of testosterone are seen in winners of competitions, compared to losers. This so-called, "competition effect" has received inconsistent empirical support, suggesting that additional psychological (e.g., mood), situational (i.e., nature of the competition) and physiological (e.g., cortisol) variables might intervene in modulating testosterone fluctuations after social contests. We investigated possible interactions between the hypothalamic-pituitary-gonadal (HPG) axis and the hypothalamic-pituitary-adrenal (HPA) stress axis in predicting transient changes in testosterone after social victory or defeat on a familiar competitive task. In particular, the present study examined the dual-hormone hypothesis - proposing that baseline cortisol potently modulates the competition effect (Mehta and Josephs, 2010) - in a sample of healthy young men engaged in head-to-head competition on a widely played commercial videogame, Tetris. We found a significant interaction between HPG and HPA axes status and the competition effect on testosterone in the randomly assigned videogame winners, such that winners with a pre-competition combination of high baseline testosterone and low baseline cortisol exhibited significantly greater post-competition testosterone concentrations. The randomly assigned videogame losers showed significantly decreased post-competition levels of testosterone. Possible biological and evolutionary mechanisms underlying this phenomenon are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

ZnO nanocubes with (101) basal plane photocatalyst prepared via a low-frequency ultrasonic assisted hydrolysis process.

PubMed

Tan, Sin Tee; Umar, Akrajas Ali; Balouch, Aamna; Yahaya, Muhammad; Yap, Chi Chin; Salleh, Muhamad Mat; Oyama, Munetaka

2014-03-01

The crystallographic plane of the ZnO nanocrystals photocatalyst is considered as a key parameter for an effective photocatalysis, photoelectrochemical reaction and photosensitivity. In this paper, we report a simple method for the synthesis of a new (101) high-energy plane bounded ZnO nanocubes photocatalyst directly on the FTO surface, using a seed-mediated ultrasonic assisted hydrolysis process. In the typical procedure, high-density nanocubes and quasi-nanocubes can be grown on the substrate surface from a solution containing equimolar (0.04 M) zinc nitrate hydrate and hexamine. ZnO nanocubes, with average edge-length of ca. 50 nm, can be obtained on the surface in as quickly as 10 min. The heterogeneous photocatalytic property of the sample has been examined in the photodegradation of methyl orange (MO) by UV light irradiation. It was found that the ZnO nanocubes exhibit excellent catalytic and photocatalytic properties and demonstrate the photodegradation efficiency as high as 5.7 percent/μg mW. This is 200 times higher than those reported results using a relatively low-powered polychromatic UV light source (4 mW). The mechanism of ZnO nanocube formation using the present approach is discussed. The new-synthesized ZnO nanocubes with a unique (101) basal plane also find potential application in photoelectrochemical devices and sensing. Copyright © 2013 Elsevier B.V. All rights reserved.

Formation of a bioconjugate composed of hemin, smectite, and quaternary ammonium chloride that is soluble and active in hydrophobic media.

PubMed

Kurosawa, Masaru; Itoh, Tetsuji; Kodera, Yoh; Matsushima, Ayako; Hiroto, Misao; Nishimura, Hiroyuki; Inada, Yuji

2002-01-01

Hemin (Fe(3+)) was adsorbed onto synthetic smectite (clay mineral) intercalated with a quaternary alkenylammonium compound, dioleyldimethylammonium chloride (DOA), to form a hemin-smectite-DOA conjugate. The hemin-smectite-DOA conjugate was soluble in organic solvents such as benzene and toluene to form a transparent colloidal solution with a light yellow color. Its absorption spectrum in benzene showed two bands, 600 and 568 nm, in the visible region and a sharp Soret band at 400 nm with the molar extinction coefficient of 7.5 x 10(4) M(-1) cm(-1). The formation of the conjugate of smectite and DOA was confirmed by X-ray diffraction analysis: the basal spacing, d(001), of hemin-smectite-DOA conjugate was 19 A which is an expansion of the interlayer space by 5 A based upon the basal spacing of smectite of 14 A. Hemin-smectite-DOA conjugate catalyzed the peroxidase-like reaction in organic solvents using benzoyl peroxide as the hydrogen acceptor and leucocrystal violet as the hydrogen donor. The temperature-dependent peroxidase-like activity of the conjugate was compared with peroxidase activity of horseradish peroxidase. The hemin-smectite-DOA conjugate exhibited higher activity as the temperature was increased from 30 to 70 degrees C, while horseradish peroxidase activity was reduced as the temperature was increased.

Synergistic effect of cationic and anionic surfactants for the modification of Ca-montmorillonite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Zepeng, E-mail: zhangzp@cugb.edu.cn; Zhang, Jichu; Liao, Libing, E-mail: bliao@cugb.edu.cn

2013-05-15

Highlights: ► The basal spacing of MMT–CTAB–SDS reaches 5.30 nm. ► MMT–CTAB–SDS shows perfect dispersion property and excellent heat resistance. ► SDS helped to improve the heat resistance and decrease the surface energy of the MMT–CTAB–SDS particles. - Abstract: The synergistic effect of cationic surfactant (CTAB) and anionic surfactant (SDS) for the modification of Ca-montmorillonite (Ca-MMT) has been developed, and the novel cation–anion modified organomontmorillonite (MMT–CTAB–SDS) was prepared. X-ray diffraction (XRD) analysis indicates that the interlayer spacing of montmorillonite was well expanded by the intercalation of CTAB and SDS and the basal spacing increased from 1.54 nm (Ca-MMT) to 5.30more » nm (MMT–CTAB–SDS). Thermogravimetric analysis (TG) showed that the MMT–CTAB–SDS displayed excellent heat resistance. Scanning electron microscopy (SEM) analysis proved that the MMT–CTAB–SDS exhibited excellent dispersion property and the plates with few silicate layers can be observed. Contact angle tests indicated that the hydrophilicity of MMT–CTAB–SDS was lower than that of Ca-MMT and higher than that of MMT–CTAB. It was verified that SDS contributed to expanding the interlayer space, further improved the heat resistance of the MMT–CTAB and decreased the surface energy of the MMT–CTAB–SDS particles.« less

A Drosophila heat shock response represents an exception rather than a rule amongst Diptera species.

PubMed

Zatsepina, O G; Przhiboro, A A; Yushenova, I A; Shilova, V; Zelentsova, E S; Shostak, N G; Evgen'ev, M B; Garbuz, D G

2016-08-01

Heat shock protein 70 (Hsp70) is the major player that underlies adaptive response to hyperthermia in all organisms studied to date. We investigated patterns of Hsp70 expression in larvae of dipteran species collected from natural populations of species belonging to four families from different evolutionary lineages of the order Diptera: Stratiomyidae, Tabanidae, Chironomidae and Ceratopogonidae. All investigated species showed a Hsp70 expression pattern that was different from the pattern in Drosophila. In contrast to Drosophila, all of the species in the families studied were characterized by high constitutive levels of Hsp70, which was more stable than that in Drosophila. When Stratiomyidae Hsp70 proteins were expressed in Drosophila cells, they became as short-lived as the endogenous Hsp70. Interestingly, three species of Ceratopogonidae and a cold-water species of Chironomidae exhibited high constitutive levels of Hsp70 mRNA and high basal levels of Hsp70. Furthermore, two species of Tabanidae were characterized by significant constitutive levels of Hsp70 and highly stable Hsp70 mRNA. In most cases, heat-resistant species were characterized by a higher basal level of Hsp70 than more thermosensitive species. These data suggest that different trends were realized during the evolution of the molecular mechanisms underlying the regulation of the responses of Hsp70 genes to temperature fluctuations in the studied families. © 2016 The Royal Entomological Society.

Rats classified as low or high cocaine locomotor responders: A unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors

PubMed Central

Yamamoto, Dorothy J.; Nelson, Anna M.; Mandt, Bruce H.; Larson, Gaynor A.; Rorabaugh, Jacki M.; Ng, Christopher M.C.; Barcomb, Kelsey M.; Richards, Toni L.; Allen, Richard M.; Zahniser, Nancy R.

2013-01-01

Individual differences are a hallmark of drug addiction. Here, we describe a rat model based on differential initial responsiveness to low dose cocaine. Despite similar brain cocaine levels, individual outbred Sprague-Dawley rats exhibit markedly different magnitudes of acute cocaine-induced locomotor activity and, thereby, can be classified as low or high cocaine responders (LCRs or HCRs). LCRs and HCRs differ in drug-induced, but not novelty-associated, hyperactivity. LCRs have higher basal numbers of striatal dopamine transporters (DATs) than HCRs and exhibit marginal cocaine inhibition of in vivo DAT activity and cocaine-induced increases in extracellular DA. Importantly, lower initial cocaine response predicts greater locomotor sensitization, conditioned place preference and greater motivation to self-administer cocaine following low dose acquisition. Further, outbred Long-Evans rats classified as LCRs, versus HCRs, are more sensitive to cocaine’s discriminative stimulus effects. Overall, results to date with the LCR/HCR model underscore the contribution of striatal DATs to individual differences in initial cocaine responsiveness and the value of assessing the influence of initial drug response on subsequent expression of addiction-like behaviors. PMID:23850581

[Sucrose reward promotes rats' motivation for cocaine].

PubMed

Li, Yan-Qing; LE, Qiu-Min; Yu, Xiang-Chen; Ma, Lan; Wang, Fei-Fei

2016-06-25

Caloric diet, such as fat and sugar intake, has rewarding effects, and has been indicated to affect the responses to addictive substances in animal experiments. However, the possible association between sucrose reward and the motivation for addictive drugs remains to be elucidated. Thus, we carried out behavioral tests after sucrose self-administration training to determine the effects of sucrose experience on rats' motivation for cocaine, locomotor sensitivity to cocaine, basal locomotor activity, anxiety level, and associative learning ability. The sucrose-experienced (sucrose) group exhibited higher lever press, cocaine infusion and break point, as well as upshift of cocaine dose-response curve in cocaine self-administration test, as compared with the control (chow) group. Additionally, despite similar locomotor activity in open field test and comparable score in cocaine-induced conditioned place preference, the sucrose group showed higher cocaine-induced locomotor sensitivity as compared with the chow group. The anxiety level and the performance in vocal-cue induced fear memory were similar between these two groups in elevated plus maze and fear conditioning tests, respectively. Taken together, our work indicates that sucrose experience promotes the rats' motivation for cocaine.

Expression of important pathway genes involved in withanolides biosynthesis in hairy root culture of Withania somnifera upon treatment with Gracilaria edulis and Sargassum wightii.

PubMed

Sivanandhan, Ganeshan; Arunachalam, Chinnathambi; Selvaraj, Natesan; Sulaiman, Ali Alharbi; Lim, Yong Pyo; Ganapathi, Andy

2015-06-01

The investigation of seaweeds, Gracilaria edulis and Sargassum wightii extracts was carried out for the estimation of growth characteristics and major withanolides production in hairy root culture of Withania somnifera. The extract of G. edulis (50%) in MS liquid basal medium enabled maximum production of dry biomass (5.46 g DW) and withanolides contents (withanolide A 5.23 mg/g DW; withaferin A 2.24 mg/g DW and withanone 4.83 mg/g DW) in hairy roots after 40 days of culture with 48 h contact time. The obtained withanolides contents were significantly higher (2.32-fold-2.66-fold) in hairy root culture when compared to the control. RT PCR analysis of important pathway genes such as SE, SS, HMGR and FPPS exhibited substantial higher expression upon the seaweed extracts treatment in hairy root culture. This experiment would paw a platform for withanolides production in hairy root culture with the influence of sea weed extracts for pharmaceutical companies in the future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Gorlin-Goltz syndrome and neoplasms: a case study.

PubMed

Lopes, Nilza N F; Caran, Eliana M; Lee, Maria Lucia; Silva, Nasjla Saba; Rocha, André Caroli; Macedo, Carla R D

2010-01-01

Gorlin syndrome is a rare autosomal dominant disorder exhibiting high penetrance and variable expressivity. It is characterized by facial dysmorphism, skeletal anomalies, multiple basal cell carcinomas, odontogenic keratocysts (OKC), palmar and plantar pits, bifid ribs, vertebral anomalies and a variety of other malformations. Various neoplasms, such as medulloblastomas, meningiomas, ovarian and cardiac fibromas are also found in this syndrome. To describe a twelve-year-old patient with Gorlin-Goltz syndrome, with basal cell carcinomas and promyelocytic leukemia developed after receiving craniospinal radiation for a medulloblastoma. Bifid ribs as well as mandibular and maxillar OKC were also diagnosed Conclusion: The patient with Gorlin-Goltz syndrome should receive close follow-up for early detection of malformations nd malignant neoplasias.

Interactions between ecology, demography, capture stress, and profiles of corticosterone and glucose in a free-living population of Australian freshwater crocodiles.

PubMed

Jessop, Tim S; Tucker, Anton D; Limpus, Colin J; Whittier, Joan M

2003-06-01

In this study we examined three aspects pertaining to adrenocortical responsiveness in free-ranging Australian freshwater crocodiles (Crocodylus johnstoni). First, we examined the ability of freshwater crocodiles to produce corticosterone in response to a typical capture-stress protocol. A second objective addressed the relationship between capture stress, plasma glucose and corticosterone. Next we examined if variation in basal and capture-stress-induced levels of plasma corticosterone was linked to ecological or demographic factors for individuals in this free-ranging population. Blood samples obtained on three field trips were taken from a cross-sectional sample of the population. Crocodiles were bled once during four time categories at 0, 0.5, 6, and 10h post-capture. Plasma corticosterone increased significantly with time post-capture. Plasma glucose also significantly increased with duration of capture-stress and exhibited a positive and significant relationship with plasma corticosterone. Significant variation in basal or stress induced levels of corticosterone in crocodiles was not associated with any ecological or demographic factors including sex, age class or the year of capture that the crocodiles were sampled from. However, three immature males had basal levels of plasma corticosterone greater than 2 standard deviations above the mean. While crocodiles exhibited a pronounced adrenocortical and hyperglycaemic response to capture stress, limited variation in adrenocortical responsiveness due to ecological and demographic factors was not evident. This feature could arise in part because this population was sampled during a period of environmental benigness.

Multisensory integration in the basal ganglia.

PubMed

Nagy, Attila; Eördegh, Gabriella; Paróczy, Zsuzsanna; Márkus, Zita; Benedek, György

2006-08-01

Sensorimotor co-ordination in mammals is achieved predominantly via the activity of the basal ganglia. To investigate the underlying multisensory information processing, we recorded the neuronal responses in the caudate nucleus (CN) and substantia nigra (SN) of anaesthetized cats to visual, auditory or somatosensory stimulation alone and also to their combinations, i.e. multisensory stimuli. The main goal of the study was to ascertain whether multisensory information provides more information to the neurons than do the individual sensory components. A majority of the investigated SN and CN multisensory units exhibited significant cross-modal interactions. The multisensory response enhancements were either additive or superadditive; multisensory response depressions were also detected. CN and SN cells with facilitatory and inhibitory interactions were found in each multisensory combination. The strengths of the multisensory interactions did not differ in the two structures. A significant inverse correlation was found between the strengths of the best unimodal responses and the magnitudes of the multisensory response enhancements, i.e. the neurons with the weakest net unimodal responses exhibited the strongest enhancement effects. The onset latencies of the responses of the integrative CN and SN neurons to the multisensory stimuli were significantly shorter than those to the unimodal stimuli. These results provide evidence that the multisensory CN and SN neurons, similarly to those in the superior colliculus and related structures, have the ability to integrate multisensory information. Multisensory integration may help in the effective processing of sensory events and the changes in the environment during motor actions controlled by the basal ganglia.

Ice-dynamical and Basal Properties of Sofiyskiy Glacier, Altai Mts, Russia, Based On GPS and Radio-echo Sounding Surveys

NASA Astrophysics Data System (ADS)

Pattyn, F.; de Smedt, B.; de Brabander, S.; Decleir, H.

It is expected that central-Asian glaciers ­ compared to other glaciers in the world ­ exhibit a different response to changing climate due to (i) the extreme continentality that gives rise to aridity and large seasonal temperature variations, and (ii) the coinci- dence of both accumulation and ablation season in summer. A detailed four-year field survey was carried out on Sofiyskiy Glacier, a glacier in the South Chuya Range (Altai Mountains), Russia. Field observations revealed that this glacier retreated steadily during the 20th Century at a rate of 18.3 m a-1. Based on radio-echo sounding (RES) and mass-balance mea- surements, we carried out numerical model experiments to simulate historic front vari- ations (De Smedt and Pattyn, in prep.). Results demonstrated that although Sofiyskiy Glacier exhibits a low static sensitivity to climatic changes, its dynamic sensitivity seems very large compared to glaciers from the European Alps. Basal sliding plays an important role in the glacier's behaviour. An analysis of RES measurements led to the determination of the bed reflection power (BRP). Applying a three-layer reflectivity model (Born and Wolf, 1986) the BRP was compared with the theoretical bed reflectivity for a conductive layer of varying porosity and thickness (considering a water layer, saturated till or frozen material). From this comparison it was possible to delineate zones of high basal water content, saturated till or ice frozen to the bedrock.

The Whole Language Approach versus the Basal Reading Approach and the Effects on Reading Achievement Scores.

ERIC Educational Resources Information Center

Puorro, Michelle

A study examined two first-grade classrooms implementing the whole language approach and two utilizing the basal reading approach to determine the differences, if any, between the treatments. The hypothesis was that the whole language reading approach when combined with a phonics program would not result in higher test scores on a standardized…

Sex differences in the phagocytic and migratory activity of microglia and their impairment by palmitic acid.

PubMed

Yanguas-Casás, Natalia; Crespo-Castrillo, Andrea; de Ceballos, Maria L; Chowen, Julie A; Azcoitia, Iñigo; Arevalo, Maria Angeles; Garcia-Segura, Luis M

2018-03-01

Sex differences in the incidence, clinical manifestation, disease course, and prognosis of neurological diseases, such as autism spectrum disorders or Alzheimer's disease, have been reported. Obesity has been postulated as a risk factor for cognitive decline and Alzheimer's disease and, during pregnancy, increases the risk of autism spectrum disorders in the offspring. Obesity is associated with increased serum and brain levels of free fatty acids, such as palmitic acid, which activate microglial cells triggering a potent inflammatory cascade. In this study, we have determined the effect of palmitic acid in the inflammatory profile, motility, and phagocytosis of primary male and female microglia, both in basal conditions and in the presence of a pro-inflammatory stimulus (interferon-γ). Male microglia in vitro showed higher migration than female microglia under basal and stimulated conditions. In contrast, female microglia had higher basal and stimulated phagocytic activity than male microglia. Palmitic acid did not affect basal migration or phagocytosis, but abolished the migration and phagocytic activity of male and female microglia in response to interferon-γ. These findings extend previous observations of sex differences in microglia and suggest that palmitic acid impairs the protective responses of these cells. © 2017 Wiley Periodicals, Inc.

A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification

PubMed Central

Florio, Marta; Namba, Takashi; Pääbo, Svante; Hiller, Michael; Huttner, Wieland B.

2016-01-01

The gene ARHGAP11B promotes basal progenitor amplification and is implicated in neocortex expansion. It arose on the human evolutionary lineage by partial duplication of ARHGAP11A, which encodes a Rho guanosine triphosphatase–activating protein (RhoGAP). However, a lack of 55 nucleotides in ARHGAP11B mRNA leads to loss of RhoGAP activity by GAP domain truncation and addition of a human-specific carboxy-terminal amino acid sequence. We show that these 55 nucleotides are deleted by mRNA splicing due to a single C→G substitution that creates a novel splice donor site. We reconstructed an ancestral ARHGAP11B complementary DNA without this substitution. Ancestral ARHGAP11B exhibits RhoGAP activity but has no ability to increase basal progenitors during neocortex development. Hence, a single nucleotide substitution underlies the specific properties of ARHGAP11B that likely contributed to the evolutionary expansion of the human neocortex. PMID:27957544

Parasympathetic activation by pyridostigmine on chemoreflex sensitivity in heart-failure rats.

PubMed

Sabino, João Paulo J; da Silva, Carlos Alberto Aguiar; Giusti, Humberto; Glass, Mogens Lesner; Salgado, Helio C; Fazan, Rubens

2013-12-01

We evaluated the effects of parasympathetic activation by pyridostigmine (PYR) on chemoreflex sensitivity in a rat model of heart failure (HF rats). HF rats demonstrated higher pulmonary ventilation (PV), which was not affected by PYR. When HF and control rats treated or untreated with PYR were exposed to 15% O2, all groups exhibited prompt increases in respiratory frequency (RF), tidal volume (TV) and PV. When HF rats were exposed to 10% O2 they showed greater PV response which was prevented by PYR. The hypercapnia triggered by either 5% CO2 or 10% CO2 promoted greater RF and PV responses in HF rats. PYR blunted the RF response in HF rats but did not affect the PV response. In conclusion, PYR prevented increased peripheral chemoreflex sensitivity, partially blunted central chemoreflex sensitivity and did not affect basal PV in HF rats. © 2013.

Ultrastructure of oogenesis in imposex females of Babylonia areolata (Caenogastropoda: Buccinidae)

NASA Astrophysics Data System (ADS)

Muenpo, C.; Suwanjarat, J.; Klepal, W.

2011-09-01

During a tributyltin (TBT)-exposure experiment, the ultrastructural features of oogenesis have been examined in TBT-induced imposex females of Babylonia areolata and compared with those of the normal female. The results obtained from such experiment demonstrates that B. areolata exhibits a low to moderate intensity of imposex because all VDSI values are never higher than 3. Ultrastructures of germ cell development including oogonia, pre-vitellogenic, early vitellogenic, late vitellogenic and mature oocytes show that oogenesis in imposex female is similar to that of normal females except for the presence of numerous lipid droplets in the cytoplasm of the oocytes and the follicle cells in imposex females, indicating the degeneration of their oocytes. Vitellogenesis in B. areolata involves both auto- and heterosynthetic processes that resemble those of the basal gastropods and the pulmonates. In addition, the presence of cortical granules and microvilli are unique structures of this species.

Preparation of C.I. Pigment 52:1 anion-pillared layered double hydroxide and the thermo- and photostability of the resulting intercalated material

NASA Astrophysics Data System (ADS)

Guo, Shengchang; Evans, David G.; Li, Dianqing

2006-05-01

Intercalation of 2-naphthalenecarboxylic acid, 4-((4-chloro-5-methyl-2-sulfophenyl) azo)-3-hydroxy-, calcium salt (1:1) (C.I. Pigment Red 52:1, also known as New Rubine S6B) into a layered double hydroxide (LDHs) host was carried out using MgAl NO3 LDHs as a precursor in an effort to improve the thermal and photo stability of the pigment. After intercalation, the powder X-ray diffraction (XRD) pattern shows that the basal spacing of the LDHs increased from 0.86 to 1.92 nm. Infrared spectra and TG DTA curves demonstrate that there are supramolecular host guest interactions. It was found that the intercalated material is more stable than the pristine pigment at high temperatures. The pigment anion-pillared LDHs also exhibit much higher photostablity to UV-light than the pristine pigment.

Three-year efficacy of complex insulin regimens in type 2 diabetes.

PubMed

Holman, Rury R; Farmer, Andrew J; Davies, Melanie J; Levy, Jonathan C; Darbyshire, Julie L; Keenan, Joanne F; Paul, Sanjoy K

2009-10-29

Evidence supporting the addition of specific insulin regimens to oral therapy in patients with type 2 diabetes mellitus is limited. In this 3-year open-label, multicenter trial, we evaluated 708 patients who had suboptimal glycated hemoglobin levels while taking metformin and sulfonylurea therapy. Patients were randomly assigned to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Sulfonylurea therapy was replaced by a second type of insulin if hyperglycemia became unacceptable during the first year of the study or subsequently if glycated hemoglobin levels were more than 6.5%. Outcome measures were glycated hemoglobin levels, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain. Median glycated hemoglobin levels were similar for patients receiving biphasic (7.1%), prandial (6.8%), and basal (6.9%) insulin-based regimens (P=0.28). However, fewer patients had a level of 6.5% or less in the biphasic group (31.9%) than in the prandial group (44.7%, P=0.006) or in the basal group (43.2%, P=0.03), with 67.7%, 73.6%, and 81.6%, respectively, taking a second type of insulin (P=0.002). [corrected] Median rates of hypoglycemia per patient per year were lowest in the basal group (1.7), higher in the biphasic group (3.0), and highest in the prandial group (5.7) (P<0.001 for the overall comparison). The mean weight gain was higher in the prandial group than in either the biphasic group or the basal group. Other adverse event rates were similar in the three groups. Patients who added a basal or prandial insulin-based regimen to oral therapy had better glycated hemoglobin control than patients who added a biphasic insulin-based regimen. Fewer hypoglycemic episodes and less weight gain occurred in patients adding basal insulin. (Current Controlled Trials number, ISRCTN51125379.) 2009 Massachusetts Medical Society

Implicit Perceptual-Motor Skill Learning in Mild Cognitive Impairment and Parkinson's Disease

PubMed Central

Gobel, Eric W.; Blomeke, Kelsey; Zadikoff, Cindy; Simuni, Tanya; Weintraub, Sandy; Reber, Paul J.

2015-01-01

Objective Implicit skill learning is hypothesized to depend on nondeclarative memory that operates independent of the medial temporal lobe (MTL) memory system and instead depends on cortico-striatal circuits between the basal ganglia and cortical areas supporting motor function and planning. Research with the Serial Reaction Time (SRT) task suggests that patients with memory-disorders due to MTL damage exhibit normal implicit sequence learning. However, reports of intact learning rely on observations of no group differences, leading to speculation whether implicit sequence learning is fully intact in these patients. Patients with Parkinson's Disease (PD) often exhibit impaired sequence learning, but this impairment is not universally observed. Method Implicit perceptual-motor sequence learning was examined using the Serial Interception Sequence Learning (SISL) task in patients with amnestic Mild Cognitive Impairment (MCI; n=11) and patients with PD (n=15). Sequence learning in SISL is resistant to explicit learning and individually adapted task difficulty controls for baseline performance differences. Results Patients with MCI exhibited robust sequence learning, equivalent to healthy older adults (n=20), supporting the hypothesis that the MTL does not contribute to learning in this task. In contrast, the majority of patients with PD exhibited no sequence-specific learning in spite of matched overall task performance. Two patients with PD exhibited performance indicative of an explicit compensatory strategy suggesting that impaired implicit learning may lead to greater reliance on explicit memory in some individuals. Conclusion The differences in learning between patient groups provides strong evidence in favor of implicit sequence learning depending solely on intact basal ganglia function with no contribution from the MTL memory system. PMID:23688213

Patterns in melanocytic lesions: impact of the geometry on growth and transport inside the epidermis

PubMed Central

Balois, Thibaut; Chatelain, Clément; Ben Amar, Martine

2014-01-01

In glabrous skin, nevi and melanomas exhibit pigmented stripes during clinical dermoscopic examination. They find their origin in the basal layer geometry which periodically exhibits ridges, alternatively large (limiting ridges) and thin (intermediate ridges). However, nevus and melanoma lesions differ by the localization of the pigmented stripes along furrows or ridges of the epidermis surface. Here, we propose a biomechanical model of avascular tumour growth which takes into account this specific geometry in the epidermis where both kinds of lesions first appear. Simulations show a periodic distribution of tumour cells inside the lesion, with a global contour stretched out along the ridges. In order to be as close as possible to clinical observations, we also consider the melanin transport by the keratinocytes. Our simulations show that reasonable assumptions on melanocytic cell repartition in the ridges favour the limiting ridges of the basal compared with the intermediate ones in agreement with nevus observations but not really with melanomas. It raises the question of cell aggregation and repartition of melanocytic cells in acral melanomas and requires further biological studies of these cells in situ. PMID:24872499

Evidence for modular evolution in a long-tailed pterosaur with a pterodactyloid skull.

PubMed

Lü, Junchang; Unwin, David M; Jin, Xingsheng; Liu, Yongqing; Ji, Qiang

2010-02-07

The fossil record is a unique source of evidence for important evolutionary phenomena such as transitions between major clades. Frustratingly, relevant fossils are still comparatively rare, most transitions have yet to be documented in detail and the mechanisms that underpin such events, typified by rapid large scale changes and for which microevolutionary processes seem insufficient, are still unclear. A new pterosaur (Mesozoic flying reptile) from the Middle Jurassic of China, Darwinopterus modularis gen. et sp. nov., provides the first insights into a prominent, but poorly understood transition between basal, predominantly long-tailed pterosaurs and the more derived, exclusively short-tailed pterodactyloids. Darwinopterus exhibits a remarkable 'modular' combination of characters: the skull and neck are typically pterodactyloid, exhibiting numerous derived character states, while the remainder of the skeleton is almost completely plesiomorphic and identical to that of basal pterosaurs. This pattern supports the idea that modules, tightly integrated complexes of characters with discrete, semi-independent and temporally persistent histories, were the principal focus of natural selection and played a leading role in evolutionary transitions.

Impairment of the proximal to distal tonic gradient in the human diabetic stomach.

PubMed

Min, Y W; Hong, Y S; Ko, E-J; Lee, J Y; Min, B-H; Sohn, T S; Kim, J J; Rhee, P-L

2014-02-01

Little has been known about the contractile characteristics of diabetic stomach. We investigated spontaneous contractions and responses to acetylcholine in the gastric muscle in diabetic patients and non-diabetic control subjects according to the region of stomach. Gastric specimens were obtained from 26 diabetics and 55 controls who underwent gastrectomy at Samsung Medical Center between February 2008 and November 2011. Isometric force measurements were performed using circular muscle strips from the different regions of stomach under basal condition and in response to acetylcholine. Basal tone of control was higher in the proximal stomach than in the distal (0.63 g vs 0.46 g, p = 0.027). However, in diabetics, basal tone was not significantly different between the proximal and distal stomach (0.75 g vs 0.62 g, p = 0.32). The distal stomach of diabetics had higher basal tone and lower frequency than that of control (0.62 g vs 0.46 g, p = 0.049 and 4.0/min vs 4.9/min, p = 0.049, respectively). After exposure to acetylcholine, dose-dependent increases of basal tone, peak, and area under the curve (AUC) were noticed in both proximal and distal stomach of the two groups. In the proximal stomach, however, the dose-dependent increase of basal tone and AUC was less prominent in diabetics than in control. On the contrary to control, the proximal to distal tonic gradient was not observed in diabetic stomach. Diabetic stomach also had lower frequency of spontaneous contraction in the distal stomach and less acetylcholine-induced positive inotropic effect in the proximal stomach than control. © 2013 John Wiley & Sons Ltd.

COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter

PubMed Central

de Godoy, Márcio A. F.; Rattan, Neeru; Rattan, Satish

2009-01-01

Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1−/− and COX-2−/− mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 ± 3.4% (mean ± SE) by SC-560 (1 × 10−5 M) and 5.4 ± 2.2% by rofecoxib (P < 0.05, n = 5). Basal tone was 0.172 ± 0.021 mN//mg in the IAS from wild-type mice and significantly less (0.080 ± 0.015 mN/mg) in the IAS from COX-1−/− mice (P < 0.05, n = 5). However, basal tone in COX-2−/− mice was not significantly different from that in wild-type mice. We conclude that COX-1-related products contribute significantly to IAS tone. PMID:19056763

COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter.

PubMed

de Godoy, Márcio A F; Rattan, Neeru; Rattan, Satish

2009-02-01

Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1(-/-) and COX-2(-/-) mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 +/- 3.4% (mean +/- SE) by SC-560 (1 x 10(-5) M) and 5.4 +/- 2.2% by rofecoxib (P < 0.05, n = 5). Basal tone was 0.172 +/- 0.021 mN//mg in the IAS from wild-type mice and significantly less (0.080 +/- 0.015 mN/mg) in the IAS from COX-1(-/-) mice (P < 0.05, n = 5). However, basal tone in COX-2(-/-) mice was not significantly different from that in wild-type mice. We conclude that COX-1-related products contribute significantly to IAS tone.

Influence of basal-plane dislocation structures on expansion of single Shockley-type stacking faults in forward-current degradation of 4H-SiC p-i-n diodes

NASA Astrophysics Data System (ADS)

Hayashi, Shohei; Yamashita, Tamotsu; Senzaki, Junji; Miyazato, Masaki; Ryo, Mina; Miyajima, Masaaki; Kato, Tomohisa; Yonezawa, Yoshiyuki; Kojima, Kazutoshi; Okumura, Hajime

2018-04-01

The origin of expanded single Shockley-type stacking faults in forward-current degradation of 4H-SiC p-i-n diodes was investigated by the stress-current test. At a stress-current density lower than 25 A cm-2, triangular stacking faults were formed from basal-plane dislocations in the epitaxial layer. At a stress-current density higher than 350 A cm-2, both triangular and long-zone-shaped stacking faults were formed from basal-plane dislocations that converted into threading edge dislocations near the interface between the epitaxial layer and the substrate. In addition, the conversion depth of basal-plane dislocations that expanded into the stacking fault was inside the substrate deeper than the interface. These results indicate that the conversion depth of basal-plane dislocations strongly affects the threshold stress-current density at which the expansion of stacking faults occurs.

Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

PubMed

Lammers, Nicolette M; Sondermeijer, Brigitte M; Twickler, Th B Marcel; de Bie, Rob M; Ackermans, Mariëtte T; Fliers, Eric; Schuurman, P Richard; La Fleur, Susanne E; Serlie, Mireille J

2014-01-01

Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

Application of Control Method on a West Antarctic Glacier

NASA Astrophysics Data System (ADS)

Schmeltz, M.; Rignot, E. J.; Macayeal, D. R.

2002-12-01

We use surface velocity inferred with Interferometric synthetic-aperture radar and a control method to estimate unknown basal characteristics of a fast-moving glacier in West Antarctica, Pine Island Glacier. Previous modelling experiments on Pine Island Glacier have shown that using a coupled ice-stream/ice-shelf flow model in a forward approach (trial and error method) we were able to reproduce fairly well the surface velocity. Some discrepancies remained, however, that are partly due to uncertainties in the thickness map and incertainty in our chosen basal stress distribution (because of the non-unicity of the solution). The control method allow us to take the basal stress (or basal friction, since they are related through the velocity), as an unknown parameter. Results given by the control method should provide better reliable inputs for further modelling experiments. We investigate the results' sensitivity to the initial value of the basal stress. The inferred ratio basal drag/driving stress seems to be always low upstream, 60 to 80 km upstream of the grounding line, as if the ice stream was behaving like an ice shelf, and also reveals the presence of a snake shape channel of low ratio basal drag/driving stress, surrounded by a higher ratio, in the main flow of increasing velocity, from 20 to 40 km upstream of the grounding line.

Overexpression of a pine Dof transcription factor in hybrid poplars: A comparative study in trees growing under controlled and natural conditions.

PubMed

Rueda-López, Marina; Pascual, María Belén; Pallero, Mercedes; Henao, Luisa María; Lasa, Berta; Jauregui, Ivan; Aparicio-Tejo, Pedro M; Cánovas, Francisco M; Ávila, Concepción

2017-01-01

In this work, the role of the pine transcriptional regulator Dof 5 in carbon and nitrogen metabolism has been examined in poplar trees. The overexpression of the gene and potential effects on growth and biomass production were compared between trees growing in a growth chamber under controlled conditions and trees growing in a field trial during two growth seasons. Ten-week-old transgenic poplars exhibited higher growth than untransformed controls and exhibited enhanced capacity for inorganic nitrogen uptake in the form of nitrate. Furthermore, the transgenic trees accumulated significantly more carbohydrates such as glucose, fructose, sucrose and starch. Lignin content increased in the basal part of the stem likely due to the thicker stem of the transformed plants. The enhanced levels of lignin were correlated with higher expression of the PAL1 and GS1.3 genes, which encode key enzymes involved in the phenylalanine deamination required for lignin biosynthesis. However, the results in the field trial experiment diverged from those observed in the chamber system. The lines overexpressing PpDof5 showed attenuated growth during the two growing seasons and no modification of carbon or nitrogen metabolism. These results were not associated with a decrease in the expression of the transgene, but they can be ascribed to the nitrogen available in the field soil compared to that available for growth under controlled conditions. This work highlights the paramount importance of testing transgenic lines in field trials.

Overexpression of a pine Dof transcription factor in hybrid poplars: A comparative study in trees growing under controlled and natural conditions

PubMed Central

Rueda-López, Marina; Pascual, María Belén; Pallero, Mercedes; Henao, Luisa María; Lasa, Berta; Jauregui, Ivan; Aparicio-Tejo, Pedro M.; Cánovas, Francisco M.

2017-01-01

In this work, the role of the pine transcriptional regulator Dof 5 in carbon and nitrogen metabolism has been examined in poplar trees. The overexpression of the gene and potential effects on growth and biomass production were compared between trees growing in a growth chamber under controlled conditions and trees growing in a field trial during two growth seasons. Ten-week-old transgenic poplars exhibited higher growth than untransformed controls and exhibited enhanced capacity for inorganic nitrogen uptake in the form of nitrate. Furthermore, the transgenic trees accumulated significantly more carbohydrates such as glucose, fructose, sucrose and starch. Lignin content increased in the basal part of the stem likely due to the thicker stem of the transformed plants. The enhanced levels of lignin were correlated with higher expression of the PAL1 and GS1.3 genes, which encode key enzymes involved in the phenylalanine deamination required for lignin biosynthesis. However, the results in the field trial experiment diverged from those observed in the chamber system. The lines overexpressing PpDof5 showed attenuated growth during the two growing seasons and no modification of carbon or nitrogen metabolism. These results were not associated with a decrease in the expression of the transgene, but they can be ascribed to the nitrogen available in the field soil compared to that available for growth under controlled conditions. This work highlights the paramount importance of testing transgenic lines in field trials. PMID:28376100

Glutamine alleviates heat stress-induced impairment of intestinal morphology, intestinal inflammatory response, and barrier integrity in broilers.

PubMed

Wu, Q J; Liu, N; Wu, X H; Wang, G Y; Lin, L

2018-05-17

The aim of this study was to investigate the protective effect of glutamine (Gln) on the intestinal morphology, intestinal inflammatory response, and barrier integrity in broilers exposed to high ambient temperature. Three-hundred-sixty 21-d-old Arbor Acres broilers (half male and half female) were randomly allocated to 4 treatment groups in a completely randomized design, each of which included 6 replicates with 15 birds per replicate, for 21 d. The 4 treatment groups were as follows: the control group, in which birds were kept in a thermoneutral room at 22 ± 1°C (no stress, NS; fed a basal diet); the heat stress group (36 ± 1°C for 10 h/d from 08:00 to 18:00 h and 22 ± 1°C for the remaining time, heat stress (HT); fed a basal diet); and heat stress + Gln group (0.5 and 1.0% Gln, respectively). Compared to the NS group, broilers in the HT group had lower villus height (P < 0.05), higher crypt depth (P < 0.05), higher D-lactic acid and diamine oxidase (DAO) activity (P < 0.05), higher soluble intercellular adhesion molecule-1 (sICAM-1) concentration (P < 0.05), higher tumor necrosis factor (TNF)-α/interleukin (IL)-10 (P < 0.05), and lower tight junction protein expression levels (P < 0.05). Compared with birds in the HT, birds in the HT + Gln group exhibited increased villus height (P < 0.05), decreased D-lactate and DAO activity (P < 0.05), decreased sICAM-1 concentration (P < 0.05), and mediate the secretion of cytokines (P < 0.05), as well as increased zonula occludens-1 (ZO-1), claudin-1, and occludin mRNA expression levels (P < 0.05). In conclusion, these results indicate that supplementation with Gln was effective in partially ameliorating the adverse effects of heat stress on intestinal barrier function in broilers by promoting epithelial cell proliferation and renewal, modifying the function of the intestinal mucosa barrier, and regulating the secretion of cytokines.

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

PubMed

Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

2016-04-01

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Experimental Modeling of the Formation of Saucer-Shaped sills

NASA Astrophysics Data System (ADS)

Galland, O.; Planke, S.; Malthe-Sorenssen, A.

2007-12-01

Many magma intrusions in sedimentary basins are sills, and especially saucer-shaped sills. These features are observed in many places (i.e. South Africa; the Norwegian and North Sea; Siberia; Argentina). Sand injectites exhibit similar geometries. The occurrence of such features in so various settings suggests that their emplacement results from fundamental processes in sedimentary basins. To understand such processes, we performed experimental modeling of saucer-shaped sill emplacement. The experiments consist of injecting a molten low viscosity vegetable oil (model magma) at a constant flow rate into a fine-grained Coulomb silica flour (model rock). When the oil starts intruding, the initially flat surface of the model inflates and forms a smooth dome. At the end of the experiment, the oil erupts at the edge of the dome. After the experiment, the oil cools and solidifies, the resulting solid intrusion is unburied and exposed, and its upper surface digitalized. For our purpose, we did our experiments without external deformation. We performed two series of experiments with varying depth of injection. The first series consisted of injection into a homogeneous medium. The resulting intrusions were cone-sheets and dykes. The second series consisted of heterogeneous models where the heterogeneity was a weak layer made of a flexible net. The resulting intrusions were made of (1) a horizontal basal sill emplaced along the weakness, and (2) inclined sheets nucleating at the edges of the basal sill and propagating upward and outward. The inclined sheets exhibited a convex shape, i.e. a decreasing slope outward. In addition, the deeper the sills emplaced, the larger they were. Our experimental results are consistent with saucer-shaped features in nature. We infer from our results that the transition between the basal sills and the inclined sheets results from a transition of emplacement processes. We suggest that the basal sill emplace by open (mode I) fracturing, whereas the inclined sheets result from shear (mode II) fracturing, i.e. along faults at the edge of the dome.

Growth, carbon-isotope discrimination, and drought-associated mortality across a Pinus ponderosa elevational transect

USGS Publications Warehouse

McDowell, N.G.; Allen, Craig D.; Marshall, L.

2010-01-01

Drought- and insect-associated tree mortality at low-elevation ecotones is a widespread phenomenon but the underlying mechanisms are uncertain. Enhanced growth sensitivity to climate is widely observed among trees that die, indicating that a predisposing physiological mechanism(s) underlies tree mortality. We tested three, linked hypotheses regarding mortality using a ponderosa pine (Pinus ponderosa) elevation transect that experienced low-elevation mortality following prolonged drought. The hypotheses were: (1) mortality was associated with greater growth sensitivity to climate, (2) mortality was associated with greater sensitivity of gas exchange to climate, and (3) growth and gas exchange were correlated. Support for all three hypotheses would indicate that mortality results at least in part from gas exchange constraints. We assessed growth using basal area increment normalized by tree basal area [basal area increment (BAI)/basal area (BA)] to account for differences in tree size. Whole-crown gas exchange was indexed via estimates of the CO2 partial pressure difference between leaf and atmosphere (pa−pc) derived from tree ring carbon isotope ratios (δ13C), corrected for temporal trends in atmospheric CO2 and δ13C and elevation trends in pressure. Trees that survived the drought exhibited strong correlations among and between BAI, BAI/BA, pa−pc, and climate. In contrast, trees that died exhibited greater growth sensitivity to climate than trees that survived, no sensitivity of pa−pc to climate, and a steep relationship between pa−pc and BAI/BA. The pa−pc results are consistent with predictions from a theoretical hydraulic model, suggesting trees that died had a limited buffer between mean water availability during their lifespan and water availability during drought – i.e., chronic water stress. It appears that chronic water stress predisposed low-elevation trees to mortality during drought via constrained gas exchange. Continued intensification of drought in mid-latitude regions may drive increased mortality and ecotone shifts in temperate forests and woodlands.

Cerebrovascular regulation in men and women: stimulus-specific role of cyclooxygenase.

PubMed

Peltonen, Garrett L; Harrell, John W; Rousseau, Cameron L; Ernst, Brady S; Marino, Mariah L; Crain, Meghan K; Schrage, William G

2015-07-01

Greater cerebral artery vasodilation mediated by cyclooxygenase (COX) in female animals is unexplored in humans. We hypothesized that young, healthy women would exhibit greater basal cerebral blood flow (CBF) and greater vasodilation during hypoxia or hypercapnia compared to men, mediated by a larger contribution of COX. We measured middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) in 42 adults (24 women, 18 men; 24 ± 1 years) during two visits, in a double-blind, placebo-controlled design (COX inhibition, 100 mg oral indomethacin, Indo). Women were studied early in the follicular phase of the menstrual cycle (days 1-5). Two levels of isocapnic hypoxia (SPO2 = 90% and 80%) were induced for 5-min each. Separately, hypercapnia was induced by increasing end-tidal carbon dioxide (PETCO 2) 10 mmHg above baseline. A positive change in MCAv (ΔMCAv) reflected vasodilation. Basal MCAv was greater in women compared to men (P < 0.01) across all conditions. Indo decreased baseline MCAv (P < 0.01) similarly between sexes. Hypoxia increased MCAv (P < 0.01), but ΔMCAv was not different between sexes. Indo did not alter hypoxic vasodilation in either sex. Hypercapnia increased MCAv (P < 0.01), but ΔMCAv was not different between sexes. Indo elicited a large decrease in hypercapnic vasodilation (P < 0.01) that was similar between sexes. During the early follicular phase, women exhibit greater basal CBF than men, but similar vasodilatory responses to hypoxia and hypercapnia. Moreover, COX is not obligatory for hypoxic vasodilation, but plays a vital and similar role in the regulation of basal CBF (~30%) and hypercapnic response (~55%) between sexes. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Caudate Nucleus Volume Mediates the Link between Cardiorespiratory Fitness and Cognitive Flexibility in Older Adults

PubMed Central

Verstynen, Timothy D.; Lynch, Brighid; Miller, Destiny L.; Voss, Michelle W.; Prakash, Ruchika Shaurya; Chaddock, Laura; Basak, Chandramallika; Szabo, Amanda; Olson, Erin A.; Wojcicki, Thomas R.; Fanning, Jason; Gothe, Neha P.; McAuley, Edward; Kramer, Arthur F.; Erickson, Kirk I.

2012-01-01

The basal ganglia play a central role in regulating the response selection abilities that are critical for mental flexibility. In neocortical areas, higher cardiorespiratory fitness levels are associated with increased gray matter volume, and these volumetric differences mediate enhanced cognitive performance in a variety of tasks. Here we examine whether cardiorespiratory fitness correlates with the volume of the subcortical nuclei that make up the basal ganglia and whether this relationship predicts cognitive flexibility in older adults. Structural MRI was used to determine the volume of the basal ganglia nuclei in a group of older, neurologically healthy individuals (mean age 66 years, N = 179). Measures of cardiorespiratory fitness (VO2max), cognitive flexibility (task switching), and attentional control (flanker task) were also collected. Higher fitness levels were correlated with higher accuracy rates in the Task Switching paradigm. In addition, the volume of the caudate nucleus, putamen, and globus pallidus positively correlated with Task Switching accuracy. Nested regression modeling revealed that caudate nucleus volume was a significant mediator of the relationship between cardiorespiratory fitness, and task switching performance. These findings indicate that higher cardiorespiratory fitness predicts better cognitive flexibility in older adults through greater grey matter volume in the dorsal striatum. PMID:22900181

Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model.

PubMed

Lindahl, Mikael; Hellgren Kotaleski, Jeanette

2016-01-01

The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion-induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN-MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion-induced changes to CTX-MSN D1, CTX-MSN D2, TA-MSN, and MSN-MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function.

Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease☆

PubMed Central

Bunzeck, Nico; Singh-Curry, Victoria; Eckart, Cindy; Weiskopf, Nikolaus; Perry, Richard J.; Bain, Peter G.; Düzel, Emrah; Husain, Masud

2013-01-01

Background In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. Methods Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. Results We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. Conclusions Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease. PMID:24025315

How does environmental enrichment reduce repetitive motor behaviors? Neuronal activation and dendritic morphology in the indirect basal ganglia pathway of a mouse model

PubMed Central

Bechard, Allison R.; Cacodcar, Nadia; King, Michael A.; Lewis, Mark H.

2015-01-01

Repetitive motor behaviors are observed in many neurodevelopmental and neurological disorders (e.g. autism spectrum disorders, Tourette syndrome, fronto-temporal dementia). Despite their clinical importance, the neurobiology underlying these highly stereotyped, apparently functionless behaviors is poorly understood. Identification of mechanisms that mediate the development of repetitive behaviors will aid in the discovery of new therapeutic targets and treatment development. Using a deer mouse model, we have shown that decreased indirect basal ganglia pathway activity is associated with high levels of repetitive behavior. Environmental enrichment (EE) markedly attenuates the development of such aberrant behaviors in mice, although mechanisms driving this effect are unknown. We hypothesized that EE would reduce repetitive motor behaviors by increasing indirect basal ganglia pathway function. We assessed neuronal activation and dendritic spine density in basal ganglia of adult deer mice reared in EE and standard housing. Significant increases in neuronal activation and dendritic spine densities were observed only in the subthalamic nucleus (STN) and globus pallidus (GP), and only for those mice that exhibited an EE-induced decrease in repetitive motor behavior. As the STN and GP lie within the indirect pathway, these data suggest that EE-induced attenuation of repetitive motor behaviors is associated with increased functional activation of the indirect basal ganglia pathway. These results are consistent with our other findings highlighting the importance of the indirect pathway in mediating repetitive motor behaviors. PMID:26620495

Directional analysis of coherent oscillatory field potentials in the cerebral cortex and basal ganglia of the rat

PubMed Central

Sharott, Andrew; Magill, Peter J; Bolam, J Paul; Brown, Peter

2005-01-01

Population activity in cortico-basal ganglia circuits is synchronized at different frequencies according to brain state. However, the structures that are likely to drive the synchronization of activity in these circuits remain unclear. Furthermore, it is not known whether the direction of transmission of activity is fixed or dependent on brain state. We have used the directed transfer function (DTF) to investigate the direction in which coherent activity is effectively driven in cortico-basal ganglia circuits. Local field potentials (LFPs) were simultaneously recorded in the subthalamic nucleus (STN), globus pallidus (GP) and substantia nigra pars reticulata (SNr), together with the ipsilateral frontal electrocorticogram (ECoG) of anaesthetized rats. Directional analysis was performed on recordings made during robust cortical slow-wave activity (SWA) and ‘global activation’. During SWA, there was coherence at ∼1 Hz between ECoG and basal ganglia LFPs, with much of the coherent activity directed from cortex to basal ganglia. There were similar coherent activities at ∼1 Hz within the basal ganglia, with more activity directed from SNr to GP and STN, and from STN to GP rather than vice versa. During global activation, peaks in coherent activity were seen at higher frequencies (15–60 Hz), with most coherence also directed from cortex to basal ganglia. Within the basal ganglia, however, coherence was predominantly directed from GP to STN and SNr. Together, these results highlight a lead role for the cortex in activity relationships with the basal ganglia, and further suggest that the effective direction of coupling between basal ganglia nuclei is dynamically organized according to brain state, with activity relationships involving the GP displaying the greatest capacity to change. PMID:15550466

Bone cysts after osteochondral allograft repair of cartilage defects in goats suggest abnormal interaction between subchondral bone and overlying synovial joint tissues.

PubMed

Pallante-Kichura, Andrea L; Cory, Esther; Bugbee, William D; Sah, Robert L

2013-11-01

The efficacy of osteochondral allografts (OCAs) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12months in vivo. The objectives of this study were to further analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCAs was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCAs did not vary compared to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to deeper regions, some "subchondral" cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These findings suggest that cysts occurring after OCAs may result from aberrant mechanobiology due to (1) altered compartmentalization that normally separates overlying cartilage and subchondral bone, either from distinct ScB channels or more general ScB plate deterioration, and (2) bone resorption at the basal graft-host interface. © 2013.

Association Analysis of Grain-setting Rates in Apical and Basal Spikelets in Bread Wheat (Triticum aestivum L.).

PubMed

Guo, Jie; Zhang, Yong; Shi, Weiping; Zhang, Boqiao; Zhang, Jingjuan; Xu, Yanhao; Cheng, Xiaoming; Cheng, Kai; Zhang, Xueyong; Hao, Chenyang; Cheng, Shunhe

2015-01-01

The rates of grain-setting in apical and basal spikelets in wheat directly affect the kernel number per spike (KNPS). In this study, 220 wheat lines from 18 Chinese provinces and five foreign countries were used as a natural population. Phenotypic analysis showed differences in grain-setting rates between apical and basal spikelets. The broad-sense heritability of grain-setting rate in apical spikelets (18.7-21.0%) was higher than that for basal spikelets (9.4-16.4%). Significant correlations were found between KNPS and grain numbers in apical (R (2) = 0.40-0.45, P < 0.01) and basal (R (2) = 0.41-0.56, P < 0.01) spikelets. Seventy two of 106 SSR markers were associated with grain setting, 32 for apical spikelets, and 34 for basal spikelets. The SSR loci were located on 17 chromosomes, except 3A, 3D, 4A, and 7D, and explained 3.7-22.9% of the phenotypic variance. Four markers, Xcfa2153-1A 202 , Xgwm186-5A 118 , Xgwm156-3B 319 , and Xgwm537-7B 210 , showed the largest effects on grain numbers in apical and basal spikelets. High grain numbers in apical and basal spikelets were associated with elite alleles. Ningmai 9, Ning 0569, and Yangmai 18 with high grain-setting rates carried larger numbers of favorable alleles. Comparison of grain numbers in basal and apical spikelets of 35 Yangmai and Ningmai lines indicated that the Ningmai lines had better grain-setting rates (mean 21.4) than the Yangmai lines (16.5).

Systemic and splanchnic metabolic response to exogenous human growth hormone.

PubMed

Dahn, M S; Lange, M P

1998-05-01

Evidence exists indicating that growth hormone (GH) resistance in some disease states such as hypercatabolic conditions may limit the metabolic benefit associated with recombinant human growth hormone (rhGH) administration. It was the purpose of this study to compare the systemic and splanchnic effects of rhGH in patients with sepsis exhibiting systemic inflammatory response syndrome (SIRS) with the response observed in normal volunteers. Because insulin-like growth factor I (IGF-I) is believed to be the dominant factor responsible for the anabolic effects of rhGH, particular attention was given to this secondary effector. The systemic and splanchnic effects of rhGH (0.15 mg/kg/day) were studied in normal volunteers (n = 5), critically ill patients with sepsis exhibiting SIRS (n = 6), and patients with sepsis exhibiting SIRS while receiving total parenteral nutrition (n = 6). Basal and end study IGF-I, urinary urea excretion, hepatic blood flow, hepatic venous oxygen content, and splanchnic oxygen exchange were measured after a 48-hour course of rhGH. Fasting basal IGF-I concentrations were reduced by 75% to 83% in patients with sepsis/SIRS relative to normal control subjects. After 48 hours of rhGH, peak IGF-I concentrations were 74% and 76% lower in patients in the Sepsis/SIRS and Sepsis/SIRS + Nutrition groups, respectively, compared with normal control subjects. Despite the attenuated IGF-I rise in patients, urea excretion declined by a similar magnitude in all three groups. Hepatic blood flow remained unaffected, but rhGH administration increased splanchnic oxygen consumption in all groups (control, +57%*; Sepsis/SIRS, +13%; Sepsis/SIRS + Nutr +42%*; *p < 0.05 relative to corresponding basal) resulting in a decline of basal to end therapy hepatic venous oxygen saturation (control, 67 +/- 4% to 62 +/- 11%; Sepsis/SIRS, 51% +/- 14% to 43% +/- 14%*; Sepsis/SIRS + Nutr, 62% +/- 11% to 55% +/- 16%; *p < 0.05 relative to corresponding control value), suggesting that rhGH may induce centrilobular hepatic hypoxia, which may contribute to the diminished IGF-I response. Although critically ill patients exhibit an IGF-I increase in response to exogenous rhGH, the rise is markedly attenuated compared with healthy volunteers, indicating the presence of GH resistance. Unexpectedly, the changes in the anabolic hormone IGF-I did not appear to be related to the reduction in urea excretion. This may provide some additional evidence for IGF-I resistance. Finally, rhGH is associated with an augmented splanchnic oxygen consumption but no corresponding increase in regional blood flow. As a result, regional tissue hypoxia may arise and contribute to the impaired or suboptimal IGF-I response pattern.

O6-methylguanine-DNA methyltransferase as a prognostic and predictive marker for basal-like breast cancer treated with cyclophosphamide-based chemotherapy

PubMed Central

ISONO, SAYURI; FUJISHIMA, MAKOTO; AZUMI, TATSUYA; HASHIMOTO, YUKIHIKO; KOMOIKE, YOSHIFUMI; YUKAWA, MASAO; WATATANI, MASAHIRO

2014-01-01

The O6-methylguanine-DNA methyltransferase (MGMT) protein protects cells from alkylating agents by removing alkyl groups from the O6-position of guanine. However, its effect on DNA damage induced by cyclophosphamide (CPM) is unclear. The present study investigated whether MGMT expression was correlated with prognosis in patients with breast cancer that was managed according to a common therapeutic protocol or treated with CPM-based chemotherapy. The intrinsic subtypes and MGMT protein expression levels were assessed in 635 consecutive patients with breast cancer using immunohistochemistry. In total, 425 (67%) luminal A, 95 (15%) luminal B, 47 (7%) human epidermal growth factor receptor-2+/estrogen receptor− (HER2+/ER−) and 48 (8%) basal-like subtypes were identified. Of these, MGMT positivity was identified in 398 (63%) of 635 breast cancers; 68% of luminal A, 67% of luminal B, 30% of HER2+/ER− and 46% of basal-like subtypes were positive. The overall survival (OS) and disease-free survival (DFS) rates did not significantly differ according to the MGMT status among patients with luminal A, luminal B or HER2+/ER− subtypes, and patients with MGMT-negative basal-like cancers tended to have a longer DFS, but not a significantly longer OS time. CPM-containing chemotherapy was administered to 26%, 40%, 47% and 31% of patients with luminal A, luminal B, HER2+/ER− and basal-like tumors, respectively. Although the MGMT status and clinical outcomes of patients with the luminal A, luminal B or HER2+/ER− subtypes treated with CPM were not significantly correlated, the patients with MGMT-negative basal-like tumors who received CPM exhibited significantly improved DFS and OS compared with the CPM-treated patients with MGMT-positive tumors. MGMT may be a useful prognostic and predictive marker for CPM-containing chemotherapy in basal-like breast cancer. PMID:24932232

O6-methylguanine-DNA methyltransferase as a prognostic and predictive marker for basal-like breast cancer treated with cyclophosphamide-based chemotherapy.

PubMed

Isono, Sayuri; Fujishima, Makoto; Azumi, Tatsuya; Hashimoto, Yukihiko; Komoike, Yoshifumi; Yukawa, Masao; Watatani, Masahiro

2014-06-01

The O 6 -methylguanine-DNA methyltransferase (MGMT) protein protects cells from alkylating agents by removing alkyl groups from the O 6 -position of guanine. However, its effect on DNA damage induced by cyclophosphamide (CPM) is unclear. The present study investigated whether MGMT expression was correlated with prognosis in patients with breast cancer that was managed according to a common therapeutic protocol or treated with CPM-based chemotherapy. The intrinsic subtypes and MGMT protein expression levels were assessed in 635 consecutive patients with breast cancer using immunohistochemistry. In total, 425 (67%) luminal A, 95 (15%) luminal B, 47 (7%) human epidermal growth factor receptor-2 + /estrogen receptor - (HER2 + /ER - ) and 48 (8%) basal-like subtypes were identified. Of these, MGMT positivity was identified in 398 (63%) of 635 breast cancers; 68% of luminal A, 67% of luminal B, 30% of HER2 + /ER - and 46% of basal-like subtypes were positive. The overall survival (OS) and disease-free survival (DFS) rates did not significantly differ according to the MGMT status among patients with luminal A, luminal B or HER2 + /ER - subtypes, and patients with MGMT-negative basal-like cancers tended to have a longer DFS, but not a significantly longer OS time. CPM-containing chemotherapy was administered to 26%, 40%, 47% and 31% of patients with luminal A, luminal B, HER2 + /ER - and basal-like tumors, respectively. Although the MGMT status and clinical outcomes of patients with the luminal A, luminal B or HER2 + /ER - subtypes treated with CPM were not significantly correlated, the patients with MGMT-negative basal-like tumors who received CPM exhibited significantly improved DFS and OS compared with the CPM-treated patients with MGMT-positive tumors. MGMT may be a useful prognostic and predictive marker for CPM-containing chemotherapy in basal-like breast cancer.

Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone.

PubMed

Saggese, G; Cesaretti, G; Franchi, G; Startari, L

1996-08-01

Pubertal development is associated with a rise in plasma insulin-like growth factor I (IGF-I) levels that is related both to the increase in sex steroids and/or to the sex steroid-induced augmentation in endogenous growth hormone (GH) secretion. In order to investigate the relationship between IGF-I, GH and testosterone, we examined 42 male subjects with various clinical conditions (classical GH deficiency (CGHD, N = 5), non-classical GH deficiency (NCGHD, N = 7), short idiopathic stature (N = 6), nutritional obesity (N = 8), GH-treated CGHD (N = 4), GH-treated NCGHD (N = 5) and normal stature (N = 7)) in which , for evaluation of hypogonadism (i.e. the absence of one or both testes from the scrotal sac), human chorionic gonadotropin (hCG) tests were performed. We measured IGF-I, total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassays before and 48 and 96 h after the start of the test. The values of IGF-I were lower (0.001 < p < 0.005) in CGHD and NCGHD than in the other groups. In comparison to basal levels, IGF-I values increased (0.005 < p < 0.05) both 48 and 96 h after the start of the hCG test in short idiopathic and normal stature children and in GH-treated subjects with NCGHD, but only 96 h in subjects with untreated NCGHD and GH-treated CGHD. No difference was demonstrated in basal values of total testosterone among any of the groups, while basal free testosterone levels were higher (0.001 < p < 0.05) in GH-treated subjects with NCGHD than in all the other groups except nutritional obesity; furthermore, free testosterone was higher (p < 0.05) in nutritional obesity than in CGHD. The values of total and free testosterone obtained both 48 and 96 h after the start of the hCG test were higher (0.001 < p < 0.05) than basal values in all groups. The DHEAS values did not show any significant change during the hCG test. Basal values were higher (0.01 < p < 0.05) in nutritional obesity than in the other groups. Considering all groups, chronological age, bone age and bone age/chronological age ratio were correlated with basal free testosterone, IGF-I and DHEAS levels (0.001 < p < 0.05), while basal free testosterone and IGF-I values were correlated with DHEAS levels (p < 0.005 and < 0.01, respectively). In conclusion, our study during the hCG test in boys with various clinical conditions demonstrated an increase in IGF-I concentrations only in those boys with sufficient GH secretion or GH replacement therapy. These findings indicate that both sex steroids and GH are necessary to allow for the pubertal increase in IGF-I levels.

The role of annular dimension and annuloplasty in tricuspid aortic valve repair.

PubMed

de Kerchove, Laurent; Mastrobuoni, Stefano; Boodhwani, Munir; Astarci, Parla; Rubay, Jean; Poncelet, Alain; Vanoverschelde, Jean-Louis; Noirhomme, Philippe; El Khoury, Gebrine

2016-02-01

Valve sparing reimplantation can improve the durability of bicuspid aortic valve repair compared with subcommissural annuloplasty, especially in patients with a large basal ring. This study analyses the effect of basal ring size and annuloplasty on valve repair in the setting of a tricuspid aortic valve. From 1995 to 2013, 382 patients underwent elective tricuspid aortic valve repair. We included only those undergoing subcommissural annuloplasty, valve sparing reimplantation or no annuloplasty and in whom intraoperative transoesophageal echocardiography images were available for retrospective pre- and post-repair basal ring measurements (n = 323, subcommissural annuloplasty: 146, valve sparing reimplantation: 154, no annuloplasty: 23). In a subgroup of patients with available echocardiographic images, basal ring was retrospectively measured at the latest follow-up or prior to reoperation. subcommissural annuloplasty and valve sparing reimplantation were compared after matching for degree of aortic regurgitation and root size. All three groups differed significantly for most of preoperative characteristics. Hospital mortality was 0.9%. The median follow-up was 4.7 years. At 8 years, overall survival was 80 ± 5%. Freedom from reoperation and freedom from aortic regurgitation >1+ were 92 ± 5% and 71 ± 8%, respectively. In multivariate analysis, predictors of aortic regurgitation >1+ were left ventricular end-diastolic diameter (P = 0.003), cusp repair (P = 0.006), body surface area (P = 0.01) and subcommissural annuloplasty (P = 0.05). In subcommissural annuloplasty, freedom from aortic regurgitation >1+ was lower for patients with basal ring ≥28 mm compared with patients with basal ring <28 mm (P = 0.0001). In valve sparing reimplantation, freedom from aortic regurgitation >1+ was independent of basal ring size (P = 0.38). In matched comparison between subcommissural annuloplasty and valve sparing reimplantation, freedom from aortic regurgitation >1+ was not significantly different (P = 0.06), but in patients with basal ring ≥28 mm, valve sparing reimplantation was superior to subcommissural annuloplasty (P = 0.04). Despite similar intraoperative reduction in basal ring size in subcommissural annuloplasty and valve sparing reimplantation, patients with subcommissural annuloplasty exhibited greater increase in basal ring size during the follow-up compared with the valve sparing reimplantation group (P < 0.001). As with a bicuspid aortic valve, a large basal ring predicts recurrence of aortic regurgitation in patients with tricuspid aortic valve undergoing repair with the subcommissural annuloplasty technique. This recurrence is caused by basal ring dilatation over time after subcommissural annuloplasty. With the valve sparing reimplantation technique, large basal ring did not predict aortic regurgitation recurrence, as prosthetic-based circumferential annuloplasty displayed better stability over time. Stable circumferential annuloplasty is recommended in tricuspid aortic valve repair whenever the basal ring size is ≥28 mm. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number.

PubMed

Lyons, Jonathan J; Yu, Xiaomin; Hughes, Jason D; Le, Quang T; Jamil, Ali; Bai, Yun; Ho, Nancy; Zhao, Ming; Liu, Yihui; O'Connell, Michael P; Trivedi, Neil N; Nelson, Celeste; DiMaggio, Thomas; Jones, Nina; Matthews, Helen; Lewis, Katie L; Oler, Andrew J; Carlson, Ryan J; Arkwright, Peter D; Hong, Celine; Agama, Sherene; Wilson, Todd M; Tucker, Sofie; Zhang, Yu; McElwee, Joshua J; Pao, Maryland; Glover, Sarah C; Rothenberg, Marc E; Hohman, Robert J; Stone, Kelly D; Caughey, George H; Heller, Theo; Metcalfe, Dean D; Biesecker, Leslie G; Schwartz, Lawrence B; Milner, Joshua D

2016-12-01

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia.

s-SHIP expression identifies a subset of murine basal prostate cells as neonatal stem cells

PubMed Central

Brocqueville, Guillaume; Chmelar, Renee S.; Bauderlique-Le Roy, Hélène; Deruy, Emeric; Tian, Lu; Vessella, Robert L.; Greenberg, Norman M.; Bourette, Roland P.

2016-01-01

Isolation of prostate stem cells (PSCs) is crucial for understanding their biology during normal development and tumorigenesis. In this aim, we used a transgenic mouse model expressing GFP from the stem cell-specific s-SHIP promoter to mark putative stem cells during postnatal prostate development. Here we show that cells identified by GFP expression are present transiently during early prostate development and localize to the basal cell layer of the epithelium. These prostate GFP+ cells are a subpopulation of the Lin− CD24+ Sca-1+ CD49f+ cells and are capable of self-renewal together with enhanced growth potential in sphere-forming assay in vitro, a phenotype consistent with that of a PSC population. Transplantation assays of prostate GFP+ cells demonstrate reconstitution of prostate ducts containing both basal and luminal cells in renal grafts. Altogether, these results demonstrate that s-SHIP promoter expression is a new marker for neonatal basal prostate cells exhibiting stem cell properties that enables PSCs in situ identification and isolation via a single consistent parameter. Transcriptional profiling of these GFP+ neonatal stem cells showed an increased expression of several components of the Wnt signaling pathway. It also identified stem cell regulators with potential applications for further analyses of normal and cancer stem cells. PMID:27081082

Differential serotonergic innervation of the amygdala in bonobos and chimpanzees.

PubMed

Stimpson, Cheryl D; Barger, Nicole; Taglialatela, Jared P; Gendron-Fitzpatrick, Annette; Hof, Patrick R; Hopkins, William D; Sherwood, Chet C

2016-03-01

Humans' closest living relatives are bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), yet these great ape species differ considerably from each other in terms of social behavior. Bonobos are more tolerant of conspecifics in competitive contexts and often use sexual behavior to mediate social interactions. Chimpanzees more frequently employ aggression during conflicts and actively patrol territories between communities. Regulation of emotional responses is facilitated by the amygdala, which also modulates social decision-making, memory and attention. Amygdala responsiveness is further regulated by the neurotransmitter serotonin. We hypothesized that the amygdala of bonobos and chimpanzees would differ in its neuroanatomical organization and serotonergic innervation. We measured volumes of regions and the length density of serotonin transporter-containing axons in the whole amygdala and its lateral, basal, accessory basal and central nuclei. Results showed that accessory basal nucleus volume was larger in chimpanzees than in bonobos. Of particular note, the amygdala of bonobos had more than twice the density of serotonergic axons than chimpanzees, with the most pronounced differences in the basal and central nuclei. These findings suggest that variation in serotonergic innervation of the amygdala may contribute to mediating the remarkable differences in social behavior exhibited by bonobos and chimpanzees. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Super-low friction and super-elastic hydrogenated carbon films originated from a unique fullerene-like nanostructure

NASA Astrophysics Data System (ADS)

Wang, Chengbing; Yang, Shengrong; Wang, Qi; Wang, Zhou; Zhang, Junyan

2008-06-01

Hydrogenated carbon films were grown by a plasma-enhanced chemical vapor deposition (PECVD) technique using CH4 and H2 as feedstock at ambient temperature. The microstructure of the films was characterized by high resolution transmission electron microscopy (HRTEM). The images showed the presence of curved basal planes in fullerene-like arrangements. An apparent amorphous graphene structure with nm-sized packages of basal planes in a turbostratic feature was observed. The fabricated fullerene-like hydrogenated carbon films (FL-C:H) possess superior mechanical properties, i.e. high hardness (19 GPa) and high elasticity (elastic recovery of 85%). More importantly, the films exhibit ultra-low friction (μ = 0.009) under ambient conditions with 20% relative humidity.

Super-low friction and super-elastic hydrogenated carbon films originated from a unique fullerene-like nanostructure.

PubMed

Wang, Chengbing; Yang, Shengrong; Wang, Qi; Wang, Zhou; Zhang, Junyan

2008-06-04

Hydrogenated carbon films were grown by a plasma-enhanced chemical vapor deposition (PECVD) technique using CH(4) and H(2) as feedstock at ambient temperature. The microstructure of the films was characterized by high resolution transmission electron microscopy (HRTEM). The images showed the presence of curved basal planes in fullerene-like arrangements. An apparent amorphous graphene structure with nm-sized packages of basal planes in a turbostratic feature was observed. The fabricated fullerene-like hydrogenated carbon films (FL-C:H) possess superior mechanical properties, i.e. high hardness (19 GPa) and high elasticity (elastic recovery of 85%). More importantly, the films exhibit ultra-low friction (μ = 0.009) under ambient conditions with 20% relative humidity.

Patterned basal seismicity shows sub-ice stream bedforms

NASA Astrophysics Data System (ADS)

Barcheck, C. G.; Tulaczyk, S. M.; Schwartz, S. Y.

2017-12-01

Patterns in seismicity emanating from the bottom of fast-moving ice streams and glaciers may indicate localized patches of higher basal resistance— sometimes called 'sticky spots', or otherwise varying basal properties. These seismogenic basal areas resist an unknown portion of the total driving stress of the Whillans Ice Plain (WIP), in West Antarctica, but may play an important role in the WIP stick-slip cycle and ice stream slowdown. To better understand the mechanism and importance of basal seismicity beneath the WIP, we analyze seismic data collected by a small aperture (< 3km) network of 8 surface and 5 borehole seismometers installed in the main central sticky spot of the WIP. We use a network beamforming technique to detect and roughly locate thousands of small (magnitude < 0), local basal micro-earthquakes in Dec 2014, and we compare the resulting map of seismicity to ice bottom depth measured by airborne radar. The number of basal earthquakes per area within the network is spatially heterogeneous, but a pattern of two 400m wide streaks of high seismicity rates is evident, with >50-500 earthquakes detected per 50x50m grid cell in 2 weeks. These seismically active streaks are elongated approximately in the ice flow direction with a spacing of 750m. Independent airborne radar measurements of ice bottom depth from Jan 2013 show a low-amplitude ( 5m) undulation in the basal topography superposed on a regional gradient in ice bottom depth. The flow-perpendicular wavelength of these low-amplitude undulations is comparable to the spacing of the high seismicity bands, and the streaks of high seismicity intersect local lows in the undulating basal topography. We interpret these seismic and radar observations as showing seismically active sub-ice stream bedforms that are low amplitude and elongated in the direction of ice flow, comparable to the morphology of mega scale glacial lineations (MSGLs), with high basal seismicity rates observed in the MSGL troughs. These results have implications for understanding the formation mechanism of MSGLS and well as understanding the interplay between basal topographic roughness, spatially varying basal till and hydrologic properties, basal resistance to fast ice flow, and ice stream stick-slip.

Mineral Resource of the Month: Graphite

USGS Publications Warehouse

Olson, Donald W.

2008-01-01

Graphite, a grayish black opaque mineral with a metallic luster, is one of four forms of pure crystalline carbon (the others are carbon nanotubes, diamonds and fullerenes). It is one of the softest minerals and it exhibits perfect basal (one-plane) cleavage. Graphite is the most electrically and thermally conductive of the nonmetals, and it is chemically inert.

The effects of extreme nutritional conditions on the neurochemistry of reward and addiction

NASA Astrophysics Data System (ADS)

Pothos, Emmanuel N.

2001-08-01

Weight loss is a frequent problem in space flights. We now claim that it may affect performance and drug-seeking behavior by altering midbrain neurochemistry. In food-deprived rats (20-30% underweight) basal extracellular dopamine levels in the nucleus accumbens decrease to 40-50% of normal and locomotion is depressed. However, amphetamine-induced dopamine release and locomotion are higher than in controls (1825% vs. 595% after a 25 μM d-amphetamine intraaccumbens infusion). The lower basal and the higher stimulated dopamine levels suggest that the neurotransmitter accumulates presynaptically in the accumbens of the underweight rats due to subnormal basal release. Psychostimulants are more rewarding for underweight subjects possibly because they release significantly more dopamine from elevated presynaptic stores into the accumbens. Consequently, weight loss can lead both to depression of performance and propensity to substance abuse. These effects should be considered when providing nutritional resources for space flights so that weight loss is limited.

Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

PubMed

Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

2017-05-01

In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

Total and free iodothyronine changes in response to transport of Equidae (Equus asinus and Equus caballus).

PubMed

Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Ferlazzo, Adriana

2017-03-31

In this study the effects of short distance road transport on total and free iodothyronine changes in 12 stallions (Equus asinus and Equus caballus) were evaluated. Donkeys (n = 6) and horses (n = 6) were transported for a distance of 50 km. Blood samples were collected 1 week before transport in basal conditions, 1 week later immediately before loading, and after transport and unloading. After transport, donkeys showed significant increases in circulating T4 (P≤0.01), fT3 (P≤0.001), and fT4 (P≤0.01) levels; while horses had significant increases in circulating T3, fT3 and fT4 (P≤0.01) levels. Compared to donkeys' values, horses showed lower T4 values in basal condition, before and after transport (P≤0.001); higher fT3 values in basal condition and before (P≤0.001), and lower values (P≤0.001) after transport; higher fT4 values (P≤0.001) in basal condition. The results indicate that short road transport of donkeys and horses induces the activation of the thyroid gland, with the same release of fT3 and fT4 iodothyronines, but with different preferential release of T3 in horses and T4 in donkeys after transport.

TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema.

PubMed

An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C; Ifedigbo, Emeka; Washko, George R; Ryter, Stefan W; Choi, Augustine M K

2012-11-01

Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.

TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema

PubMed Central

An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C.; Ifedigbo, Emeka; Washko, George R.; Ryter, Stefan W.

2012-01-01

Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS. PMID:22983353

cAMP-secretion coupling is impaired in diabetic GK/Par rat β-cells: a defect counteracted by GLP-1.

PubMed

Dolz, Manuel; Movassat, Jamileh; Bailbé, Danielle; Le Stunff, Hervé; Giroix, Marie-Hélène; Fradet, Magali; Kergoat, Micheline; Portha, Bernard

2011-11-01

cAMP-raising agents with glucagon-like peptide-1 (GLP-1) as the first in class, exhibit multiple actions that are beneficial for the treatment of type 2 diabetic (T2D) patients, including improvement of glucose-induced insulin secretion (GIIS). To gain additional insight into the role of cAMP in the disturbed stimulus-secretion coupling within the diabetic β-cell, we examined more thoroughly the relationship between changes in islet cAMP concentration and insulin release in the GK/Par rat model of T2D. Basal cAMP content in GK/Par islets was significantly higher, whereas their basal insulin release was not significantly different from that of Wistar (W) islets. Even in the presence of IBMX or GLP-1, their insulin release did not significantly change despite further enhanced cAMP accumulation in both cases. The high basal cAMP level most likely reflects an increased cAMP generation in GK/Par compared with W islets since 1) forskolin dose-dependently induced an exaggerated cAMP accumulation; 2) adenylyl cyclase (AC)2, AC3, and G(s)α proteins were overexpressed; 3) IBMX-activated cAMP accumulation was less efficient and PDE-3B and PDE-1C mRNA were decreased. Moreover, the GK/Par insulin release apparatus appears less sensitive to cAMP, since GK/Par islets released less insulin at submaximal cAMP levels and required five times more cAMP to reach a maximal secretion rate no longer different from W. GLP-1 was able to reactivate GK/Par insulin secretion so that GIIS became indistinguishable from that of W. The exaggerated cAMP production is instrumental, since GLP-1-induced GIIS reactivation was lost in the presence the AC blocker 2',5'-dideoxyadenosine. This GLP-1 effect takes place in the absence of any improvement of the [Ca(2+)](i) response and correlates with activation of the cAMP-dependent PKA-dependent pathway.

Application of Dredged Materials and Steelmaking Slag as Basal Media to Restore and Create Seagrass Beds: Mesocosm and Core Incubation Experiments

NASA Astrophysics Data System (ADS)

Tsukasaki, A.; Suzumura, M.; Tsurushima, N.; Nakazato, T.; Huang, Y.; Tanimoto, T.; Yamada, N.; Nishijima, W.

2016-02-01

Seagrass beds stabilize bottom sediments, improve water quality and light conditions, enhance species diversity, and provide habitat complexity in coastal marine environments. Seagrass beds are now experiencing worldwide decline by rapid environmental changes. Possible options of seagrass bed restoration are civil engineering works including mounding to raise the bottom to elevations with suitable light for seagrass growth. Reuse or recycling of dredged materials (DM) and various industrial by-products including steelmaking slags is a beneficial option to restore and create seagrass beds. To evaluate the applicability of DM and dephosphorization slag (Slag) as basal media of seagrass beds, we carried out mesocosm experiments and core incubation experiments in a land-based flow-through seawater tank over a year. During the mesocosm experiment, no difference was found in growth of eelgrass (Zostera marina L.) and macrobenthic community structures between Slag-based sediments and sand-based control experiments, even though Slag-based sediments exhibited substantially higher pH than sand-based sediments. During the core incubation experiment, we investigated detailed variation and distributions of pH and nutrients, and diffusion fluxes of nutrients between the sediment/seawater interface. Though addition of Slag induced high pH up to 10.7 in deep layers (< 5 cm), the surface pH decreased rapidly within 10 days. Concentrations of dissolved inorganic nitrogen were comparable between Slag- and sand-based sediments, whereas dissolved phosphate concentration was substantially reduced by the addition of Slag. The low concentrations of phosphate was likely due to precipitation with calcium under high pH condition. Diffusion fluxes of nutrients from the cores were comparable with those reported in natural coastal systems. It was suggested that the mixture of Slag and DM is applicable as basal media for construction of artificial seagrass beds.

Limiting hydrophobic behavior and reflectance response of dragonfly and damselfly wings

NASA Astrophysics Data System (ADS)

Aideo, Swati Nawami; Mohanta, Dambarudhar

2016-11-01

In this work, through water contact angle (CA) measurements, we explore hydrophobic behavior of different parts of the hind wings of a dragonfly, Gynacantha Dravida and of a damselfly, Pseudagrion Microcephalum. As we move from the basal to distal region, the contact angle (θ) was found to vary in the range of 120-136° for both the species. Moreover, the wing of the dragonfly was seen to be more hydrophobic than that of the damselfly one. An attempt has also been made to link roughness factor (rφ) and solid-water fraction (φ) through the simplified Wenzel and Cassie-Baxter models. We noticed that, rφ and φ tend to follow a linear relation that gives rφ = 1.47 in the limit, Δθ < 10.1°, latter being recognized as the difference in angle between the measured CA over a surface to that of the CA (∼105°) known for a smooth surface. Our experimental data, however, revealed empirical relations which predicted higher rφ values, particularly when Δθ is large. While the overall reflectance response of the distal segment was believed to be stronger than that of the basal part, the edge parts of the dragonfly and damselfly wings exhibited exponential associated growing trends with increasing wavelength. The relative reflectance response, corresponding to ∼494 nm and 370 nm peaks, gets nearly doubled for the edge specimen as compared to the distal and basal parts. The edge- specimen, which comprises of rectangular shaped, periodic microstructures, displayed carotenoid based two broad peak maxima at ∼422 nm and ∼494 nm. The surface roughness which arises through the distribution of oblate-shaped nano-fibrils is believed to be the basis of sub-surface volume scattering. Interrelating nanostructure surface roughness based wettability and reflectance characteristics would provide new insights on structure-property relationship in naturally available soft matter systems including templates of biological origin.

Quantitative imaging of radial oxygen loss from Valisneria spiralis roots with a fluorescent planar optode.

PubMed

Han, Chao; Ren, Jinghua; Tang, Hao; Xu, Di; Xie, Xianchuan

2016-11-01

Oxygen (O2) availability within the sediment-root interface is critical to the survival of macrophytes in O2-deficient sediment; however, our knowledge of the fine-scale impact of macrophyte roots upon the spatiotemporal dynamics of O2 is relatively limited. In this study, a non-invasive imaging technology was utilized to map O2 micro-distribution around Vallisneria spiralis. Long-term imaging results gathered during a 36day-period revealed an abundance of O2 spatiotemporal patterns ranging from 0 to 250μmolL(-1). The root-induced O2 leakage and consequent oxygenated area were stronger in the vicinity of the basal root compared to that found in the root tip. The O2 images revealed V. spiralis exhibited radial O2 loss (ROL) along the entire root, and the O2 distribution along the root length showed a high degree of small-scale spatial heterogeneity decreasing from 80% at the basal root surface to 10% at the root tip. The oxygenated zone area around the roots increased as O2 levels increased with root growth and irradiance intensities ranging from 0 to 216μmol photons m(-2)s(-1). A weak ROL measuring <20% air saturation around the basal root surface was maintained in darkness, which was presumably attributed to the O2 supply from overlying water via plant aerenchyma. The estimated total O2 release to the rhizosphere of V. spiralis was determined to range from 8.80±7.32 to 30.34±17.71nmolm(-2)s(-1), which is much higher than many other macrophyte species. This O2 release may be an important contribution to the high-capacity of V. spiralis for quickly colonizing anaerobic sediment. Copyright © 2016 Elsevier B.V. All rights reserved.

A second soundly sleeping dragon: new anatomical details of the Chinese troodontid Mei long with implications for phylogeny and taphonomy.

PubMed

Gao, Chunling; Morschhauser, Eric M; Varricchio, David J; Liu, Jinyuan; Zhao, Bo

2012-01-01

A second nearly complete, articulated specimen of the basal troodontid Mei long (DNHM D2154) is reported from the Early Cretaceous (Hauterivian-Valanginian) lower Yixian Formation, Liaoning Province, China. New diagnostic features of Mei long are identified, including: a uniquely shaped maxilla, low with small, low maxillary fenestra; sacrum with an extremely wide caudal portion and elongate 4(th) and 5(th) sacral processes; and a large distal articular surface on the tibiotarsus which continues caudally on the tibia. A phylogenetic analysis including new data from the second specimen recovered Mei as a basal troodontid, in keeping with previous analyses. Although the skeleton exhibits several juvenile-like features including free cervical ribs, unfused frontals and nasals, and a short snouted skull, other attributes, full fusion of all neurocentral synostoses and the sacrum, and dense exteriors to cortical bone, suggest a small, mature individual. Microscopic examination of tibia and fibula histology confirms maturity and suggests an individual greater than two years old with slowed growth. Despite being one of the smallest dinosaurs, Mei long exhibits multi-year growth and cortical bone consisting largely of fibro-lamellar tissue marked by lines of arrested growth as in much larger and more basal theropods. This Mei long specimen lies in a similar but mirrored sleeping position to that of the holotype, strengthening the hypothesis that both specimens were preserved in a stereotypical life position. Like many Liaoning specimens, the new specimen also lacks extensive taphonomic and stratigraphic data, making further behavioral inference problematic.

A Second Soundly Sleeping Dragon: New Anatomical Details of the Chinese Troodontid Mei long with Implications for Phylogeny and Taphonomy

PubMed Central

Gao, Chunling; Morschhauser, Eric M.; Varricchio, David J.; Liu, Jinyuan; Zhao, Bo

2012-01-01

A second nearly complete, articulated specimen of the basal troodontid Mei long (DNHM D2154) is reported from the Early Cretaceous (Hauterivian-Valanginian) lower Yixian Formation, Liaoning Province, China. New diagnostic features of Mei long are identified, including: a uniquely shaped maxilla, low with small, low maxillary fenestra; sacrum with an extremely wide caudal portion and elongate 4th and 5th sacral processes; and a large distal articular surface on the tibiotarsus which continues caudally on the tibia. A phylogenetic analysis including new data from the second specimen recovered Mei as a basal troodontid, in keeping with previous analyses. Although the skeleton exhibits several juvenile-like features including free cervical ribs, unfused frontals and nasals, and a short snouted skull, other attributes, full fusion of all neurocentral synostoses and the sacrum, and dense exteriors to cortical bone, suggest a small, mature individual. Microscopic examination of tibia and fibula histology confirms maturity and suggests an individual greater than two years old with slowed growth. Despite being one of the smallest dinosaurs, Mei long exhibits multi-year growth and cortical bone consisting largely of fibro-lamellar tissue marked by lines of arrested growth as in much larger and more basal theropods. This Mei long specimen lies in a similar but mirrored sleeping position to that of the holotype, strengthening the hypothesis that both specimens were preserved in a stereotypical life position. Like many Liaoning specimens, the new specimen also lacks extensive taphonomic and stratigraphic data, making further behavioral inference problematic. PMID:23028847

Children's externalizing and internalizing symptoms over time: the role of individual differences in patterns of RSA responding.

PubMed

Hinnant, James Benjamin; El-Sheikh, Mona

2009-11-01

We examined associations between basal respiratory sinus arrhythmia (RSA) in conjunction with RSA regulation with the hypothesis that their interaction would explain unique variability in children's prospective adjustment 2 years later. Participants were 176 children (98 girls; 78 boys) in middle childhood. RSA regulation was assessed through social and problem-solving challenges. Parents reported on children's internalizing and externalizing symptoms. Interactions between RSA baseline and regulation to the social stressor predicted children's later internalizing symptoms. Interactions between RSA baseline and responding to the problem-solving stressor predicted children's externalizing symptoms. The highest levels of internalizing symptoms were predicted for children with both lower basal RSA and higher RSA suppression. The highest levels of externalizing symptoms were predicted for children who demonstrated lower basal RSA in conjunction with RSA augmentation. Findings highlight the importance of the contemporaneous consideration of basal RSA and RSA regulation in the prediction of developmental psychopathology symptomology.

The edge- and basal-plane-specific electrochemistry of a single-layer graphene sheet

PubMed Central

Yuan, Wenjing; Zhou, Yu; Li, Yingru; Li, Chun; Peng, Hailin; Zhang, Jin; Liu, Zhongfan; Dai, Liming; Shi, Gaoquan

2013-01-01

Graphene has a unique atom-thick two-dimensional structure and excellent properties, making it attractive for a variety of electrochemical applications, including electrosynthesis, electrochemical sensors or electrocatalysis, and energy conversion and storage. However, the electrochemistry of single-layer graphene has not yet been well understood, possibly due to the technical difficulties in handling individual graphene sheet. Here, we report the electrochemical behavior at single-layer graphene-based electrodes, comparing the basal plane of graphene to its edge. The graphene edge showed 4 orders of magnitude higher specific capacitance, much faster electron transfer rate and stronger electrocatalytic activity than those of graphene basal plane. A convergent diffusion effect was observed at the sub-nanometer thick graphene edge-electrode to accelerate the electrochemical reactions. Coupling with the high conductivity of a high-quality graphene basal plane, graphene edge is an ideal electrode for electrocatalysis and for the storage of capacitive charges. PMID:23896697

Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients

PubMed Central

Kim, Sung-Tae; Kim, Byung-Joon; Song, In-Geol; Jung, Jang-Han; Lee, Kang-Woo; Park, Keun-Young; Cho, Youn-Zoo; Lee, Dae-Ho; Koh, Gwan-Pyo

2011-01-01

Background Recent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM) patients. Methods Data was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed. Results A simple correlation was found between basal C-peptide and components of metabolic syndrome (MS). Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program's (NCEP's), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029). The multiple regression analysis between intima-media thickness (IMT) and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043), while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226). Conclusion Basal C-peptide is related to cardiovascular predictors (IMT) of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease. PMID:21537412

Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma.

PubMed

Zhang, Leilei; Huang, Xiaolin; Zhu, Xiaowei; Ge, Shengfang; Gilson, Eric; Jia, Renbing; Ye, Jing; Fan, Xianqun

2016-03-15

Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed MGC and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty diagnosed BCC cases were collected to determine the telomere length, the presence of senescent cells, and the expression levels of the telomere capping shelterin complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the shelterin subunits, shortened telomere length, over-expressed Ki-67, and Bcl2 as well as mutations in P53 were detected both in MGC and BCC. It suggests that the decreased protein levels of the shelterin complex and the shortened telomere length contribute to the tumorigenesis of MGC and BCC. However, several parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly mutated in MGC; (iii) Siah1 mRNA was over-expressed in BCC; (iv) BCC samples contain a higher level of senescent cells; (v) Ki-67 and Bcl2 expression were lower in BCC. These results support a model where a preserved P53 checkpoint in BCC leads to cellular senescence and reduced tumor proliferation as compared to MGC. © 2015 UICC.

Physicochemical and nutraceutical properties of moringa (Moringa oleifera) leaves and their effects in an in vivo AOM/DSS-induced colorectal carcinogenesis model.

PubMed

Cuellar-Nuñez, M L; Luzardo-Ocampo, I; Campos-Vega, R; Gallegos-Corona, M A; González de Mejía, E; Loarca-Piña, G

2018-03-01

Moringa (Moringa oleifera) is a plant that has generated great interest in recent years because of its attributed medicinal properties. The aim of this study was to characterize the bioactive compounds of moringa leaves (MO) and evaluate their effect on a colorectal carcinogenesis model. Twenty-four male CD-1 mice were divided into 4 groups: Group 1 fed with basal diet (negative control/NC); Group 2 received AOM/DSS (positive control); Groups 3 and 4 were fed with basal diet supplemented with moringa leaves (2.5% w/w and 5% w/w, respectively) for 12weeks. Moringa leaves exhibited a high content of dietary fiber (~18.75%) and insoluble dietary fiber (2.29%). There were identified 9 phenolic compounds whereas the chlorogenic and ρ-coumaric acid showed the higher contents (44.23-63.34μg/g and 180.45-707.42μg/g, respectively). Moringa leaves decreased the activity of harmful fecal enzymes (β-glucosidase, β-glucuronidase, tryptophanase and urease up to 40%, 43%, 103% and 266%, respectively) as well tumors incidence in male CD1-mice (~50% with 5% w/v of moringa dose). These findings suggest that the bioactive compounds of moringa such as total dietary fiber and phenolic compounds may have chemopreventive capacity. This is the first study of the suppressive effect of moringa leaves in an in vivo model of AOM/DSS-induced colorectal carcinogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes in gene expression in PBMCs profiles of PPARα target genes in obese and non-obese individuals during fasting.

PubMed

Felicidade, Ingrid; Marcarini, Juliana Cristina; Carreira, Clísia Mara; Amarante, Marla Karine; Afman, Lydia A; Mantovani, Mário Sérgio; Ribeiro, Lúcia Regina

2015-01-01

The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. This study aimed to evaluate the differences in the expression of PPARα target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARα target genes in PBMCs under fasting conditions. Q-PCR was utilized to assess the mRNA expression levels of target genes. In both groups, the FFA concentrations increased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in β-oxidation and glucose level maintenance are affected by these factors. © 2014 S. Karger AG, Basel.

GROα regulates human embryonic stem cell self-renewal or adoption of a neuronal fate

PubMed Central

Krtolica, Ana; Larocque, Nick; Genbacev, Olga; Ilic, Dusko; Coppe, Jean-Philippe; Patil, Christopher K.; Zdravkovic, Tamara; McMaster, Michael; Campisi, Judith; Fisher, Susan J.

2012-01-01

Previously we reported that feeders formed from human placental fibroblasts (hPFs) support derivation and long-term self-renewal of human embryonic stem cells (hESCs) under serum-free conditions. Here, we show, using antibody array and ELISA platforms, that hPFs secrete ~6-fold higher amounts of the CXC-type chemokine, GROα, than IMR 90, a human lung fibroblast line, which does not support hESC growth. Furthermore, immunocytochemistry and immunoblot approaches revealed that hESCs express CXCR, a GROα receptor. We used this information to develop defined culture medium for feeder-free propagation of hESCs in an undifferentiated state. Cells passaged as small aggregates and maintained in the GROα-containing medium had a normal karyotype, expressed pluripotency markers, and exhibited apical–basal polarity, i.e., had the defining features of pluripotent hESCs. They also differentiated into the three primary (embryonic) germ layers and formed teratomas in immunocompromised mice. hESCs cultured as single cells in the GROα-containing medium also had a normal karyotype, but they downregulated markers of pluripotency, lost apical–basal polarity, and expressed markers that are indicative of the early stages of neuronal differentiation—βIII tubulin, vimentin, radial glial protein, and nestin. These data support our hypothesis that establishing and maintaining cell polarity is essential for the long-term propagation of hESCs in an undifferentiated state and that disruption of cell–cell contacts can trigger adoption of a neuronal fate. PMID:21396766

Interactions between β-amyloid and central cholinergic neurons: implications for Alzheimer's disease

PubMed Central

Kar, Satyabrata; Slowikowski, Stephen P.M.; Westaway, David; Mount, Howard T.J.

2004-01-01

Alzheimer's disease is an age-related neurodegenerative disorder that is characterized by a progressive loss of memory and deterioration of higher cognitive functions. The brain of an individual with Alzheimer's disease exhibits extracellular plaques of aggregated β-amyloid protein (Aβ), intracellular neurofibrillary tangles that contain hyperphosphorylated tau protein and a profound loss of basal forebrain cholinergic neurons that innervate the hippocampus and the neocortex. Aβ accumulation may trigger or contribute to the process of neurodegeneration. However, the mechanisms whereby Aβ induces basal forebrain cholinergic cell loss and cognitive impairment remain obscure. Physiologically relevant concentrations of Aβ-related peptides have acute, negative effects on multiple aspects of acetylcholine (ACh) synthesis and release, without inducing toxicity. These data suggest a neuromodulatory influence of the peptides on central cholinergic functions. Long-term exposure to micromolar Aβ induces cholinergic cell toxicity, possibly via hyperphosphorylation of tau protein. Conversely, activation of selected cholinergic receptors has been shown to alter the processing of the amyloid precursor protein as well as phosphorylation of tau protein. A direct interaction between Aβ and nicotinic ACh receptors has also been demonstrated. This review addresses the role of Aβ-related peptides in regulating the function and survival of central cholinergic neurons and the relevance of these effects to cholinergic deficits in Alzheimer's disease. Understanding the functional interrelations between Aβ peptides, cholinergic neurons and tau phosphorylation will unravel the biologic events that precede neurodegeneration and may lead to the development of more effective pharmacotherapies for Alzheimer's disease. PMID:15644984

Effect of long-term stress on H3Ser10 histone phosphorylation in neuronal nuclei of the sensorimotor cortex and midbrain reticular formation in rats with different nervous system excitability.

PubMed

Pavlova, M B; Dyuzhikova, N A; Shiryaeva, N V; Savenko, Yu N; Vaido, A I

2013-07-01

The effects of long-term mental and pain stress on H3Ser10 histone phosphorylation in neurons of the the sensorimotor corex and midbrain reticular formation were studied 24 h, 2 weeks, and 2 months after exposure of rats differing by the nervous system excitability. Rats with high excitability threshold exhibited higher basal level of H3Ser10 histone phosphorylation in the midbrain reticular formation neurons than rats with low excitability threshold. The sensorimotor cortical neurons of the two strains did not differ by this parameter. Stress led to a significant increase in the counts of immunopositive neuronal nuclei in rats with low excitability threshold: the parameter increased significantly in the sensorimotor cortex 24 h after exposure and normalized in 2 weeks after neurotization. In the midbrain reticular formation of this rat strain stress stimulated H3Ser10 histone phosphorylation after 24 h and after 2 weeks; the parameter normalized after neurotization in 2 months. Hence, genetically determined level of the nervous system excitability was essential for the basal level of neuron phosphorylation and for the time course of this process after long-term exposure to mental and pain stress, depending on the brain structure. A probable relationship between H3Ser10 histone phosphorylation process and liability to obsessive compulsive mental disorders in humans was discussed.

Dynamic thiol/disulphide homeostasis in patients with basal cell carcinoma.

PubMed

Demirseren, Duriye Deniz; Cicek, Cagla; Alisik, Murat; Demirseren, Mustafa Erol; Aktaş, Akın; Erel, Ozcan

2017-09-01

The aim of this study is to measure and compare the dynamic thiol/disulphide homeostasis of patients with basal cell carcinoma and healthy subjects with a newly developed and original method. Thirty four patients attending our outpatient clinic and clinically and histopathologically diagnosed as nodular basal cell carcinoma, and age and gender matched 30 healthy individuals have been involved in the study. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. Serum native thiol and disulphide levels in the patient and control group show a considerable variance statistically (p = 0.028, 0.039, respectively). Total thiol levels do not reveal a considerable variation (p = 0.094). Disulphide/native thiol ratios and native thiol/total thiol ratios also show a considerable variance statistically (p = 0.012, 0.013, 0.010, respectively). Thiol disulphide homeostasis in patients with basal cell carcinoma alters in the way that disulphide gets lower and thiols get higher. Thiol/disulphide level is likely to have a role in basal cell carcinoma pathogenesis.

Organoclay nanocomposites of post-industrial waste poly(butylene terephthalate) from automotive parts.

PubMed

Quispe, Noe B; Fernandes, Elizabeth G; Zanata, Fernanda; Bartoli, Julio R; Souza, Diego H S; Ito, Edson N

2015-10-01

Polymeric nanocomposites are novel materials of huge interest owing to their favourable cost/performance ratio with low amount of nanofillers, improved thermal resistance, flame retardancy and mechanical properties in relation to their matrices. In this work, composites based on post-industrial waste or primary recycled poly(butylene terephthalate) and 5 wt.% of organic modified montmorillonite clays were melt compounded using a twin-screw extruder. A 2(2) factorial experimental design was used to study the compounding and processing variables: Organic modified montmorillonite with one or two hydrogenated tallow (initial basal spacing) and screw speed of the extruder. X-ray diffraction and transmission electron microscopy suggest that a partial exfoliation of the organoclay in the recycled poly(butylene terephthalate) matrix was achieved for organic modified montmorillonite with lower initial basal spacing. On the other hand, formulations containing organic modified montmorillonite with higher initial basal spacing showed only intercalated structure. The recycled poly(butylene terephthalate)-organic modified montmorillonite nanocomposites did not drip flaming material during burning tests. Storage of dynamic-mechanical, tensile and flexural moduli of the recycled poly(butylene terephthalate)-organic modified montmorillonite were improved when compared with both virgin and recycled poly(butylene terephthalate)s, mainly for nanocomposites formulated at a lower initial basal spacing organoclay. This could be related to a better diffusion of polymer into organic modified montmorillonite layers compared with the higher initial basal spacing organoclay. The improvements on the physical properties of recycled poly(butylene terephthalate) showed the feasibility to add value to primary recycled engineering thermoplastics with a very small amount of organic modified montmorillonite. © The Author(s) 2015.

Three cell recognition changes accompany the ingression of sea urchin primary mesenchyme cells.

PubMed

Fink, R D; McClay, D R

1985-01-01

At gastrulation the primary mesenchyme cells of sea urchin embryos lose contact with the extracellular hyaline layer and with neighboring blastomeres as they pass through the basal lamina and enter the blastocoel. This delamination process was examined using a cell-binding assay to follow changes in affinities between mesenchyme cells and their three substrates: hyalin, early gastrula cells, and basal lamina. Sixteen-cell-stage micromeres (the precursors of primary mesenchyme cells), and mesenchyme cells obtained from mesenchyme-blastula-stage embryos were used in conjunction with micromeres raised in culture to intermediate ages. The micromeres exhibited an affinity for hyalin, but the affinity was lost at the time of mesenchyme ingression in vivo. Similarly, micromeres had an affinity for monolayers of gastrula cells but the older mesenchyme cells lost much of their cell-to-cell affinity. Presumptive ectoderm and endoderm cells tested against the gastrula monolayers showed no decrease in binding over the same time interval. When micromeres and primary mesenchyme cells were tested against basal lamina preparations, there was an increase in affinity that was associated with developmental time. Presumptive ectoderm and endoderm cells showed no change in affinity over the same interval. Binding measurements using isolated basal laminar components identified fibronectin as one molecule for which the wandering primary mesenchyme cells acquired a specific affinity. The data indicate that as the presumptive mesenchyme cells leave the vegetal plate of the embryo they lose affinities for hyalin and for neighboring cells, and gain an affinity for fibronectin associated with the basal lamina and extracellular matrix that lines the blastocoel.

SUBTHALAMIC NUCLEUS NEURONS DIFFERENTIALLY ENCODE EARLY AND LATE ASPECTS OF SPEECH PRODUCTION.

PubMed

Lipski, W J; Alhourani, A; Pirnia, T; Jones, P W; Dastolfo-Hromack, C; Helou, L B; Crammond, D J; Shaiman, S; Dickey, M W; Holt, L L; Turner, R S; Fiez, J A; Richardson, R M

2018-05-22

Basal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery in humans with Parkinson's disease, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in sync with motor execution aspects of speech. Nearly half of seventy-nine unit recordings exhibited firing rate modulation, during a syllable reading task across twelve subjects (male and female). Trial-to-trial timing of changes in subthalamic neuronal activity, relative to cue onset versus production onset, revealed that locking to cue presentation was associated more with units that decreased firing rate, while locking to speech onset was associated more with units that increased firing rate. These unique data indicate that subthalamic activity is dynamic during the production of speech, reflecting temporally-dependent inhibition and excitation of separate populations of subthalamic neurons. SIGNIFICANCE STATEMENT The basal ganglia are widely assumed to participate in speech production, yet no prior studies have reported detailed examination of speech-related activity in basal ganglia nuclei. Using microelectrode recordings from the subthalamic nucleus during a single syllable reading task, in awake humans undergoing deep brain stimulation implantation surgery, we show that the firing rate of subthalamic nucleus neurons is modulated in response to motor execution aspects of speech. These results are the first to establish a role for subthalamic nucleus neurons in encoding of aspects of speech production, and they lay the groundwork for launching a modern subfield to explore basal ganglia function in human speech. Copyright © 2018 the authors.

Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model

PubMed Central

2016-01-01

Abstract The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson’s disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion–induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN–MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion–induced changes to CTX–MSN D1, CTX–MSN D2, TA–MSN, and MSN–MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function. PMID:28101525

Discrete element simulations of gravitational volcanic deformation. 1; Deformation structures and geometries

NASA Technical Reports Server (NTRS)

Morgan, Julia K.; McGovern, Patrick J.

2005-01-01

We have carried out two-dimensional particle dynamics simulations of granular piles subject to frictional Coulomb failure criteria to gain a first-order understanding of different modes of gravitational deformation within volcanoes. Under uniform basal and internal strength conditions, granular piles grow self-similarly, developing distinctive stratigraphies, morphologies, and structures. Piles constructed upon cohesive substrates exhibit particle avalanching, forming outward dipping strata and angle of repose slopes. Systematic decreases in basal strength lead to progressively deeper and steeper internal detachment faults and slip along a basal decollement; landslide forms grade from shallow slumps to deep-seated landslide and, finally, to axial subsidence and outward flank displacements, or volcanic spreading. Surface slopes decrease and develop concave up morphologies with decreasing decollement strength; depositional layers tilt progressively inward. Spatial variations in basal strength cause lateral transitions in pile structure, stratigraphy, and morphology. This approximation of volcanoes as Coulomb granular piles reproduces the richness of deformational structures and surface morphologies in many volcanic settings. The gentle slopes of Hawaiian volcanoes and Olympus Mons on Mars suggest weak basal decollements that enable volcanic spreading. High-angle normal faults, favored above weak decollements, are interpreted in both settings and may explain catastrophic sector collapse in Hawaii and broad aureole deposits surrounding Olympus Mons. In contrast, steeper slopes and shallow detachment faults predominate in the Canary Islands, thought to lack a weak decollement, favoring smaller, more frequent slope failures than predicted for Hawaii. The numerical results provide a useful predictive tool for interpreting dynamic behavior and associated geologic hazards of active volcanoes.

NCAM (CD56) expression in keratin-producing odontogenic cysts: aberrant expression in KCOT.

PubMed

Vera-Sirera, Beatriz; Forner-Navarro, Leopoldo; Vera-Sempere, Francisco

2015-02-12

To investigate immunohistochemically the expression of neural cell adhesion molecule (NCAM), which has been identified as a signaling receptor with frequent reactivity in ameloblastomas (AB), in a series of keratin-producing odontogenic cysts (KPOCs). Immunohistochemical expression of NCAM, using a monoclonal antibody, was determined in a series of 58 KPOCs comprising 12 orthokeratinized odontogenic cysts (OOCs) and 46 keratocystic odontogenic tumors (KCOTs), corresponding to 40 non-syndromic KCOT (NS-KCOTs) and 6 syndromic KCOT (S-KCOTs), associated with nevic basocellular syndrome (NBCS). NCAM expression was negative in all OOCs, but 36.45% of KCOTs exhibited focal and heterogeneous expression at the basal cell level, as well as in basal budding areas and the basal cells of daughter cysts. The latter two locations were especially applicable to S-KCOTs, with focal NCAM reactivity occurring in 66.66% of cases. Aberrant NCAM expression, in KCOTs but especially in S-KCOTs, together with its immunomorphological location, suggests that this adhesion molecule and signaling receptor plays a role in the pathogenesis of KCOTs, with a probable impact on lesional recurrence.

Work-hardening behaviour of Mg single crystals oriented for basal slip

NASA Astrophysics Data System (ADS)

Bhattacharya, B.; Niewczas, M.

2011-06-01

Work-hardening behaviour of Mg single crystals oriented for basal slip was studied by means of tensile tests carried out at 4, 78 and 295 K. The crystals show critical resolved shear stress values (CRSS) for a {0001} ? basal slip system in the range 1-1.5 MPa. The samples exhibit two-stage work hardening characteristics consisting of a long easy glide stage and a stage of rapid hardening terminated by failure. The onset of the plastic flow up to the point of fracture is accompanied by a low work-hardening rate in the range 5 × 10-5-5 × 10-4 µ, corresponding to the hardening rate in Stage I of copper single crystals. The analysis of thermally activated glide parameters suggests that forest interactions are rate-controlling processes. The very low value of the activation distance found at 4 K, ∼0.047 b, is attributed to zero-point energy effects. The failure of crystals occurs well before their hardening capacity is exhausted by mechanisms which are characteristic of deformation temperature.

Correlates of basal insulin persistence among insulin-naïve people with type 2 diabetes: results from a multinational survey.

PubMed

Peyrot, Mark; Perez-Nieves, Magaly; Ivanova, Jasmina; Cao, Dachuang; Schmerold, Luke; Kalirai, Samaneh; Hadjiyianni, Irene

2017-10-01

People with T2DM who initiate basal insulin therapy often stop therapy temporarily or permanently soon after initiation. This study analyzes the reasons for and correlates of stopping and restarting basal insulin therapy among people with T2DM. An online survey was completed by 942 insulin-naïve adults with self-reported T2DM from Brazil, France, Germany, Japan, Spain, UK, and US. Respondents had initiated basal insulin therapy within the 3-24 months before survey participation and met criteria for one of three persistence groups: continuers had no gaps of ≥7 days in basal insulin treatment; interrupters had at least one gap in insulin therapy of ≥7 days within the first 6 months after initiation and had since restarted basal insulin; and discontinuers stopped using basal insulin within the first 6 months after initiation and had not restarted. Physician recommendations and cost were strongly implicated in patients stopping and not resuming insulin therapy. Continuous persistence was lower for patients with more worries about insulin initiation, greater difficulties and weight gain while using insulin, and higher for those using pens and perceiving their diabetes as severe. Repeated interruption of insulin therapy was associated with hyperglycemia and treatment burden while using insulin. Resumption and perceived likelihood of resumption were associated with hyperglycemia upon insulin cessation. Perceived likelihood of resumption among discontinuers was associated with perceived benefits of insulin. Better understanding of the risk factors for patient cessation and resumption of basal insulin therapy may help healthcare providers improve persistence with therapy.

Fortune favours the bold: a higher predator reduces the impact of a native but not an invasive intermediate predator.

PubMed

Barrios-O'Neill, Daniel; Dick, Jaimie T A; Emmerson, Mark C; Ricciardi, Anthony; MacIsaac, Hugh J; Alexander, Mhairi E; Bovy, Helene C

2014-05-01

Emergent multiple predator effects (MPEs) might radically alter predictions of predatory impact that are based solely on the impact of individuals. In the context of biological invasions, determining if and how the individual-level impacts of invasive predators relates to their impacts in multiple-individual situations will inform understanding of how such impacts might propagate through recipient communities. Here, we use functional responses (the relationship between prey consumption rate and prey density) to compare the impacts of the invasive freshwater mysid crustacean Hemimysis anomala with a native counterpart Mysis salemaai when feeding on basal cladoceran prey (i) as individuals, (ii) in conspecific groups and (iii) in conspecific groups in the presence of a higher fish predator, Gasterosteus aculeatus. In the absence of the higher predator, the invader consumed significantly more basal prey than the native, and consumption was additive for both mysid species - that is, group consumption was predictable from individual-level consumption. Invaders and natives were themselves equally susceptible to predation when feeding with the higher fish predator, but an MPE occurred only between the natives and higher predator, where consumption of basal prey was significantly reduced. In contrast, consumption by the invaders and higher predator remained additive. The presence of a higher predator serves to exacerbate the existing difference in individual-level consumption between invasive and native mysids. We attribute the mechanism responsible for the MPE associated with the native to a trait-mediated indirect interaction, and further suggest that the relative indifference to predator threat on the part of the invader contributes to its success and impacts within invaded communities. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

On the Origin of Tremor in Parkinson’s Disease

PubMed Central

Dovzhenok, Andrey; Rubchinsky, Leonid L.

2012-01-01

The exact origin of tremor in Parkinson’s disease remains unknown. We explain why the existing data converge on the basal ganglia-thalamo-cortical loop as a tremor generator and consider a conductance-based model of subthalamo-pallidal circuits embedded into a simplified representation of the basal ganglia-thalamo-cortical circuit to investigate the dynamics of this loop. We show how variation of the strength of dopamine-modulated connections in the basal ganglia-thalamo-cortical loop (representing the decreasing dopamine level in Parkinson’s disease) leads to the occurrence of tremor-like burst firing. These tremor-like oscillations are suppressed when the connections are modulated back to represent a higher dopamine level (as it would be the case in dopaminergic therapy), as well as when the basal ganglia-thalamo-cortical loop is broken (as would be the case for ablative anti-parkinsonian surgeries). Thus, the proposed model provides an explanation for the basal ganglia-thalamo-cortical loop mechanism of tremor generation. The strengthening of the loop leads to tremor oscillations, while the weakening or disconnection of the loop suppresses them. The loop origin of parkinsonian tremor also suggests that new tremor-suppression therapies may have anatomical targets in different cortical and subcortical areas as long as they are within the basal ganglia-thalamo-cortical loop. PMID:22848541

Learning Discloses Abnormal Structural and Functional Plasticity at Hippocampal Synapses in the APP23 Mouse Model of Alzheimer's Disease

ERIC Educational Resources Information Center

Middei, Silvia; Roberto, Anna; Berretta, Nicola; Panico, Maria Beatrice; Lista, Simone; Bernardi, Giorgio; Mercuri, Nicola B.; Ammassari-Teule, Martine; Nistico, Robert

2010-01-01

B6-Tg/Thy1APP23Sdz (APP23) mutant mice exhibit neurohistological hallmarks of Alzheimer's disease but show intact basal hippocampal neurotransmission and synaptic plasticity. Here, we examine whether spatial learning differently modifies the structural and electrophysiological properties of hippocampal synapses in APP23 and wild-type mice. While…

A high throughput respirometric assay for mitochondrial biogenesis and toxicity

PubMed Central

Beeson, Craig C.; Beeson, Gyda C.; Schnellmann, Rick G.

2010-01-01

Mitochondria are a common target of toxicity for drugs and other chemicals, and results in decreased aerobic metabolism and cell death. In contrast, mitochondrial biogenesis restores cell vitality and there is a need for new agents to induce biogenesis. Current cell-based models of mitochondrial biogenesis or toxicity are inadequate because cultured cell lines are highly glycolytic with minimal aerobic metabolism and altered mitochondrial physiology. In addition, there are no high-throughput, real-time assays that assess mitochondrial function. We adapted primary cultures of renal proximal tubular cells (RPTC) that exhibit in vivo levels of aerobic metabolism, are not glycolytic, and retain higher levels of differentiated functions and used the Seahorse Biosciences analyzer to measure mitochondrial function in real time in multi-well plates. Using uncoupled respiration as a marker of electron transport chain (ETC) integrity, the nephrotoxicants cisplatin, HgCl2 and gentamicin exhibited mitochondrial toxicity prior to decreases in basal respiration and cell death. Conversely, using FCCP-uncoupled respiration as a marker of maximal ETC activity, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), SRT1720, resveratrol, daidzein, and metformin produced mitochondrial biogenesis in RPTC. The merger of the RPTC model and multi-well respirometry results in a single high throughput assay to measure mitochondrial biogenesis and toxicity, and nephrotoxic potential. PMID:20465991

Asian longhorned beetle complicates the relationship ...

EPA Pesticide Factsheets

Urban foresters routinely emphasise the importance of taxonomic diversity to reduce the vulnerability of tree assemblages to invasive pests, but it is unclear to what extent diversity reduces vulnerability to polyphagous (i.e. generalist) pests. Drawing on field data from seven communities in metropolitan Cincinnati, Ohio, USA, we tested the hypothesis that communities with higher diversity would exhibit lower vulnerability to the polyphagous Asian longhorned beetle, which currently threatens the region. Based on street tree compositions and the beetle?s host preferences, Asian longhorned beetle threatened up to 35.6% of individual street trees and 47.5% of the total basal area across the study area, but we did not see clear connections between taxonomic diversity and beetle vulnerability among study communities. For example, the city of Fairfield was among the least diverse communities but had the lowest proportion of trees vulnerable to Asian longhorned beetle, whereas the city of Wyoming exhibited high diversity and high vulnerability. On the other hand, Forest Park aligned with our original hypothesis, as it was characterised by low diversity and high vulnerability. Our results demonstrate that relatively high taxonomic diversity in street tree assemblages does not necessarily lead to reduced vulnerability to a polyphagous pest. Considering the threats posed by polyphagous pests, selecting a set of relatively pest resistant trees known to perform well in urb

taxonomic diversity and pest vulnerability in street tree assemblages

EPA Pesticide Factsheets

Urban foresters routinely emphasise the importance of taxonomic diversity to reduce the vulnerability of tree assemblages to invasive pests, but it is unclear to what extent diversity reduces vulnerability to polyphagous (i.e. generalist) pests. Drawing on field data from seven communities in metropolitan Cincinnati, Ohio, USA, we tested the hypothesis that communities with higher diversity would exhibit lower vulnerability to the polyphagous Asian longhorned beetle, which currently threatens the region. Based on street tree compositions and the beetle??s host preferences, Asian longhorned beetle threatened up to 35.6% of individual street trees and 47.5% of the total basal area across the study area, but we did not see clear connections between taxonomic diversity and beetle vulnerability among study communities. For example, the city of Fairfield was among the least diverse communities but had the lowest proportion of trees vulnerable to Asian longhorned beetle, whereas the city of Wyoming exhibited high diversity and high vulnerability. On the other hand, Forest Park aligned with our original hypothesis, as it was characterised by low diversity and high vulnerability. Our results demonstrate that relatively high taxonomic diversity in street tree assemblages does not necessarily lead to reduced vulnerability to a polyphagous pest. Considering the threats posed by polyphagous pests, selecting a set of relatively pest resistant trees known to perform well in ur

Mammalian metabolic rates in the hottest fish on earth.

PubMed

Wood, Chris M; Brix, Kevin V; De Boeck, Gudrun; Bergman, Harold L; Bianchini, Adalto; Bianchini, Lucas F; Maina, John N; Johannsson, Ora E; Kavembe, Geraldine D; Papah, Michael B; Letura, Kisipan M; Ojoo, Rodi O

2016-06-03

The Magadi tilapia, Alcolapia grahami, a small cichlid fish of Lake Magadi, Kenya lives in one of the most challenging aquatic environments on earth, characterized by very high alkalinity, unusual water chemistry, and extreme O2, ROS, and temperature regimes. In contrast to most fishes which live at temperatures substantially lower than the 36-40 °C of mammals and birds, an isolated population (South West Hot Springs, SWHS) of Magadi tilapia thrives in fast-flowing hotsprings with daytime highs of 43 °C and night-time lows of 32 °C. Another population (Fish Springs Lagoon, FSL) lives in a lagoon with fairly stable daily temperatures (33-36 °C). The upper critical temperatures (Ctmax) of both populations are very high; moreover the SWHS tilapia exhibit the highest Ctmax (45.6 °C) ever recorded for a fish. Routine rates of O2 consumption (MO2) measured on site, together with MO2 and swimming performance at 25, 32, and 39 °C in the laboratory, showed that the SWHS tilapia exhibited the greatest metabolic performance ever recorded in a fish. These rates were in the basal range of a small mammal of comparable size, and were all far higher than in the FSL fish. The SWHS tilapia represents a bellwether organism for global warming.

Intracellular Position of Centrioles and the Direction of Homeostatic Epithelial Cell Movements in the Mouse Cornea.

PubMed

Silverman, Erika; Zhao, Jin; Merriam, John C; Nagasaki, Takayuki

2017-02-01

Corneal epithelial cells exhibit continuous centripetal movements at a rate of about 30 µm per day, but neither the driving force nor the mechanism that determines the direction of movements is known. To facilitate the investigation of homeostatic cell movement, we examined if the intracellular position of a centriole can be used as a directional marker of epithelial cell movements in the mouse cornea. A direction of cell movements was estimated in fixed specimens from a pattern of underlying subepithelial nerve fibers. Intracellular position of centrioles was determined by gamma-tubulin immunohistology and plotted in a narrow strip along the entire diameter of a cornea from limbus to limbus. When we determined the position of centrioles in the peripheral cornea where cell movements proceed generally along a radial path, about 55% of basal epithelial cells contained a centriole in the front half of a cell. However, in the central cornea where cells exhibit a spiral pattern of movements, centrioles were distributed randomly. These results suggest that centrioles tend to be positioned toward the direction of movement in corneal basal epithelial cells when they are moving centripetally at a steady rate.

Life history of the most complete fossil primate skeleton: exploring growth models for Darwinius

PubMed Central

López-Torres, Sergi; Schillaci, Michael A.; Silcox, Mary T.

2015-01-01

Darwinius is an adapoid primate from the Eocene of Germany, and its only known specimen represents the most complete fossil primate ever found. Its describers hypothesized a close relationship to Anthropoidea, and using a Saimiri model estimated its age at death. This study reconstructs the ancestral permanent dental eruption sequences for basal Euprimates, Haplorhini, Anthropoidea, and stem and crown Strepsirrhini. The results show that the ancestral sequences for the basal euprimate, haplorhine and stem strepsirrhine are identical, and similar to that of Darwinius. However, Darwinius differs from anthropoids by exhibiting early development of the lower third molars relative to the lower third and fourth premolars. The eruption of the lower second premolar marks the point of interruption of the sequence in Darwinius. The anthropoid Saimiri as a model is therefore problematic because it exhibits a delayed eruption of P2. Here, an alternative strepsirrhine model based on Eulemur and Varecia is presented. Our proposed model shows an older age at death than previously suggested (1.05–1.14 years), while the range for adult weight is entirely below the range proposed previously. This alternative model is more consistent with hypotheses supporting a stronger relationship between adapoids and strepsirrhines. PMID:26473056

Epidermal dysplasia and abnormal hair follicles in transgenic mice overexpressing homeobox gene MSX-2.

PubMed

Jiang, T X; Liu, Y H; Widelitz, R B; Kundu, R K; Maxson, R E; Chuong, C M

1999-08-01

The homeobox gene Msx-2 is expressed specifically in sites of skin appendage formation. To explore its part in skin morphogenesis, we produced transgenic mice expressing Msx-2 under the control of the cytomegalovirus promoter. The skin of these transgenic mice was flaky, exhibiting desquamation and shorter hairs. Histologic analysis showed thickened epidermis with hyperproliferation, which was restricted to the basal layer. Hyperkeratosis was also evident. A wide zone of suprabasal cells were misaligned and coexpressed keratins 14 and 10. There was reduced expression of integrin beta 1 and DCC in the basal layer. Hair follicles were misaligned with a shrunken matrix region. The dermis showed increased cellularity and empty vacuoles. We suggest that Msx-2 is involved in the growth control of skin and skin appendages.

Microstructural dependency of optical properties of m-plane InGaN multiple quantum wells grown on 2° misoriented bulk GaN substrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Fengzai; Barnard, Jonathan S.; Zhu, Tongtong

A non-polar m-plane structure consisting of five InGaN/GaN quantum wells (QWs) was grown on ammonothermal bulk GaN by metal-organic vapor phase epitaxy. Surface step bunches propagating through the QW stack were found to accommodate the 2° substrate miscut towards the -c direction. Both large steps with heights of a few tens of nanometres and small steps between one and a few atomic layers in height are observed, the former of which exhibit cathodoluminescence at longer wavelengths than the adjacent m-plane terraces. This is attributed to the formation of semi-polar facets at the steps on which the QWs are shown tomore » be thicker and have higher Indium contents than those in the adjacent m-plane regions. Discrete basal-plane stacking faults (BSFs) were occasionally initiated from the QWs on the main m-plane terraces, but groups of BSFs were frequently observed to initiate from those on the large steps, probably related to the increased strain associated with the locally higher indium content and thickness.« less

Basal Subtype of Invasive Breast Cancer Is Associated With a Higher Risk of True Recurrence After Conventional Breast-Conserving Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hattangadi-Gluth, Jona A.; Wo, Jennifer Y.; Nguyen, Paul L.

2012-03-01

Purpose: To determine whether breast cancer subtype is associated with patterns of ipsilateral breast tumor recurrence (IBTR), either true recurrence (TR) or elsewhere local recurrence (ELR), among women with pT1-T2 invasive breast cancer (IBC) who receive breast-conserving therapy (BCT). Methods and Materials: From Jan 1998 to Dec 2003, 1,223 women with pT1-T2N0-3 IBC were treated with BCT (lumpectomy plus whole-breast radiation). Ninety percent of patients received adjuvant systemic therapy, but none received trastuzumab. Biologic cancer subtypes were approximated by determining estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and human epidermal growth factor receptor-2-positive (HER-2+) expression, classified as luminal A (ER+ ormore » PR+ and HER-2 negative [HER-2-]), luminal B (ER+ or PR+ and HER-2+), HER-2 (ER- and PR- and HER-2+), and basal (ER- and PR- and HER-2- ) subtypes. Imaging, pathology, and operative reports were reviewed by two physicians independently, including an attending breast radiologist. Readers were blinded to subtype and outcome. TR was defined as IBTR within the same quadrant and within 3 cm of the primary tumor. All others were defined as ELR. Results: At a median follow-up of 70 months, 24 patients developed IBTR (5-year cumulative incidence of 1.6%), including 15 TR and 9 ELR patients. At 5 years, basal (4.4%) and HER-2 (9%) subtypes had a significantly higher incidence of TR than luminal B (1.2%) and luminal A (0.2%) subtypes (p < 0.0001). On multivariate analysis, basal subtype (hazard ratio [HR], 4.8, p = 0.01), younger age at diagnosis (HR, 0.97; p = 0.05), and increasing tumor size (HR, 2.1; p = 0.04) were independent predictors of TR. Only younger age (HR, 0.95; p = 0.01) significantly predicted for ELR. Conclusions: Basal and HER-2 subtypes are significantly associated with higher rates of TR among women with pT1-T2 IBC after BCT. Younger age predicts for both TR and ELR. Strategies to reduce TR in basal breast cancers, such as increased boost doses, concomitant radiation and chemotherapy, or targeted therapy agents, should be explored.« less

Learning fast accurate movements requires intact frontostriatal circuits

PubMed Central

Shabbott, Britne; Ravindran, Roshni; Schumacher, Joseph W.; Wasserman, Paula B.; Marder, Karen S.; Mazzoni, Pietro

2013-01-01

The basal ganglia are known to play a crucial role in movement execution, but their importance for motor skill learning remains unclear. Obstacles to our understanding include the lack of a universally accepted definition of motor skill learning (definition confound), and difficulties in distinguishing learning deficits from execution impairments (performance confound). We studied how healthy subjects and subjects with a basal ganglia disorder learn fast accurate reaching movements. We addressed the definition and performance confounds by: (1) focusing on an operationally defined core element of motor skill learning (speed-accuracy learning), and (2) using normal variation in initial performance to separate movement execution impairment from motor learning abnormalities. We measured motor skill learning as performance improvement in a reaching task with a speed-accuracy trade-off. We compared the performance of subjects with Huntington's disease (HD), a neurodegenerative basal ganglia disorder, to that of premanifest carriers of the HD mutation and of control subjects. The initial movements of HD subjects were less skilled (slower and/or less accurate) than those of control subjects. To factor out these differences in initial execution, we modeled the relationship between learning and baseline performance in control subjects. Subjects with HD exhibited a clear learning impairment that was not explained by differences in initial performance. These results support a role for the basal ganglia in both movement execution and motor skill learning. PMID:24312037

Cooperative Adaptive Responses in Gene Regulatory Networks with Many Degrees of Freedom

PubMed Central

Inoue, Masayo; Kaneko, Kunihiko

2013-01-01

Cells generally adapt to environmental changes by first exhibiting an immediate response and then gradually returning to their original state to achieve homeostasis. Although simple network motifs consisting of a few genes have been shown to exhibit such adaptive dynamics, they do not reflect the complexity of real cells, where the expression of a large number of genes activates or represses other genes, permitting adaptive behaviors. Here, we investigated the responses of gene regulatory networks containing many genes that have undergone numerical evolution to achieve high fitness due to the adaptive response of only a single target gene; this single target gene responds to changes in external inputs and later returns to basal levels. Despite setting a single target, most genes showed adaptive responses after evolution. Such adaptive dynamics were not due to common motifs within a few genes; even without such motifs, almost all genes showed adaptation, albeit sometimes partial adaptation, in the sense that expression levels did not always return to original levels. The genes split into two groups: genes in the first group exhibited an initial increase in expression and then returned to basal levels, while genes in the second group exhibited the opposite changes in expression. From this model, genes in the first group received positive input from other genes within the first group, but negative input from genes in the second group, and vice versa. Thus, the adaptation dynamics of genes from both groups were consolidated. This cooperative adaptive behavior was commonly observed if the number of genes involved was larger than the order of ten. These results have implications in the collective responses of gene expression networks in microarray measurements of yeast Saccharomyces cerevisiae and the significance to the biological homeostasis of systems with many components. PMID:23592959

Social-emotional competence and early adolescents' peer acceptance in school: Examining the role of afternoon cortisol.

PubMed

Oberle, Eva

2018-01-01

The present study investigated the role of afternoon cortisol in social-emotional competence and peer acceptance in early adolescence. To date, research on basal cortisol activity and social development in childhood and adolescence has predominately focused on understanding maladjustment and dysfunction in development. The degree to which basal cortisol is also involved in positive adjustment and social functioning remains largely unexplored. A total of 154 early adolescents (46% female; Mean age = 11.26; SD = .65) from diverse ethnic backgrounds provided self-reports of perspective taking, peer reports of acceptance by classmates, peer reports of prosocial behaviors, and saliva samples to assess basal cortisol. As expected and in alignment with previous research, afternoon cortisol, perspective taking, prosocial behaviors, and peer acceptance were all positively correlated. Path analyses followed by bootstrapping analyses revealed that the direct path from higher afternoon cortisol to higher levels of prosocial behavior was fully mediated by perspective taking skills. The direct path from higher afternoon cortisol to peer acceptance was fully mediated by perspective taking skills and prosocial behavior. The findings are discussed within the broader context of previous research on cortisol and social adjustment in childhood and early adolescence. The practical relevance of the findings is considered.

Individual differences in brainstem and basal ganglia structure predict postural control and balance loss in young and older adults.

PubMed

Boisgontier, Matthieu P; Cheval, Boris; Chalavi, Sima; van Ruitenbeek, Peter; Leunissen, Inge; Levin, Oron; Nieuwboer, Alice; Swinnen, Stephan P

2017-02-01

It remains unclear which specific brain regions are the most critical for human postural control and balance, and whether they mediate the effect of age. Here, associations between postural performance and corticosubcortical brain regions were examined in young and older adults using multiple structural imaging and linear mixed models. Results showed that of the regions involved in posture, the brainstem was the strongest predictor of postural control and balance: lower brainstem volume predicted larger center of pressure deviation and higher odds of balance loss. Analyses of white and gray matter in the brainstem showed that the pedunculopontine nucleus area appeared to be critical for postural control in both young and older adults. In addition, the brainstem mediated the effect of age on postural control, underscoring the brainstem's fundamental role in aging. Conversely, lower basal ganglia volume predicted better postural performance, suggesting an association between greater neural resources in the basal ganglia and greater movement vigor, resulting in exaggerated postural adjustments. Finally, results showed that practice, shorter height and heavier weight (i.e., higher body mass index), higher total physical activity, and larger ankle active (but not passive) range of motion were predictive of more stable posture, irrespective of age. Copyright © 2016 Elsevier Inc. All rights reserved.

Metric analysis of basal sphenoid angle in adult human skulls

PubMed Central

Netto, Dante Simionato; Nascimento, Sergio Ricardo Rios; Ruiz, Cristiane Regina

2014-01-01

Objective To analyze the variations in the angle basal sphenoid skulls of adult humans and their relationship to sex, age, ethnicity and cranial index. Methods The angles were measured in 160 skulls belonging to the Museum of the Universidade Federal de São Paulo Department of Morphology. We use two flexible rules and a goniometer, having as reference points for the first rule the posterior end of the ethmoidal crest and dorsum of the sella turcica, and for the second rule the anterior margin of the foramen magnum and clivus, measuring the angle at the intersection of two. Results The average angle was 115.41°, with no statistical correlation between the value of the angle and sex or age. A statistical correlation was noted between the value of the angle and ethnicity, and between the angle and the horizontal cranial index. Conclusions The distribution of the angle basal sphenoid was the same in sex, and there was correlation between the angle and ethnicity, being the proportion of non-white individuals with an angle >125° significantly higher than that of whites with an angle >125°. There was correlation between the angle and the cranial index, because skulls with higher cranial index tend to have higher basiesfenoidal angle too. PMID:25295452

Field Assessment of Gopher Tortoise Habitat at Camp Shelby, MS. Phase II: Overstory and Combined Assessments

DTIC Science & Technology

2010-10-17

conditions between active, recently active and randomly selected non-burrow locations at this site. Field surveys were completed in three study areas ...at the installation. On average, burrow sites had a much higher overall occurrence of longleaf pine and significantly lower total basal area as...East Area burrow and non-burrow locations, Camp Shelby, MS 2007 .................. 10 2 Mean basal area per acre for pine and hardwood on T-44, Mars

Breed- and age-related differences in canine mammary tumors

PubMed Central

Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

2016-01-01

Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin.

PubMed

Morris, Jill K; Vidoni, Eric D; Mahnken, Jonathan D; Montgomery, Robert N; Johnson, David K; Thyfault, John P; Burns, Jeffrey M

2016-03-01

Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p < 0.0001) and no change in performance on an additional task (delayed logical memory). In this study, although insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND (p = 0.0002) but not in cognitively impaired (p = 0.884) subjects, indicating potentially important physiological differences between these cohorts. Copyright © 2016 Elsevier Inc. All rights reserved.

Microbial biomass and basal respiration in Sub-Antarctic and Antarctic soils in the areas of some Russian polar stations

NASA Astrophysics Data System (ADS)

Abakumov, E.; Mukhametova, N.

2014-03-01

Antarctica is the unique place for pedological investigations. Soils of Antarctica have been studied intensively during the last century. Antarctic logistic provides the possibility to scientists access the terrestrial landscapes mainly in the places of polar stations. That is why the main and most detailed pedological investigations were conducted in Mc Murdo Valleys, Transantarctic Mountains, South Shetland Islands, Larsemann hills and Schirmacher Oasis. Investigations were conducted during the 53rd and 55th Russian Antarctic expeditions on the base of soil pits and samples collected in Sub-Antarctic and Antarctic regions. Soils of diverse Antarctic landscapes were studied with aim to assess the microbial biomass level, basal respiration rates and metabolic activity of microbial communities. The investigation conducted shows that soils of Antarctic are quite different in profile organization and carbon content. In general, Sub-Antarctic soils are characterized by more developed humus (sod) organo-mineral horizons as well as the upper organic layer. The most developed organic layers were revealed in peat soils of King-George Island, where its thickness reach even 80 cm. These soils as well as soils under guano are characterized by the highest amount of total organic carbon (TOC) 7.22-33.70%. Coastal and continental soils of Antarctic are presented by less developed Leptosols, Gleysols, Regolith and rare Ornhitosol with TOC levels about 0.37-4.67%. The metabolic ratios and basal respiration were higher in Sub-Antarctic soils than in Antarctic ones which can be interpreted as result of higher amounts of fresh organic remnants in organic and organo-mineral horizons. Also the soils of King-George island have higher portion of microbial biomass (max 1.54 mg g-1) than coastal (max 0.26 mg g-1) and continental (max 0.22 mg g-1) Antarctic soils. Sub-Antarctic soils mainly differ from Antarctic ones in increased organic layers thickness and total organic carbon content, higher microbial biomass carbon content, basal respiration and metabolic activity levels.

Structural and elastic properties of La{sub 2}Mg{sub 17} from first-principles calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Tao-Peng; Ma, Li; Pan, Rong-Kai

2013-10-15

Structural and elastic properties of La{sub 2}Mg{sub 17} with layer structure have been investigated within framework of the density functional theory. Different from the general layer-structured materials, the obtained c/a is less than unity. The calculated elastic constants C{sub 33} is larger than C{sub 11}, being novel in comparison with other alloys with layer structure. The calculated bulk, shear and Young’s modulus of La{sub 2}Mg{sub 17} are higher than other Mg–La alloys with higher La content, implying the stronger covalent bonding. Moreover, the elastic isotropies of La{sub 2}Mg{sub 17} are more excellent. The electronic structure within basal plane is highlymore » symmetric, and the electronic interaction within basal plane is slightly weaker than one between basal planes, which reveal the underlying mechanism for the structural and elastic properties of La{sub 2}Mg{sub 17}. - Graphical abstract: The crystal structure (a) and the atomic positions for (b) (0 0 0 2), (c) (0 0 0 4) and (d) (1 2{sup ¯} 1 0) plane of La{sub 2}Mg{sub 17}. Display Omitted - Highlights: • The c/a of La{sub 2}Mg{sub 17} is anomalously less than unity. • It is novel that for La{sub 2}Mg{sub 17} the elastic constants C{sub 33} is larger than C{sub 11}. • The elastic modulus of La{sub 2}Mg{sub 17} is higher than other Mg–La alloys. • The elastic isotropy of La{sub 2}Mg{sub 17} is excellent. • The electronic structure within basal plane is highly symmetric.« less

Polyunsaturated fatty acids reduce insulin and very low density lipoprotein levels in broiler chickens.

PubMed

Crespo, N; Esteve-Garcia, E

2003-07-01

An experiment was conducted to study the effect of different dietary fatty acid profiles on plasma levels of insulin, very low density lipoproteins (VLDL), cholesterol, and glucose. Diets with four types of fat (tallow, olive, sunflower, and linseed oils) at an inclusion level of 10% and a basal diet without additional fat were administered to female broiler chickens. Serum insulin, cholesterol, and plasma VLDL were affected by the different treatments; however, glucose concentrations were similar among treatments. In the fasted state, broilers fed diets with sunflower or linseed oil presented lower levels of insulin and cholesterol with respect to those fed tallow or olive oil (P < 0.05). VLDL in the fasted state was reduced in broilers fed sunflower and linseed oils (P < 0.05) with respect to those fed tallow, olive oil, or the basal diet. Plasma levels of VLDL were only significantly correlated with abdominal fat in birds fed the basal diet, in the fed and in the fasted state, and in those fed linseed oil in the fed state (P < 0.05). Results of this experiment suggest that higher insulin levels in broilers fed diets rich in saturated fatty acids could be related to higher fat deposition. Fat deposition in birds fed high fat diets was not correlated with circulating VLDL, which suggested direct dietary fat deposition, except for birds fed linseed oil diets. Although birds fed linseed oil diets presented lower levels of VLDL than those fed tallow, olive oil, or the basal diet, the higher correlation with abdominal fat suggests that in these birds, fat deposition is more dependent on hepatic VLDL secretion, despite the high dietary fat level.

Effects of dietary β-glucan and glycyrrhizin on non-specific immunity and disease resistance of the sea cucumber ( Apostichopus japonicus Selenka) challenged with Vibrio splendidus

NASA Astrophysics Data System (ADS)

Chang, Jie; Zhang, Wenbing; Mai, Kangsen; Ma, Hongming; Xu, Wei

2010-12-01

Sea cucumbers, Apostichopus japonicus Selenka, were fed diets containing non-immunostimulant (basal diet), 0.2% β-glucan and 0.02% glycyrrhizin in a recirculatory water system for 45 days, and subsequently challenged with Vibrio splendidus by injection at 1.0×108 cfu / sea cucumber for 15 days. Phagocytic capacity (PC), intracellular superoxide anion production (ISAP), lysozyme (LSZ) activity and superoxide dismutase (SOD) activity in the coelomic fluid were analyzed on the 0th, 5th, 10th and 15th days after injection. Results showed that after the 45-day feeding period, PC, ISAP, LSZ activity and SOD activity in sea cucumbers fed with dietary β-glucan or glycyrrhizin were significantly higher than in those fed with the basal diet. On the 5th day after infection, all the immune parameters examined in the sea cucumbers injected with V. splendidus decreased in value significantly. On the 15th day, PC, ISAP and LSZ activity returned to levels similar to those on the 0th day. For the sea cucumbers injected with saline, there were no significant differences in all the immune parameters examined and in the cumulative morbidity during the 15-day challenging trial. After injecting with V. splendidus, the cumulative morbidity of sea cucumbers fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin when challenged with V. splendidus challenged sea cucumber fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin. There was no significant difference in cumulative morbidity between the dietary β-glucan and glycyrrhizin treatments over time.

Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity.

PubMed

Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

2017-02-23

The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer-methylene blue (MB). As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS) generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an) was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

Large-scale patterns of turnover and Basal area change in Andean forests.

PubMed

Báez, Selene; Malizia, Agustina; Carilla, Julieta; Blundo, Cecilia; Aguilar, Manuel; Aguirre, Nikolay; Aquirre, Zhofre; Álvarez, Esteban; Cuesta, Francisco; Duque, Álvaro; Farfán-Ríos, William; García-Cabrera, Karina; Grau, Ricardo; Homeier, Jürgen; Linares-Palomino, Reynaldo; Malizia, Lucio R; Cruz, Omar Melo; Osinaga, Oriana; Phillips, Oliver L; Reynel, Carlos; Silman, Miles R; Feeley, Kenneth J

2015-01-01

General patterns of forest dynamics and productivity in the Andes Mountains are poorly characterized. Here we present the first large-scale study of Andean forest dynamics using a set of 63 permanent forest plots assembled over the past two decades. In the North-Central Andes tree turnover (mortality and recruitment) and tree growth declined with increasing elevation and decreasing temperature. In addition, basal area increased in Lower Montane Moist Forests but did not change in Higher Montane Humid Forests. However, at higher elevations the lack of net basal area change and excess of mortality over recruitment suggests negative environmental impacts. In North-Western Argentina, forest dynamics appear to be influenced by land use history in addition to environmental variation. Taken together, our results indicate that combinations of abiotic and biotic factors that vary across elevation gradients are important determinants of tree turnover and productivity in the Andes. More extensive and longer-term monitoring and analyses of forest dynamics in permanent plots will be necessary to understand how demographic processes and woody biomass are responding to changing environmental conditions along elevation gradients through this century.

Large-Scale Patterns of Turnover and Basal Area Change in Andean Forests

PubMed Central

Blundo, Cecilia; Aguilar, Manuel; Aguirre, Nikolay; Aquirre, Zhofre; Álvarez, Esteban; Cuesta, Francisco; Farfán-Ríos, William; García-Cabrera, Karina; Grau, Ricardo; Linares-Palomino, Reynaldo; Malizia, Lucio R.; Cruz, Omar Melo; Osinaga, Oriana; Reynel, Carlos; Silman, Miles R.

2015-01-01

General patterns of forest dynamics and productivity in the Andes Mountains are poorly characterized. Here we present the first large-scale study of Andean forest dynamics using a set of 63 permanent forest plots assembled over the past two decades. In the North-Central Andes tree turnover (mortality and recruitment) and tree growth declined with increasing elevation and decreasing temperature. In addition, basal area increased in Lower Montane Moist Forests but did not change in Higher Montane Humid Forests. However, at higher elevations the lack of net basal area change and excess of mortality over recruitment suggests negative environmental impacts. In North-Western Argentina, forest dynamics appear to be influenced by land use history in addition to environmental variation. Taken together, our results indicate that combinations of abiotic and biotic factors that vary across elevation gradients are important determinants of tree turnover and productivity in the Andes. More extensive and longer-term monitoring and analyses of forest dynamics in permanent plots will be necessary to understand how demographic processes and woody biomass are responding to changing environmental conditions along elevation gradients through this century. PMID:25973977

Effects of chronic ammonium sulfate treatment on the forest at the Bear Brook Watershed in Maine.

PubMed

Elvir, Jose Alexander; Wiersma, G Bruce; Bethers, Suzanne; Kenlan, Peter

2010-12-01

At the Bear Brook Watershed in Maine (BBWM), the forest tree composition was characterized and the effects of the chronic ammonium sulfate ((NH(4))(2)SO(4)) treatment on basal area growth, foliar chemistry, and gas exchange were investigated on forest species. The BBWM is a paired watershed forest ecosystem study with one watershed, West Bear (WB), treated since 1989 with 26.6 kg N ha(-1) year(-1) and 30 kg S ha(-1) year(-1)applied bimonthly as (NH(4))(2)SO(4), while the other watershed, East Bear (EB), serves as a reference. Tree species richness, density, and mortality were found to be similar between watersheds. Basal area increment was estimated from red spruce and sugar maple, showing that, for the first 7 years of treatment, it was significantly higher for sugar maple growing in WB compared to EB, but no differences were observed for red spruce between watersheds. However, the initial higher sugar maple basal area growth in WB subsequently decreased after 8 years of treatment. Foliar chemical analysis performed in trees, saplings, and ground flora showed higher N concentrations in the treated WB compared to the reference EB. But, foliar cation concentrations, especially Ca and Mg, were significantly lower for most of the species growing in WB compared with those growing in EB. For sugar maple, foliar N was higher on WB, but there were no differences in foliar Ca and Mg concentrations between treated and reference watersheds. In addition, only sugar maple trees in the treated WB showed significantly higher photosynthetic rates compared to reference EB trees.

Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice.

PubMed

Alcalde, Ignacio; Íñigo-Portugués, Almudena; González-González, Omar; Almaraz, Laura; Artime, Enol; Morenilla-Palao, Cruz; Gallar, Juana; Viana, Félix; Merayo-Lloves, Jesús; Belmonte, Carlos

2018-08-01

Morphological and functional alterations of peripheral somatosensory neurons during the aging process lead to a decline of somatosensory perception. Here, we analyze the changes occurring with aging in trigeminal ganglion (TG), TRPM8-expressing cold thermoreceptor neurons innervating the mouse cornea, which participate in the regulation of basal tearing and blinking and have been implicated in the pathogenesis of dry eye disease (DED). TG cell bodies and axonal branches were examined in a mouse line (TRPM8 BAC -EYFP) expressing a fluorescent reporter. In 3 months old animals, about 50% of TG cold thermoreceptor neurons were intensely fluorescent, likely providing strongly fluorescent axons and complex corneal nerve terminals with ongoing activity at 34°C and low-threshold, robust responses to cooling. The remaining TRPM8 + corneal axons were weakly fluorescent with nonbeaded axons, sparsely ramified nerve terminals, and exhibited a low-firing rate at 34°C, responding moderately to cooling pulses as do weakly fluorescent TG neurons. In aged (24 months) mice, the number of weakly fluorescent TG neurons was strikingly high while the morphology of TRPM8 + corneal axons changed drastically; 89% were weakly fluorescent, unbranched, and often ending in the basal epithelium. Functionally, 72.5% of aged cold terminals responded as those of young animals, but 27.5% exhibited very low-background activity and abnormal responsiveness to cooling pulses. These morpho-functional changes develop in parallel with an enhancement of tear's basal flow and osmolarity, suggesting that the aberrant sensory inflow to the brain from impaired peripheral cold thermoreceptors contributes to age-induced abnormal tearing and to the high incidence of DED in elderly people. © 2018 Wiley Periodicals, Inc.

Nigrostriatal lesion induces D2-modulated phase-locked activity in the basal ganglia of rats.

PubMed

Zold, Camila L; Ballion, Bérangère; Riquelme, Luis A; Gonon, François; Murer, M Gustavo

2007-04-01

There is a debate as to what modifications of neuronal activity underlie the clinical manifestations of Parkinson's disease and the efficacy of antiparkinsonian pharmacotherapy. Previous studies suggest that release of GABAergic striatopallidal neurons from D2 receptor-mediated inhibition allows spreading of cortical rhythms to the globus pallidus (GP) in rats with 6-hydroxydopamine-induced nigrostriatal lesions. Here this abnormal spreading was thoroughly investigated. In control urethane-anaesthetized rats most GP neurons were excited during the active part of cortical slow waves ('direct-phase' neurons). Two neuronal populations having opposite phase relationships with cortical and striatal activity coexisted in the GP of 6-hydroxydopamine-lesioned rats. 'Inverse-phase' GP units exhibited reduced firing coupled to striatal activation during slow waves, suggesting that this GP oscillation was driven by striatopallidal hyperactivity. Half of the pallidonigral neurons identified by antidromic stimulation exhibited inverse-phase activity. Therefore, spreading of inverse-phase oscillations through pallidonigral axons might contribute to the abnormal direct-phase cortical entrainment of basal ganglia output described previously. Systemic administration of the D2 agonist quinpirole to 6-hydroxydopamine-lesioned rats reduced GP inverse-phase coupling with slow waves, and this effect was reversed by the D2 antagonist eticlopride. Because striatopallidal hyperactivity was only slightly reduced by quinpirole, other mechanisms might have contributed to the effect of quinpirole on GP oscillations. These results suggest that antiparkinsonian efficacy may rely on other actions of D2 agonists on basal ganglia activity. However, abnormal slow rhythms may promote enduring changes in functional connectivity along the striatopallidal axis, contributing to D2 agonist-resistant clinical signs of parkinsonism.

Identification of amino acids in the tetratricopeptide repeat and C-terminal domains of protein phosphatase 5 involved in autoinhibition and lipid activation.

PubMed

Kang, H; Sayner, S L; Gross, K L; Russell, L C; Chinkers, M

2001-09-04

Protein phosphatase 5 (PP5) exhibits low basal activity due to the autoinhibitory properties of its N-terminal and C-terminal domains but can be activated approximately 40-fold in vitro by polyunsaturated fatty acids. To identify residues involved in regulating PP5 activity, we performed scanning mutagenesis of its N-terminal tetratricopeptide repeat (TPR) domain and deletion mutagenesis of its C-terminal domain. Mutating residues in a groove of the TPR domain that binds to heat shock protein 90 had no effect on basal phosphatase activity. Mutation of Glu-76, however, whose side chain projects away from this groove, resulted in a 10-fold elevation of basal activity without affecting arachidonic acid-stimulated activity. Thus, the interface of the TPR domain involved in PP5 autoinhibition appears to be different from that involved in heat shock protein 90 binding. We also observed a 10-fold elevation of basal phosphatase activity upon removing the C-terminal 13 amino acids of PP5, with a concomitant 50% decrease in arachidonic acid-stimulated activity. These two effects were accounted for by two distinct amino acid deletions: deleting the four C-terminal residues (496-499) of PP5 had no effect on its activity, but removing Gln-495 elevated basal activity 10-fold. Removal of a further three amino acids had no additional effect, but deleting Asn-491 resulted in a 50% reduction in arachidonic acid-stimulated activity. Thus, Glu-76 in the TPR domain and Gln-495 at the C-terminus were implicated in maintaining the low basal activity of PP5. While the TPR domain alone has been thought to mediate fatty acid activation of PP5, our data suggest that Asn-491, near its C-terminus, may also be involved in this process.

Accelerated cell-sheet recovery from a surface successively grafted with polyacrylamide and poly(N-isopropylacrylamide).

PubMed

Akiyama, Yoshikatsu; Kikuchi, Akihiko; Yamato, Masayuki; Okano, Teruo

2014-08-01

A double polymeric nanolayer consisting of poly(N-isopropylacrylamide) (PIPAAm) and hydrophilic polyacrylamide (PAAm) was deposited on tissue culture polystyrene (TCPS) surfaces using electron beam irradiation to form a new temperature-responsive cell culture surface in which the basal hydrophilic PAAm component in the double polymeric layer promotes the hydration of the upper PIPAAm layer and induces rapid cell detachment compared to a conventional temperature-responsive cell culture surface, PIPAAm-grafted TCPS (PIPAAm-TCPS). Take-off angle-dependent X-ray photoelectron spectroscopy spectral analysis demonstrated that the grafted PIPAAm and PAAm components were located in the upper and basal regions of the double polymeric layer, respectively, suggesting that the double polymeric layer forms an inter-penetrating-network-like structure with PAAm at the basal portion of the PIPAAm grafted chains. The wettability of the temperature-responsive cell culture surfaces with the double polymeric layer tended to be more hydrophilic, with an increase in the basal PAAm graft density at a constant PIPAAm graft density. However, when the graft densities of the upper PIPAAm and basal PAAm were optimized, the resulting temperature-responsive cell culture surface with the double polymeric layer exhibited rapid cell detachment while maintaining cell adhesive character comparable to that of PIPAAm-TCPS. The cell adhesive character was altered from cell-adhesive to cell-repellent with increasing PAAm or PIPAAm graft density. The cell adhesive character of the temperature-responsive cell culture surfaces was relatively consistent with their contact angles. These results strongly suggest that the basal PAAm surface properties affect the degree of hydration and dehydration of the subsequently grafted PIPAAm. In addition, the roles of the hydrophilic component in accelerating cell detachment are further discussed in terms of the mobility of the grafted PIPAAm chains. Applications of this insight might be useful for designing temperature-responsive cell culture surfaces for achieving efficient cell culture and quick target cell detachment. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Geothermal flux and basal melt rate in the Dome C region inferred from radar reflectivity and heat modelling

NASA Astrophysics Data System (ADS)

Passalacqua, Olivier; Ritz, Catherine; Parrenin, Frédéric; Urbini, Stefano; Frezzotti, Massimo

2017-09-01

Basal melt rate is the most important physical quantity to be evaluated when looking for an old-ice drilling site, and it depends to a great extent on the geothermal flux (GF), which is poorly known under the East Antarctic ice sheet. Given that wet bedrock has higher reflectivity than dry bedrock, the wetness of the ice-bed interface can be assessed using radar echoes from the bedrock. But, since basal conditions depend on heat transfer forced by climate but lagged by the thick ice, the basal ice may currently be frozen whereas in the past it was generally melting. For that reason, the risk of bias between present and past conditions has to be evaluated. The objective of this study is to assess which locations in the Dome C area could have been protected from basal melting at any time in the past, which requires evaluating GF. We used an inverse approach to retrieve GF from radar-inferred distribution of wet and dry beds. A 1-D heat model is run over the last 800 ka to constrain the value of GF by assessing a critical ice thickness, i.e. the minimum ice thickness that would allow the present local distribution of basal melting. A regional map of the GF was then inferred over a 80 km × 130 km area, with a N-S gradient and with values ranging from 48 to 60 mW m-2. The forward model was then emulated by a polynomial function to compute a time-averaged value of the spatially variable basal melt rate over the region. Three main subregions appear to be free of basal melting, two because of a thin overlying ice and one, north of Dome C, because of a low GF.

Low-density lipoproteins modulate endothelial cells to secrete endothelin-1 in a polarized pattern: a study using a culture model system simulating arterial intima.

PubMed

Unoki, H; Fan, J; Watanabe, T

1999-01-01

We investigated the structural and functional properties of human umbilical vein endothelial cells (HUVECs) cultured on a two-chamber culture model system using an amnion membrane. Compared to HUVECs cultured on a plastic dish, HUVECs cultured on the model system exhibited several features similar to those of in vivo vessels, including formation of the intercellular junctional devices and expression of tight junction-associated protein ZO-1 and adherence junction-associated protein alpha-catenin. Furthermore, we found that HUVECs had a property of polar secretion of endothelin-1 (ET-1). About 90% of the total amount of synthesized ET-1 was found in the lower well, designated as the basal side. When HUVECs were incubated with either native low-density lipoproteins (nLDLs) or oxidized LDLs (oxLDLs) at a concentration of 100 microgram/ml, ET-1 secretion was significantly increased, dependent on the cell side (apical vs basal) on which the nLDLs or oxLDLs were loaded. When the LDLs were loaded on the apical side, the secretion of ET-1 from HUVECs on the apical side was increased by 48% (nLDL) and 61% (oxLDL), whereas it was accompanied by a concomitant decrease of ET-1 on the basal side (45% by nLDLs and 38% by oxLDLs). When loaded on the basal side, however, ET-1 was increased by 23% (nLDLs) and 53% (oxLDLs) on the basal side, with a 26% simultaneous decrease of ET-1 on the opposite side for both nLDLs and oxLDLs. On the contrary, high-density lipoproteins (HDLs) inhibited ET-1 secretion from HUVECs on the opposite side of the well on which HDLs were loaded; there was a 57% decrease on the basal side when HDLs were loaded on the apical side, and a 46% decrease on the apical side when loaded on the basal side. These results indicate that modulation of ET-1 secretion from ECs by lipoproteins is virtually dependent on the place (apical vs basal) where these proteins are present. The finding that nLDLs and oxLDLs enhance ET-1 secretion by ECs in a polarized pattern suggests that ET-1 may be involved in pathophysiological processes such as atherogenesis.

The Molecular Pathway Regulating Bergmann Glia and Folia Generation in the Cerebellum.

PubMed

Leung, Alan W; Li, James Y H

2018-02-01

Evolution of complex behaviors in higher vertebrates and primates require the development of sophisticated neuronal circuitry and the expansion of brain surface area to accommodate the vast number of neuronal and glial populations. To achieve these goals, the neocortex in primates and the cerebellum in amniotes have developed specialized types of basal progenitors to aid the folding of their cortices. In the cerebellum, Bergmann glia constitute such a basal progenitor population, having a distinctive morphology and playing a critical role in cerebellar corticogenesis. Here, we review recent studies on the induction of Bergmann glia and their crucial role in mediating folding of the cerebellar cortex. These studies uncover a key function of FGF-ERK-ETV signaling cascade in the transformation of Bergmann glia from radial glia in the ventricular zone. Remarkably, in the neocortex, the same signaling axis operates to facilitate the transformation of ventricular radial glia into basal radial glia, a Bergmann glia-like basal progenitor population, which have been implicated in the establishment of neocortical gyri. These new findings draw a striking similarity in the function and ontogeny of the two basal progenitor populations born in distinct brain compartments.

Insulin appearance of subcutaneously infused insulin: influence of the basal rate pulse interval of the infusion pump.

PubMed

Birch, K; Hildebrandt, P; Jensen, B M; Kühl, C; Brange, J

1985-05-01

To compare the metabolic control and the pharmacokinetics of infused insulin using an insulin pump (Auto-Syringe AS 6C) which provides the basal rate in pulses every 2-10 min with a pump (Medix Syringe Driver 209) providing the basal rate in pulses every 15-60 min, 6 C-peptide negative diabetic patients received, in random order, identical, but individual, insulin treatment during one 4-day period using the Auto-Syringe pump and another 4-day period using the Medix pump. On the fourth day of each period, blood glucose and plasma-free insulin were estimated every 30 min for 7 hr and every 5 min for the next hour. Plasma-free insulin was significantly higher on 3 time points out of the 26 possible when using the Medix pump, but this was not reflected in the blood glucose concentrations which were similar in the 2 periods. The results indicate that, from a metabolic and pharmacokinetic point of view, insulin pumps working with larger intervals between the basal rate pulses are just as good as the more technically advanced and hence often more expensive pumps which provide the basal rate in more and smaller pulses.

Fish glucose transporter (GLUT)-4 differs from rat GLUT4 in its traffic characteristics but can translocate to the cell surface in response to insulin in skeletal muscle cells.

PubMed

Díaz, Mònica; Antonescu, Costin N; Capilla, Encarnación; Klip, Amira; Planas, Josep V

2007-11-01

In mammals, glucose transporter (GLUT)-4 plays an important role in glucose homeostasis mediating insulin action to increase glucose uptake in insulin-responsive tissues. In the basal state, GLUT4 is located in intracellular compartments and upon insulin stimulation is recruited to the plasma membrane, allowing glucose entry into the cell. Compared with mammals, fish are less efficient restoring plasma glucose after dietary or exogenous glucose administration. Recently our group cloned a GLUT4-homolog in skeletal muscle from brown trout (btGLUT4) that differs in protein motifs believed to be important for endocytosis and sorting of mammalian GLUT4. To study the traffic of btGLUT4, we generated a stable L6 muscle cell line overexpressing myc-tagged btGLUT4 (btGLUT4myc). Insulin stimulated btGLUT4myc recruitment to the cell surface, although to a lesser extent than rat-GLUT4myc, and enhanced glucose uptake. Interestingly, btGLUT4myc showed a higher steady-state level at the cell surface under basal conditions than rat-GLUT4myc due to a higher rate of recycling of btGLUT4myc and not to a slower endocytic rate, compared with rat-GLUT4myc. Furthermore, unlike rat-GLUT4myc, btGLUT4myc had a diffuse distribution throughout the cytoplasm of L6 myoblasts. In primary brown trout skeletal muscle cells, insulin also promoted the translocation of endogenous btGLUT4 to the plasma membrane and enhanced glucose transport. Moreover, btGLUT4 exhibited a diffuse intracellular localization in unstimulated trout myocytes. Our data suggest that btGLUT4 is subjected to a different intracellular traffic from rat-GLUT4 and may explain the relative glucose intolerance observed in fish.

Understory plant diversity in riparian alder-conifer stands after logging in southeast Alaska.

Treesearch

Robert L. Deal

1997-01-01

Stand structure, tree height growth, and understory plant diversity were assessed in five mixed alder-conifer stands after logging in southeast Alaska. Tree species composition ranged from 7- to 91-percent alder, and basal area ranged from 30 to 55 m2/ha. The alder exhibited rapid early height growth, but recent growth has slowed considerably. Some conifers have...

Basal and thermal control mechanisms of the Ragnhild glaciers, East Antarctica

NASA Astrophysics Data System (ADS)

Pattyn, Frank; de Brabander, Sang; Huyghe, Ann

The Ragnhild glaciers are three enhanced-flow features situated between the Sør Rondane and Yamato Mountains in eastern Dronning Maud Land, Antarctica. We investigate the glaciological mechanisms controlling their existence and behavior, using a three-dimensional numerical thermomechanical ice-sheet model including higher-order stress gradients. This model is further extended with a steady-state model of subglacial water flow, based on the hydraulic potential gradient. Both static and dynamic simulations are capable of reproducing the enhanced ice-flow features. Although basal topography is responsible for the existence of the flow pattern, thermomechanical effects and basal sliding seem to locally soften and lubricate the ice in the main trunks. Lateral drag is a contributing factor in balancing the driving stress, as shear margins can be traced over a distance of hundreds of kilometers along west Ragnhild glacier. Different basal sliding scenarios show that central Ragnhild glacier stagnates as west Ragnhild glacier accelerates and progressively drains the whole catchment area by ice and water piracy.

Identification and characterization of a gibberellin-regulated protein, which is ASR5, in the basal region of rice leaf sheaths.

PubMed

Takasaki, Hironori; Mahmood, Tariq; Matsuoka, Makoto; Matsumoto, Hiroshi; Komatsu, Setsuko

2008-04-01

Gibberellins (GAs) regulate growth and development in higher plants. To identify GA-regulated proteins during rice leaf sheath elongation, a proteomic approach was used. Proteins from the basal region of leaf sheath in rice seedling treated with GA(3) were analyzed by fluorescence two-dimensional difference gel electrophoresis. The levels of abscisic acid-stress-ripening-inducible 5 protein (ASR5), elongation factor-1 beta, translationally controlled tumor protein, fructose-bisphosphate aldolase and a novel protein increased; whereas the level of RuBisCO subunit binding-protein decreased by GA(3) treatment. ASR5 out of these six proteins was significantly regulated by GA(3) at the protein level but not at the mRNA level in the basal region of leaf sheaths. Since this protein is regulated not only by abscisic acid but also by GA(3), these results indicate that ASR5 might be involved in plant growth in addition to stress in the basal regions of leaf sheaths.

Molecular Subtypes of Indonesian Breast Carcinomas - Lack of Association with Patient Age and Tumor Size

PubMed Central

Rahmawati, Yeni; Setyawati, Yunita; Widodo, Irianiwati; Ghozali, Ahmad; Purnomosari, Dewajani

2018-01-01

Objective: Breast carcinoma (BC) is a heterogeneous disease that exhibits variation in biological behaviour, prognosis and response to therapy. Molecular classification is generally into Luminal A, Luminal B, HER2+ and triple negative/basal-like, depending on receptor characteristics. Clinical factors that determined the BC prognosis are age and tumor size. Since information on molecular subtypes of Indonesian BCs is limited, the present study was conducted, with attention to subtypes in relation to age and tumor size. Methods: A retrospective cross-sectional study of 247 paraffin-embedded samples of invasive BC from Dr. Sardjito General Hospital Yogyakarta in the year 2012- 2015 was performed. Immunohistochemical staining using anti- ER, PR, HER2, Ki-67 and CK 5/6 antibodies was applied to classify molecular subtypes. Associations with age and tumor size were analyzed using the Chi Square Test. Results: The Luminal A was the most common subtype of Indonesian BC (41.3%), followed by triple negative (25.5%), HER2 (19.4%) and luminal B (13.8%). Among the triple negative lesions, the basal-like subtype was more frequent than the non basal-like (58.8 % vs 41.2%). Luminal B accounted for the highest percentage of younger age cases (< 40 years old) while HER2+ was most common in older age (> 50 years old) patients. Triple negative/basal-like were commonly large in size. Age (p = 0.080) and tumor size (p = 0.462) were not significantly associated with molecular subtypes of BC. Conclusion: The most common molecular subtype of Indonesian BC is luminal A, followed by triple-negative, HER2+ and luminal B. The majority of triple-negative lesions are basal-like. There are no association between age and tumor size with molecular subtypes of Indonesian BCs. PMID:29373908

Molecular Subtypes of Indonesian Breast Carcinomas - Lack of Association with Patient Age and Tumor Size

PubMed

Rahmawati, Yeni; Setyawati, Yunita; Widodo, Irianiwati; Ghozali, Ahmad; Purnomosari, Dewajani

2018-01-27

Objective: Breast carcinoma (BC) is a heterogeneous disease that exhibits variation in biological behaviour, prognosis and response to therapy. Molecular classification is generally into Luminal A, Luminal B, HER2+ and triple negative/basal-like, depending on receptor characteristics. Clinical factors that determined the BC prognosis are age and tumor size. Since information on molecular subtypes of Indonesian BCs is limited, the present study was conducted, with attention to subtypes in relation to age and tumor size. Methods: A retrospective cross-sectional study of 247 paraffin-embedded samples of invasive BC from Dr. Sardjito General Hospital Yogyakarta in the year 2012- 2015 was performed. Immunohistochemical staining using anti- ER, PR, HER2, Ki-67 and CK 5/6 antibodies was applied to classify molecular subtypes. Associations with age and tumor size were analyzed using the Chi Square Test. Results: The Luminal A was the most common subtype of Indonesian BC (41.3%), followed by triple negative (25.5%), HER2 (19.4%) and luminal B (13.8%). Among the triple negative lesions, the basal-like subtype was more frequent than the non basal-like (58.8 % vs 41.2%). Luminal B accounted for the highest percentage of younger age cases (< 40 years old) while HER2+ was most common in older age (> 50 years old) patients. Triple negative/basal-like were commonly large in size. Age (p = 0.080) and tumor size (p = 0.462) were not significantly associated with molecular subtypes of BC. Conclusion: The most common molecular subtype of Indonesian BC is luminal A, followed by triple-negative, HER2+ and luminal B. The majority of triple-negative lesions are basal-like. There are no association between age and tumor size with molecular subtypes of Indonesian BCs. Creative Commons Attribution License

Glacier seismology: eavesdropping on the ice-bed interface

NASA Astrophysics Data System (ADS)

Walter, F.; Röösli, C.

2015-12-01

Glacier sliding plays a central role in ice dynamics. A number of remote sensing and deep drilling initiatives have therefore focused on the ice-bed interface. Although these techniques have provided valuable insights into bed properties, they do not supply theorists with data of sufficient temporal and spatial resolution to rigorously test mathematical sliding laws. As an alternative, passive seismic techniques have gained popularity in glacier monitoring. Analysis of glacier-related seismic sources ('icequakes') has become a useful technique to study inaccessible regions of the cryosphere, including the ice-bed interface. Seismic monitoring networks on the polar ice sheets have shown that ice sliding is not only a smooth process involving viscous deformation and regelation of basal ice layers. Instead, ice streams exhibit sudden slip episodes over their beds and intermittent phases of partial or complete stagnation. Here we discuss new and recently published discoveries of basal seismic sources beneath various glacial bodies. We revisit basal seismicity of hard-bedded Alpine glaciers, which is not the result of pure stick-slip motion. Sudden changes in seismicity suggest that the local configuration of the subglacial drainage system undergoes changes on sub daily time scales. Accordingly, such observations place constraints on basal resistance and sliding of hard-bedded glaciers. In contrast, certain clusters of stick-slip dislocations associated with micro seismicity beneath the Greenland ice sheet undergo diurnal variations in magnitudes and inter event times. This is best explained with a soft till bed, which hosts the shear dislocations and whose strength varies in response to changes in subglacial water pressure. These results suggest that analysis of basal icequakes is well suited for characterizing glacier and ice sheet beds. Future studies should address the relative importance between "smooth" and seismogenic sliding in different glacial environments.

Hydrogeologic Controls on Water Dynamics in a Discontinuous Permafrost, Lake-Rich Landscape

NASA Astrophysics Data System (ADS)

Walvoord, M. A.; Briggs, M. A.; Day-Lewis, F. D.; Jepsen, S. M.; Lane, J. W., Jr.; McKenzie, J. M.; Minsley, B. J.; Striegl, R. G.; Voss, C. I.; Wellman, T. P.

2014-12-01

Glacier sliding plays a central role in ice dynamics. A number of remote sensing and deep drilling initiatives have therefore focused on the ice-bed interface. Although these techniques have provided valuable insights into bed properties, they do not supply theorists with data of sufficient temporal and spatial resolution to rigorously test mathematical sliding laws. As an alternative, passive seismic techniques have gained popularity in glacier monitoring. Analysis of glacier-related seismic sources ('icequakes') has become a useful technique to study inaccessible regions of the cryosphere, including the ice-bed interface. Seismic monitoring networks on the polar ice sheets have shown that ice sliding is not only a smooth process involving viscous deformation and regelation of basal ice layers. Instead, ice streams exhibit sudden slip episodes over their beds and intermittent phases of partial or complete stagnation. Here we discuss new and recently published discoveries of basal seismic sources beneath various glacial bodies. We revisit basal seismicity of hard-bedded Alpine glaciers, which is not the result of pure stick-slip motion. Sudden changes in seismicity suggest that the local configuration of the subglacial drainage system undergoes changes on sub daily time scales. Accordingly, such observations place constraints on basal resistance and sliding of hard-bedded glaciers. In contrast, certain clusters of stick-slip dislocations associated with micro seismicity beneath the Greenland ice sheet undergo diurnal variations in magnitudes and inter event times. This is best explained with a soft till bed, which hosts the shear dislocations and whose strength varies in response to changes in subglacial water pressure. These results suggest that analysis of basal icequakes is well suited for characterizing glacier and ice sheet beds. Future studies should address the relative importance between "smooth" and seismogenic sliding in different glacial environments.

Oriented graphite layer formation in Ti/C and TiC/C multilayers deposited by high current pulsed cathodic arc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Persson, P. O. A.; Ryves, L.; Tucker, M. D.

2008-10-01

Ti/C and TiC/C multilayers with periods ranging from 2 to 18 nm were grown by filtered high current pulsed cathodic arc. The growth was monitored in situ by ellipsometry and cantilever stress measurements. The ellipsometry results reveal that the optical properties of the carbon vary as a function of thickness. Correspondingly, the stress in each carbon layer as measured in situ exhibits two well defined values: initially the stress is low and then takes on a higher value for the remainder of the layer. Transmission electron microscopy shows that the initial growth of carbon on Ti or TiC layer ismore » oriented with graphitic basal planes aligned parallel to the interface. After 2-4 nm of growth, the graphitic structure transforms to amorphous carbon. Electron energy loss spectroscopy shows that the carbon layer simultaneously undergoes a transition from sp{sup 2} rich to sp{sup 3} rich material.« less

Oxidative Stress Response Tips the Balance in Aspergillus terreus Amphotericin B Resistance

PubMed Central

Blatzer, Michael; Posch, Wilfried; Steger, Marion; Binder, Ulrike; Lass-Flörl, Cornelia

2017-01-01

ABSTRACT In this study, we characterize the impact of antioxidative enzymes in amphotericin B (AmB)-resistant (ATR) and rare AmB-susceptible (ATS) clinical Aspergillus terreus isolates. We elucidate expression profiles of superoxide dismutase (SOD)- and catalase (CAT)-encoding genes, enzymatic activities of SODs, and superoxide anion production and signaling pathways involved in the oxidative stress response (OSR) in ATS and ATR strains under AmB treatment conditions. We show that ATR strains possess almost doubled basal SOD activity compared to that of ATS strains and that ATR strains exhibit an enhanced OSR, with significantly higher sod2 mRNA levels and significantly increased cat transcripts in ATR strains upon AmB treatment. In particular, inhibition of SOD and CAT proteins renders resistant isolates considerably susceptible to the drug in vitro. In conclusion, this study shows that SODs and CATs are crucial for AmB resistance in A. terreus and that targeting the OSR might offer new treatment perspectives for resistant species. PMID:28739793

Development and comparison of processing maps of Mg-3Sn-1Ca alloy from data obtained in tension versus compression

NASA Astrophysics Data System (ADS)

Rao, K. P.; Suresh, K.; Prasad, Y. V. R. K.; Hort, N.

2018-01-01

The hot workability of extruded Mg-3Sn-1Ca alloy has been evaluated by developing processing maps with flow stress data from compression and tensile tests with a view to find the effect of the applied state-of-stress. The processing maps developed at a strain of 0.2 are essentially similar irrespective of the mode of deformation - compression or tension, and exhibit three domains in the temperature ranges: (1) 350 - 425 °C, and (2) 450 - 550 °C and (3) 400 - 500 °C, the first two occurring at lower strain rates and the third occurring at higher strain rates. In all the three domains, dynamic recrystallization occurs and is caused by non-basal slip and controlled by lattice self-diffusion in the first and second domains and grain boundary self-diffusion in the third domain. The state-of-stress imposed on the specimen (compression or tension) does not have any significant effect on the processing maps.

Tension-compression asymmetry of a rolled Mg-Y-Nd alloy

NASA Astrophysics Data System (ADS)

Song, Bo; Pan, Hucheng; Ren, Weijie; Guo, Ning; Wu, Zehong; Xin, Renlong

2017-07-01

In this work, tension and compression deformation behaviors of rolled and aged Mg-Y-Nd alloys were investigated. The microstructure evolution and plastic deformation mechanism during tension and compression were analyzed by combined use of electron backscatter diffraction and a visco-plastic self-consistent crystal plasticity model. The results show that both rolled and aged Mg-Y-Nd sheets show an extremely low yield asymmetry. Elimination of yield asymmetry can be ascribed to the tilted basal texture and suppression of {10-12} twinning. The rolled sheet has almost no yield asymmetry, however exhibits a remarkable strain-hardening behavior asymmetry. Compressed sample shows lower initial strain hardening rate and keeps higher strain hardening rate at the later stage compared with tension. The strain-hardening asymmetry can be aggravated by aging at 280 C. It is considered the limited amount of twins in compression plays the critical role in the strain hardening asymmetry. Finally, the relevant mechanism was analyzed and discussed.

Regional cholinesterase activity in white-throated sparrow brain is differentially affected by acephate (Orthene®)

USGS Publications Warehouse

Vyas, N.B.; Kuenzel, W.J.; Hill, E.F.; Romo, G.A.; Komaragiri, M.V.S.

1996-01-01

Effects of a 14-day dietary exposure to an organophosphorus pesticide, acephate (acetylphosphoramidothioic acid O,S-dimethyl ester), were determined on cholinesterase activity in three regions (basal ganglia, hippocampus, and hypothalamus) of the white-throated sparrow, Zonotrichia albicollis, brain. All three regions experienced depressed cholinesterase activity between 0.5–2 ppm acephate. The regions exhibited cholinesterase recovery at 2–16 ppm acephate; however, cholinesterase activity dropped and showed no recovery at higher dietary levels (>16 ppm acephate). Evidence indicates that the recovery is initiated by the magnitude of depression, not the duration. In general, as acephate concentration increased, differences in ChE activity among brain regions decreased. Three terms are introduced to describe ChE response to acephate exposure: 1) ChE resistance threshold, 2) ChE compensation threshold, and 3) ChE depression threshold. It is hypothesized that adverse effects to birds in the field may occur at pesticide exposure levels customarily considered negligible.

Exploring Jordan's rule in Pacific three-spined stickleback Gasterosteus aculeatus.

PubMed

Morris, M R J; Petrovitch, E; Bowles, E; Jamniczky, H A; Rogers, S M

2017-08-01

Coastal marine Gasterosteus aculeatus were captured from seven locations along the Pacific coast of North America, ranging across 21·8° latitude to test Jordan's rule, i.e. that vertebral number should increase with increasing latitude for related populations of fish. Vertebral number significantly increased with increasing latitude for both total and caudal vertebral number. Increasing length with latitude (sensu Bergmann's rule) was also supported, but the predictions for Jordan's rule held when controlling for standard length. Pleomerism was weakly evidenced. Gasterosteus aculeatus exhibited sexual dimorphism for Jordan's rule, with both sexes having more vertebrae at higher latitudes, but only males showing a positive association between latitude and the ratio of caudal to abdominal vertebrae. The number of dorsal- and anal-fin rays and basals increased with increasing latitude, while pectoral-fin ray number decreased. This study reinforces the association between phenotypic variation and environmental variation in marine populations of G. aculeatus. © 2017 The Fisheries Society of the British Isles.

Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

PubMed

Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

2016-01-01

Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

Deformation of Fold-and-Thrust Belts above a Viscous Detachment: New Insights from Analogue Modelling Experiments

NASA Astrophysics Data System (ADS)

Nogueira, Carlos R.; Marques, Fernando O.

2015-04-01

Theoretical and experimental studies on fold-and-thrusts belts (FTB) have shown that, under Coulomb conditions, deformation of brittle thrust wedges above a dry frictional basal contact is characterized by dominant frontward vergent thrusts (forethrusts) with thrust spacing and taper angle being directly influenced by the basal strength (increase in basal strength leading to narrower thrust spacing and higher taper angles); whereas thrust wedges deformed above a weak viscous detachment, such as salt, show a more symmetric thrust style (no prevailing vergence of thrusting) with wider thrust spacing and shallower wedges. However, different deformation patterns can be found on this last group of thrust wedges both in nature and experimentally. Therefore we focused on the strength (friction) of the wedge basal contact, the basal detachment. We used a parallelepiped box with four fixed walls and one mobile that worked as a vertical piston drove by a computer controlled stepping motor. Fine dry sand was used as the analogue of brittle rocks and silicone putty (PDMS) with Newtonian behaviour as analogue of the weak viscous detachment. To investigate the strength of basal contact on thrust wedge deformation, two configurations were used: 1) a horizontal sand pack with a dry frictional basal contact; and 2) a horizontal sand pack above a horizontal PDMS layer, acting as a basal weak viscous contact. Results of the experiments show that: the model with a dry frictional basal detachment support the predictions for the Coulomb wedges, showing a narrow wedge with dominant frontward vergence of thrusting, close spacing between FTs and high taper angle. The model with a weak viscous frictional basal detachment show that: 1) forethrusts (FT) are dominant showing clearly an imbricate asymmetric geometry, with wider spaced thrusts than the dry frictional basal model; 2) after FT initiation, the movement on the thrust can last up to 15% model shortening, leading to great amount of displacement along the FT; 3) intermittent reactivation of FTs also occurs despite the steepening of the FT plane and existence of new FT ahead, creating a high critical taper angle; 4) injection of PDMS from the basal weak layer into the FTs planes also favours to the long living of FTs and to the high critical taper angle; 5) vertical sand thickening in the hanging block also added to the taper angle.

Greater left cerebral hemispheric metabolism in bulimia assessed by positron emission tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, J.C.; Hagman, J.; Buchsbaum, M.S.

1990-03-01

Eight women with bulimia and eight age- and sex-matched normal control subjects were studied with positron emission tomography using (18F)-fluorodeoxyglucose (FDG) as a tracer of brain metabolic rate. Subjects performed a visual vigilance task during FDG uptake. In control subjects, the metabolic rate was higher in the right hemisphere than in the left, but patients with bulimia did not have this normal asymmetry. Lower metabolic rates in the basal ganglia, found in studies of depressed subjects, and higher rates in the basal ganglia, reported in a study of anorexia nervosa, were not found. This is consistent with the suggestion thatmore » bulimia is a diagnostic grouping distinct from these disorders.« less

Cognitive-motor interactions of the basal ganglia in development

PubMed Central

Leisman, Gerry; Braun-Benjamin, Orit; Melillo, Robert

2014-01-01

Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-based learning, sequencing, discrete elements that constitute a complete motor act, and cognitive function. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to attention deficit/hyperactivity disorder (ADHD) with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition. PMID:24592214

Characterizing Microbial Diversity and the Potential for Metabolic Function at −15 °C in the Basal Ice of Taylor Glacier, Antarctica

PubMed Central

Doyle, Shawn M.; Montross, Scott N.; Skidmore, Mark L.; Christner, Brent C.

2013-01-01

Measurement of gases entrapped in clean ice from basal portions of the Taylor Glacier, Antarctica, revealed that CO2 ranged from 229 to 328 ppmv and O2 was near 20% of the gas volume. In contrast, vertically adjacent sections of the sediment laden basal ice contained much higher concentrations of CO2 (60,000 to 325,000 ppmv), whereas O2 represented 4 to 18% of the total gas volume. The deviation in gas composition from atmospheric values occurred concurrently with increased microbial cell concentrations in the basal ice profile, suggesting that in situ microbial processes (i.e., aerobic respiration) may have altered the entrapped gas composition. Molecular characterization of 16S rRNA genes amplified from samples of the basal ice indicated a low diversity of bacteria, and most of the sequences characterized (87%) were affiliated with the phylum, Firmicutes. The most abundant phylotypes in libraries from ice horizons with elevated CO2 and depleted O2 concentrations were related to the genus Paenisporosarcina, and 28 isolates from this genus were obtained by enrichment culturing. Metabolic experiments with Paenisporosarcina sp. TG14 revealed its capacity to conduct macromolecular synthesis when frozen in water derived from melted basal ice samples and incubated at −15 °C. The results support the hypothesis that the basal ice of glaciers and ice sheets are cryospheric habitats harboring bacteria with the physiological capacity to remain metabolically active and biogeochemically cycle elements within the subglacial environment. PMID:24833055

Skeletal stem cell and bone implant interactions are enhanced by LASER titanium modification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sisti, Karin E., E-mail: karinellensisti@gmail.com; Biomaterials Group, Institute of Chemistry, São Paulo State University; Federal University of Mato Grosso do Sul

Purpose: To evaluate the osteo-regenerative potential of Titanium (Ti) modified by Light Amplification by Stimulated Emission of Radiation (LASER) beam (Yb-YAG) upon culture with human Skeletal Stem Cells (hSSCs{sup 1}). Methods: Human skeletal cell populations were isolated from the bone marrow of haematologically normal patients undergoing primary total hip replacement following appropriate consent. STRO-1{sup +} hSSC{sup 1} function was examined for 10 days across four groups using Ti discs: i) machined Ti surface group in basal media (Mb{sup 2}), ii) machined Ti surface group in osteogenic media (Mo{sup 3}), iii) LASER-modified Ti group in basal media (Lb{sup 4}) and, iv)more » LASER-modified Ti group in osteogenic media (Lo{sup 5}). Molecular analysis and qRT-PCR as well as functional analysis including biochemistry (DNA, Alkaline Phosphatase (ALP{sup 6}) specific activity), live/dead immunostaining (Cell Tracker Green (CTG{sup 7})/Ethidium Homodimer-1 (EH-1{sup 8})), and fluorescence staining (for vinculin and phalloidin) were undertaken. Inverted, confocal and Scanning Electron Microscopy (SEM) approaches were used to characterise cell adherence, proliferation, and phenotype. Results: Enhanced cell spreading and morphological rearrangement, including focal adhesions were observed following culture of hSSCs{sup 1} on LASER surfaces in both basal and osteogenic conditions. Biochemical analysis demonstrated enhanced ALP{sup 6} specific activity on the hSSCs{sup 1}-seeded on LASER-modified surface in basal culture media. Molecular analysis demonstrated enhanced ALP{sup 6} and osteopontin expression on titanium LASER treated surfaces in basal conditions. SEM, inverted microscopy and confocal laser scanning microscopy confirmed extensive proliferation and migration of human bone marrow stromal cells on all surfaces evaluated. Conclusions: LASER-modified Ti surfaces modify the behaviour of hSSCs.{sup 1} In particular, SSC{sup 1} adhesion, osteogenic gene expression, cell morphology and cytoskeleton structure were affected. The current studies show Ti LASER modification can enhance the osseointegration between Ti and skeletal cells, with important implications for orthopaedic application. - Highlights: • Bone stem cells on LASER Ti surface display enhanced cell growth and viability. • Bone stem cells on LASER Ti surface exhibit marked biocompatibility. • Human bone stem cells on LASER Ti surface exhibit altered morphology. • LASER Ti enhance osteogenic differentiation of human bone skeletal stem cells. • LASER Ti provides a unique approach to enhance osseointegration with the material.« less

Plasmids encoding PKI(1-31), a specific inhibitor of cAMP-stimulated gene expression, inhibit the basal transcriptional activity of some but not all cAMP-regulated DNA response elements in JEG-3 cells.

PubMed

Grove, J R; Deutsch, P J; Price, D J; Habener, J F; Avruch, J

1989-11-25

Plasmids that encode a bioactive amino-terminal fragment of the heat-stable inhibitor of the cAMP-dependent protein kinase, PKI(1-31), were employed to characterize the role of this protein kinase in the control of transcriptional activity mediated by three DNA regulatory elements in the JEG-3 human placental cell line. The 5'-flanking sequence of the human collagenase gene contains the heptameric sequence, 5'-TGAGTCA-3', previously identified as a "phorbol ester" response element. Reporter genes containing either the intact 1.2-kilobase 5'-flanking sequence from the human collagenase gene or just the 7-base pair (bp) response element, when coupled to an enhancerless promoter, each exhibit both cAMP and phorbol ester-stimulated expression in JEG-3 cells. Cotransfection of either construct with plasmids encoding PKI(1-31) inhibits cAMP-stimulated but not basal- or phorbol ester-stimulated expression. Pretreatment of cells with phorbol ester for 1 or 2 days abrogates completely the response to rechallenge with phorbol ester but does not alter the basal expression of either construct; cAMP-stimulated expression, while modestly inhibited, remains vigorous. The 5'-flanking sequence of the human chorionic gonadotropin-alpha subunit (HCG alpha) gene has two copies of the sequence, 5'-TGACGTCA-3', contained in directly adjacent identical 18-bp segments, previously identified as a cAMP-response element. Reporter genes containing either the intact 1.5 kilobase of 5'-flanking sequence from the HCG alpha gene, or just the 36-bp tandem repeat cAMP response element, when coupled to an enhancerless promoter, both exhibit a vigorous cAMP stimulation of expression but no response to phorbol ester in JEG-3 cells. Cotransfection with plasmids encoding PKI(1-31) inhibits both basal and cAMP-stimulated expression in a parallel fashion. The 5'-flanking sequence of the human enkephalin gene mediates cAMP-stimulated expression of reporter genes in both JEG-3 and CV-1 cells. Plasmids encoding PKI(1-31) inhibit the expression that is stimulated by the addition of cAMP analogs in both cell lines; basal expression, however, is inhibited by PKI(1-31) only in the JEG-3 cell line and not in the CV-1 cells. These observations indicate that, in JEG-3 cells, PKI(1-31) is a specific inhibitor of kinase A-mediated gene transcription, but it does not modify kinase C-directed transcription.(ABSTRACT TRUNCATED AT 400 WORDS)

Short-Term Chromospheric Variability in alpha Tauri (K5 III): Results from IUE Time Series Observations

NASA Technical Reports Server (NTRS)

Cuntz, Manfred; Deeney, Bryan D.; Brown, Alexander; Stencel, Robert E.

1996-01-01

We evaluate time series observations of chromospheric lines (Mg II, Mg I, and C II) for the K giant alpha Tau obtained using the IUE LWP camera at high dispersion. These observations cover a time span of about 2 weeks in 1994 February-March and were designed to resolve variations occurring within hours, days, and weeks. We consider the observational results in relation to theoretical acoustic heating models, motivated by the fact that alpha Tau may exhibit a basal (i.e., minimum) level of chromospheric activity. The data reveal flux variations between the extremes of 8% in Mg II h+k and 15% in each emission component. These variations occur on timescales as short as 8 hr but not on timescales longer than approx.3 days. For the h and k components, flux variations occurring on a timescale as short as 1.5 hr are also found. These changes are often not correlated (and are sometimes even anticorrelated), leading to remarkable differences in the h/k ratios. We argue that these results are consistent with the presence of strong acoustic shocks, which can lead to variable Mg II line emission when only a small number of strong shocks are propagating through the atmosphere. We deduce the electron density in the C II lambda 2325 line formation region to be log(base e) of N. approx. equals 9.0, in agreement with previous studies. Our data provide evidence that the Mg II basal flux limit for K giants might be a factor of 4 higher than suggested by Rutten et al.

Study of the pelvic floor muscles in vaginismus: a concept of pathogenesis.

PubMed

Shafik, Ahmed; El-Sibai, Olfat

2002-10-10

Neither the cause of vaginismus nor the muscles involved are precisely identified. To define the involved muscles and their role in the pathogenesis of vaginismus. The EMG activity of the levator ani (LA), puborectalis (PR) and bulbocavernosus (BC) muscles was studied in seven female patients (age (years): 25.6(mean)+/-1.2(S.D.)) and seven healthy volunteers who matched the patients in age. Recordings were performed at rest and during induction of vaginismus by a vaginal dilator. Upon approximating the vaginal dilator to the vaginal introitus or introducing it into the vagina of the healthy volunteers, the EMG activity of the LA, PR and BC muscles showed no significant difference from the basal activity. In the patients, the basal EMG activity of the examined muscles was significantly higher than that of the healthy volunteers (P<0.05). Upon vaginismus induction, the muscles showed a significant increase of the EMG activity (P<0.01). The latency recorded a mean of 14.2+/-2.3, 13.9+/-2.3 and 14.1+/-2.2ms (P>0.05) in the LA, PR and BC muscles, respectively. The muscle response was momentary lasting a mean of 31.2+/-5.7s. It was reproducible provided an off-time of a mean of 13.2+/-2.3s was observed. The pelvic floor muscles of vaginismus patients exhibited increased EMG activity at rest and on vaginismus induction; the cause is unknown. The concept of a disordered sacral reflex arc is put forward but needs further studies to be verified.

Temperature regulation and metabolism of an Australian bat, Chalinolobus gouldii (Chiroptera:Vespertilionidae) when euthermic and torpid.

PubMed

Hosken, D J; Withers, P C

1997-01-01

The thermal and metabolic physiology of Chalinolobus gouldii, an Australian vespertilionid bat, was studied in the laboratory using flow-through respirometry. Chalinolobus gouldii exhibits a clear pattern of euthermic thermoregulation, typical of endotherms with respect to body temperature and rate of oxygen consumption. The basal metabolic rate of euthermic Chalinolobus gouldii is approximately 86% of that predicted for a 17.5-g mammal and falls into the range of mass-specific basal metabolic rates ascribed to vespertilionid bats. However, like most vespertilionid bats, Chalinolobus gouldii displays extreme thermolability. It is able to enter into torpor and spontaneously arouse at ambient temperatures as low as 5 degrees C. Torpid bats thermoconform at moderate ambient temperature, with body temperature approximately ambient temperature, and have a low rate of oxygen consumption determined primarily by Q10 effects. At low ambient temperature (< 10 degrees C), torpid C. gouldii begin to regulate their body temperature by increased metabolic heat production; they tend to maintain a higher body temperature at low ambient temperature than do many northern hemisphere hibernating bats. Use of torpor leads to significant energy savings. The evaporative water loss of euthermic bats is relatively high, which seems unusual for a bat whose range includes extremely arid areas of Australia, and is reduced during torpor. The thermal conductance of euthermic C. gouldii is less than that predicted for a mammal of its size. The thermal conductance is considerably lower for torpid bats at intermediate body temperature and ambient temperature, but increases to euthermic values for torpid bats when thermoregulating at low ambient temperature.

Defective ciliogenesis in thyroid hürthle cell tumors is associated with increased autophagy

PubMed Central

Lee, Junguee; Yi, Shinae; Kang, Yea Eun; Chang, Joon Young; Kim, Jung Tae; Sul, Hae Joung; Kim, Jong Ok; Kim, Jin Man; Kim, Joon; Porcelli, Anna Maria; Kim, Koon Soon; Shong, Minho

2016-01-01

Primary cilia are found in the apical membrane of thyrocytes, where they may play a role in the maintenance of follicular homeostasis. In this study, we examined the distribution of primary cilia in the human thyroid cancer to address the involvement of abnormal ciliogenesis in different thyroid cancers. We examined 92 human thyroid tissues, including nodular hyperplasia, Hashimoto's thyroiditis, follicular tumor, Hürthle cell tumor, and papillary carcinoma to observe the distribution of primary cilia. The distribution and length of primary cilia facing the follicular lumen were uniform across variable-sized follicles in the normal thyroid gland. However, most Hürthle cells found in benign and malignant thyroid diseases were devoid of primary cilia. Conventional variant of papillary carcinoma (PTC) displayed longer primary cilia than those of healthy tissue, whereas both the frequency and length of primary cilia were decreased in oncocytic variant of PTC. In addition, ciliogenesis was markedly defective in primary Hürthle cell tumors, including Hürthle cell adenomas and carcinomas, which showed higher level of autophagosome biogenesis. Remarkably, inhibition of autophagosome formation by Atg5 silencing or treatment with pharmacological inhibitors of autophagosome formation restored ciliogenesis in the Hürthle cell carcinoma cell line XTC.UC1 which exhibits a high basal autophagic flux. Moreover, the inhibition of autophagy promoted the accumulation of two factors critical for ciliogenesis, IFT88 and ARL13B. These results suggest that abnormal ciliogenesis, a common feature of Hürthle cells in diseased thyroid glands, is associated with increased basal autophagy. PMID:27816963

Expression profile of desiccation tolerance factors in intertidal seaweed species during the tidal cycle.

PubMed

Fierro, Camila; López-Cristoffanini, Camilo; Meynard, Andrés; Lovazzano, Carlos; Castañeda, Francisco; Guajardo, Eduardo; Contreras-Porcia, Loretto

2017-06-01

The transcriptional modulation of desiccation tolerance factors in P. orbicularis explains its successful recuperation after water deficit. Differential responses to air exposure clarify seaweed distribution along intertidal rocky zones. Desiccation-tolerant seaweed species, such as Pyropia orbicularis, can tolerate near 96% water loss during air exposure. To understand the phenotypic plasticity of P. orbicularis to desiccation, several tolerance factors were assessed by RT-qPCR, Western-blot analysis, and enzymatic assays during the natural desiccation-rehydration cycle. Comparative enzymatic analyses were used to evidence differential responses between P. orbicularis and desiccation-sensitive species. The results showed that during desiccation, the relative mRNA levels of genes associated with basal metabolism [trehalose phosphate synthase (tps) and pyruvate dehydrogenase (pdh)] were overexpressed in P. orbicularis. Transcript levels related to antioxidant metabolism [peroxiredoxin (prx); thioredoxin (trx); catalase (cat); lipoxygenase (lox); ferredoxin (fnr); glutathione S-transferase (gst)], cellular detoxification [ABC transporter (abc) and ubiquitin (ubq)], and signal transduction [calmodulin (cam)] increased approximately 15- to 20-fold, with the majority returning to basal levels during the final hours of rehydration. In contrast, actin (act) and transcription factor 1 (tf1) transcripts were down-regulated. ABC transporter protein levels increased in P. orbicularis during desiccation, whereas PRX transcripts decreased. The antioxidant enzymes showed higher specific activity in P. orbicularis under desiccation, and sensitive species exhibited enzymatic inactivation and scarce ABC and PRX protein detection following prolonged desiccation. In conclusion, the reported findings contribute towards understanding the ecological distribution of intertidal seaweeds at the molecular and functional levels.

Anxiety response and restraint-induced stress differentially affect ethanol intake in female adolescent rats.

PubMed

Acevedo, María Belén; Fabio, Maria Carolina; Fernández, Macarena Soledad; Pautassi, Ricardo Marcos

2016-10-15

Anxiety disorders are more likely to occur in women than in men, usually emerge during adolescence and exhibit high comorbidity with alcohol use disorders (AUD). Adolescents with high levels of anxiety or heightened reactivity to stress may be at-risk for developing AUD. An approach to analyze if high levels of inborn anxiety predict greater ethanol drinking is to assess the latter variable in subjects classified as high- or low-anxiety responders. The present study assessed ethanol drinking in adolescent, female Wistar, rats classified as high-, low- or average-anxiety responders and exposed or not to restraint stress (RS, Exp. 1). Classification was made through a multivariate index derived from testing anxiety responses in an elevated plus maze and a light-dark box tests. RS was applied after animals had been initiated to ethanol drinking. Intake of sweetened ethanol was unaffected by level of anxiety response. Adolescents with high levels of inborn anxiety exhibited significantly higher intake of unsweetened ethanol than counterparts with standard levels of anxiety, yet this effect was inhibited by RS exposure. Experiment 2 assessed FOS immunoreactivity after RS. Stress induced a significant increase in FOS immunoreactivity at the paraventricular nucleus, yet this effect was unaffected by level of anxiety response. Female adolescents with high levels of basal anxiety may be at-risk for exhibiting increased predisposition for ethanol intake and preference. The study also indicates that stress may exert differential effects on adolescent ethanol intake as a function of the level of anxiety response. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Steroid intracochlear distribution differs by administration method: Systemic versus intratympanic injection.

PubMed

Lee, Jong Joo; Jang, Jeong Hun; Choo, Oak-Sung; Lim, Hye Jin; Choung, Yun-Hoon

2018-01-01

Steroids have been widely used to treat inner-ear diseases such as sudden sensorineural hearing loss, tinnitus, and Meniere's disease. They can be given via either systemic or intratympanic (IT) injection. The purpose of the present study was to explore differences in intracochlear steroid distribution by the administration method employed (systemic vs. IT injection). Animal study. Twenty-three Sprague-Dawley rats were given fluorescein isothiocyanate-labeled dexamethasone (FITC-DEX) three times (on successive days) via intraperitoneal (IP) or IT injection. Cochlear uptake of FITC-DEX was evaluated via immunohistochemistry and flow cytometry at 6 hours, and 3 and 7 days after the final injection. FITC-DEX uptake was evident in spiral ganglion cells (SGs), the organ of Corti (OC), and the lateral walls (LWs), the basal turns of which were stained relatively prominently in both groups. Animals receiving IP injections exhibited higher FITC-DEX uptakes by the SGs and OC, whereas IT injection triggered higher-level FITC-DEX accumulation by the OC and LWs. Flow cytometry revealed that intracochlear FITC-DEX uptake by IT-injected animals was higher and more prolonged than in animals subjected to IP injections. We thus describe differences in cochlear steroid distributions after systemic and IT injections. This finding could help our understanding of the pharmacokinetics of steroids in the cochlea. NA. Laryngoscope, 128:189-194, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Synaptotagmin 4 Regulates Pancreatic β Cell Maturation by Modulating the Ca2+ Sensitivity of Insulin Secretion Vesicles.

PubMed

Huang, Chen; Walker, Emily M; Dadi, Prasanna K; Hu, Ruiying; Xu, Yanwen; Zhang, Wenjian; Sanavia, Tiziana; Mun, Jisoo; Liu, Jennifer; Nair, Gopika G; Tan, Hwee Yim Angeline; Wang, Sui; Magnuson, Mark A; Stoeckert, Christian J; Hebrok, Matthias; Gannon, Maureen; Han, Weiping; Stein, Roland; Jacobson, David A; Gu, Guoqiang

2018-05-07

Islet β cells from newborn mammals exhibit high basal insulin secretion and poor glucose-stimulated insulin secretion (GSIS). Here we show that β cells of newborns secrete more insulin than adults in response to similar intracellular Ca 2+ concentrations, suggesting differences in the Ca 2+ sensitivity of insulin secretion. Synaptotagmin 4 (Syt4), a non-Ca 2+ binding paralog of the β cell Ca 2+ sensor Syt7, increased by ∼8-fold during β cell maturation. Syt4 ablation increased basal insulin secretion and compromised GSIS. Precocious Syt4 expression repressed basal insulin secretion but also impaired islet morphogenesis and GSIS. Syt4 was localized on insulin granules and Syt4 levels inversely related to the number of readily releasable vesicles. Thus, transcriptional regulation of Syt4 affects insulin secretion; Syt4 expression is regulated in part by Myt transcription factors, which repress Syt4 transcription. Finally, human SYT4 regulated GSIS in EndoC-βH1 cells, a human β cell line. These findings reveal the role that altered Ca 2+ sensing plays in regulating β cell maturation. Copyright © 2018 Elsevier Inc. All rights reserved.

Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by beta-amyloid25-35 injection into Meynert basal nuclei of rats).

PubMed

Ostrovskaya, R U; Belnik, A P; Storozheva, Z I

2008-07-01

Experiments on adult Wistar rats showed that injection of beta-amyloid25-35 (2 microg) into Meynert basal nuclei caused long-term memory deficiency which was detected 24 days after this injection by the memory trace retrieval in conditioned passive avoidance reflex (CPAR). The effects of noopept, an original nootropic and neuroprotective dipeptide, on the severity of this cognitive deficiency were studied. Preventive (for 7 days before the injury) intraperitoneal injections of noopept in a dose of 0.5 mg/kg completely prevented mnestic disorders under conditions of this model. Noopept exhibited a significant normalizing effect, if the treatment was started 15 days after the injury, when neurodegenerative changes in the basal nuclei, cortex, and hippocampus were still acutely pronounced. The mechanisms of this effect of the drug are studied, including, in addition to the choline-positive effect, its multicomponent neuroprotective effect and stimulation of production of antibodies to beta-amyloid25-35. Noopept efficiency in many models of Alzheimer disease, its high bioavailability and low toxicity suggest this dipeptide for further studies as a potential agent for the treatment of this condition (initial and moderate phases).

Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model

PubMed Central

Lockrow, Jason; Prakasam, Annamalai; Huang, Peng; Bimonte-Nelson, Heather; Sambamurti, Kumar; Granholm, Ann-Charlotte

2009-01-01

Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated oxidative stress in Ts65Dn mice, and assessed the efficacy of long-term antioxidant supplementation on memory and basal forebrain pathology. We report that oxidative stress was elevated in the adult Ts65Dn brain, and that supplementation with the antioxidant vitamin E effectively reduced these markers. Also, Ts65Dn mice receiving vitamin E exhibited improved performance on a spatial working memory task and showed an attenuation of cholinergic neuron pathology in the basal forebrain. This study provides evidence that vitamin E delays onset of cognitive and morphological abnormalities in a mouse model of DS, and may represent a safe and effective treatment early in the progression of DS neuropathology. PMID:19135442

Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium

PubMed Central

Hong, Kyung U.; Reynolds, Susan D.; Watkins, Simon; Fuchs, Elaine; Stripp, Barry R.

2004-01-01

Commitment of the pulmonary epithelium to bronchial and bronchiolar airway lineages occurs during the transition from pseudoglandular to cannalicular phases of lung development, suggesting that regional differences exist with respect to the identity of stem and progenitor cells that contribute to epithelial maintenance in adulthood. We previously defined a critical role for Clara cell secretory protein-expressing (CE) cells in renewal of bronchiolar airway epithelium following injury. Even though CE cells are also the principal progenitor for maintenance of the bronchial airway epithelium, CE cell injury is resolved through a mechanism involving recruitment of a second progenitor cell population that we now identify as a GSI-B4 reactive, cytokeratin-14-expressing basal cell. These cells exhibit multipotent differentiation capacity as assessed by analysis of cellular phenotype within clones of LacZ-tagged cells. Clones were derived from K14-expressing cells tagged in a cell-type-specific fashion by ligand-regulable Cre recombinase-mediated genomic rearrangement of the ROSA26 recombination substrate allele. We conclude that basal cells represent an alternative multipotent progenitor cell population of bronchial airways and that progenitor cell selection is dictated by the type of airway injury. PMID:14742263

The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression.

PubMed

Heuchel, R; Radtke, F; Georgiev, O; Stark, G; Aguet, M; Schaffner, W

1994-06-15

We have described and cloned previously a factor (MTF-1) that binds specifically to heavy metal-responsive DNA sequence elements in the enhancer/promoter region of metallothionein genes. MTF-1 is a protein of 72.5 kDa that contains six zinc fingers and multiple domains for transcriptional activation. Here we report the disruption of both alleles of the MTF-1 gene in mouse embryonic stem cells by homologous recombination. The resulting null mutant cell line fails to produce detectable amounts of MTF-1. Moreover, due to the loss of MTF-1, the endogenous metallothionein I and II genes are silent, indicating that MTF-1 is required for both their basal and zinc-induced transcription. In addition to zinc, other heavy metals, including cadmium, copper, nickel and lead, also fail to activate metal-responsive promoters in null mutant cells. However, cotransfection of an MTF-1 expression vector and metal-responsive reporter genes yields strong basal transcription that can be further boosted by zinc treatment of cells. These results demonstrate that MTF-1 is essential for metallothionein gene regulation. Finally, we present evidence that MTF-1 itself is a zinc sensor, which exhibits increased DNA binding activity upon zinc treatment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cornford, S. L.; Martin, D. F.; Lee, V.

At least in conventional hydrostatic ice-sheet models, the numerical error associated with grounding line dynamics can be reduced by modifications to the discretization scheme. These involve altering the integration formulae for the basal traction and/or driving stress close to the grounding line and exhibit lower – if still first-order – error in the MISMIP3d experiments. MISMIP3d may not represent the variety of real ice streams, in that it lacks strong lateral stresses, and imposes a large basal traction at the grounding line. We study resolution sensitivity in the context of extreme forcing simulations of the entire Antarctic ice sheet, using the BISICLES adaptive mesh ice-sheet model with two schemes: the original treatment, and a scheme, which modifies the discretization of the basal traction. The second scheme does indeed improve accuracy – by around a factor of two – for a given mesh spacing, butmore » $$\\lesssim 1$$ km resolution is still necessary. For example, in coarser resolution simulations Thwaites Glacier retreats so slowly that other ice streams divert its trunk. In contrast, with $$\\lesssim 1$$ km meshes, the same glacier retreats far more quickly and triggers the final phase of West Antarctic collapse a century before any such diversion can take place.« less

Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quoilin, C., E-mail: cquoilin@ulg.ac.be; Mouithys-Mickalad, A.; Duranteau, J.

Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonancemore » spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.« less

Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia

PubMed Central

Foster, K. Wade; Liu, Zhaoli; Nail, Clinton D.; Li, Xingnan; Fitzgerald, Thomas J.; Bailey, Sarah K.; Frost, Andra R.; Louro, Iuri D.; Townes, Tim M.; Paterson, Andrew J.; Kudlow, Jeffrey E.; Lobo-Ruppert, Susan M.; Ruppert, J. Michael

2006-01-01

KLF4/GKLF normally functions in differentiating epithelial cells, but also acts as a transforming oncogene in vitro. To examine the role of this zinc finger protein in skin, we expressed the wild-type human allele from inducible and constitutive promoters. When induced in basal keratinocytes KLF4 rapidly abolished the distinctive properties of basal and parabasal epithelial cells. KLF4 caused a transitory apoptotic response and the skin progressed through phases of hyperplasia and dysplasia. By 6 weeks, lesions exhibited nuclear KLF4 and other morphologic and molecular similarities to squamous cell carcinoma in situ. p53 determined the patch size sufficient to establish lesions, as induction in a mosaic pattern produced skin lesions only when p53 was deficient. Compared with p53 wild-type animals, p53 hemizygous animals had early onset of lesions and a pronounced fibrovascular response that included outgrowth of subcutaneous sarcoma. A KLF4-estrogen receptor fusion protein showed tamoxifen-dependent nuclear localization and conditional transformation in vitro. The results suggest that KLF4 can function in the nucleus to induce squamous epithelial dysplasia, and indicate roles for p53 and epithelial-mesenchymal signaling in these early neoplastic lesions. PMID:15674344

Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia.

PubMed

Foster, K Wade; Liu, Zhaoli; Nail, Clinton D; Li, Xingnan; Fitzgerald, Thomas J; Bailey, Sarah K; Frost, Andra R; Louro, Iuri D; Townes, Tim M; Paterson, Andrew J; Kudlow, Jeffrey E; Lobo-Ruppert, Susan M; Ruppert, J Michael

2005-02-24

KLF4/GKLF normally functions in differentiating epithelial cells, but also acts as a transforming oncogene in vitro. To examine the role of this zinc finger protein in skin, we expressed the wild-type human allele from inducible and constitutive promoters. When induced in basal keratinocytes, KLF4 rapidly abolished the distinctive properties of basal and parabasal epithelial cells. KLF4 caused a transitory apoptotic response and the skin progressed through phases of hyperplasia and dysplasia. By 6 weeks, lesions exhibited nuclear KLF4 and other morphologic and molecular similarities to squamous cell carcinoma in situ. p53 determined the patch size sufficient to establish lesions, as induction in a mosaic pattern produced skin lesions only when p53 was deficient. Compared with p53 wild-type animals, p53 hemizygous animals had early onset of lesions and a pronounced fibrovascular response that included outgrowth of subcutaneous sarcoma. A KLF4-estrogen receptor fusion protein showed tamoxifen-dependent nuclear localization and conditional transformation in vitro. The results suggest that KLF4 can function in the nucleus to induce squamous epithelial dysplasia, and indicate roles for p53 and epithelial-mesenchymal signaling in these early neoplastic lesions.

Cost-effectiveness of liraglutide versus lixisenatide as add-on therapies to basal insulin in type 2 diabetes

PubMed Central

2018-01-01

Background We assessed the cost-effectiveness of the glucagon-like peptide 1 receptor agonists liraglutide 1.8 mg and lixisenatide 20 μg (both added to basal insulin) in patients with type 2 diabetes (T2D) in Sweden. Methods The Swedish Institute for Health Economics cohort model for T2D was used to compare liraglutide and lixisenatide (both added to basal insulin), with a societal perspective and with comparative treatment effects derived by indirect treatment comparison (ITC). Drug prices were 2016 values, and all other costs 2015 values. The cost-effectiveness of IDegLira (fixed-ratio combination of insulin degludec and liraglutide) versus lixisenatide plus basal insulin was also assessed, under different sets of assumptions. Results From the ITC, decreases in HbA1c were –1.32% and –0.43% with liraglutide and lixisenatide, respectively; decreases in BMI were –1.29 and –0.65 kg/m2, respectively. An estimated 2348 cases of retinopathy, 265 of neuropathy and 991 of nephropathy would be avoided with liraglutide compared with lixisenatide in a cohort of 10,000 patients aged over 40 years. In the base-case analysis, total direct costs were higher with liraglutide than lixisenatide, but costs associated with complications were lower. The cost/quality-adjusted life-year (QALY) for liraglutide added to basal insulin was SEK30,802. Base-case findings were robust in sensitivity analyses, except when glycated haemoglobin (HbA1c) differences for liraglutide added to basal insulin were abolished, suggesting these benefits were driving the cost/QALY. With liraglutide 1.2 mg instead of liraglutide 1.8 mg (adjusted for efficacy and cost), liraglutide added to basal insulin was dominant over lixisenatide 20μg.IDegLira was dominant versus lixisenatide plus basal insulin when a defined daily dose was used in the model. Conclusions The costs/QALY for liraglutide, 1.8 or 1.2 mg, added to basal insulin, and for IDegLira (all compared with lixisenatide 20 μg added to basal insulin) were below the threshold considered low by Swedish authorities. In some scenarios, liraglutide and IDegLira were cost-saving. PMID:29408938

Potential long-term effects of MDMA on the basal ganglia-thalamocortical circuit: a proton MR spectroscopy and diffusion-tensor imaging study.

PubMed

Liu, Hua-Shan; Chou, Ming-Chung; Chung, Hsiao-Wen; Cho, Nai-Yu; Chiang, Shih-Wei; Wang, Chao-Ying; Kao, Hung-Wen; Huang, Guo-Shu; Chen, Cheng-Yu

2011-08-01

To investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA, commonly known as "ecstasy") on the alterations of brain metabolites and anatomic tissue integrity related to the function of the basal ganglia-thalamocortical circuit by using proton magnetic resonance (MR) spectroscopy and diffusion-tensor MR imaging. This study was approved by a local institutional review board, and written informed consent was obtained from all subjects. Thirty-one long-term (>1 year) MDMA users and 33 healthy subjects were enrolled. Proton MR spectroscopy from the middle frontal cortex and bilateral basal ganglia and whole-brain diffusion-tensor MR imaging were performed with a 3.0-T system. Absolute concentrations of metabolites were computed, and diffusion-tensor data were registered to the International Consortium for Brain Mapping template to facilitate voxel-based group comparison. The mean myo-inositol level in the basal ganglia of MDMA users (left: 4.55 mmol/L ± 2.01 [standard deviation], right: 4.48 mmol/L ± 1.33) was significantly higher than that in control subjects (left: 3.25 mmol/L ± 1.30, right: 3.31 mmol/L ± 1.19) (P < .001). Cumulative lifetime MDMA dose showed a positive correlation with the levels of choline-containing compounds (Cho) in the right basal ganglia (r = 0.47, P = .02). MDMA users also showed a significant increase in fractional anisotropy (FA) in the bilateral thalami and significant changes in water diffusion in several regions related to the basal ganglia-thalamocortical circuit as compared with control subjects (P < .05; cluster size, >50 voxels). Increased myo-inositol and Cho concentrations in the basal ganglia of MDMA users are suggestive of glial response to degenerating serotonergic functions. The abnormal metabolic changes in the basal ganglia may consequently affect the inhibitory effect of the basal ganglia to the thalamus, as suggested by the increased FA in the thalamus and abnormal changes in water diffusion in the corresponding basal ganglia-thalamocortical circuit. © RSNA, 2011.

Cost-effectiveness of liraglutide versus lixisenatide as add-on therapies to basal insulin in type 2 diabetes.

PubMed

Ericsson, Åsa; Glah, Divina; Lorenzi, Maria; Jansen, Jeroen P; Fridhammar, Adam

2018-01-01

We assessed the cost-effectiveness of the glucagon-like peptide 1 receptor agonists liraglutide 1.8 mg and lixisenatide 20 μg (both added to basal insulin) in patients with type 2 diabetes (T2D) in Sweden. The Swedish Institute for Health Economics cohort model for T2D was used to compare liraglutide and lixisenatide (both added to basal insulin), with a societal perspective and with comparative treatment effects derived by indirect treatment comparison (ITC). Drug prices were 2016 values, and all other costs 2015 values. The cost-effectiveness of IDegLira (fixed-ratio combination of insulin degludec and liraglutide) versus lixisenatide plus basal insulin was also assessed, under different sets of assumptions. From the ITC, decreases in HbA1c were -1.32% and -0.43% with liraglutide and lixisenatide, respectively; decreases in BMI were -1.29 and -0.65 kg/m2, respectively. An estimated 2348 cases of retinopathy, 265 of neuropathy and 991 of nephropathy would be avoided with liraglutide compared with lixisenatide in a cohort of 10,000 patients aged over 40 years. In the base-case analysis, total direct costs were higher with liraglutide than lixisenatide, but costs associated with complications were lower. The cost/quality-adjusted life-year (QALY) for liraglutide added to basal insulin was SEK30,802. Base-case findings were robust in sensitivity analyses, except when glycated haemoglobin (HbA1c) differences for liraglutide added to basal insulin were abolished, suggesting these benefits were driving the cost/QALY. With liraglutide 1.2 mg instead of liraglutide 1.8 mg (adjusted for efficacy and cost), liraglutide added to basal insulin was dominant over lixisenatide 20μg.IDegLira was dominant versus lixisenatide plus basal insulin when a defined daily dose was used in the model. The costs/QALY for liraglutide, 1.8 or 1.2 mg, added to basal insulin, and for IDegLira (all compared with lixisenatide 20 μg added to basal insulin) were below the threshold considered low by Swedish authorities. In some scenarios, liraglutide and IDegLira were cost-saving.

CYP1A1 and CYP1A2 expression: Comparing ‘humanized’ mouse lines and wild-type mice; comparing human and mouse hepatoma-derived cell lines

PubMed Central

Uno, Shigeyuki; Endo, Kaori; Ishida, Yuji; Tateno, Chise; Makishima, Makoto; Yoshizato, Katsutoshi; Nebert, Daniel W.

2009-01-01

Human and rodent cytochrome P450 (CYP) enzymes sometimes exhibit striking species-specific differences in substrate preference and rate of metabolism. Human risk assessment of CYP substrates might therefore best be evaluated in the intact mouse by replacing mouse Cyp genes with human CYP orthologs; however, how “human-like” can human gene expression be expected in mouse tissues? Previously a bacterial-artificial-chromosome-transgenic mouse, carrying the human CYP1A1_CYP1A2 locus and lacking the mouse Cyp1a1 and Cyp1a2 orthologs, was shown to express robustly human dioxin-inducible CYP1A1 and basal versus inducible CYP1A2 (mRNAs, proteins, enzyme activities) in each of nine mouse tissues examined. Chimeric mice carrying humanized liver have also been generated, by transplanting human hepatocytes into a urokinase-type plasminogen activator(+/+)_severe-combined-immunodeficiency (uPA/SCID) line with most of its mouse hepatocytes ablated. Herein we compare basal and dioxin-induced CYP1A mRNA copy numbers, protein levels, and four enzymes (benzo[a]pyrene hydroxylase, ethoxyresorufin O-deethylase, acetanilide 4-hydroxylase, methoxyresorufin O-demethylase) in liver of these two humanized mouse lines versus wild-type mice; we also compare these same parameters in mouse Hepa-1c1c7 and human HepG2 hepatoma-derived established cell lines. Most strikingly, mouse liver CYP1A1-specific enzyme activities are between 38- and 170-fold higher than human CYP1A1-specific enzyme activities (per unit of mRNA), whereas mouse versus human CYP1A2 enzyme activities (per unit of mRNA) are within 2.5-fold of one another. Moreover, both the mouse and human hepatoma cell lines exhibit striking differences in CYP1A mRNA levels and enzyme activities. These findings are relevant to risk assessment involving human CYP1A1 and CYP1A2 substrates, when administered to mice as environmental toxicants or drugs. PMID:19285097

CYP1A1 and CYP1A2 expression: Comparing 'humanized' mouse lines and wild-type mice; comparing human and mouse hepatoma-derived cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uno, Shigeyuki; Endo, Kaori; Ishida, Yuji

2009-05-15

Human and rodent cytochrome P450 (CYP) enzymes sometimes exhibit striking species-specific differences in substrate preference and rate of metabolism. Human risk assessment of CYP substrates might therefore best be evaluated in the intact mouse by replacing mouse Cyp genes with human CYP orthologs; however, how 'human-like' can human gene expression be expected in mouse tissues? Previously a bacterial-artificial-chromosome-transgenic mouse, carrying the human CYP1A1{sub C}YP1A2 locus and lacking the mouse Cyp1a1 and Cyp1a2 orthologs, was shown to express robustly human dioxin-inducible CYP1A1 and basal versus inducible CYP1A2 (mRNAs, proteins, enzyme activities) in each of nine mouse tissues examined. Chimeric mice carryingmore » humanized liver have also been generated, by transplanting human hepatocytes into a urokinase-type plasminogen activator(+/+){sub s}evere-combined-immunodeficiency (uPA/SCID) line with most of its mouse hepatocytes ablated. Herein we compare basal and dioxin-induced CYP1A mRNA copy numbers, protein levels, and four enzymes (benzo[a]pyrene hydroxylase, ethoxyresorufin O-deethylase, acetanilide 4-hydroxylase, methoxyresorufin O-demethylase) in liver of these two humanized mouse lines versus wild-type mice; we also compare these same parameters in mouse Hepa-1c1c7 and human HepG2 hepatoma-derived established cell lines. Most strikingly, mouse liver CYP1A1-specific enzyme activities are between 38- and 170-fold higher than human CYP1A1-specific enzyme activities (per unit of mRNA), whereas mouse versus human CYP1A2 enzyme activities (per unit of mRNA) are within 2.5-fold of one another. Moreover, both the mouse and human hepatoma cell lines exhibit striking differences in CYP1A mRNA levels and enzyme activities. These findings are relevant to risk assessment involving human CYP1A1 and CYP1A2 substrates, when administered to mice as environmental toxicants or drugs.« less

Dermatoscopy-guided therapy of pigmented basal cell carcinoma with imiquimod*

PubMed Central

Husein-ElAhmed, Husein; Fernandez-Pugnaire, Maria Antonia

2016-01-01

BACKGROUND Dermatoscopy is a non-invasive diagnostic tool used to examine skin lesions with an optical magnification. It has been suggested as a useful tool for monitoring therapeutic response in lentigo maligna patients treated with imiquimod. OBJECTIVE To examine the accuracy of dermatoscopy as a tool to monitor the therapeutic response of pigmented basal cell carcinoma treated with imiquimod. METHOD The authors designed a prospective study. Patients with pigmented basal cell carcinoma were included and data regarding the dermatoscopy features were collected following the Menzies criteria, prior to initiating the imiquimod treatment. Subsequent dermatoscopic evaluations were performed at weeks 4 and 8, following imiquimod discontinuation. RESULTS Twenty lesions were included. The most common pigmented dermatoscopy features were large blue-grey ovoid nests (80%), followed by blue-grey globules (50%) and leaf-like areas (30%). No spoke wheel areas were observed. In 17 out of 20 patients, a response was noted during the first evaluation at 4 weeks, while the clearance was noted at the second check-up after 8 weeks. In two patients, the clearance was found at the initial evaluation at 4 weeks, while in one patient, the response remained unchanged. Blue-grey globules were the fastest to exhibit clearance (50% at week 4), followed by leaf-like areas (15%) and large blue-grey ovoid nests (6.25%). CONCLUSION According to our results, dermatoscopic evaluation enhances the accuracy in the assessment of the clinical response to imiquimod in pigmented basal cell carcinoma. PMID:28099598

Brain correlates of constituent structure in sign language comprehension.

PubMed

Moreno, Antonio; Limousin, Fanny; Dehaene, Stanislas; Pallier, Christophe

2018-02-15

During sentence processing, areas of the left superior temporal sulcus, inferior frontal gyrus and left basal ganglia exhibit a systematic increase in brain activity as a function of constituent size, suggesting their involvement in the computation of syntactic and semantic structures. Here, we asked whether these areas play a universal role in language and therefore contribute to the processing of non-spoken sign language. Congenitally deaf adults who acquired French sign language as a first language and written French as a second language were scanned while watching sequences of signs in which the size of syntactic constituents was manipulated. An effect of constituent size was found in the basal ganglia, including the head of the caudate and the putamen. A smaller effect was also detected in temporal and frontal regions previously shown to be sensitive to constituent size in written language in hearing French subjects (Pallier et al., 2011). When the deaf participants read sentences versus word lists, the same network of language areas was observed. While reading and sign language processing yielded identical effects of linguistic structure in the basal ganglia, the effect of structure was stronger in all cortical language areas for written language relative to sign language. Furthermore, cortical activity was partially modulated by age of acquisition and reading proficiency. Our results stress the important role of the basal ganglia, within the language network, in the representation of the constituent structure of language, regardless of the input modality. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Inoculation of Acacia senegal mature trees with Mycorrhiza and Rhizobia on soil properties and microbial community structure

NASA Astrophysics Data System (ADS)

Assigbetsé, K.; Ciss, I.; Bakhoum, N.; Dieng, L.

2012-04-01

Inoculation of legume plants with symbiotic microorganisms is widely used to improve their development and productivity. The objective of this study was to investigate the effect of inoculation of Acacia senegal mature trees with rhizobium (Sinorhizobium) and arbuscular mycorrhizal fungus (G. mosseae, G. fasciculatum, G. intraradices) either singly or in combination, on soil properties, activity and the genetic structure of soil microbial communities. The experiment set up in Southern Senegal consisted of 4 randomized blocks of A. senegal mature trees with 4 treatments including inoculated trees with Rhizobium (R), mycorrhizal fungus (M) and with Rhizobium+mycorhizal fungus (RM) and non-inoculated control (CON). Soil were sampled 2 years after the inoculation. Soil pH, C and N and available P contents were measured. The microbial abundance and activity were measured in terms of microbial biomass C (MBC) and basal soil respiration. The community structure of the total bacterial, diazotrophic and denitrifying communities was assessed by denaturing gradient gel electrophoresis of 16S rDNA, nifH and nirK genes respectively. Inoculations with symbiont under field conditions have increased soil pH. The C and N contents were enhanced in the dual-inoculated treatments (RM). The mycorrhized treatment have displayed the lowest available P contents while RM and R treatments exhibited higher contents rates. The microbial biomass C rates were higher in treatments co-inoculated with AM fungi and Rhizobium than in those inoculated singly with AM fungi or Rhizobium strains. The basal soil respiration were positively correlated to MBC, and the highest rates were found in the co-inoculated treatments. Fingerprints of 16S rDNA gene exhibited similar patterns between inoculated treatments and the control showing that the inoculation of mature trees have not impacted the total bacterial community structure. In contrast, the inoculated treatments have displayed individually different diazotrophic and denitrifying communities fingerprints, indicating that the inoculation with microsymbionts have modified the genetic structure of the two functional communities in soil. Further, the diazotrophic community richness was reduced over the control indicating the impact of the addition of symbionts on the free-living N2-fixing bacterial (nifH) diversity. This study shows that inoculation of A. senegal mature trees with rhizobium and arbuscular mycorrhizal fungus has enhanced soil biofunctioning and modified the genetic structure of microbial community involved in N-cycling. Combined inoculation of AM fungi and Rhizobium have improved these effects on chemical characteristics, microbial community abundance and activity demonstrating synergism between the two microsymbionts.

Probing the Surface Charge on the Basal Planes of Kaolinite Particles with High-Resolution Atomic Force Microscopy

PubMed Central

2017-01-01

High-resolution atomic force microscopy is used to map the surface charge on the basal planes of kaolinite nanoparticles in an ambient solution of variable pH and NaCl or CaCl2 concentration. Using DLVO theory with charge regulation, we determine from the measured force–distance curves the surface charge distribution on both the silica-like and the gibbsite-like basal plane of the kaolinite particles. We observe that both basal planes do carry charge that varies with pH and salt concentration. The silica facet was found to be negatively charged at pH 4 and above, whereas the gibbsite facet is positively charged at pH below 7 and negatively charged at pH above 7. Investigations in CaCl2 at pH 6 show that the surface charge on the gibbsite facet increases for concentration up to 10 mM CaCl2 and starts to decrease upon further increasing the salt concentration to 50 mM. The increase of surface charge at low concentration is explained by Ca2+ ion adsorption, while Cl– adsorption at higher CaCl2 concentrations partially neutralizes the surface charge. Atomic resolution imaging and density functional theory calculations corroborate these observations. They show that hydrated Ca2+ ions can spontaneously adsorb on the gibbsite facet of the kaolinite particle and form ordered surface structures, while at higher concentrations Cl– ions will co-adsorb, thereby changing the observed ordered surface structure. PMID:29140711

Probing the Surface Charge on the Basal Planes of Kaolinite Particles with High-Resolution Atomic Force Microscopy.

PubMed

Kumar, N; Andersson, M P; van den Ende, D; Mugele, F; Siretanu, I

2017-12-19

High-resolution atomic force microscopy is used to map the surface charge on the basal planes of kaolinite nanoparticles in an ambient solution of variable pH and NaCl or CaCl 2 concentration. Using DLVO theory with charge regulation, we determine from the measured force-distance curves the surface charge distribution on both the silica-like and the gibbsite-like basal plane of the kaolinite particles. We observe that both basal planes do carry charge that varies with pH and salt concentration. The silica facet was found to be negatively charged at pH 4 and above, whereas the gibbsite facet is positively charged at pH below 7 and negatively charged at pH above 7. Investigations in CaCl 2 at pH 6 show that the surface charge on the gibbsite facet increases for concentration up to 10 mM CaCl 2 and starts to decrease upon further increasing the salt concentration to 50 mM. The increase of surface charge at low concentration is explained by Ca 2+ ion adsorption, while Cl - adsorption at higher CaCl 2 concentrations partially neutralizes the surface charge. Atomic resolution imaging and density functional theory calculations corroborate these observations. They show that hydrated Ca 2+ ions can spontaneously adsorb on the gibbsite facet of the kaolinite particle and form ordered surface structures, while at higher concentrations Cl - ions will co-adsorb, thereby changing the observed ordered surface structure.

Actual Proliferating Index and p53 protein expression as prognostic marker in odontogenic cysts.

PubMed

Gadbail, A R; Chaudhary, M; Patil, S; Gawande, M

2009-10-01

The purpose of this study was to evaluate the biological aggressiveness of odontogenic keratocyst/keratocystic odontogenic tumour (KCOT), radicular cyst (RC) and dentigerous cyst (DC) by observing the actual proliferative activity of epithelium, and p53 protein expression. The actual proliferative activity was measured by Ki-67 Labelling Index and argyrophilic nucleolar organizing regions (AgNOR) count per nucleus. The p53 protein expression was also evaluated. Ki-67 positive cells were observed higher in suprabasal cell layers of KCOT with uniform distribution, a few of them were predominantly observed in basal cell layer in RC and DC. The AgNOR count was significantly higher in suprabasal cell layers of KCOT. The actual proliferative activity was noted to be higher in suprabasal cell layers of KCOT. The p53 immunolabelling was dense and scattered in basal and suprabasal cell layers in KCOT. The weakly stained p53 positive cells were observed diffusely distributed in KCOT, whereas they were mainly seen in basal cell layer of RC and DC. The quantitative and qualitative differences of the proliferative activity and the p53 protein expression in sporadic KCOT may be associated with intrinsic growth potential that could play a role in its development and explain locally aggressive biological behaviour. AgNOR count and p53 protein detection in odontogenic lesions can be of great consequence to predict the biological behaviour and prognosis.

The role of Toujeo®, insulin glargine U-300, in the treatment of diabetes mellitus.

PubMed

Brown, Meagan A; Davis, Courtney S; Fleming, Laurie W; Fleming, Joshua W

2016-09-01

The purpose of this article is to educate nurse practitioners about the role of Toujeo®, insulin glargine U-300 (Gla-300), which is a new option for the treatment of diabetes mellitus. A comprehensive literature search was conducted using MEDLINE with the key terms: insulin glargine 300, Toujeo, Gla-300, and EDITION for clinical trial data. Other resources included package inserts, drug information websites, and the World Health Organization (WHO). Gla-300 appears to be a safe and effective option for basal insulin therapy. In clinical trials, it was shown to be equally efficacious as Gla-100 with fewer episodes of hypoglycemia and slightly less weight gain, and subjects receiving Gla-300 required approximately 10 units more basal insulin to obtain the same hemoglobin A1c (HbA1c) as subjects receiving Gla-100. This new basal therapy option represents a potential advantage for patients who require higher doses of insulin because of the higher concentration of Gla-300. The lower incidence of hypoglycemia and more predictable pharmacokinetics could offer a significant therapeutic benefit in difficult-to-control patients with diabetes mellitus. The biggest disadvantage of this product is the slightly higher insulin dosage that is required to improve and/or maintain patients' HbA1c. ©2016 American Association of Nurse Practitioners.

Cyclic estrogenic fluctuation influences synaptic transmission of the medial vestibular nuclei in female rats.

PubMed

Pettorossi, Vito E; Frondaroli, Adele; Grassi, Silvarosa

2011-04-01

The estrous cycle in female rats influences the basal synaptic responsiveness and plasticity of the medial vestibular nucleus (MVN) neurons through different levels of circulating 17β-estradiol (cE(2)). The aim of this study was to verify, in the female rat, whether cyclic fluctuations of cE(2) influence long-term synaptic effects induced by high frequency afferent stimulation (HFS) in the MVN, since we found that HFS in the male rat induces fast long-term potentiation (fLTP), which depends on the neural synthesis of E(2) (nE(2)) from testosterone (T). We analyzed the field potential (FP) evoked in the MVN by vestibular afferent stimulation, under basal conditions, and after HFS, in brainstem slices of female rats during high levels (proestrus, PE) and low levels (diestrus, DE) of cE(2). Selective blocking agents of converting T enzymes were used. Unlike in the male rat, HFS induced three effects: fLTP through T conversion into E(2), and slow LTP (sLTP) and long-term depression (LTD), through T conversion into DHT. The occurrence of these effects depended on the estrous cycle phase: the frequency of fLTP was higher in DE, and those of sLTP and LTD were higher in PE. Conversely, the basal FP was also higher in PE than in DE.

Impaired viscosity of gastric secretion and its mucin content as potential contributing factors to the development of chronic constipation.

PubMed

Castro-Combs, Juan; Garcia, Cesar J; Majewski, Marek; Wallner, Grzegorz; Sarosiek, Jerzy

2014-11-01

The alimentary tract mucosa continuously releases mucus-rich secretion. Mucin, the major component of mucus, determines its viscosity and provides lubrication for the luminal content of indigestible food particles. To measure mucin secretion rate and its viscosity in patients with chronic constipation (CC) and in asymptomatic volunteers. Nineteen patients with symptoms of CC and 19 controls were included in the study. Mucin secretion and viscosity were assessed in aspirated gastric juice in basal conditions and after stimulation with pentagastrin (1 h each). Mucin content was tested by PAS methodology. Viscosity was measured using cone/plate digital viscometer. Mucin secretion rates in basal and stimulated conditions in controls were 65 and 42 % higher than in patients with CC (P < 0.05 and P < 0.001, respectively). Basal viscosity in controls was 48 % higher than in CC (P < 0.05) at the lowest and 55 % higher (P < 0.05) at the middle velocities. Viscosity in pentagastrin-stimulated conditions in controls was 71 % higher than in CC (P < 0.01) at the lowest and 35 % higher (P < 0.05) at the middle velocities. (1) The significantly lower rate of soluble mucin secretion in patients with CC than in normal volunteers may reflect impairment in mucin-related lubrication. (2) Significantly lower viscosity of gastric secretion in patients with CC may result from the lower rate of mucin secretion and may also diminish lubrication within the alimentary tract. (3) This may potentially set the stage for the development of symptoms related to chronic constipation and open a new therapeutic avenue for this patient population.

Disruption of spatial organization and interjoint coordination in Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy.

PubMed

Leiguarda, R; Merello, M; Balej, J; Starkstein, S; Nogues, M; Marsden, C D

2000-07-01

Patients with basal ganglia diseases may exhibit ideomotor apraxia. To define the nature of the impairment of the action production system, we studied a repetitive gesture of slicing bread by three-dimensional computergraphic analysis in eight nondemented patients with Parkinson's disease in the "on" state, five with progressive supranuclear palsy and four with multiple system atrophy. Two patients with Parkinson's disease and two with progressive supranuclear palsy showed ideomotor apraxia for transitive movements on standard testing. A Selspott II system was used for kinematic analysis of wrist trajectories and angular motions of the shoulder and elbow joints. Patients with Parkinson's disease, progressive supranuclear palsy, and even some with multiple system atrophy exhibited kinematic deficits in the spatial precision of movement and velocity-curvature relationships; in addition, they failed to maintain proper angle/angle relationships and to apportion their relative joint amplitudes normally. Spatial disruption of wrist trajectories was more severe in patients with ideomotor apraxia. We posit that the basal ganglia are part of the parallel parieto-frontal circuits devoted to sensorimotor integration for object-oriented behavior. The severity and characteristics of spatial abnormalities of a transitive movement would therefore depend on the location and distribution of the pathologic process within these circuits.

Phenotypic plasticity in the scaling of avian basal metabolic rate

PubMed Central

McKechnie, Andrew E; Freckleton, Robert P; Jetz, Walter

2006-01-01

Many birds exhibit short-term, reversible adjustments in basal metabolic rate (BMR), but the overall contribution of phenotypic plasticity to avian metabolic diversity remains unclear. The available BMR data include estimates from birds living in natural environments and captive-raised birds in more homogenous, artificial environments. All previous analyses of interspecific variation in BMR have pooled these data. We hypothesized that phenotypic plasticity is an important contributor to interspecific variation in avian BMR, and that captive-raised populations exhibit general differences in BMR compared to wild-caught populations. We tested this hypothesis by fitting general linear models to BMR data for 231 bird species, using the generalized least-squares approach to correct for phylogenetic relatedness when necessary. The scaling exponent relating BMR to body mass in captive-raised birds (0.670) was significantly shallower than in wild-caught birds (0.744). The differences in metabolic scaling between captive-raised and wild-caught birds persisted when migratory tendency and habitat aridity were controlled for. Our results reveal that phenotypic plasticity is a major contributor to avian interspecific metabolic variation. The finding that metabolic scaling in birds is partly determined by environmental factors provides further support for models that predict variation in scaling exponents, such as the allometric cascade model. PMID:16627278

Pepper pectin methylesterase inhibitor protein CaPMEI1 is required for antifungal activity, basal disease resistance and abiotic stress tolerance.

PubMed

An, Soo Hyun; Sohn, Kee Hoon; Choi, Hyong Woo; Hwang, In Sun; Lee, Sung Chul; Hwang, Byung Kook

2008-06-01

Pectin is one of the main components of the plant cell wall that functions as the primary barrier against pathogens. Among the extracellular pectinolytic enzymes, pectin methylesterase (PME) demethylesterifies pectin, which is secreted into the cell wall in a highly methylesterified form. Here, we isolated and functionally characterized the pepper (Capsicum annuum L.) gene CaPMEI1, which encodes a pectin methylesterase inhibitor protein (PMEI), in pepper leaves infected by Xanthomonas campestris pv. vesicatoria (Xcv). CaPMEI1 transcripts are localized in the xylem of vascular bundles in leaf tissues, and pathogens and abiotic stresses can induce differential expression of this gene. Purified recombinant CaPMEI1 protein not only inhibits PME, but also exhibits antifungal activity against some plant pathogenic fungi. Virus-induced gene silencing of CaPMEI1 in pepper confers enhanced susceptibility to Xcv, accompanied by suppressed expression of some defense-related genes. Transgenic Arabidopsis CaPMEI1-overexpression lines exhibit enhanced resistance to Pseudomonas syringae pv. tomato, mannitol and methyl viologen, but not to the biotrophic pathogen Hyaloperonospora parasitica. Together, these results suggest that CaPMEI1, an antifungal protein, may be involved in basal disease resistance, as well as in drought and oxidative stress tolerance in plants.

Carcinoma ex basal cell adenoma of the parotid gland: A report of an extremely rare case.

PubMed

Kusafuka, Kimihide; Kawasaki, Takuya; Nakajima, Takashi; Sugino, Takashi

2017-07-01

Malignant non-basaloid tumors that arise from basal cell adenoma (BCA) are extremely rare. The patient was a 72-year-old Japanese male, who had noticed swelling of the left parotid region 21 years ago. A superficial lobectomy was performed. About 60% of the tumor was made up of cribriform and trabecular tissue composed of basaloid cells, which exhibited mild atypia and nuclear expression of β-catenin. This portion of the tumor was considered to be a BCA. In the other part of the tumor, the proliferation of large eosinophilic atypical cells, most of which formed intraductal structures, was observed. These tumor cells displayed cellular atypia, and some of them formed Roman bridge structures or contributed to intracapsular invasion. Immunohistochemically, these cells were positive for cytokeratin 7, gross cystic disease fluid proten-15 (GCDFP-15), androgen receptor (AR), and mammaglobin (MMG) and exhibited a high Ki-67 labeling index. So, this portion of the tumor was considered to be a salivary duct carcinoma (SDC). The tumor's final diagnosis was SDC ex BCA (intracapsular type), which is extremely rare. GCDFP-15, AR, MMG, and Ki-67 are useful immunohistochemical markers for diagnosing SDC ex BCA. © 2017 The Authors. Pathology International Published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

The effect of dietary supplementation with calcium salts of long chain fatty acids and/or L-carnitine on ovarian activity of Rahmani ewes.

PubMed

El-Shahat, K H; Abo-El maaty, Amal M

2010-01-01

This study investigated the effect of dietary supplementation with calcium salts of long chain fatty acids with or without of l-carnitine on ovarian activity using 24 Rahmani ewes randomly allocated to four treatments. Control animals (n=6) were fed a basal diet of hay (64.2%) and barley grain (35.0%) plus minerals and vitamins (0.8%). Ewes on the three treatments received the same basal diet supplemented with calcium salts of long chain fatty acids (CSFA) at 3% of the basal diet dry matter intake (1.4 kg/ewe/d); 250 ppm l-carnitine (LC); or both these supplements (CSFA+LC). All use exhibited natural estrus on one or two occasions and were weighed at the start and the end of the study as well as body condition score was assessed at the end of study. All ewes were then synchronised for estrus using intravaginal sponges for 12 d prior to the start of the nutritional treatments and three weeks after the nutritional treatments began. The nutritional treatments were imposed for a total of 8 weeks. Blood samples were collected prior to the start of treatments and every two weeks thereafter except after sponge removal of first and second synchronisation where the blood samples were collected daily for progesterone assay. The results revealed that Rahmani ewes received basal diet (control) and l-carnitine had significantly decrease final body weight and body condition score (36.3+/-0.4; 36.8+/-0.3; 2.2+/-0.04; 2.1+/-0.05; p<0.05, respectively) than those on CSFA and CSFA+LC (38.6+/-0.9; 39.5+/-0.6; 3.3+/-0.07; 3.4+/-0.06; respectively). At the second ultrasound examination, the control animals had significantly fewer total follicles (7.3+/-0.8; p<0.05) than those on the CSFA (8.4+/-0.8), l-carnitine (8.7+/-1.5) and CSFA+LC (8.0+/-0.6) treatments. The increased numbers occurred in the medium and large categories of follicles. In addition, the ovulation rates were significantly lower (p<0.05) for control (1.3+/-0.2) and l-carnitine (1.5+/-0.00) than for CSFA (2.5+/-0.3) and CSFA+LC (2.3+/-0.2). Furthermore, serum progesterone concentrations had risen and were significantly higher (p<0.05) for CSFA (2.5+/-0.3 ng/ml) and CSFA+LC (2.7+/-0.1 ng/ml) than for control (1.1+/-0.7 ng/ml) and l-carnitine (1.5+/-0.4 ng/ml). It was concluded that supplementation of the basal diet with l-carnitine alone did not improve performance of ewes or the ovarian response. However, the addition of calcium salts of long chain fatty acids to the basal diet alone or in combination with l-carnitine significantly improved the number and size of ovarian preovulatory follicles, and the ovulation rate of Rahmani ewes. Further evidence was required to study their influence on follicular atresia.

Long term safety and tolerability of Tafluprost 0.0015% vs Timolol 0.1% preservative-free in ocular hypertensive and in primary open-angle glaucoma patients: a cross sectional study.

PubMed

Rolle, Teresa; Spinetta, Roberta; Nuzzi, Raffaele

2017-08-03

The effects of preservatives of antiglaucoma medications on corneal surface and tear function have been widely shown in literature; it's not the same as regards the active compounds themselves. The purpose of our study was to compare Ocular Surface Disease (OSD) signs and symptoms of Tafluprost 0.0015% versus preservative free (PF) Timolol 0.1% eyedrops in ocular hypertensive (OH) and in primary open-angle glaucoma (POAG) patients. A cross-sectional study included patients in monotherapy for at least 36 months with Tafluprost 0.0015% (27) or PF Timolol 0.1% (24) and 20 healthy age and sex-matched volunteers. All subjects underwent clinical tests (Schirmer I and break-up time), in vivo confocal microscopy (IVCM) and were surveyed using Ocular Surface Disease Index (OSDI) and Glaucoma Symptoms Scale (GSS) questionnaires. The groups were compared with ANOVA, Kruskal-Wallis test, t-test, Mann-Whitney test and Bonferroni's adjustment of p-values. No significant differences were found in questionnaires scores, clinical tests, IVCM variables between therapy groups. Tafluprost 0.0015% group showed significantly higher OSDI score, basal epithelial cells density, stromal reflectivity, sub-basal nerves tortuosity (p = 0.0000, 0.037, 0.006, 0.0000) and less GSS score, number of sub-basal nerves (p = 0.0000, 0.037) than controls but similar clinical tests results (p > 0.05). PF Timolol group had significantly higher OSDI score, basal epithelial cells density, stromal reflectivity and sub-basal nerve tortuosity (p = 0.000, 0.014, 0.008, 0.002), less GSS score, BUT and number of sub-basal nerves (p = 0.0000, 0.026, 0.003) than controls. Compared to PF Timolol 0.1%, Tafluprost 0.0015% showed similar safety with regards to tear function and corneal status and a similar tolerability profile. Both therapy groups show some alterations in corneal microstructure but no side effects on tear function except for an increased tear instability in PF Timolol 0.1% group. Ophtalmologists should be aware that even PF formulations may lead to a mild ocular surface impairment.

Effects of dietary Lactobacillus plantarum B1 on growth performance, intestinal microbiota, and short chain fatty acid profiles in broiler chickens.

PubMed

Peng, Q; Zeng, X F; Zhu, J L; Wang, S; Liu, X T; Hou, C L; Thacker, P A; Qiao, S Y

2016-04-01

Two experiments were conducted to determine the effects of Lactobacillus plantarum B1 on broiler performance, cecal bacteria, and ileal and cecal short chain fatty acids (SCFA). The study also determined whether it was necessary to feed Lactobacillus throughout the entire growth period or if the beneficial effects could be obtained by supplementation during the starter or finisher period only. Experiment 1 was conducted with 72 broilers assigned to 2 treatments (N=6). One treatment was the basal diet (Con), and the other was the basal diet supplemented with 2×10(9) cfu/kg L. plantarum B1 (Wh). In experiment 2, 144 one-day-old broilers were assigned to 4 treatments (N=6) including a basal diet (Con), the basal diet supplemented with 2×10(9) cfu/kgL. plantarum B1 during d one to 21 only (St), the basal diet supplemented with L. plantarum B1 during d 22 to 42 only (Fn), and, finally, the basal diet supplemented with L. plantarum B1 from d one to 42 (Wh). Experiment 1 showed that L. plantarum B1 enhanced broiler average daily gain (ADG) and feed conversion ratio (FCR). In experiment 2, during the starter period, broilers in the Wh and St treatments had higher ADG (P<0.05) than broilers in the Con and Fn, while during the finisher period, broilers in the Wh and Fn had higher ADG (P<0.01) and improved FCR (P<0.01) compared with broilers in the Con and St. On d 42, broilers in the Wh and Fn had decreased E. coli (P<0.05) and increased lactic acid bacteria (P<0.05) in their cecal digesta. L. plantarum B1 also increased (P<0.05) ileal mucosal sIgA as well as ileal and cecal SCFA. However, L. plantarum B1 had no effect on intestinal morphology. In conclusion,L. plantarum B1 plays a positive role in broilers. Supplementation during the finisher period or the entire growth period is superior to supplementation during the starter period only. © 2016 Poultry Science Association Inc.

Exploring the effects of inclusion of dietary fresh Azolla on the performance of White Pekin broiler ducks.

PubMed

Acharya, Parag; Mohanty, G P; Pradhan, C R; Mishra, S K; Beura, N C; Moharana, B

2015-11-01

The objective of this study was to investigate the dietary advantages of inclusion of unconventional nutrient source, i.e., Azolla in the basal diet of White Pekin broilers. All ducklings were randomly distributed into three treatment groups with three replicates each and each replicate having 12 ducklings and were reared in deep litter system. Groups were subjected to three dietary treatments such as G1: Basal diet, G2: Basal diet + 5% fresh Azolla of basal diet, G3: Basal diet + 10% fresh Azolla of basal diet. During experimental period, parameters, such as bodyweight, bodyweight gain, feed consumption,feed conversion ratio(FCR), and economic of production,wererecorded. The result showed that body weights in every week, except the 5(th) week, did not differ significantly between groups. However, no significant difference was observed between the groups in any week in terms of absolute body weight gain and feed consumption. As regard to FCR, the 10% Azolla group (G3) showed the best feed efficiency followed by the 5% Azolla group (G2) and the control group (G1). On the basis of profit/bird or profit/kg live weight, each of the Azolla-fed group showed a higher economic efficiency than the control. From the experiment, it was concluded that Azollaat 5 or 10% level can be included in the diet to economize the White Pekin broiler farming, and it can be great impetus to poultry farming to include unconventional nutrient source as a dietary supplement.

Number of Langerhans cells is decreased in premalignant keratosis and skin cancers.

PubMed

Shevchuk, Z; Filip, A; Shevchuk, V; Kashuba, E

2014-03-01

It was shown earlier that a number of CD207 positive Langerhans cells was lower in basal cell carcinomas than in the normal epidermis. Moreover, benign skin lesions presented a higher number of Langerhans cells when they were compared to malignant tumors. To count Langerhans cells, assessing expression levels of CD1A and CD207 markers in actinic keratosis, basal and squamous cell carcinomas, compared with the normal skin. Comparison of Langerhans cells might give a valuable prognostic marker for skin cancer. Immunohistochemistry and methods of statistics were used. Expression of CD1A and CD207 markers was assessed in tumor samples of actinic keratosis, cutaneous basal and squamous cell carcinomas, in comparison with the normal skin. In each cohort there were 40 patients (and 11 healthy individuals). We have shown that the number of Langerhans cells is considerably lower in cutaneous basal and squamous cell carcinomas, compared with their number in the normal skin (p < 0.0001). CD1A expression correlated with CD207 expression only in the control group. There was no correlation in actinic keratosis, basal and squamous cell carcinoma. This may suggest an alteration of Langerhans cells phenotype in skin neoplastic diseases, making the number of Langerhans cells a valuable prognostic factor for skin tumors.

Changing basal conditions during the speed-up of Jakobshavn Isbræ, Greenland

NASA Astrophysics Data System (ADS)

Habermann, M.; Truffer, M.; Maxwell, D.

2013-06-01

Ice-sheet outlet glaciers can undergo dynamic changes such as the rapid speed-up of Jakobshavn Isbræ following the disintegration of its floating ice tongue. These changes are associated with stress changes on the boundary of the ice mass. We investigate the basal conditions throughout a well-observed period of rapid change and evaluate parameterizations currently used in ice-sheet models. A Tikhonov inverse method with a Shallow Shelf Approximation forward model is used for diagnostic inversions for the years 1985, 2000, 2005, 2006 and 2008. Our ice softness, model norm, and regularization parameter choices are justified using the data-model misfit metric and the L-curve method. The sensitivity of the inversion results to these parameter choices is explored. We find a lowering of basal yield stress in the first 7 km of the 2008 grounding line and no significant changes higher upstream. The temporal evolution in the fast flow area is in broad agreement with a Mohr-Coulomb parameterization of basal shear stress, but with a till friction angle much lower than has been measured for till samples. The lowering of basal yield stress is significant within the uncertainties of the inversion, but it cannot be ruled out that there are other significant contributors to the acceleration of the glacier.

Increased R2* in the caudate nucleus of asymptomatic welders

PubMed Central

Lee, Eun-Young; Flynn, Michael R.; Du, Guangwei; Li, Yunqing; Lewis, Mechelle M.; Herring, Amy H.; Van Buren, Eric; Van Buren, Scott; Kong, Lan; Fry, Rebecca C.; Snyder, Amanda M.; Connor, James R.; Yang, Qing X.; Mailman, Richard B.; Huang, Xuemei

2017-01-01

Welding has been associated with neurobehavioral disorders. Welding fumes contain several metals including copper (Cu), manganese (Mn), and iron (Fe) that may interact to influence welding-related neuro-toxicity. Although welding-related airborne Fe levels are about ten-fold higher than Mn, previous studies have focused on Mn and its accumulation in the basal ganglia. This study examined differences in the apparent transverse relaxation rates [R2* (1/T2*), estimate of Fe accumulation] in the basal ganglia (caudate nucleus, putamen, and globus pallidus) between welders and controls, and the dose-response relationship between estimated Fe exposure and R2* values. Occupational questionnaires estimated recent and lifetime Fe exposure, and blood Fe levels and brain MRI were obtained. Complete exposure and MRI R2* and R1 (1/T1: measure to estimate Mn accumulation) data from 42 subjects with welding exposure and 29 controls were analyzed. Welders had significantly greater exposure metrics and higher whole blood Fe levels compared to controls. R2* in the caudate nucleus was significantly higher in welders after controlling for age, body mass index, respirator use, caudate R1, and blood metals of Cu and Mn, whereas there was no difference in R1 values in the basal ganglia between groups. The R2* in the caudate nucleus was positively correlated with whole blood Fe concentration. The present study provides the first evidence of higher R2* in the caudate nucleus of welders, which is suggestive of increased Fe accumulation in this area. Further studies are needed to replicate the findings and determine the neurobehavioral relevance. PMID:27871916

Increased R2* in the Caudate Nucleus of Asymptomatic Welders

PubMed Central

Lee, Eun-Young; Flynn, Michael R.; Du, Guangwei; Li, Yunqing; Lewis, Mechelle M.; Herring, Amy H.; Van Buren, Eric; Van Buren, Scott; Kong, Lan; Fry, Rebecca C.; Snyder, Amanda M.; Connor, James R.; Yang, Qing X.; Mailman, Richard B.; Huang, Xuemei

2016-01-01

Welding has been associated with neurobehavioral disorders. Welding fumes contain several metals including copper (Cu), manganese (Mn), and iron (Fe) that may interact to influence welding-related neurotoxicity. Although welding-related airborne Fe levels are about 10-fold higher than Mn, previous studies have focused on Mn and its accumulation in the basal ganglia. This study examined differences in the apparent transverse relaxation rates [R2* (1/T2*), estimate of Fe accumulation] in the basal ganglia (caudate nucleus, putamen, and globus pallidus) between welders and controls, and the dose–response relationship between estimated Fe exposure and R2* values. Occupational questionnaires estimated recent and lifetime Fe exposure, and blood Fe levels and brain magnetic resonance imaging (MRI) were obtained. Complete exposure and MRI R2* and R1 (1/T1: measure to estimate Mn accumulation) data from 42 subjects with welding exposure and 29 controls were analyzed. Welders had significantly greater exposure metrics and higher whole-blood Fe levels compared with controls. R2* in the caudate nucleus was significantly higher in welders after controlling for age, body mass index, respirator use, caudate R1, and blood metals of Cu and Mn, whereas there was no difference in R1 values in the basal ganglia between groups. The R2* in the caudate nucleus was positively correlated with whole-blood Fe concentration. This study provides the first evidence of higher R2* in the caudate nucleus of welders, which is suggestive of increased Fe accumulation in this area. Further studies are needed to replicate the findings and determine the neurobehavioral relevance. PMID:26769335

Metabolic syndrome in children and adolescents with phenylketonuria.

PubMed

Kanufre, Viviane C; Soares, Rosângelis D L; Alves, Michelle Rosa A; Aguiar, Marcos J B; Starling, Ana Lúcia P; Norton, Rocksane C

2015-01-01

This study aimed to identify markers of metabolic syndrome (MS) in patients with phenylketonuria (PKU). This was a cross-sectional study consisting of 58 PKU patients (ages of 4-15 years): 29 patients with excess weight, and 29 with normal weight. The biochemical variables assessed were phenylalanine (phe), total cholesterol, HDL-c, triglycerides, glucose, and basal insulin. The patients had Homeostasis Model Assessment (HOMA) and waist circumference assessed. No inter-group difference was found for phe. Overweight patients had higher levels of triglycerides, basal insulin, and HOMA, but lower concentrations of HDL-cholesterol, when compared to the eutrophic patients. Total cholesterol/HDL-c was significantly higher in the overweight group. A positive correlation between basal insulin level and HOMA with waist circumference was found only in the overweight group. The results of this study suggest that patients with PKU and excess weight are potentially vulnerable to the development of metabolic syndrome. Therefore, it is necessary to conduct clinical and laboratory monitoring, aiming to prevent metabolic changes, as well as excessive weight gain and its consequences, particularly cardiovascular risk. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Discharge of debris from ice at the margin of the Greenland ice sheet

USGS Publications Warehouse

Knight, P.G.; Waller, R.I.; Patterson, C.J.; Jones, A.P.; Robinson, Z.P.

2002-01-01

Sediment production at a terrestrial section of the ice-sheet margin in West Greenland is dominated by debris released through the basal ice layer. The debris flux through the basal ice at the margin is estimated to be 12-45 m3 m-1 a-1. This is three orders of magnitude higher than that previously reported for East Antarctica, an order of magnitude higher than sites reported from in Norway, Iceland and Switzerland, but an order of magnitude lower than values previously reported from tidewater glaciers in Alaska and other high-rate environments such as surging glaciers. At our site, only negligible amounts of debris are released through englacial, supraglacial or subglacial sediment transfer. Glacio-fluvial sediment production is highly localized, and long sections of the ice-sheet margin receive no sediment from glaciofluvial sources. These findings differ from those of studies at more temperate glacial settings where glaciofluvial routes are dominant and basal ice contributes only a minor percentage of the debris released at the margin. These data on debris flux through the terrestrial margin of an outlet glacier contribute to our limited knowledge of debris production from the Greenland ice sheet.

Catecholaminergic and serotoninergic fibres innervate the ventricular system of the hedgehog CNS.

PubMed Central

Michaloudi, H C; Papadopoulos, G C

1996-01-01

Immunocytochemistry with antisera against serotonin (5-HT), dopamine (DA) and noradrenaline (NA) was used to detect monoaminergic (MA) fibres in the ventricular system of the hedgehog Erinaceus europaeus. Light microscopic examination of immunocytochemically stained sections revealed that the ventricular system of the hedgehog is unique among mammals in that the choroid plexuses receive CA axons and that the supraependyma and subependyma of the cerebral ventricles and the spinal central canal are innervated both by serotoninergic and catecholaminergic (CA) fibres. Supraependymal 5-HT axons were generally more abundant and created at places a large number of interconnected basket-like structures, whereas CA fibres were usually directed towards the ventricular lumen. In the lateral ventricles, CA fibres were more numerous in the ependyma lining grey matter, whereas a higher 5-HT innervation density was observed in the area between the corpus callosum and the caudate nucleus or the septum. In the 3rd ventricle, the ependyma of its dorsal part exhibited a higher 5-HT and NA innervation density, whereas DA fibres were preferentially distributed in the ventral half of the basal region. The ependyma lining the cerebral aqueduct displayed a higher MA innervation density in its ventral part. The ependymal wall of the 4th ventricle exhibited an extremely dense 5-HT innervation, mainly in the floor of the ventricle, relatively fewer NA fibres and only sparse DA ones. Few NA and relatively more 5-HT fibres were detected in the ependyma of the central canal. Finally, the circumventricular organs were unevenly innervated by the 3 types of MA fibres. The extensive monoaminergic innervation of the hedgehog ventricular system described here probably reflects a transitory evolutionary stage in the phylogeny of the MA systems with presently unknown functional implications. Images Fig. 1 Fig. 2 Figs 3-8 Figs 9-14 Figs 15-20 PMID:8886949

Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes*

PubMed Central

Collins, John A.; Wood, Scott T.; Nelson, Kimberly J.; Rowe, Meredith A.; Carlson, Cathy S.; Chubinskaya, Susan; Poole, Leslie B.; Furdui, Cristina M.; Loeser, Richard F.

2016-01-01

Oxidative stress-mediated post-translational modifications of redox-sensitive proteins are postulated as a key mechanism underlying age-related cellular dysfunction and disease progression. Peroxiredoxins (PRX) are critical intracellular antioxidants that also regulate redox signaling events. Age-related osteoarthritis is a common form of arthritis that has been associated with mitochondrial dysfunction and oxidative stress. The objective of this study was to determine the effect of aging and oxidative stress on chondrocyte intracellular signaling, with a specific focus on oxidation of cytosolic PRX2 and mitochondrial PRX3. Menadione was used as a model to induce cellular oxidative stress. Compared with chondrocytes isolated from young adult humans, chondrocytes from older adults exhibited higher levels of PRX1–3 hyperoxidation basally and under conditions of oxidative stress. Peroxiredoxin hyperoxidation was associated with inhibition of pro-survival Akt signaling and stimulation of pro-death p38 signaling. These changes were prevented in cultured human chondrocytes by adenoviral expression of catalase targeted to the mitochondria (MCAT) and in cartilage explants from MCAT transgenic mice. Peroxiredoxin hyperoxidation was observed in situ in human cartilage sections from older adults and in osteoarthritic cartilage. MCAT transgenic mice exhibited less age-related osteoarthritis. These findings demonstrate that age-related oxidative stress can disrupt normal physiological signaling and contribute to osteoarthritis and suggest peroxiredoxin hyperoxidation as a potential mechanism. PMID:26797130

Beneficial effects of exercise on offspring obesity and insulin resistance are reduced by maternal high-fat diet

PubMed Central

Schreiber, Saskia; Klaus, Susanne; Kanzleiter, Isabel

2017-01-01

Scope We investigated the long-term effects of maternal high-fat consumption and post-weaning exercise on offspring obesity susceptibility and insulin resistance. Methods C57BL/6J dams were fed either a high-fat (HFD, 40% kcal fat) or low-fat (LFD, 10% kcal fat) semi-synthetic diet during pregnancy and lactation. After weaning, male offspring of both maternal diet groups (mLFD; mHFD) received a LFD. At week 7, half of the mice got access to a running wheel (+RW) as voluntary exercise training. To induce obesity, all offspring groups (mLFD +/-RW and mHFD +/-RW) received HFD from week 15 until week 25. Results Compared to mLFD, mHFD offspring were more prone to HFD-induced body fat gain and exhibited an increased liver mass which was not due to increased hepatic triglyceride levels. RW improved the endurance capacity in mLFD, but not in mHFD offspring. Additionally, mHFD offspring +RW exhibited higher plasma insulin levels during glucose tolerance test and an elevated basal pancreatic insulin production compared to mLFD offspring. Conclusion Taken together, maternal HFD reduced offspring responsiveness to the beneficial effects of voluntary exercise training regarding the improvement of endurance capacity, reduction of fat mass gain, and amelioration of HFD-induced insulin resistance. PMID:28235071

Mammalian metabolic rates in the hottest fish on earth

PubMed Central

Wood, Chris M.; Brix, Kevin V.; De Boeck, Gudrun; Bergman, Harold L.; Bianchini, Adalto; Bianchini, Lucas F.; Maina, John N.; Johannsson, Ora E.; Kavembe, Geraldine D.; Papah, Michael B.; Letura, Kisipan M.; Ojoo, Rodi O.

2016-01-01

The Magadi tilapia, Alcolapia grahami, a small cichlid fish of Lake Magadi, Kenya lives in one of the most challenging aquatic environments on earth, characterized by very high alkalinity, unusual water chemistry, and extreme O2, ROS, and temperature regimes. In contrast to most fishes which live at temperatures substantially lower than the 36–40 °C of mammals and birds, an isolated population (South West Hot Springs, SWHS) of Magadi tilapia thrives in fast-flowing hotsprings with daytime highs of 43 °C and night-time lows of 32 °C. Another population (Fish Springs Lagoon, FSL) lives in a lagoon with fairly stable daily temperatures (33–36 °C). The upper critical temperatures (Ctmax) of both populations are very high; moreover the SWHS tilapia exhibit the highest Ctmax (45.6 °C) ever recorded for a fish. Routine rates of O2 consumption (MO2) measured on site, together with MO2 and swimming performance at 25, 32, and 39 °C in the laboratory, showed that the SWHS tilapia exhibited the greatest metabolic performance ever recorded in a fish. These rates were in the basal range of a small mammal of comparable size, and were all far higher than in the FSL fish. The SWHS tilapia represents a bellwether organism for global warming. PMID:27257105

Involuntary movements and coma as the prognostic marker for acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Lee, Sooyoung; Sanefuji, Masafumi; Torio, Michiko; Kaku, Noriyuki; Ichimiya, Yuko; Mizuguchi, Soichi; Baba, Haruhisa; Sakai, Yasunari; Ishizaki, Yoshito; Torisu, Hiroyuki; Kira, Ryutaro; Hara, Toshiro; Ohga, Shouichi

2016-11-15

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) occurs in children associated with infection. It is characterized by a prolonged febrile seizure in the first phase, and a cluster of seizures, deterioration of consciousness and the white matter lesions with reduced diffusion in the second phase. The patients often have severe neurological sequelae, but the prognostic indicators remain unknown. The present study aimed to clarify the characteristics of AESD patients who subsequently exhibited severe neurological sequelae. We retrospectively analyzed the clinical and laboratory findings along with the brain imaging in patients who had severe (n=8) and non-severe neurodevelopmental outcomes (n=12). Severe group more frequently showed coma (p=0.014) or involuntary movements including dystonia and oral dyskinesia (p=0.018) before the second phase than non-severe group. Severe group exhibited higher levels of serum alanine aminotransferase than non-severe group (p=0.001). Quantitatively assessed MRI in the second phase revealed that severe group had more extensive lesions than non-severe group, in the anterior (p=0.015) and posterior parts (p=0.011) of the cerebrum and basal ganglia (p=0.020). Early appearing involuntary movements or coma might account for the extension of acute brain lesions and the poor neurological outcomes in AESD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Predictors of early discontinuation of basal insulin therapy in type 2 diabetes in primary care.

PubMed

Kostev, K; Dippel, F W; Rathmann, W

2016-04-01

To identify patient-related characteristics and other impact factors predicting early discontinuation of basal insulin therapy in type 2 diabetes in primary care. A total of 4837 patients who started basal insulin therapy (glargine: n=3175; NPH: n=1662) in 1072 general and internal medicine practices throughout Germany were retrospectively analyzed (Disease Analyser Database: 01/2008-03/2014). Early discontinuation was defined as switching back to oral antidiabetic drugs (OAD) therapy within 90 days after first basal insulin prescription (index date, ID). Patient records were assessed 365 days prior and post ID. Logistic regression models were used to adjust for age, sex, diabetes duration, diabetologist care, disease management program participation, HbA1c, and comorbidity. Within 3 months after ID, 202 (6.8%) of glargine patients switched back to OAD (NPH: 130 (8.5%); p<0.05). In multivariable logistic regression, predictors of early basal insulin discontinuation were ≥1 documented hypoglycemia before ID (adjusted Odds ratio; 95% CI: 2.20; 1.27-3.82), diagnosed depression (1.31; 1.01-1.70) and referrals to specialists within 90 days after ID (2.06; 1.61-2.63). Diabetologist care (0.57; 0.36-0.89) and glargine treatment (vs. NPH: 0.78; 0.61-0.98) were related to a lower odds of having early insulin discontinuation. Less than 10% of type 2 diabetes patients switched back to oral antidiabetic drugs within 90 days after start of basal insulin therapy. In particular, patients with baseline depression and frequent or severe hypoglycemia have a higher likelihood for early discontinuation of basal insulin, whereas use of insulin glargine and diabetologist care are related to an increased chance of continuous insulin treatment. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Effect of dietary carbohydrate source on the development of obesity in agouti transgenic mice.

PubMed

Morris, Kristin L; Zemel, Michael B

2005-01-01

Our objective was to evaluate the effects of a qualitative change in dietary carbohydrate source on body weight and adiposity in a rodent model of diet-induced obesity. We evaluated the effects of high-fat diets (basal) varying in carbohydrate source in aP2-agouti transgenic mice. In the ad libitum study, animals were given free access to the basal diet or one of four test diets for 6 weeks. In two of the diets, dietary carbohydrate was derived from a single source: mung bean noodles (MUNG) or rolled oats (ROLL). The remaining diets were designed to mimic commercially available instant oatmeal with added sugar (IO-S) or flavored instant oatmeal (IO-F). In the energy-restricted study, animals were given ad libitum access to the basal diet for 6 weeks. Subsequently, animals were assigned to one of six treatment groups for 6 weeks. One group was continued on the basal diet ad libitum. The remaining groups were maintained with energy restriction (70% ad libitum) on either the basal, MUNG, ROLL, IO-S, or IO-F diet. Subcutaneous fat pad mass was significantly higher (p<0.05) in the energy-restricted basal and IO-S groups compared with the energy-restricted ROLL diet. Similarly, visceral fat pad mass was significantly lower with ROLL and MUNG diets (p<0.05 for both) compared with basal and IO-S diets, and the insulin:glucose ratio was reduced (by 23% to 34%, p<0.05) in these two diets compared with all others. In ad libitum-fed animals, liver fatty acid synthase expression was 43% to 62% lower (p<0.05) with ROLL and MUNG diets compared with all others. These data suggest that a qualitative change in dietary carbohydrate source modulates body weight and adiposity.

Immunoexpression of P63 and SOX2 in triple-negative breast cancers, Indonesia

PubMed Central

Kamarlis, Reno K; Lubis, Muhammad ND; Hernowo, Bethy S; Kar, Azmi S

2018-01-01

Background: Using immunohistochemical stains to target specific breast cancer markers has become indispensable for evaluation of small diagnostic tissue specimens, and therefore novel marker cocktails for specific breast cancers are required. This study was conducted to assess the immunoexpression of P63 and SOX2 in triple negative breast cancer (TNBC), and to evaluate the predictive diagnostic value of these markers for specific types of TNBC. Methods: Histological slides and paraffin blocks of TNBC cases were collected from Dr. Hasan Sadikin Hospital, Bandung, Indonesia from 5-years period (2011-2015). Each histological slide was subjected to immunohistochemical staining for P63 (nucleus and cytoplasm) and SOX2 (nucleus), with specific primer antibodies. Immunoexpression of P63 and SOX2 was evaluated using immunoreactivity scoring. Associations between P63 and SOX2 immunoexpression and TNBC types were assessed using Mann Whitney tests. In addition, the predictive diagnostic values of these markers were assessed. Results: Forty TNBC histological slides were included, and 23 (57.5%) were Basal-like type TNBC and 17 (42.5%) were Non basal-like type TNBC. Immunoexpression of P63 nucleus and SOX2 was not different between types of TNBC. However, immunoexpression of P63 in the cytoplasm in Basal-like type TNBC was significantly higher than in Non basal-like type TNBC ( p=0.021). Predictor diagnostic value analysis suggested that immunoexpression of P63 in cytoplasm had 56.5% sensitivity and 70.6% specificity for diagnosing Basal-like type TNBC, with area under curve of 0.64.    Conclusions: Immunoexpression of P63 in the cytoplasm has a relatively weak diagnostic value to discriminate Basal-like and Non basal-like types of TNBC. PMID:29527291

Mental Symptoms in Huntington's Disease and a Possible Primary Aminergic Neuron Lesion

NASA Astrophysics Data System (ADS)

Mann, J. John; Stanley, Michael; Gershon, Samuel; Rossor, M.

1980-12-01

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.

FAD-induced in vitro activation of glutathione reductase in the lens of B2 deficient rats.

PubMed

Ono, S; Hirano, H

1984-04-01

We studied the FAD-induced in vitro stimulation of lenticular glutathione reductase in riboflavin-deficient rats. The stimulatory effect of FAD on lenticular glutathione reductase in rats fed a B2-deficient diet for 4 weeks was remarkably higher than in paired control rats fed a B2-supplemented basal diet and control rats had ad libitum access to a B2-supplemented basal diet. The in vitro FAD stimulation effect on rat lenticular glutathione reductase represents a sensitive indicator of the B2 deficient status.

Bone Cysts After Osteochondral Allograft Repair of Cartilage Defects in Goats Suggest Abnormal Interaction Between Subchondral Bone and Overlying Synovial Joint Tissues

PubMed Central

Pallante-Kichura, Andrea L.; Cory, Esther; Bugbee, William D.; Sah, Robert L.

2013-01-01

The efficacy of osteochondral allografts (OCA) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12 months in vivo. The objectives of this study were to further analyze OCA and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral (ScB) and trabecular (TB) bone structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCA was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCA was lower than Non-Op and other OCA. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCA did not vary compared to Non-Op, but BS/TV was lower. (2) OCA contained “basal” cysts, localized to deeper regions, some “subchondral” cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These findings suggest that cysts occurring after OCA may result from aberrant mechanobiology due to (1) altered compartmentalization that normally separates overlying cartilage and subchondral bone, either from distinct ScB channels or more general ScB plate deterioration, and (2) bone resorption at the basal graft-host interface. PMID:23958821

Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: Linkage and loss of heterozygosity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chenevix-Trench, G.; Wicking, C.; Berkman, J.

Nevoid basal cell carcinoma syndrome (NBCCS; basal cell nevus syndrome or Gorlin syndrome) is a cancer-predisposition syndrome characterized by multiple basal cell carcinomas (BCCs) and diverse developmental defects. The gene for NBCCS has been mapped to 9q23.1-q31 in North Americal and European families. In addition, loss of heterozygosity (LOH) for genetic markers in this region has been detected in sporadic BCCs, indicating that the NBCCs gene is probably a tumor-suppressor gene. In this study the authors have determined that the NBCCS gene is also linked to this region in Australasian pedigrees and that there is no significant evidence of heterogeneity.more » They have defined the localization of the gene by multipoint and haplotype analysis of 15 families, using four microsatellite markers. LOH at these loci was detected in 50% of sporadic BCCs, a rate that is significantly higher than that in other skin lesions used as controls. 21 refs., 3 figs., 2 tabs.« less

Controlling microstructure and texture in magnesium alloy sheet by shear-based deformation processing

NASA Astrophysics Data System (ADS)

Sagapuram, Dinakar

Application of lightweight Mg sheet is limited by its low workability, both in production of sheet (typically by multistep hot and cold-rolling) and forming of sheet into components. Large strain extrusion machining (LSEM), a constrained chip formation process, is used to create Mg alloy AZ31B sheet in a single deformation step. The deformation in LSEM is shown to be intense simple shear that is confined to a narrow zone, which results in significant deformation-induced heating up to ~ 200°C and reduces the need for pre-heating to realize continuous sheet forms. This study focuses on the texture and microstructure development in the sheet processed by LSEM. Interestingly, deep, highly twinned steady-state layer develops in the workpiece subsurface due to the compressive field ahead of the shear zone. The shear deformation, in conjunction with this pre-deformed twinned layer, results in tilted-basal textures in the sheet with basal planes tilted well away from the surface. These textures are significantly different from those in rolled sheet, where basal planes are nearly parallel to the surface. By controlling the strain path, the basal plane inclination from the surface could be varied in the range of 32-53°. B-fiber (basal plane parallel to LSEM shear plane), associated with basal slip, is the major texture component in the sheet. An additional minor C2-fiber component appears above 250°C due to the thermal activation of pyramidal slip. Together with these textures, microstructure ranges from severely cold-worked to (dynamically) recrystallized type, with the corresponding grain sizes varying from ultrafine- (~ 200 nm) to fine- (2 mum) grained. Small-scale limiting dome height (LDH) confirmed enhanced formability (~ 50% increase in LDH) of LSEM sheet over the conventional rolled sheet. Premature, twinning-driven shear fractures are observed in the rolled sheet with the basal texture. In contrast, LSEM sheet with a tilted-basal texture favorably oriented for basal slip exhibits ductile tensile-type fracture. A two-fold increase in ductility is also observed for the LSEM sheet under uniaxial tensile testing without significant changes in the strength. Among texture and microstructure (grain size), texture is shown to be more critical for Mg sheet formability. However, in conjunction with a favorable texture, fine recrystallized microstructure provides for additional enhancement of strain-hardening capacity and formability. In-situ imaging of material flow during uniaxial tensile testing revealed new, interesting flow localization phenomena and fracture behavior. It is shown that the deformation behavior of Mg sheet is highly texture dependent, and also radically different from that of conventional ductile metals both in terms of necking and fracture. The implications of these observations for the LDH test results and formability of Mg sheet, in general, are briefly discussed.

Identification and analysis of low molecular weight dissolved organic carbon in subglacial basal ice ecosystems by ion chromatography

NASA Astrophysics Data System (ADS)

Lawson, E. C.; Wadham, J. L.; Lis, G. P.; Tranter, M.; Pickard, A. E.; Stibal, M.; Dewsbury, P.; Fitzsimons, S.

2015-08-01

Glacial runoff is an important source of dissolved organic carbon (DOC) for downstream heterotrophic activity, despite the low overall DOC concentrations. This is because of the abundance of bioavailable, low molecular weight (LMW) DOC species. However, the provenance and character of LMW-DOC is not fully understood. We investigated the abundance and composition of DOC in subglacial environments via a molecular level DOC analysis of basal ice, which forms by water/sediment freeze-on to the glacier sole. Spectrofluorometry and a novel ion chromatographic method, which has been little utilised in glacial science for LMW-DOC determinations, were employed to identify and quantify the major LMW fractions (free amino acids, carbohydrates and carboxylic acids) in basal ice from four glaciers, each with a different basal debris type. Basal ice from Joyce Glacier (Antarctica) was unique in that 98 % of the LMW-DOC was derived from the extremely diverse FAA pool, comprising 14 FAAs. LMW-DOC concentrations in basal ice were dependent on the bioavailability of the overridden organic carbon (OC), which in turn, was influenced by the type of overridden material. Mean LMW-DOC concentrations in basal ice from Russell Glacier (Greenland), Finsterwalderbreen (Svalbard) and Engabreen (Norway) were low (0-417 nM C), attributed to the relatively refractory nature of the OC in the overridden paleosols and bedrock. In contrast, mean LMW-DOC concentrations were an order of magnitude higher (4430 nM C) in basal ice from Joyce Glacier, a reflection of the high bioavailability of the overridden lacustrine material (>17 % of the sediment OC comprised extractable carbohydrates, a proxy for bioavailable OC). We find that the overridden material may act as a direct (via abiotic leaching) and indirect (via microbial cycling) source of DOC to the subglacial environment and provides a range of LMW-DOC compounds that may stimulate microbial activity in wet sediments in current subglacial environments.

Magellanic penguin telomeres do not shorten with age with increased reproductive effort, investment, and basal corticosterone.

PubMed

Cerchiara, Jack A; Risques, Rosa Ana; Prunkard, Donna; Smith, Jeffrey R; Kane, Olivia J; Boersma, P Dee

2017-08-01

All species should invest in systems that enhance longevity; however, a fundamental adult life-history trade-off exists between the metabolic resources allocated to maintenance and those allocated to reproduction. Long-lived species will invest more in reproduction than in somatic maintenance as they age. We investigated this trade-off by analyzing correlations among telomere length, reproductive effort and output, and basal corticosterone in Magellanic penguins ( Spheniscus magellanicus ). Telomeres shorten with age in most species studied to date, and may affect adult survival. High basal corticosterone is indicative of stressful conditions. Corticosterone, and stress, has been linked to telomere shortening in other species. Magellanic penguins are a particularly good model organism for this question as they are an unusually long-lived species, exceeding their mass-adjusted predicted lifespan by 26%. Contrary to our hypothesis, we found adults aged 5 years to over 24 years of age had similar telomere lengths. Telomeres of adults did not shorten over a 3-year period, regardless of the age of the individual. Neither telomere length, nor the rate at which the telomeres changed over these 3 years, correlated with breeding frequency or investment. Older females also produced larger volume clutches until approximately 15 years old and larger eggs produced heavier fledglings. Furthermore, reproductive success ( chicks fledged/eggs laid ) is maintained as females aged. Basal corticosterone, however, was not correlated with telomere length in adults and suggests that low basal corticosterone may play a role in the telomere maintenance we observed. Basal corticosterone also declined during the breeding season and was positively correlated with the age of adult penguins. This higher basal corticosterone in older individuals, and consistent reproductive success, supports the prediction that Magellanic penguins invest more in reproduction as they age. Our results demonstrate that telomere maintenance may be a component of longevity even with increased reproductive effort, investment, and basal corticosterone.

Hypoglycemia After Initiation of Basal Insulin in Patients with Type 2 Diabetes in the United States: Implications for Treatment Discontinuation and Healthcare Costs and Utilization.

PubMed

Dalal, Mehul R; Kazemi, Mahmood; Ye, Fen; Xie, Lin

2017-09-01

Hypoglycemia and fear of hypoglycemia may contribute to basal insulin discontinuation, poor glycemic control, and increased healthcare burden in patients with type 2 diabetes (T2D). This study aimed to determine the impact of hypoglycemia soon after basal insulin initiation on treatment discontinuation and economic outcomes in patients with T2D. Hypoglycemic events within 6 months of basal insulin initiation were identified using retrospective cohort data from patients with T2D, at least 18 years of age, initiated on basal insulin therapy in the Clinformatics™ Data Mart for Multiplan claims database from January 1, 2008, through August 31, 2012. Data were adjusted for baseline characteristics. Discontinuation was established for patients with 12-month follow-up data, while discontinuation risk was assessed in the extended analysis (6- to 24-month follow-up) by Cox regression analysis. Healthcare use and costs were determined. Of 55,608 patients, 4.5% experienced hypoglycemia within 6 months of basal insulin initiation. Patients with hypoglycemia were more likely to discontinue basal insulin within 12 months of initiation (79.0% vs. 74.2%; P < 0.001). Data, adjusted for baseline characteristics such as age, any baseline hypoglycemia, and use of oral antidiabetes drugs, showed that patients with hypoglycemia had a greater risk of discontinuation (hazard ratio 1.16; 95% confidence interval 1.03, 1.32; P = 0.0164), were more likely to have a hospitalization (41.0% vs. 24.3%; P < 0.001) or an ED visit (55.8% vs. 35.1%; P < 0.001), and had higher diabetes-related ($13,662 vs. $7506; P < 0.001) and all-cause ($30,719 vs. $19,079; P < 0.001) healthcare costs. US patients with T2D who experienced hypoglycemia within 6 months of basal insulin initiation were more likely to discontinue treatment, accompanied by a greater healthcare burden. Sanofi US, Inc.

Where neuroscience and dynamic system theory meet autonomous robotics: a contracting basal ganglia model for action selection.

PubMed

Girard, B; Tabareau, N; Pham, Q C; Berthoz, A; Slotine, J-J

2008-05-01

Action selection, the problem of choosing what to do next, is central to any autonomous agent architecture. We use here a multi-disciplinary approach at the convergence of neuroscience, dynamical system theory and autonomous robotics, in order to propose an efficient action selection mechanism based on a new model of the basal ganglia. We first describe new developments of contraction theory regarding locally projected dynamical systems. We exploit these results to design a stable computational model of the cortico-baso-thalamo-cortical loops. Based on recent anatomical data, we include usually neglected neural projections, which participate in performing accurate selection. Finally, the efficiency of this model as an autonomous robot action selection mechanism is assessed in a standard survival task. The model exhibits valuable dithering avoidance and energy-saving properties, when compared with a simple if-then-else decision rule.

Automated thin-film analyses of hydrated interplanetary dust particles in the analytical electron microscope

NASA Technical Reports Server (NTRS)

Germani, M. S.; Bradley, J. P.; Brownlee, D. E.

1990-01-01

A 200 keV electron microscope was used to obtain elemental analyses from over 4000 points on thin sections of eight 'layer silicate' class interplanetary dust particles (IDPs). Major and minor element abundances from a volume approaching that of a cylinder 50 nm in diameter were observed. Mineral phases and their relative abundances in the thin sections were identified and petrographic characteristics were determined. Three of the particles contained smectite (1.0-1.2 nm basal spacing) and two contained serpentine (0.7 nm basal spacing). The point count analyses and Mg-Si-Fe ternary diagrams show that one of the serpentine-containing IDPs is similar to CI and CM chondritic meteorites. The IDPs exhibit evidence of aqueous processing, but they have typically experienced only short range, submicrometer scale alteration. The IDPs may provide a broad sampling of the asteroid belt.

Calcium Imaging of Basal Forebrain Activity during Innate and Learned Behaviors

PubMed Central

Harrison, Thomas C.; Pinto, Lucas; Brock, Julien R.; Dan, Yang

2016-01-01

The basal forebrain (BF) plays crucial roles in arousal, attention, and memory, and its impairment is associated with a variety of cognitive deficits. The BF consists of cholinergic, GABAergic, and glutamatergic neurons. Electrical or optogenetic stimulation of BF cholinergic neurons enhances cortical processing and behavioral performance, but the natural activity of these cells during behavior is only beginning to be characterized. Even less is known about GABAergic and glutamatergic neurons. Here, we performed microendoscopic calcium imaging of BF neurons as mice engaged in spontaneous behaviors in their home cages (innate) or performed a go/no-go auditory discrimination task (learned). Cholinergic neurons were consistently excited during movement, including running and licking, but GABAergic and glutamatergic neurons exhibited diverse responses. All cell types were activated by overt punishment, either inside or outside of the discrimination task. These findings reveal functional similarities and distinctions between BF cell types during both spontaneous and task-related behaviors. PMID:27242444

Pharyngeal satellite cells undergo myogenesis under basal conditions and are required for pharyngeal muscle maintenance

PubMed Central

Randolph, Matthew E.; Phillips, Brittany L.; Choo, Hyo-Jung; Vest, Katherine E.; Vera, Yandery; Pavlath, Grace K.

2015-01-01

The pharyngeal muscles of the nasal, oral, and laryngeal pharynxes are required for swallowing. Pharyngeal muscles are preferentially affected in some muscular dystrophies yet spared in others. Muscle stem cells, called satellite cells, may be critical factors in the development of pharyngeal muscle disorders; however, very little is known about pharyngeal satellite cells (PSC) and their role in pharyngeal muscles. We show that PSC are distinct from the commonly studied hindlimb satellite cells both transcriptionally and biologically. Under basal conditions PSC proliferate, progress through myogenesis, and fuse with pharyngeal myofibers. Furthermore, PSC exhibit biologic differences dependent on anatomic location in the pharynx. Importantly, PSC are required to maintain myofiber size and myonuclear number in pharyngeal myofibers. Together, these results demonstrate that PSC are critical for pharyngeal muscle maintenance and suggest that satellite cell impairment could contribute to pharyngeal muscle pathology associated with various muscular dystrophies and aging. PMID:26178867

Neonatal Procedural Pain and Preterm Infant Cortisol Response to Novelty at 8 Months

PubMed Central

Weinberg, Joanne; Whitfield, Michael F.

2005-01-01

Objectives. Stress systems may be altered in the long term in preterm infants for multiple reasons, including early exposure to procedural pain in neonatal intensive care. This question has received little attention beyond hospital discharge. Stress responses (cortisol) to visual novelty in preterm infants who were born at extremely low gestational age (ELGA; ≤28 weeks), very low gestational age (VLGA; 29–32 weeks), and term were compared at 8 months of age corrected for prematurity (corrected chronological age [CCA]). In addition, among the preterm infants, we evaluated whether cortisol levels at 8 months were related to neonatal exposure to procedural pain and morphine in the neonatal intensive care unit. Methods. Seventy-six infants, 54 preterm (≤32 weeks' GA at birth) and 22 term-born infants who were seen at 8 months CCA composed the study sample, after excluding those with major sensory, motor, or cognitive impairment. Salivary cortisol was measured before (basal) and 20 minutes after introduction of novel toys (post 1) and after developmental assessment (post 2). Results. Salivary cortisol was significantly higher in ELGA infants at 8 months, compared with the VLGA and term groups before and after introduction of visual novelty. Term-born and VLGA infants showed a slight decrease in cortisol when playing with novel toys, whereas the ELGA group showed higher basal and sustained levels of cortisol. After controlling for early illness severity and duration of supplemental oxygen, higher basal cortisol levels in preterm infants at 8 months' CCA were associated with higher number of neonatal skin-breaking procedures. In contrast, cortisol responses to novelty were predicted equally well by neonatal pain or GA at birth. No relationship between morphine dosing and cortisol response was demonstrated in these infants. Conclusions. ELGA preterm infants show a different pattern of cortisol levels before and after positive stimulation of visual novelty than more maturely born, VLGA preterm and term-born infants. Exposure to high numbers of skin-breaking procedures may contribute to “resetting” basal arousal systems in preterm infants. PMID:15231977

Glycophenotype evaluation in cutaneous tumors using lectins labeled with acridinium ester.

PubMed

Lima, Luiza Rayanna Amorim; Bezerra, Matheus Filgueira; Almeida, Sinara Mônica Vitalino; Silva, Lúcia Patrícia Bezerra Gomes; Beltrão, Eduardo Isidoro Carneiro; Carvalho Júnior, Luiz Bezerra

2013-01-01

Tumor cells show alterations in their glycosylation patterns when compared to normal cells. Lectins can be used to evaluate these glycocode changes. Chemiluminescence assay is an effective technique for quantitative analysis of proteins, nucleic acids, and carbohydrates due to its high sensitivity, specificity, and rapid testing. To use histochemiluminescence based on lectin conjugated to acridinium ester (AE) for the investigation of glycophenotype changes in cutaneous tumors. Concanavalin A (Con A), Peanut agglutinin (PNA), Ulex europaeus agglutinin-I (UEA-I), and Maackia amurensis agglutinin (MAA) were conjugated to acridinium ester. Biopsies of cutaneous tumors and normal skin were incubated with the lectins-AE, and chemiluminescence was quantified and expressed as Relative Light Units (RLU). Results. Actinic keratosis (AK), keratoacanthoma (KA), squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) showed lower expression of α -D-glucose/mannose and α -L-fucose residues compared to normal tissue. Cutaneous tumors displayed higher expression of Gal- β (1-3)-GalNAc residues than normal tissue. AK and SCC exhibited higher expression of Neu5Ac- α (2,3)Gal residues than normal epidermis. KA and BCC showed equivalent RLU values compared to normal tissue. Lectin histochemiluminescence allowed quantitative assessment of the carbohydrate expression in cutaneous tissues, contributing to eliminate the subjectivity of conventional techniques used in the histopathological diagnosis.

Targeting Adenosine A2A Receptors in Parkinson’s Disease

DTIC Science & Technology

2006-11-01

events, which are important for information processing within the nucleus accumbens and more largely in the striatum, should have a high impact on basal...half that of men who do not consume caffeine, whereas consumption of decaffeinated coffee is unrelated to PD risk. Results among women, however, are...immunopositive cells showed swollen and hyper-trophic cell bodies as well as processes and exhibited morphological features of activated microglia. In the

A New Basal Sauropodomorph (Dinosauria: Saurischia) from Quebrada del Barro Formation (Marayes-El Carrizal Basin), Northwestern Argentina

PubMed Central

Apaldetti, Cecilia; Martinez, Ricardo N.; Alcober, Oscar A.; Pol, Diego

2011-01-01

Background Argentinean basal sauropodomorphs are known by several specimens from different basins; Ischigualasto, El Tranquilo, and Mogna. The Argentinean record is diverse and includes some of the most primitive known sauropodomorphs such as Panphagia and Chromogisaurus, as well as more derived forms, including several massospondylids. Until now, the Massospondylidae were the group of basal sauropodomorphs most widely spread around Pangea with a record in almost all continents, mostly from the southern hemisphere, including the only record from Antarctica. Methodology/Principal Finding We describe here a new basal sauropodomorph, Leyesaurus marayensis gen. et sp. nov., from the Quebrada del Barro Formation, an Upper Triassic-Lower Jurassic unit that crops out in northwestern Argentina. The new taxon is represented by a partial articulated skeleton that includes the skull, vertebral column, scapular and pelvic girdles, and hindlimb. Leyesaurus is diagnosed by a set of unique features, such as a sharply acute angle (50 degrees) formed by the ascending process of the maxilla and the alveolar margin, a straight ascending process of the maxilla with a longitudinal ridge on its lateral surface, noticeably bulging labial side of the maxillary teeth, greatly elongated cervical vertebrae, and proximal articular surface of metatarsal III that is shelf-like and medially deflected. Phylogenetic analysis recovers Leyesaurus as a basal sauropodomorph, sister taxon of Adeopapposaurus within the Massospondylidae. Moreover, the results suggest that massospondylids achieved a higher diversity than previously thought. Conclusions/Significance Our phylogenetic results differ with respect to previous analyses by rejecting the massospondylid affinities of some taxa from the northern hemisphere (e.g., Seitaad, Sarahsaurus). As a result, the new taxon Leyesaurus, coupled with other recent discoveries, suggests that the diversity of massospondylids in the southern hemisphere was higher than in other regions of Pangea. Finally, the close affinities of Leyesaurus with the Lower Jurassic Massospondylus suggest a younger age for the Quebrada del Barro Formation than previously postulated. PMID:22096511

A new basal sauropodomorph (Dinosauria: Saurischia) from Quebrada del Barro Formation (Marayes-El Carrizal Basin), northwestern Argentina.

PubMed

Apaldetti, Cecilia; Martinez, Ricardo N; Alcober, Oscar A; Pol, Diego

2011-01-01

Argentinean basal sauropodomorphs are known by several specimens from different basins; Ischigualasto, El Tranquilo, and Mogna. The Argentinean record is diverse and includes some of the most primitive known sauropodomorphs such as Panphagia and Chromogisaurus, as well as more derived forms, including several massospondylids. Until now, the Massospondylidae were the group of basal sauropodomorphs most widely spread around Pangea with a record in almost all continents, mostly from the southern hemisphere, including the only record from Antarctica. We describe here a new basal sauropodomorph, Leyesaurus marayensis gen. et sp. nov., from the Quebrada del Barro Formation, an Upper Triassic-Lower Jurassic unit that crops out in northwestern Argentina. The new taxon is represented by a partial articulated skeleton that includes the skull, vertebral column, scapular and pelvic girdles, and hindlimb. Leyesaurus is diagnosed by a set of unique features, such as a sharply acute angle (50 degrees) formed by the ascending process of the maxilla and the alveolar margin, a straight ascending process of the maxilla with a longitudinal ridge on its lateral surface, noticeably bulging labial side of the maxillary teeth, greatly elongated cervical vertebrae, and proximal articular surface of metatarsal III that is shelf-like and medially deflected. Phylogenetic analysis recovers Leyesaurus as a basal sauropodomorph, sister taxon of Adeopapposaurus within the Massospondylidae. Moreover, the results suggest that massospondylids achieved a higher diversity than previously thought. Our phylogenetic results differ with respect to previous analyses by rejecting the massospondylid affinities of some taxa from the northern hemisphere (e.g., Seitaad, Sarahsaurus). As a result, the new taxon Leyesaurus, coupled with other recent discoveries, suggests that the diversity of massospondylids in the southern hemisphere was higher than in other regions of Pangea. Finally, the close affinities of Leyesaurus with the Lower Jurassic Massospondylus suggest a younger age for the Quebrada del Barro Formation than previously postulated.

Effect of dietary supplementation of l-tryptophan on thermal tolerance and oxygen consumption rate in Cirrhinus mrigala fingerlings under varied stocking density.

PubMed

Tejpal, C S; Sumitha, E B; Pal, A K; Shivananda Murthy, H; Sahu, N P; Siddaiah, G M

2014-04-01

A 60 day feeding trial was conducted to study the effect of dietary l-tryptophan on thermal tolerance and oxygen consumption rate of freshwater fish, mrigala, Cirrhinus mrigala reared under ambient temperature at low and high stocking density. Four hundred eighty fingerlings were distributed into eight experimental groups. Four groups each of low density group (10 fishes/75L water) and higher density group (30 fishes/75L water) were fed a diet containing 0, 0.68, 1.36 or 2.72% l-tryptophan in the diet, thus forming eight experimental groups namely, Low density control (LC) (basal feed +0% l-tryptophan); LT1 (basal feed+0.68% l-tryptophan); LT2 (basal feed+1.36% l-tryptophan); LT3 (basal feed+2.72% l-tryptophan); high density control (HC) (basal feed+0% l-tryptophan); HT1 (basal feed+0.68% l-tryptophan); HT2 (basal feed+1.36% l-tryptophan); and HT3 (basal feed+2.72% l-tryptophan) were fed at 3% of the body weight. The test diets having crude protein 34.33±0.23 to 35.81±0.18% and lipid 423.49±1.76 to 425.85±0.31KCal/100g were prepared using purified ingredients. The possible role of dietary l-tryptophan on thermal tolerance and oxygen consumption rate was assessed in terms of critical thermal maxima (CTMax), critical thermal minima (CTMin), lethal thermal maxima (LTMax) and lethal thermal minima (LTMin). The CTMax, CTMin, LTMax and LTMin values were found to be significantly higher (p<0.05) in the treatment groups with CTMax 42.94±0.037 (LT2); LT Max 43.18±0.070 (LT2); CTMin 10.47±0.088 (LT2) and LTMin 9.42±0.062 (LT3), whereas the control group showed a lower tolerance level. The same trend was observed in the high density group (CTMax 42.09±0.066 (LT3); LTMax 43 23±0.067 (HT3); CTMin 10.98±0.040 (HT3) and LTMin 9.74±0.037 (HT3). However, gradual supplementation of dietary l-tryptophan in the diet significantly reduced the oxygen consumption rate in both the low density group (Y=-26.74x+222.4, r²=0.915) and the high density group (Y=-32.96x+296.5, r²=0.8923). Dietary supplementation of l-tryptophan at a level of 1.36% improved the thermal tolerance level and reduced the oxygen consumption rate in C. mrigala fingerlings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dietary supplementation of a mixture of Lactobacillus strains enhances performance of broiler chickens raised under heat stress conditions

NASA Astrophysics Data System (ADS)

Faseleh Jahromi, Mohammad; Wesam Altaher, Yassir; Shokryazdan, Parisa; Ebrahimi, Roohollah; Ebrahimi, Mahdi; Idrus, Zulkifli; Tufarelli, Vincenzo; Liang, Juan Boo

2016-07-01

High ambient temperature is a major problem in commercial broiler production in the humid tropics because high producing broiler birds consume more feed, have higher metabolic activity, and thus higher body heat production. To evaluate the effects of two previously isolated potential probiotic strains ( Lactobacillus pentosus ITA23 and Lactobacillus acidophilus ITA44) on broilers growing under heat stress condition, a total of 192 chicks were randomly allocated into four treatment groups of 48 chickens each as follows: CL, birds fed with basal diet raised in 24 °C; PL, birds fed with basal diet plus 0.1 % probiotic mixture raised in 24 °C; CH, birds fed with basal diet raised in 35 °C; and PH, birds fed with basal diet plus 0.1 % probiotic mixture raised in 35 °C. The effects of probiotic mixture on the performance, expression of nutrient absorption genes of the small intestine, volatile fatty acids (VFA) and microbial population of cecal contents, antioxidant capacity of liver, and fatty acid composition of breast muscle were investigated. Results showed that probiotic positively affected the final body weight under both temperature conditions (PL and PH groups) compared to their respective control groups (CL and CH). Probiotic supplementation numerically improved the average daily gain (ADG) under lower temperature, but significantly improved ADG under the higher temperature ( P < 0.05) by sustaining high feed intake. Under the lower temperature environment, supplementation of the two Lactobacillus strains significantly increased the expression of the four sugar transporter genes tested (GLUT2, GLUT5, SGLT1, and SGLT4) indicating probiotic enhances the absorption of this nutrient. Similar but less pronounced effect was also observed under higher temperature (35 °C) condition. In addition, the probiotic mixture improved bacterial population of the cecal contents, by increasing beneficial bacteria and decreasing Escherichia coli population, which could be because of higher production of VFA in the cecum, especially at heat stress condition. The two Lactobacillus strains also improved the fatty acid profile of meat, including at heat stress. Generally, the two Lactobacillus strains can be considered as good potential probiotics for chickens due to their good probiotic properties and remarkable efficacy on broiler chickens.

Prenatal binge-like alcohol exposure alters brain and systemic responses to reach sodium and water balance.

PubMed

Godino, A; Abate, P; Amigone, J L; Vivas, L; Molina, J C

2015-12-17

The aim of the present work is to analyze how prenatal binge-like ethanol exposure to a moderate dose (2.0 g/kg; group Pre-EtOH) during gestational days (GD) 17-20 affects hydroelectrolyte regulatory responses. This type of exposure has been observed to increase ethanol consumption during adolescence (postnatal day 30-32). In this study we analyzed basal brain neural activity and basal-induced sodium appetite (SA) and renal response stimulated by sodium depletion (SD) as well as voluntary ethanol consumption as a function of vehicle or ethanol during late pregnancy. In adolescent offspring, SD was induced by furosemide and a low-sodium diet treatment (FURO+LSD). Other animals were analyzed in terms of immunohistochemical detection of Fra-like (Fra-LI-ir) protein and serotonin (5HT) and/or vasopressin (AVP). The Pre-EtOH group exhibited heightened voluntary ethanol intake and a reduction in sodium and water intake induced by SD relative to controls. Basal Na and K concentrations in urine were also reduced in Pre-EtOH animals while the induced renal response after FURO treatment was similar across prenatal treatments. However, the correlation between urine volume and water intake induced by FURO significantly varied across these treatments. At the brain level of analysis, the number of basal Fra-LI-ir was significantly increased in AVP magnocellular neurons of the paraventricular nucleus (PVN) and in 5HT neurons in the dorsal raphe nucleus (DRN) in Pre-EtOH pups. In the experimental group, we also observed a significant increase in Fra-LI along the nucleus of the solitary tract (NTS) and in the central extended amygdala nuclei. In summary, moderate Pre-EtOH exposure produces long-lasting changes in brain organization, affecting basal activity of central extended amygdala nuclei, AVP neurons and the inhibitory areas of SA such as the NTS and the 5HT-DRN. These changes possibly modulate the above described variations in basal-induced drinking behaviors and renal regulatory responses. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A20 Regulates Atherogenic Interferon (IFN)-γ Signaling in Vascular Cells by Modulating Basal IFNβ Levels*

PubMed Central

Moll, Herwig P.; Lee, Andy; Minussi, Darlan C.; da Silva, Cleide G.; Csizmadia, Eva; Bhasin, Manoj; Ferran, Christiane

2014-01-01

IFNγ signaling in endothelial (EC) and smooth muscle cells (SMC) is a key culprit of pathologic vascular remodeling. The impact of NF-κB inhibitory protein A20 on IFNγ signaling in vascular cells remains unknown. In gain- and loss-of-function studies, A20 inversely regulated expression of IFNγ-induced atherogenic genes in human EC and SMC by modulating STAT1 transcription. In vivo, inadequate A20 expression in A20 heterozygote mice aggravated intimal hyperplasia following partial carotid artery ligation. This outcome uniquely associated with increased levels of Stat1 and super-induction of Ifnγ-dependent genes. Transcriptome analysis of the aortic media from A20 heterozygote versus wild-type mice revealed increased basal Ifnβ signaling as the likely cause for higher Stat1 transcription. We confirmed higher basal IFNβ levels in A20-silenced human SMC and showed that neutralization or knockdown of IFNβ abrogates heightened STAT1 levels in these cells. Upstream of IFNβ, A20-silenced EC and SMC demonstrated higher levels of phosphorylated/activated TANK-binding kinase-1 (TBK1), a regulator of IFNβ transcription. This suggested that A20 knockdown increased STAT1 transcription by enhancing TBK1 activation and subsequently basal IFNβ levels. Altogether, these results uncover A20 as a key physiologic regulator of atherogenic IFNγ/STAT1 signaling. This novel function of A20 added to its ability to inhibit nuclear factor-κB (NF-κB) activation solidifies its promise as an ideal therapeutic candidate for treatment and prevention of vascular diseases. In light of recently discovered A20/TNFAIP3 (TNFα-induced protein 3) single nucleotide polymorphisms that impart lower A20 expression or function, these results also qualify A20 as a reliable clinical biomarker for vascular risk assessment. PMID:25217635

Left ventricular rotation and torsion in patients with perimembranous ventricular septal defect.

PubMed

Zhuang, Yan; Yong, Yong-hong; Yao, Jing; Ji, Ling; Xu, Di

2014-03-01

Assessment of left ventricular (LV) rotation has become an important approach for quantifying LV function. In this study, we sought to analyze LV rotation and twist using speckle tracking imaging (STI) in adult patients with isolated ventricular septal defects. Using STI, the peak rotation and time to peak rotation of 6 segments in basal and apical short-axis were measured, respectively, in 32 patients with ventricular septal defect and 30 healthy subjects as controls. The global rotation of the 6 segments in basal and apical and LV twist versus time profile were drawn, the peak rotation and twist of LV were calculated. All the time to peak rotation/twist were expressed as a percentage of end-systole (end-systole = 100%). Left ventricular ejection fraction was measured by biplane Simpson method. In patients group, the peak rotation of posterior, inferior, and postsept wall in basal was higher(P ≤ 0.05) and LV twist was also higher (P ≤ 0.05) than healthy controls. There were no significant differences between 2 groups in the peak rotation of the other 9 segments and left ventricular ejection fraction. Different from the control group, the time to peak rotation of the 6 segments in basal were delayed and the global rotation of the base was delayed (P ≤ 0.05) in ventricular septal defect group. Left ventricular volume overload due to ventricular septal defect has significant effect on LV rotation and twist, and LV rotation and twist may be a new index predicting LV systolic function. © 2013, Wiley Periodicals, Inc.

Expensive Egos: Narcissistic Males Have Higher Cortisol

PubMed Central

Reinhard, David A.; Konrath, Sara H.; Lopez, William D.; Cameron, Heather G.

2012-01-01

Background Narcissism is characterized by grandiosity, low empathy, and entitlement. There has been limited research regarding the hormonal correlates of narcissism, despite the potential health implications. This study examined the role of participant narcissism and sex on basal cortisol concentrations in an undergraduate population. Methods and Findings Participants were 106 undergraduate students (79 females, 27 males, mean age 20.1 years) from one Midwestern and one Southwestern American university. Narcissism was assessed using the Narcissistic Personality Inventory, and basal cortisol concentrations were collected from saliva samples in a laboratory setting. Regression analyses examined the effect of narcissism and sex on cortisol (log). There were no sex differences in basal cortisol, F(1,97) = .20, p = .65, and narcissism scores, F(1,97) = .00, p = .99. Stepwise linear regression models of sex and narcissism and their interaction predicting cortisol concentrations showed no main effects when including covariates, but a significant interaction, β = .27, p = .04. Narcissism was not related to cortisol in females, but significantly predicted cortisol in males. Examining the effect of unhealthy versus healthy narcissism on cortisol found that unhealthy narcissism was marginally related to cortisol in females, β = .27, p = .06, but significantly predicted higher basal cortisol in males, β = .72, p = .01, even when controlling for potential confounds. No relationship was found between sex, narcissism, or their interaction on self-reported stress. Conclusions Our findings suggest that the HPA axis is chronically activated in males with unhealthy narcissism. This constant activation of the HPA axis may have important health implications. PMID:22292062

Long-range correlation properties in timing of skilled piano performance: the influence of auditory feedback and deep brain stimulation.

PubMed

Herrojo Ruiz, María; Hong, Sang Bin; Hennig, Holger; Altenmüller, Eckart; Kühn, Andrea A

2014-01-01

Unintentional timing deviations during musical performance can be conceived of as timing errors. However, recent research on humanizing computer-generated music has demonstrated that timing fluctuations that exhibit long-range temporal correlations (LRTC) are preferred by human listeners. This preference can be accounted for by the ubiquitous presence of LRTC in human tapping and rhythmic performances. Interestingly, the manifestation of LRTC in tapping behavior seems to be driven in a subject-specific manner by the LRTC properties of resting-state background cortical oscillatory activity. In this framework, the current study aimed to investigate whether propagation of timing deviations during the skilled, memorized piano performance (without metronome) of 17 professional pianists exhibits LRTC and whether the structure of the correlations is influenced by the presence or absence of auditory feedback. As an additional goal, we set out to investigate the influence of altering the dynamics along the cortico-basal-ganglia-thalamo-cortical network via deep brain stimulation (DBS) on the LRTC properties of musical performance. Specifically, we investigated temporal deviations during the skilled piano performance of a non-professional pianist who was treated with subthalamic-deep brain stimulation (STN-DBS) due to severe Parkinson's disease, with predominant tremor affecting his right upper extremity. In the tremor-affected right hand, the timing fluctuations of the performance exhibited random correlations with DBS OFF. By contrast, DBS restored long-range dependency in the temporal fluctuations, corresponding with the general motor improvement on DBS. Overall, the present investigations demonstrate the presence of LRTC in skilled piano performances, indicating that unintentional temporal deviations are correlated over a wide range of time scales. This phenomenon is stable after removal of the auditory feedback, but is altered by STN-DBS, which suggests that cortico-basal ganglia-thalamocortical circuits play a role in the modulation of the serial correlations of timing fluctuations exhibited in skilled musical performance.

Short Communication: Low Expression of Activation and Inhibitory Molecules on NK Cells and CD4(+) T Cells Is Associated with Viral Control.

PubMed

Taborda, Natalia A; Hernández, Juan C; Lajoie, Julie; Juno, Jennifer A; Kimani, Joshua; Rugeles, María T; Fowke, Keith R

2015-06-01

Chronic HIV-1 infection induces severe immune alterations, including hyperactivation, exhaustion, and apoptosis. In fact, viral control has been associated with low frequencies of these processes. Here, we evaluated the expression of activation and inhibitory molecules on natural killer (NK) and CD4(+) T cells and plasma levels of proinflammatory cytokines in individuals exhibiting viral control: a cohort of HIV-1-exposed-seronegative individuals (HESN) and a cohort of HIV controllers. There was lower expression of CD69, LAG-3, PD-1, and TIM-3 in both cohorts when compared to a low-risk population or HIV progressors. In addition, HIV controllers exhibited lower plasma levels of proinflamatory molecules TNF-α and IP-10. These findings suggest that individuals exhibiting viral control have lower basal expression of markers associated with cellular activation and particularly immune exhaustion.

Development and intra-institutional and inter-institutional validation of a comprehensive new hepatobiliary software: Part 1--Liver and gallbladder function.

PubMed

Krishnamurthy, Gerbail T; Krishnamurthy, Shakuntala; Gambhir, Sanjiv Sam; Rodrigues, Cesar; Rosenberg, Jarrett; Schiepers, Christiaan; Buxton-Thomas, Muriel

2009-12-01

To develop a software tool for quantification of liver and gallbladder function, and to assess the repeatability and reproducibility of measurements made with it. The software tool developed with the JAVA programming language uses the JAVA2 Standard Edition framework. After manual selection of the regions of interest on a 99mTc hepatic iminodiacetic acid study, the program calculates differential hepatic bile flow, basal duodeno-gastric bile reflux (B-DGBR), hepatic extraction fraction (HEF) of both the lobes with deconvolutional analysis and excretion half-time with nonlinear least squares fit. Gallbladder ejection fraction, ejection period (EP), ejection rate (ER), and postcholecystokinin (CCK) DGBR are calculated after stimulation with CCK-8. To assess intra-observer repeatability and intra-observer reproducibility, measurements from 10 normal participants were analyzed twice by three nuclear medicine technologists at the primary center. To assess inter-site reproducibility, measurements from a superset of 24 normal participants were also assessed once by three observers at the primary center and single observer at three other sites. For the 24 control participants, mean+/-SD of hepatic bile flow into gallbladder was 63.87+/-28.7%, HEF of the right lobe 100+/-0%, left lobe 99.43+2.63%, excretion half-time of the right lobe 21.50+6.98 min, left lobe 28.3+/-11.3 min. Basal DGBR was 1.2+/-1.0%. Gallbladder ejection fraction was 80+/-11%, EP 15.0+/-3.0 min, ER 5.8+/-1.6%/min, and DGBR-CCK 1.3+/-2.3%. Left and right lobe HEF was virtually identical across readers. All measures showed high repeatability except for gallbladder bile flow, basal DGBR, and EP, which exhibited marginal repeatability. Ejection fraction exhibited high reproducibility. There was high concordance among the three primary center observers except for basal DGBR, EP, and ER. Concordance between the primary site and one of the other sites was high, one was fair, and one was poor. New United States Food and Drug Administration-approved personal computer-based Krishnamurthy Hepato-Biliary Software for quantification of the liver and gallbladder function shows promise for consistently repeatable and reproducible results both within and between institutions, and may help to promote universal standardization of data acquisition and analysis in nuclear hepatology.

Kv2.2: A Novel Molecular Target to Study the Role of Basal Forebrain GABAergic Neurons in the Sleep-Wake Cycle

PubMed Central

Hermanstyne, Tracey O.; Subedi, Kalpana; Le, Wei Wei; Hoffman, Gloria E.; Meredith, Andrea L.; Mong, Jessica A.; Misonou, Hiroaki

2013-01-01

Study Objectives: The basal forebrain (BF) has been implicated as an important brain region that regulates the sleep-wake cycle of animals. Gamma-aminobutyric acidergic (GABAergic) neurons are the most predominant neuronal population within this region. However, due to the lack of specific molecular tools, the roles of the BF GABAergic neurons have not been fully elucidated. Previously, we have found high expression levels of the Kv2.2 voltage-gated potassium channel on approximately 60% of GABAergic neurons in the magnocellular preoptic area and horizontal limb of the diagonal band of Broca of the BF and therefore proposed it as a potential molecular target to study this neuronal population. In this study, we sought to determine the functional roles of the Kv2.2-expressing neurons in the regulation of the sleep-wake cycle. Design: Sleep analysis between two genotypes and within each genotype before and after sleep deprivation. Setting: Animal sleep research laboratory. Participants: Adult mice. Wild-type and Kv2.2 knockout mice with C57/BL6 background. Interventions: EEG/EMG recordings from the basal state and after sleep-deprivation which was induced by mild aggitation for 6 h. Results: Immunostaining of a marker of neuronal activity indicates that these Kv2.2-expressing neurons appear to be preferentially active during the wake state. Therefore, we tested whether Kv2.2-expressing neurons in the BF are involved in arousal using Kv2.2-deficient mice. BF GABAergic neurons exhibited augmented expression of c-Fos. These knockout mice exhibited longer consolidated wake bouts than wild-type littermates, and that phenotype was further exacerbated by sleep deprivation. Moreover, in-depth analyses of their cortical electroencephalogram revealed a significant decrease in the delta-frequency activity during the nonrapid eye movement sleep state. Conclusions: These results revealed the significance of Kv2.2-expressing neurons in the regulation of the sleep-wake cycle. Citation: Hermanstyne TO; Subedi K; Le WW; Hoffman GE; Meredith AL; Mong JA; Misonou H. Kv2.2: a novel molecular target to study the role of basal forebrain GABAergic neurons in the sleep-wake cycle. SLEEP 2013;36(12):1839-1848. PMID:24293758

Acid-base characteristics of the Grass Pond watershed in the Adirondack Mountains of New York State, USA: interactions among soil, vegetation and surface waters

NASA Astrophysics Data System (ADS)

McEathron, K. M.; Mitchell, M. J.; Zhang, L.

2013-07-01

Grass Pond watershed is located within the southwestern Adirondack Mountain region of New York State, USA. This region receives some of the highest rates of acidic deposition in North America and is particularly sensitive to acidic inputs due to many of its soils having shallow depths and being generally base poor. Differences in soil chemistry and tree species between seven subwatersheds were examined in relation to acid-base characteristics of the seven major streams that drain into Grass Pond. Mineral soil pH, stream water BCS (base-cation surplus) and pH exhibited a positive correlation with sugar maple basal area (p = 0.055; 0.48 and 0.39, respectively). Black cherry basal area was inversely correlated with stream water BCS, ANC (acid neutralizing capacity)c and NO3- (p = 0.23; 0.24 and 0.20, respectively). Sugar maple basal areas were positively associated with watershed characteristics associated with the neutralization of atmospheric acidic inputs while in contrast, black cherry basal areas showed opposite relationships to these same watershed characteristics. Canonical correspondence analysis indicated that black cherry had a distinctive relationship with forest floor chemistry apart from the other tree species, specifically a strong positive association with forest floor NH4, while sugar maple had a distinctive relationship with stream chemistry variables, specifically a strong positive association with stream water ANCc, BCS and pH. Our results provide evidence that sugar maple is acid-intolerant or calciphilic tree species and also demonstrate that black cherry is likely an acid-tolerant tree species.

Muscle-Specific Deletion of Rictor Impairs Insulin-Stimulated Glucose Transport and Enhances Basal Glycogen Synthase Activity▿

PubMed Central

Kumar, Anil; Harris, Thurl E.; Keller, Susanna R.; Choi, Kin M.; Magnuson, Mark A.; Lawrence, John C.

2008-01-01

Rictor is an essential component of mTOR (mammalian target of rapamycin) complex 2 (mTORC2), a kinase complex that phosphorylates Akt at Ser473 upon activation of phosphatidylinositol 3-kinase (PI-3 kinase). Since little is known about the role of either rictor or mTORC2 in PI-3 kinase-mediated physiological processes in adult animals, we generated muscle-specific rictor knockout mice. Muscle from male rictor knockout mice exhibited decreased insulin-stimulated glucose uptake, and the mice showed glucose intolerance. In muscle lacking rictor, the phosphorylation of Akt at Ser473 was reduced dramatically in response to insulin. Furthermore, insulin-stimulated phosphorylation of the Akt substrate AS160 at Thr642 was reduced in rictor knockout muscle, indicating a defect in insulin signaling to stimulate glucose transport. However, the phosphorylation of Akt at Thr308 was normal and sufficient to mediate the phosphorylation of glycogen synthase kinase 3 (GSK-3). Basal glycogen synthase activity in muscle lacking rictor was increased to that of insulin-stimulated controls. Consistent with this, we observed a decrease in basal levels of phosphorylated glycogen synthase at a GSK-3/protein phosphatase 1 (PP1)-regulated site in rictor knockout muscle. This change in glycogen synthase phosphorylation was associated with an increase in the catalytic activity of glycogen-associated PP1 but not increased GSK-3 inactivation. Thus, rictor in muscle tissue contributes to glucose homeostasis by positively regulating insulin-stimulated glucose uptake and negatively regulating basal glycogen synthase activity. PMID:17967879

Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium

PubMed Central

Ewald, Andrew J.; Huebner, Robert J.; Palsdottir, Hildur; Lee, Jessie K.; Perez, Melissa J.; Jorgens, Danielle M.; Tauscher, Andrew N.; Cheung, Kevin J.; Werb, Zena; Auer, Manfred

2012-01-01

Normal mammary morphogenesis involves transitions between simple and multilayered epithelial organizations. We used electron microscopy and molecular markers to determine whether intercellular junctions and apico-basal polarity were maintained in the multilayered epithelium. We found that multilayered elongating ducts had polarized apical and basal tissue surfaces both in three-dimensional culture and in vivo. However, individual cells were only polarized on surfaces in contact with the lumen or extracellular matrix. The basolateral marker scribble and the apical marker atypical protein kinase C zeta localized to all interior cell membranes, whereas PAR3 displayed a cytoplasmic localization, suggesting that the apico-basal polarity was incomplete. Despite membrane localization of E-cadherin and β-catenin, we did not observe a defined zonula adherens connecting interior cells. Instead, interior cells were connected through desmosomes and exhibited complex interdigitating membrane protrusions. Single-cell labeling revealed that individual cells were both protrusive and migratory within the epithelial multilayer. Inhibition of Rho kinase (ROCK) further reduced intercellular adhesion on apical and lateral surfaces but did not disrupt basal tissue organization. Following morphogenesis, segregated membrane domains were re-established and junctional complexes re-formed. We observed similar epithelial organization during mammary morphogenesis in organotypic culture and in vivo. We conclude that mammary epithelial morphogenesis involves a reversible, spatially limited, reduction in polarity and intercellular junctions and active individualistic cell migration. Our data suggest that reductions in polarity and adhesion during breast cancer progression might reflect partial recapitulation of a normal developmental program. PMID:22344263

Obesity-driven prepartal hepatic lipid accumulation in dairy cows is associated with increased CD36 and SREBP-1 expression.

PubMed

Prodanović, Radiša; Korićanac, Goran; Vujanac, Ivan; Djordjević, Ana; Pantelić, Marija; Romić, Snježana; Stanimirović, Zoran; Kirovski, Danijela

2016-08-01

We investigated the hypothesis that obesity in dairy cows enhanced expression of proteins involved in hepatic fatty acid uptake and metabolism. Sixteen Holstein-Friesian close-up cows were divided into 2 equal groups based on their body condition score (BCS) as optimal (3.25≤BCS≤3.5) and high (4.0≤BCS≤4.25). Intravenous glucose tolerance test (GTT) and liver biopsies were carried out at day 10 before calving. Blood samples were collected before (basal) and after glucose infusion, and glucose, insulin and non-esterified fatty acid (NEFA) levels were determined at each sample point. In addition, β-hydroxybutyrate and triglycerides levels were measured in the basal samples. The liver biopsies were analyzed for total lipid content and protein expression of insulin receptor beta (IRβ), fatty acid translocase (FAT/CD36) and sterol regulatory element-binding protein-1 (SREBP-1). Basal glucose and insulin were higher in high-BCS cows, which coincided with higher circulating triglycerides and hepatic lipid content. Clearance rate and AUC for NEFA during GTT were higher in optimal-BCS cows. The development of insulin resistance and fatty liver in obese cows was paralleled by increased hepatic expression of the IRβ, CD36 and SREBP-1. These results suggest that increased expression of hepatic CD36 and SREBP-1 is relevant in the obesity-driven lipid accumulation in the liver of dairy cows during late gestation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative endocrinological responses to short transportation of Equidae (Equus asinus and Equus caballus).

PubMed

Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Aveni, Francesca; Ferlazzo, Adriana

2013-03-01

In order to evaluate the effects of short transportation on β-endorphin, adrenocorticotropic hormone (ACTH) and cortisol changes, 12 healthy stallions of Equidae (Equus asinus and Equus caballus) were studied before and after transportation of 50 km. Blood samples were collected 1 week before transportation in basal conditions, immediately before loading and after transportation and unloading, on their arrival at the breeding station. Compared to basal and before values, donkeys showed an increase in circulating ACTH (P < 0.001) and cortisol (P < 0.0005) levels after transportation and higher ACTH (P < 0.01) levels than horses after transportation. A positive and significant correlation (r = 0.885; P < 0.01) between ACTH and cortisol levels after transportation was found. No significant differences were observed for β-endorphin levels. Compared to basal and before values, horses showed higher cortisol (P < 0.005) levels after transportation and no significant differences were observed for ACTH and β-endorphin levels in donkeys. Horses facing forward (direction of travel) showed higher (P < 0.01) β-endorphin levels after transportation than donkeys; horses facing backward (the opposite direction of travel) showed lower (P < 0.05) ACTH levels after transportation. The results indicate that short transportation induces a preferential activation of the hypothalamus-pituitary-axis (HPA), with significant release of ACTH and cortisol in donkeys and only of cortisol in horses, suggesting that transportation for donkeys may be more stressful than horses. © 2012 The Authors Animal Science Journal © 2012 Japanese Society of Animal Science.

Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival.

PubMed

Tiong, Kai Hung; Tan, Boon Shing; Choo, Heng Lungh; Chung, Felicia Fei-Lei; Hii, Ling-Wei; Tan, Si Hoey; Khor, Nelson Tze Woei; Wong, Shew Fung; See, Sze-Jia; Tan, Yuen-Fen; Rosli, Rozita; Cheong, Soon-Keng; Leong, Chee-Onn

2016-09-06

Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.

Exploring the effects of inclusion of dietary fresh Azolla on the performance of White Pekin broiler ducks

PubMed Central

Acharya, Parag; Mohanty, G. P.; Pradhan, C. R.; Mishra, S. K.; Beura, N. C.; Moharana, B.

2015-01-01

Aim: The objective of this study was to investigate the dietary advantages of inclusion of unconventional nutrient source, i.e., Azolla in the basal diet of White Pekin broilers. Materials and Methods: All ducklings were randomly distributed into three treatment groups with three replicates each and each replicate having 12 ducklings and were reared in deep litter system. Groups were subjected to three dietary treatments such as G1: Basal diet, G2: Basal diet + 5% fresh Azolla of basal diet, G3: Basal diet + 10% fresh Azolla of basal diet. During experimental period, parameters, such as bodyweight, bodyweight gain, feed consumption,feed conversion ratio(FCR), and economic of production,wererecorded. Results: The result showed that body weights in every week, except the 5th week, did not differ significantly between groups. However, no significant difference was observed between the groups in any week in terms of absolute body weight gain and feed consumption. As regard to FCR, the 10% Azolla group (G3) showed the best feed efficiency followed by the 5% Azolla group (G2) and the control group (G1). On the basis of profit/bird or profit/kg live weight, each of the Azolla-fed group showed a higher economic efficiency than the control. Conclusion: From the experiment, it was concluded that Azollaat 5 or 10% level can be included in the diet to economize the White Pekin broiler farming, and it can be great impetus to poultry farming to include unconventional nutrient source as a dietary supplement. PMID:27047032

Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson's case.

PubMed

Marquié, Marta; Verwer, Eline E; Meltzer, Avery C; Kim, Sally Ji Who; Agüero, Cinthya; Gonzalez, Jose; Makaretz, Sara J; Siao Tick Chong, Michael; Ramanan, Prianca; Amaral, Ana C; Normandin, Marc D; Vanderburg, Charles R; Gomperts, Stephen N; Johnson, Keith A; Frosch, Matthew P; Gómez-Isla, Teresa

2017-10-19

[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD type and mild cognitive impairment in regions that are known to contain tau lesions. In vivo uptake has also consistently been observed in midbrain, basal ganglia and choroid plexus in elderly individuals regardless of their clinical diagnosis, including clinically normal whose brains are not expected to harbor tau pathology in those areas. We and others have shown that [F-18]-AV-1451 exhibits off-target binding to neuromelanin, melanin and blood products on postmortem material; and this is important for the correct interpretation of PET images. In the present study, we further investigated [F-18]-AV-1451 off-target binding in the first autopsy-confirmed Parkinson's disease (PD) subject who underwent antemortem PET imaging. The PET scan showed elevated [F-18]-AV-1451 retention predominantly in inferior temporal cortex, basal ganglia, midbrain and choroid plexus. Neuropathologic examination confirmed the PD diagnosis. Phosphor screen and high resolution autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined with the exception of neuromelanin-containing neurons in the substantia nigra, leptomeningeal melanocytes adjacent to ventricles and midbrain, and microhemorrhages in the occipital cortex (all reflecting off-target binding), in addition to incidental age-related neurofibrillary tangles in the entorhinal cortex. Additional legacy postmortem brain samples containing basal ganglia, choroid plexus, and parenchymal hemorrhages from 20 subjects with various neuropathologic diagnoses were also included in the autoradiography experiments to better understand what [F-18]-AV-1451 in vivo positivity in those regions means. No detectable [F-18]-AV-1451 autoradiographic binding was present in the basal ganglia of the PD case or any of the other subjects. Off-target binding in postmortem choroid plexus samples was only observed in subjects harboring leptomeningeal melanocytes within the choroidal stroma. Off-target binding to parenchymal hemorrhages was noticed in postmortem material from subjects with cerebral amyloid angiopathy. The imaging-postmortem correlation analysis in this PD case reinforces the notion that [F-18]-AV-1451 has strong affinity for neurofibrillary tau pathology but also exhibits off-target binding to neuromelanin, melanin and blood components. The robust off-target in vivo retention in basal ganglia and choroid plexus, in the absence of tau deposits, meningeal melanocytes or any other identifiable binding substrate by autoradiography in the PD case reported here, also suggests that the PET signal in those regions may be influenced, at least in part, by biological or technical factors that occur in vivo and are not captured by autoradiography.

Transitional epithelial lesions of the ureter in renal transplant rejection.

PubMed

Katz, J P; Greenstein, S M; Hakki, A; Miller, A; Katz, S M; Simonian, S

1988-04-01

The spectrum of ureteric lesions of human renal allografts, long attributed exclusively to postsurgical complications such as ischemia, has recently been shown to include the types of rejection seen in the kidney. Since the rejected ureter also exhibits transitional epithelial lesions that may impact on renal and ureteral function, we studied, by light, immunohistochemical, immunofluorescent, and electron microscopic techniques, ureters of 65 irreversibly rejected kidneys. Seven unused cadaver kidneys served as controls. Urothelial lesions, noticed in 57 of 65 ureters (88%), ranged from minimal basal vacuolization to complete sloughing with or without necrosis of the epithelial lining. Epithelial exfoliation was noticed in 31 cases (54.4%), and basal vacuolization, severe enough to produce cleavage of the epithelial junctions and thus create bullae, was noticed in 21 cases (36.8%). Immunofluorescent and immunoperoxidase stains, performed in 16 cases, were all positive for immunoglobulins but yielded varied results ranging from granular to linear staining, particularly in the region of the basal cells and the basement membrane. Electron microscopic findings confirmed the light microscopic alterations. By contrast, control ureters showed no lesions. Urothelial ureteric lesions might impede ureteral functions and result in obstruction or infection, thus compounding the consequences of renal allograft rejection. Moreover, elucidation of the pathophysiology of the process will advance the understanding of various cutaneous and transitional epithelial autoimmune conditions.

Effect of dietary intake of avocado oil and olive oil on biochemical markers of liver function in sucrose-fed rats.

PubMed

Carvajal-Zarrabal, Octavio; Nolasco-Hipolito, Cirilo; Aguilar-Uscanga, Ma Guadalupe; Melo Santiesteban, Guadalupe; Hayward-Jones, Patricia M; Barradas-Dermitz, Dulce Ma

2014-01-01

Metabolic changes, along with cardiovascular and hepatic factors, are associated with the development of diseases such as diabetes, dyslipidemia, and obesity. We evaluated the effect of avocado oil supplementation (centrifuged and solvent extracted), compared with olive oil, upon the hepatic function in sucrose-fed rats. Twenty-five rats were divided into five groups: control (basal diet), a sucrose-fed group (basal diet plus 30% sucrose solution), and three other groups (S-OO, S-AOC, and S-AOS, indicating basal diet plus 30% sucrose solution plus olive oil OO, avocado oil extracted by centrifugation AOC or using solvent AOS, resp.). Glucose, total cholesterol, triglycerides, total protein, albumin, globulin, direct bilirubin, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase, cholinesterase, and α -amylase concentrations were determined and avocado oil effect on them was studied. In some cases the induced metabolic alteration significantly affected total protein and bilirubin levels and also had a highly significant effect on α -amylase levels. AOC and AOS exhibited effects similar to those of olive oil, according to the nonsignificant difference in fatty acid profile observed by other authors. Avocado oil consumption could be beneficial in the control of altered metabolic profile illnesses as it presents effects on hepatic function biochemical markers similar to olive oil.

The Enhancement of Phototropin-Induced Phototropic Curvature in Arabidopsis Occurs via a Photoreversible Phytochrome A-Dependent Modulation of Auxin Responsiveness1

PubMed Central

Stowe-Evans, Emily L.; Luesse, Darron R.; Liscum, Emmanuel

2001-01-01

The induction of phototropism in etiolated (dark-grown) seedlings exposed to an unidirectional pulse or extended irradiation with low fluence rate blue light (BL) requires the action of the phototropin (nph1) BL receptor. Although cryptochromes and phytochromes are not required for phototropic induction, these photoreceptors do modulate the magnitude of curvature resulting from phototropin activation. Modulatory increases in the magnitude of phototropic curvature have been termed “enhancement.” Here, we show that phototropic enhancement is primarily a phytochrome A (phyA)-dependent red/far-red-reversible low fluence response. This phyA-dependent response is genetically separable from the basal phototropin-dependent response, as demonstrated by its retention under extended irradiation conditions in the nph4 mutant background, which normally lacks the basal BL-induced response. It is interesting that the nph4 mutants fail to exhibit the basal phototropin-dependent and phyA-dependent enhancement responses under limiting light conditions. Given that NPH4 encodes a transcriptional activator, auxin response factor 7 (ARF7), we hypothesize that the ultimate target(s) of phyA action during the phototropic enhancement response is a rate-limiting ARF-containing transcriptional complex in which the constituent ARFs can vary in identity or activity depending upon the irradiation condition. PMID:11402210

Effects of acidic deposition and soil acidification on sugar maple trees in the Adirondack Mountains, New York.

PubMed

Sullivan, T J; Lawrence, G B; Bailey, S W; McDonnell, T C; Beier, C M; Weathers, K C; McPherson, G T; Bishop, D A

2013-11-19

We documented the effects of acidic atmospheric deposition and soil acidification on the canopy health, basal area increment, and regeneration of sugar maple (SM) trees across the Adirondack region of New York State, in the northeastern United States, where SM are plentiful but not well studied and where widespread depletion of soil calcium (Ca) has been documented. Sugar maple is a dominant canopy species in the Adirondack Mountain ecoregion, and it has a high demand for Ca. Trees in this region growing on soils with poor acid-base chemistry (low exchangeable Ca and % base saturation [BS]) that receive relatively high levels of atmospheric sulfur and nitrogen deposition exhibited a near absence of SM seedling regeneration and lower crown vigor compared with study plots with relatively high exchangeable Ca and BS and lower levels of acidic deposition. Basal area increment averaged over the 20th century was correlated (p < 0.1) with acid-base chemistry of the Oa, A, and upper B soil horizons. A lack of Adirondack SM regeneration, reduced canopy condition, and possibly decreased basal area growth over recent decades are associated with low concentrations of nutrient base cations in this region that has undergone soil Ca depletion from acidic deposition.

Adaptive mesh refinement versus subgrid friction interpolation in simulations of Antarctic ice dynamics

DOE PAGES

Cornford, S. L.; Martin, D. F.; Lee, V.; ...

2016-05-13

At least in conventional hydrostatic ice-sheet models, the numerical error associated with grounding line dynamics can be reduced by modifications to the discretization scheme. These involve altering the integration formulae for the basal traction and/or driving stress close to the grounding line and exhibit lower – if still first-order – error in the MISMIP3d experiments. MISMIP3d may not represent the variety of real ice streams, in that it lacks strong lateral stresses, and imposes a large basal traction at the grounding line. We study resolution sensitivity in the context of extreme forcing simulations of the entire Antarctic ice sheet, using the BISICLES adaptive mesh ice-sheet model with two schemes: the original treatment, and a scheme, which modifies the discretization of the basal traction. The second scheme does indeed improve accuracy – by around a factor of two – for a given mesh spacing, butmore » $$\\lesssim 1$$ km resolution is still necessary. For example, in coarser resolution simulations Thwaites Glacier retreats so slowly that other ice streams divert its trunk. In contrast, with $$\\lesssim 1$$ km meshes, the same glacier retreats far more quickly and triggers the final phase of West Antarctic collapse a century before any such diversion can take place.« less

Microstructure and Texture Evolution in a Yttrium-Containing ZM31 Alloy: Effect of Pre- and Post-deformation Annealing

NASA Astrophysics Data System (ADS)

Tahreen, N.; Zhang, D. F.; Pan, F. S.; Jiang, X. Q.; Li, D. Y.; Chen, D. L.

2016-12-01

Microstructure and texture evolution of as-extruded ZM31 magnesium alloys with different amounts of yttrium (Y) during pre- and post-deformation annealing were examined with special attention given to the effect of Y on recrystallization. It was observed that the extruded ZM31 alloys exhibited a basal texture with the basal planes parallel to the extrusion direction (ED). The compression of the extruded alloys in the ED to a strain amount of 10 pct resulted in c-axes of hcp unit cells rotating toward the anti-compression direction due to the occurrence of extension twinning. Annealing of the extruded alloys altered the microstructure and texture, and the subsequent compression after annealing showed a relatively weak texture and a lower degree of twinning. A reverse procedure of pre-compression and subsequent annealing was found to further weaken the texture with a more scattered distribution of orientations and to lead to the vanishing of the original basal texture. With increasing Y content, both the extent of extension twinning during compression and the fraction of recrystallization during annealing decreased due to the role of Y present in the substitutional solid solution and in the second-phase particles, leading to a significant increase in the compressive yield strength.

Complex Expression of the Cellulolytic Transcriptome of Saccharophagus degradans † ▿

PubMed Central

Zhang, Haitao; Hutcheson, Steven W.

2011-01-01

Saccharophagus degradans is an aerobic marine bacterium that can degrade cellulose by the induced expression of an unusual cellulolytic system composed of multiple endoglucanases and glucosidases. To understand the regulation of the cellulolytic system, transcript levels for the genes predicted to contribute to the cellulolytic system were monitored by quantitative real-time PCR (qRT-PCR) during the transition to growth on cellulose. Four glucanases of the cellulolytic system exhibited basal expression during growth on glucose. All but one of the predicted cellulolytic system genes were induced strongly during growth on Avicel, with three patterns of expression observed. One group showed increased expression (up to 6-fold) within 4 h of the nutritional shift, with the relative expression remaining constant over the next 22 h. A second group of genes was strongly induced between 4 and 10 h after nutritional transfer, with relative expression declining thereafter. The third group of genes was slowly induced and was expressed maximally after 24 h. Cellodextrins and cellobiose, products of the predicted basally expressed endoglucanases, stimulated expression of representative cellulase genes. A model is proposed by which the activity of basally expressed endoglucanases releases cellodextrins from Avicel that are then perceived and transduced to initiate transcription of each of the regulated cellulolytic system genes forming an expression pattern. PMID:21705539

Effects of acidic deposition and soil acidification on sugar maple trees in the Adirondack Mountains, New York

USGS Publications Warehouse

Sullivan, Timothy J.; Lawrence, Gregory B.; Bailey, Scott W.; McDonnell, Todd C.; Beier, Colin M.; Weathers, K.C.; McPherson, G.T.; Bishop, Daniel A.

2013-01-01

We documented the effects of acidic atmospheric deposition and soil acidification on the canopy health, basal area increment, and regeneration of sugar maple (SM) trees across the Adirondack region of New York State, in the northeastern United States, where SM are plentiful but not well studied and where widespread depletion of soil calcium (Ca) has been documented. Sugar maple is a dominant canopy species in the Adirondack Mountain ecoregion, and it has a high demand for Ca. Trees in this region growing on soils with poor acid–base chemistry (low exchangeable Ca and % base saturation [BS]) that receive relatively high levels of atmospheric sulfur and nitrogen deposition exhibited a near absence of SM seedling regeneration and lower crown vigor compared with study plots with relatively high exchangeable Ca and BS and lower levels of acidic deposition. Basal area increment averaged over the 20th century was correlated (p < 0.1) with acid–base chemistry of the Oa, A, and upper B soil horizons. A lack of Adirondack SM regeneration, reduced canopy condition, and possibly decreased basal area growth over recent decades are associated with low concentrations of nutrient base cations in this region that has undergone soil Ca depletion from acidic deposition.

Effect of Dietary Intake of Avocado Oil and Olive Oil on Biochemical Markers of Liver Function in Sucrose-Fed Rats

PubMed Central

Carvajal-Zarrabal, Octavio; Nolasco-Hipolito, Cirilo; Aguilar-Uscanga, Ma. Guadalupe; Melo Santiesteban, Guadalupe; Hayward-Jones, Patricia M.; Barradas-Dermitz, Dulce Ma.

2014-01-01

Metabolic changes, along with cardiovascular and hepatic factors, are associated with the development of diseases such as diabetes, dyslipidemia, and obesity. We evaluated the effect of avocado oil supplementation (centrifuged and solvent extracted), compared with olive oil, upon the hepatic function in sucrose-fed rats. Twenty-five rats were divided into five groups: control (basal diet), a sucrose-fed group (basal diet plus 30% sucrose solution), and three other groups (S-OO, S-AOC, and S-AOS, indicating basal diet plus 30% sucrose solution plus olive oil OO, avocado oil extracted by centrifugation AOC or using solvent AOS, resp.). Glucose, total cholesterol, triglycerides, total protein, albumin, globulin, direct bilirubin, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase, cholinesterase, and α-amylase concentrations were determined and avocado oil effect on them was studied. In some cases the induced metabolic alteration significantly affected total protein and bilirubin levels and also had a highly significant effect on α-amylase levels. AOC and AOS exhibited effects similar to those of olive oil, according to the nonsignificant difference in fatty acid profile observed by other authors. Avocado oil consumption could be beneficial in the control of altered metabolic profile illnesses as it presents effects on hepatic function biochemical markers similar to olive oil. PMID:24860825

Tamoxifen enhances choline acetyltransferase mRNA expression in rat basal forebrain cholinergic neurons.

PubMed

McMillan, Pamela J; LeMaster, Ann M; Dorsa, Daniel M

2002-06-30

Novel estrogen-like molecules known as SERMs (selective estrogen receptor modulators) produce many of the beneficial estrogen-like actions without the detrimental side-effects. The SERM, tamoxifen, an estrogen-like molecule with both agonist and antagonist properties, is widely prescribed for the treatment of breast cancer. While the effects of tamoxifen are being evaluated in many peripheral tissues, its effects in the central nervous system (CNS) have been largely ignored. In the present study, we begin to evaluate the effects of tamoxifen in the rat basal forebrain, a region known to be highly responsive to estrogen. We compared the effects of short-term (24 h) tamoxifen treatment to that of estrogen on ChAT mRNA expression in cholinergic neurons. In addition, we examined the effect of tamoxifen in the presence and absence of estrogen. Our results indicate that tamoxifen enhances ChAT expression in a manner similar to that of estrogen in several basal forebrain regions. In contrast, tamoxifen exhibits antagonist properties with respect to estrogen-induction of progesterone receptor mRNA in the medial preoptic nucleus. These results indicate tamoxifen has estrogenic properties with respect to cholinergic neurons, suggesting a previously unidentified effect of this agent in the CNS. Copyright 2002 Elsevier Science B.V.

Adult Leigh disease without failure to thrive.

PubMed

Sakushima, Ken; Tsuji-Akimoto, Sachiko; Niino, Masaaki; Saitoh, Shinji; Yabe, Ichiro; Sasaki, Hidenao

2011-07-01

Most Leigh disease (LD) patients die before reaching adulthood, but there are reports of "adult LD." The clinical features of adult LD were quite different from those in infant or childhood cases. Here, we describe a normally developed patient with adult LD, who presented with spastic paraplegia that was followed several years later by acute encephalopathy. We also conducted a systemic literature search on adult LD and integrated its various manifestations to arrive at a diagnostic procedure for adult LD. A 26-year-old woman presented with acute encephalopathy after spastic paraplegia. On her first admission, she exhibited bilateral basal ganglia lesion on magnetic resonance images and normal serum lactate levels. On second admission, she had acute encephalopathy with lactic acidosis and bilateral basal ganglia and brainstem lesions. A muscle biopsy revealed cytochrome c oxidase deficiency, and a diagnosis of adult LD was made. Despite treatment in the intensive care unit, she died 9 days after admission. A review of the literature describing adult LD revealed that developmental delay, COX deficiency, serum lactate elevation, and basal ganglia lesions occurred less frequently than they did in children with LD. Cranial nerve disturbance, pyramidal signs, and cerebellar dysfunction were the primary symptoms in adult LD. Thus, the many differences between childhood and adult LD may be helpful for diagnosing adult LD.

An Enantiomer of an Oral Small-Molecule TSH Receptor Agonist Exhibits Improved Pharmacologic Properties.

PubMed

Neumann, Susanne; Padia, Umesh; Cullen, Mary Jane; Eliseeva, Elena; Nir, Eshel A; Place, Robert F; Morgan, Sarah J; Gershengorn, Marvin C

2016-01-01

We are developing an orally available small-molecule, allosteric TSH receptor (TSHR) agonist for follow-up diagnostics of patients with thyroid cancer. The agonist C2 (NCGC00161870) that we have studied so far is a racemic mixture containing equal amounts of two enantiomers, E1 and E2. As enantiomers of many drugs exhibit different pharmacologic properties, we assessed the properties of E1 and E2. We separated the two enantiomers by chiral chromatography and determined E2 as the (S)-(+) isomer via crystal structure analysis. E1 and E2 were shown to bind differently to a homology model of the transmembrane domain of TSHR in which E2 was calculated to exhibit lower binding energy than E1 and was, therefore, predicted to be more potent than E1. In HEK293 cells expressing human TSHRs, C2, E1, and E2 were equally efficacious in stimulating cAMP production, but their potencies were different. E2 was more potent (EC50 = 18 nM) than C2 (EC50 = 46 nM), which was more potent than E1 (EC50 = 217 nM). In primary cultures of human thyrocytes, C2, E1, and E2 stimulated increases in thyroperoxidase mRNA of 92-, 55-, and 137-fold and in sodium-iodide symporter mRNA of 20-, 4-, and 121-fold above basal levels, respectively. In mice, C2 stimulated an increase in radioactive iodine uptake of 1.5-fold and E2 of 2.8-fold above basal level, whereas E1 did not have an effect. C2 stimulated an increase in serum T4 of 2.4-fold, E1 of 1.9-fold, and E2 of 5.6-fold above basal levels, and a 5-day oral dosing regimen of E2 increased serum T4 levels comparable to recombinant human TSH (rhTSH, Thyrogen(®)). Thus, E2 is more effective than either C2 or E1 in stimulating thyroid function and as efficacious as rhTSH in vivo. E2 represents the next step toward developing an oral drug for patients with thyroid cancer.

Contribution of early environmental stress to alcoholism vulnerability.

PubMed

Campbell, Joannalee C; Szumlinski, Karen K; Kippin, Tod E

2009-11-01

The most problematic aspects of alcohol abuse disorder are excessive alcohol consumption and the inability to refrain from alcohol consumption during attempted abstinence. The root causes that predispose certain individuals to these problems are poorly understood but are believed to be produced by a combination of genetic and environmental factors. Early environmental trauma alters neurodevelopmental trajectories that can predispose an individual to a number of neuropsychiatric disorders, including substance abuse. Prenatal stress (PNS) is a well-established protocol that produces perturbations in nervous system development, resulting in behavioral alterations that include hyperresponsiveness to stress, novelty, and psychomotor stimulant drugs (e.g., cocaine, amphetamine). Moreover, PNS animals exhibit enduring alterations in basal and cocaine-induced changes in dopamine and glutamate transmission within limbic structures, which exhibit pathology in drug addiction and alcoholism, suggesting that these alterations may contribute to an increased propensity to self-administer large amounts of drugs of abuse or to relapse after periods of drug withdrawal. Given that cocaine and alcohol have actions on common limbic neural substrates (albeit by different mechanisms), we hypothesized that PNS would elevate the motivation for, and consumption of, alcohol. Accordingly, we have found that male C57BL/6J mice subject to PNS exhibit higher operant responding and consume more alcohol during alcohol reinforcement as adults. Alterations in glutamate and dopamine neurotransmission within the forebrain structures appear to contribute to the PNS-induced predisposition to high alcohol intake and are induced by excessive alcohol intake. Accordingly, we are exploring the interactions between neurochemical changes produced by PNS and changes induced by consumption of alcohol in adulthood to model the biological bases of high vulnerability to alcohol abuse.

Contribution of early environmental stress to alcoholism vulnerability

PubMed Central

Campbell, Joannalee C.; Szumlinski, Karen K.; Kippin, Tod E.

2011-01-01

The most problematic aspects of alcohol abuse disorder are excessive alcohol consumption and the inability to refrain from alcohol consumption during attempted abstinence. The root causes that predispose certain individuals to these problems are poorly understood but are believed to be produced by a combination of genetic and environmental factors. Early environmental trauma alters neurodevelopmental trajectories that can predispose an individual to a number of neuropsychiatric disorders, including substance abuse. Prenatal stress (PNS) is a well-established protocol that produces perturbations in nervous system development, resulting in behavioral alterations that include hyperresponsiveness to stress, novelty, and psychomotor stimulant drugs (e.g., cocaine, amphetamine). Moreover, PNS animals exhibit enduring alterations in basal and cocaine-induced changes in dopamine and glutamate transmission within limbic structures, which exhibit pathology in drug addiction and alcoholism, suggesting that these alterations may contribute to an increased propensity to self-administer large amounts of drugs of abuse or to relapse after periods of drug withdrawal. Given that cocaine and alcohol have actions on common limbic neural substrates (albeit by different mechanisms), we hypothesized that PNS would elevate the motivation for, and consumption of, alcohol. Accordingly, we have found that male C57BL/6J mice subject to PNS exhibit higher operant responding and consume more alcohol during alcohol reinforcement as adults. Alterations in glutamate and dopamine neurotransmission within the forebrain structures appear to contribute to the PNS-induced predisposition to high alcohol intake and are induced by excessive alcohol intake. Accordingly, we are exploring the interactions between neurochemical changes produced by PNS and changes induced by consumption of alcohol in adulthood to model the biological bases of high vulnerability to alcohol abuse. PMID:19913199

Basal ganglia function, stuttering, sequencing, and repair in adult songbirds.

PubMed

Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D

2014-10-13

A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations.

Variability of insulin degludec and glargine U300: A matter of methodology or just marketing?

PubMed

Heise, Tim; Heckermann, Sascha; DeVries, J Hans

2018-05-17

The variability in the time-action profiles of insulin preparations, in particular basal insulins, has been a matter of debate ever since the publication of a glucose clamp study comparing the day-to-day variability of three different basal insulins (glargine U100, detemir and NPH) in 2004 [1]. While critics did not contest the findings of a lower variability of some basal insulins in this and a later [2] glucose clamp study, they did question the relevance of a lower pharmacokinetic (PK) and pharmacodynamic (PD) variability for clinical endpoints [3, 4]. Nevertheless, this has not stopped marketeers to widely use the results of glucose clamp studies promoting insulins for higher predictability or a suggested flat PK/PD-profile fully covering 24 hours [5]. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix

PubMed Central

Mekhdjian, Armen H.; Kai, FuiBoon; Rubashkin, Matthew G.; Prahl, Louis S.; Przybyla, Laralynne M.; McGregor, Alexandra L.; Bell, Emily S.; Barnes, J. Matthew; DuFort, Christopher C.; Ou, Guanqing; Chang, Alice C.; Cassereau, Luke; Tan, Steven J.; Pickup, Michael W.; Lakins, Jonathan N.; Ye, Xin; Davidson, Michael W.; Lammerding, Jan; Odde, David J.; Dunn, Alexander R.; Weaver, Valerie M.

2017-01-01

Metastasis requires tumor cells to navigate through a stiff stroma and squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data show that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype. Metastatic tumor cells and basal-like tumor cells exert higher integrin-mediated traction forces at the bulk and molecular levels, consistent with a motor-clutch model in which motors and clutches are both increased. Basal-like nonmalignant mammary epithelial cells also display an altered integrin adhesion molecular organization at the nanoscale and recruit a suite of paxillin-associated proteins implicated in invasion and metastasis. Phosphorylation of paxillin by Src family kinases, which regulates adhesion turnover, is similarly enhanced in the metastatic and basal-like tumor cells, fostered by a stiff matrix, and critical for tumor cell invasion in our assays. Bioinformatics reveals an unappreciated relationship between Src kinases, paxillin, and survival of breast cancer patients. Thus adoption of the basal-like adhesion phenotype may favor the recruitment of molecules that facilitate tumor metastasis to integrin-based adhesions. Analysis of the physical properties of tumor cells and integrin adhesion composition in biopsies may be predictive of patient outcome. PMID:28381423

Changing basal conditions during the speed-up of Jakobshavn Isbræ, Greenland

NASA Astrophysics Data System (ADS)

Habermann, M.; Truffer, M.; Maxwell, D.

2013-11-01

Ice-sheet outlet glaciers can undergo dynamic changes such as the rapid speed-up of Jakobshavn Isbræ following the disintegration of its floating ice tongue. These changes are associated with stress changes on the boundary of the ice mass. We invert for basal conditions from surface velocity data throughout a well-observed period of rapid change and evaluate parameterizations currently used in ice-sheet models. A Tikhonov inverse method with a shallow-shelf approximation forward model is used for diagnostic inversions for the years 1985, 2000, 2005, 2006 and 2008. Our ice-softness, model norm, and regularization parameter choices are justified using the data-model misfit metric and the L curve method. The sensitivity of the inversion results to these parameter choices is explored. We find a lowering of effective basal yield stress in the first 7 km upstream from the 2008 grounding line and no significant changes higher upstream. The temporal evolution in the fast flow area is in broad agreement with a Mohr-Coulomb parameterization of basal shear stress, but with a till friction angle much lower than has been measured for till samples. The lowering of effective basal yield stress is significant within the uncertainties of the inversion, but it cannot be ruled out that there are other significant contributors to the acceleration of the glacier.

Despite higher glucocorticoid levels and stress responses in female rats, both sexes exhibit similar stress-induced changes in hippocampal neurogenesis.

PubMed

Hulshof, Henriëtte J; Novati, Arianna; Luiten, Paul G M; den Boer, Johan A; Meerlo, Peter

2012-10-01

Sex differences in stress reactivity may be one of the factors underlying the increased sensitivity for the development of psychopathologies in women. Particularly, an increased hypothalamic-pituitary-adrenal (HPA) axis reactivity in females may exacerbate stress-induced changes in neuronal plasticity and neurogenesis, which in turn may contribute to an increased sensitivity to psychopathology. The main aim of the present study was to examine male-female differences in stress-induced changes in different aspects of hippocampal neurogenesis, i.e. cell proliferation, differentiation and survival. Both sexes were exposed to a wide variety of stressors, where after differences in HPA-axis reactivity and neurogenesis were assessed. To study the role of oestradiol in potential sex differences, ovariectomized females received low or high physiological oestradiol level replacement pellets. The results show that females in general have a higher basal and stress-induced HPA-axis activity than males, with minimal differences between the two female groups. Cell proliferation in the dorsal hippocampus was significantly higher in high oestradiol females compared to low oestradiol females and males, while doublecortin (DCX) expression as a marker of cell differentiation was significantly higher in males compared to females, independent of oestradiol level. Stress exposure did not significantly influence cell proliferation or survival of new cells, but did reduce DCX expression. In conclusion, despite the male-female differences in HPA-axis activity, the effect of repeated stress exposure on hippocampal cell differentiation was not significantly different between sexes. Copyright © 2012 Elsevier B.V. All rights reserved.

Abdominal muscle and epipubic bone function during locomotion in Australian possums: insights to basal mammalian conditions and Eutherian-like tendencies in Trichosurus.

PubMed

Reilly, Stephen M; McElroy, Eric J; White, Thomas D; Biknevicius, Audrone R; Bennett, Michael B

2010-04-01

Mammals have four hypaxial muscle layers that wrap around the abdomen between the pelvis, ribcage, and spine. However, the marsupials have epipubic bones extending anteriorly into the ventral hypaxial layers with two additional muscles extending to the ventral midline and femur. Comparisons of South American marsupials to basal eutherians have shown that all of the abdominal hypaxials are active bilaterally in resting ventilation. However, during locomotion marsupials employ an asymmetrical pattern of activity as the hypaxial muscles form a crosscouplet linkage that uses the epipubic bone as a lever to provide long-axis support of the body between diagonal limb couplets during each step. In basal eutherians, this system shifts off the femur and epipubic bones (which are lost) resulting in a shoulder to pelvis linkage associated with shifts in both the positions and activity patterns of the pectineus and rectus abdominis muscles during locomotion. In this study, we present data on hypaxial function in two species (Pseudocheirus peregrinus and Trichosurus vulpecula) representing the two major radiations of possums in Australia: the Pseudocheiridae (within the Petauroidea) and the Phalangeridae. Patterns of gait, motor activity, and morphology in these two Australian species were compared with previous work to examine the generality of 1) the crosscouplet lever system as the basal condition for the Marsupialia and 2) several traits hypothesized to be common to all mammals (hypaxial tonus during resting ventilation, ventilation to step synchrony during locomotion, and bilateral transversus abdominis activity during locomotor expiration). Our results validate the presence of the crosscouplet pattern and basic epipubic bone lever system in Australian possums and confirm the generality of basal mammalian patterns. However, several novelties discovered in Trichosurus, reveal that it exhibits an evolutionary transition to intermediate eutherian-like morphological and motor patterns paralleling many other unique features of this species. (c) 2009 Wiley-Liss, Inc.

Disparate effects of non-steroidal anti-inflammatory drugs on apoptosis in guinea-pig gastric mucous cells: inhibition of basal apoptosis by diclofenac

PubMed Central

Ashton, Miranda; Hanson, Peter J

2002-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in gastrointestinal cancer cell lines. Similar actions on normal gastric epithelial cells could contribute to NSAID gastropathy. The present work therefore compared the actions of diclofenac, ibuprofen, indomethacin, and the cyclo-oxygenase-2 selective inhibitor, NS-398, on a primary culture of guinea-pig gastric mucous epithelial cells. Cell number was assessed by staining with crystal violet. Apoptotic activity was determined by condensation and fragmentation of nuclei and by assay of caspase-3-like activity. Necrosis was evaluated from release of cellular enzymes. Ibuprofen (250 μM for 24 h) promoted cell loss, and apoptosis, under both basal conditions and when apoptosis was increased by 25 μM N-Hexanoyl-D-sphingosine (C6-ceramide). Diclofenac (250 μM for 24 h) reduced the proportion of apoptotic nuclei from 5.2 to 2.1%, and caused inhibition of caspase-3-like activity, without causing necrosis under basal conditions. No such reduction in apoptotic activity was evident in the presence of 25 μM C6-ceramide. The inhibitory effect of diclofenac on basal caspase-3-like activity was also exhibited by the structurally similar mefenamic and flufenamic acids (1–250 μM), but not by niflumic acid. Inhibition of superoxide production by the cells increased caspase-3-like activity, but the inhibitory action of diclofenac on caspase activity remained. Diclofenac did not affect superoxide production. Diclofenac inhibited caspase-3-like activity in cell homogenates and also inhibited human recombinant caspase-3. In conclusion, NSAIDs vary in their effect on apoptotic activity in a primary culture of guinea-pig gastric mucous epithelial cells, and the inhibitory effect of diclofenac on basal apoptosis could involve an action on caspase activity. PMID:11815376

Forage and sugar in dairy calves' starter diet and their interaction on performance, weaning age and rumen fermentation.

PubMed

Beiranvand, H; Ghorbani, G R; Khorvash, M; Kazemi-Bonchenari, M

2014-06-01

The effects of sugar and forage inclusion in calves' starter and their interaction on animal performance and rumen fermentation parameters were investigated. Twenty-eight neonatal Holstein male calves 3 days of age with average body weights of 42 ± 4 kg were allocated to four different treatments. All calves were fed a similar basal diet consisting of milk and concentrate. The experimental treatments were: (i) basal diet with no supplementation (Control, hereafter designated by C), (ii) basal diet plus 5% granular sugar cane (Sugar, designated by S), (iii) basal diet plus 5% forage (Forage, designated by F) and (iv) basal diet plus 5% forage with 5% granular sugar cane (F × S). Supplement ingredients were used on a dry matter (DM) basis. Rumen fluid parameters were measured twice on days 35 and 70 of the study period. The calves were weaned when they could consume 1 kg of starter for three consecutive days. The results show that starter intake was not affected by treatment; however, the lowest ADG was observed with calves in the sugar treatment. Weaning age was affected by treatments, and forage showed to reduce milk consumption period down to its shortest. Forage-sugar interaction was found to have no effects on animal performance. The structural body indices as well as the health status of the calves were similar in different treatments. Rumen pH did not differ among the treatment groups. Among the rumen parameters, total VFA concentration and molar proportions of butyrate and propionate did not exhibit any significant differences among the treatments. However, ruminal acetate concentration decreased in calves that fed sugar cane during the early weeks of the study period. Comparison of forage and sugar included in the starter diets revealed that forage reduced weaning age, while sugar cane had a negative effect on calves' performance. Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.

Involvement of Endogenous Brain-Derived Neurotrophic Factor in Hypothalamic-Pituitary-Adrenal Axis Activity.

PubMed

Naert, G; Zussy, C; Tran Van Ba, C; Chevallier, N; Tang, Y-P; Maurice, T; Givalois, L

2015-11-01

Brain-derived neurotrophic factor (BDNF) appears to be highly involved in hypothalamic-pituitary-adrenal (HPA) axis regulation during adulthood, playing an important role in homeostasis maintenance. The present study aimed to determine the involvement of BDNF in HPA axis activity under basal and stress conditions via partial inhibition of this endogenous neurotrophin. Experiments were conducted in rats and mice with two complementary approaches: (i) BDNF knockdown with stereotaxic delivery of BDNF-specific small interfering RNA (siRNA) into the lateral ventricle of adult male rats and (ii) genetically induced knockdown (KD) of BDNF expression specifically in the central nervous system during the first ontogenesis in mice (KD mice). Delivery of siRNA in the rat brain decreased BDNF levels in the hippocampus (-31%) and hypothalamus (-35%) but not in the amygdala, frontal cortex and pituitary. In addition, siRNA induced no change of the basal HPA axis activity. BDNF siRNA rats exhibited decreased BDNF levels and concomitant altered adrenocortoctrophic hormone (ACTH) and corticosterone responses to restraint stress, suggesting the involvement of BDNF in the HPA axis adaptive response to stress. In KD mice, BDNF levels in the hippocampus and hypothalamus were decreased by 20% in heterozygous and by 60% in homozygous animals compared to wild-type littermates. Although, in heterozygous KD mice, no significant change was observed in the basal levels of plasma ACTH and corticosterone, both hormones were significantly increased in homozygous KD mice, demonstrating that robust cerebral BDNF inhibition (60%) is necessary to affect basal HPA axis activity. All of these results in both rats and mice demonstrate the involvement and importance of a robust endogenous pool of BDNF in basal HPA axis regulation and the pivotal function of de novo BDNF synthesis in the establishment of an adapted response to stress. © 2015 British Society for Neuroendocrinology.

A study of the effects of rare-earth elements on the microstructural evolution and deformation behavior of magnesium alloys at temperatures up to 523K

NASA Astrophysics Data System (ADS)

Chakkedath, Ajith

Due to their high specific strength, lightweight magnesium (Mg) alloys are being increasingly used for applications, such as the automotive industry, where weight savings are critical. In order to develop new alloys and processing methods to achieve higher strength and better formability to compete with currently used metal alloys, it is important to understand the effects of alloying elements, processing, and temperature on the microstructure, mechanical properties, and the deformation behavior. In this dissertation, a systematic investigation on the effects of Nd additions (0-1wt.%) and temperature (298-523K) on the microstructure and the activity of different deformation modes in as-cast and cast-then-extruded Mg-1Mn (wt.%) alloys were performed. For this study, an in-situ testing technique which combines tension and compression testing inside a scanning electron microscope (SEM) with electron backscatter diffraction (EBSD) analysis was employed. The main findings of this work were that the microstructure, strength, and the distribution of the deformation modes varied significantly as a function of Nd content, temperature, and processing. An increase in the Nd content resulted in a weaker texture after extrusion in Mg-1Mn alloys. A combination of slip and twinning mechanisms controlled the tensile deformation in the extruded alloys at ambient temperatures. With an increase in temperature, the twinning activity decreased, and slip mechanisms dominated the deformation. In the extruded Nd-containing alloys, basal slip dominated the deformation, especially at elevated temperatures, suggesting that Nd additions strengthen basal slip. This resulted in excellent elevated-temperature strength retention in extruded Mg-1Mn-1Nd alloy, and a decrease in the Nd content to 0-0.3wt.% resulted in a decrease in the tensile strength at elevated temperatures. In extruded Mg-1Mn, contraction twinning dominated the tensile deformation and this alloy exhibited a lower elongation-to-failure (epsilon f) than the other alloys at 323K. With an increase in strain, these twins evolved into {101¯1} - {101¯2} double twins. Crystal plasticity modeling and simulation of the contraction twins and double twins showed that the activity of these twin modes is detrimental to the epsilon f of Mg alloys due to the strain localization that happens within the twinned volume due to the enhanced activity of basal slip. This agreed with the experimental observations. Compared to the extruded materials, the as-cast alloys exhibited significantly larger grain sizes and lower tensile strengths. The deformation in the as-cast alloys was dominated by a combination of basal slip and extension twinning at all test temperatures. A novel methodology which combines in-situ annealing inside a SEM with EBSD analysis was developed and employed to understand the effects of dilute Ce additions (0.2-0.6wt.%) on the recrystallization behavior in Mg-2Zn (wt.%) alloys. Texture weakening in these alloys resulted from the formation of an enhanced number of grain boundaries with rotation axis during recrystallization. The developed testing methodology will be valuable for future recrystallization studies on Mg and other alloy systems. Overall, the insights gained from this dissertation will have a broad impact on understanding the deformation behavior and microstructural evolution of RE-containing Mg alloys, and such insights can serve as guidance for the development of new alloys and processes. The information and data provided in this dissertation can also serve as inputs for the development of accurate crystal plasticity models.

Ecological Importance of Small-Diameter Trees to the Structure, Diversity and Biomass of a Tropical Evergreen Forest at Rabi, Gabon.

PubMed

Memiaghe, Hervé R; Lutz, James A; Korte, Lisa; Alonso, Alfonso; Kenfack, David

2016-01-01

Tropical forests have long been recognized for their biodiversity and ecosystem services. Despite their importance, tropical forests, and particularly those of central Africa, remain understudied. Until recently, most forest inventories in Central Africa have focused on trees ≥10 cm in diameter, even though several studies have shown that small-diameter tree population may be important to demographic rates and nutrient cycling. To determine the ecological importance of small-diameter trees in central African forests, we used data from a 25-ha permanent plot that we established in the rainforest of Gabon to study the diversity and dynamics of these forests. Within the plot, we censused 175,830 trees ≥1 cm dbh from 54 families, 192 genera, and 345 species. Average tree density was 7,026 trees/ha, basal area 31.64 m2/ha, and above-ground biomass 369.40 Mg/ha. Fabaceae, Ebenaceae and Euphorbiaceae were the most important families by basal area, density and above-ground biomass. Small-diameter trees (1 cm ≥ dbh <10 cm) comprised 93.7% of the total tree population, 16.5% of basal area, and 4.8% of the above-ground biomass. They also had diversity 18% higher at family level, 34% higher at genus level, and 42% higher at species level than trees ≥10 cm dbh. Although the relative contribution of small-diameter trees to biomass was comparable to other forests globally, their contribution to forest density, and diversity was disproportionately higher. The high levels of diversity within small-diameter classes may give these forests high levels of structural resilience to anthropogenic/natural disturbance and a changing climate.

Ecological Importance of Small-Diameter Trees to the Structure, Diversity and Biomass of a Tropical Evergreen Forest at Rabi, Gabon

PubMed Central

Memiaghe, Hervé R.; Lutz, James A.; Korte, Lisa; Alonso, Alfonso; Kenfack, David

2016-01-01

Tropical forests have long been recognized for their biodiversity and ecosystem services. Despite their importance, tropical forests, and particularly those of central Africa, remain understudied. Until recently, most forest inventories in Central Africa have focused on trees ≥10 cm in diameter, even though several studies have shown that small-diameter tree population may be important to demographic rates and nutrient cycling. To determine the ecological importance of small-diameter trees in central African forests, we used data from a 25-ha permanent plot that we established in the rainforest of Gabon to study the diversity and dynamics of these forests. Within the plot, we censused 175,830 trees ≥1 cm dbh from 54 families, 192 genera, and 345 species. Average tree density was 7,026 trees/ha, basal area 31.64 m2/ha, and above-ground biomass 369.40 Mg/ha. Fabaceae, Ebenaceae and Euphorbiaceae were the most important families by basal area, density and above-ground biomass. Small-diameter trees (1 cm ≥ dbh <10 cm) comprised 93.7% of the total tree population, 16.5% of basal area, and 4.8% of the above-ground biomass. They also had diversity 18% higher at family level, 34% higher at genus level, and 42% higher at species level than trees ≥10 cm dbh. Although the relative contribution of small-diameter trees to biomass was comparable to other forests globally, their contribution to forest density, and diversity was disproportionately higher. The high levels of diversity within small-diameter classes may give these forests high levels of structural resilience to anthropogenic/natural disturbance and a changing climate. PMID:27186658

Fructose diet alleviates acetaminophen-induced hepatotoxicity in mice.

PubMed

Cho, Sungjoon; Tripathi, Ashutosh; Chlipala, George; Green, Stefan; Lee, Hyunwoo; Chang, Eugene B; Jeong, Hyunyoung

2017-01-01

Acetaminophen (APAP) is a commonly used analgesic and antipyretic that can cause hepatotoxicity due to production of toxic metabolites via cytochrome P450 (Cyp) 1a2 and Cyp2e1. Previous studies have shown conflicting effects of fructose (the major component in Western diet) on the susceptibility to APAP-induced hepatotoxicity. To evaluate the role of fructose-supplemented diet in modulating the extent of APAP-induced liver injury, male C57BL/6J mice were given 30% (w/v) fructose in water (or regular water) for 8 weeks, followed by oral administration of APAP. APAP-induced liver injury (determined by serum levels of liver enzymes) was decreased by two-fold in mice pretreated with fructose. Fructose-treated mice exhibited (~1.5 fold) higher basal glutathione levels and (~2 fold) lower basal (mRNA and activity) levels of Cyp1a2 and Cyp2e1, suggesting decreased bioactivation of APAP and increased detoxification of toxic metabolite in fructose-fed mice. Hepatic mRNA expression of heat shock protein 70 was also found increased in fructose-fed mice. Analysis of bacterial 16S rRNA gene amplicons from the cecal samples of vehicle groups showed that the fructose diet altered gut bacterial community, leading to increased α-diversity. The abundance of several bacterial taxa including the genus Anaerostipes was found to be significantly correlated with the levels of hepatic Cyp2e1, Cyp1a2 mRNA, and glutathione. Together, these results suggest that the fructose-supplemented diet decreases APAP-induced liver injury in mice, in part by reducing metabolic activation of APAP and inducing detoxification of toxic metabolites, potentially through altered composition of gut microbiota.

Asymmetric pallidal neuronal activity in patients with cervical dystonia

PubMed Central

Moll, Christian K. E.; Galindo-Leon, Edgar; Sharott, Andrew; Gulberti, Alessandro; Buhmann, Carsten; Koeppen, Johannes A.; Biermann, Maxine; Bäumer, Tobias; Zittel, Simone; Westphal, Manfred; Gerloff, Christian; Hamel, Wolfgang; Münchau, Alexander; Engel, Andreas K.

2014-01-01

The origin of asymmetric clinical manifestation of symptoms in patients suffering from cervical dystonia (CD) is hitherto poorly understood. Dysregulated neuronal activity in the basal ganglia has been suggested to have a role in the pathophysiology of CD. Here, we re-assessed the question to what extent relative changes occur in the direct vs. indirect basal ganglia pathway in CD, whether these circuit changes are lateralized, and how these alterations relate to CD symptoms. To this end, we recorded ongoing single cell and local field potential (LFP) activity from the external (GPe) and internal pallidal segment (GPi) of 13 CD patients undergoing microelectrode-guided stereotactic surgery for deep brain stimulation in the GPi. We compared pallidal recordings from CD patients operated under local anaesthesia (LA) with those obtained in CD patients operated under general anaesthesia (GA). In awake patients, mean GPe discharge rate (52 Hz) was lower than that of GPi (72 Hz). Mean GPi discharge ipsilateral to the side of head turning was higher than contralateral and correlated with torticollis symptom severity. Lateralized differences were absent at the level of the GPe and in recordings from patients operated under GA. Furthermore, in the GPi of CD patients there was a subpopulation of theta-oscillatory cells with unique bursting characteristics. Power and coherence of GPe– and GPi–LFPs were dominated by a theta peak and also exhibited band-specific interhemispheric differences. Strong cross-frequency coupling of low-gamma amplitude to theta phase was a feature of pallidal LFPs recorded under LA, but not GA. These results indicate that CD is associated with an asymmetric pallidal outflow. Based on the finding of symmetric neuronal discharges in the GPe, we propose that an imbalanced interhemispheric direct pathway gain may be involved in CD pathophysiology. PMID:24574981

Distribution and Intrinsic Membrane Properties of Basal Forebrain GABAergic and Parvalbumin Neurons in the Mouse

PubMed Central

McKenna, James T.; Yang, Chun; Franciosi, Serena; Winston, Stuart; Abarr, Kathleen K.; Rigby, Matthew S.; Yanagawa, Yuchio; McCarley, Robert W.; Brown, Ritchie E.

2013-01-01

The basal forebrain (BF) strongly regulates cortical activation, sleep homeostasis, and attention. Many BF neurons involved in these processes are GABAergic, including a subpopulation of projection neurons containing the calcium-binding protein, parvalbumin (PV). However, technical difficulties in identification have prevented a precise mapping of the distribution of GABAergic and GABA/PV+ neurons in the mouse or a determination of their intrinsic membrane properties. Here we used mice expressing fluorescent proteins in GABAergic (GAD67-GFP knock-in mice) or PV+ neurons (PV-Tomato mice) to study these neurons. Immunohistochemical staining for GABA in GAD67-GFP mice confirmed that GFP selectively labeled BF GABAergic neurons. GFP+ neurons and fibers were distributed throughout the BF, with the highest density in the magnocellular preoptic area (MCPO). Immunohistochemistry for PV indicated that the majority of PV+ neurons in the BF were large (>20 μm) or medium-sized (15–20 μm) GFP+ neurons. Most medium and large-sized BF GFP+ neurons, including those retrogradely labeled from the neocortex, were fast-firing and spontaneously active in vitro. They exhibited prominent hyperpolarization-activated inward currents and subthreshold “spikelets,” suggestive of electrical coupling. PV+ neurons recorded in PV-Tomato mice had similar properties but had significantly narrower action potentials and a higher maximal firing frequency. Another population of smaller GFP+ neurons had properties similar to striatal projection neurons. The fast firing and electrical coupling of BF GABA/PV+ neurons, together with their projections to cortical interneurons and the thalamic reticular nucleus, suggest a strong and synchronous control of the neocortical fast rhythms typical of wakefulness and REM sleep. PMID:23254904

Pituitary-hormone secretion by thyrotropinomas.

PubMed

Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M; Biermasz, Nienke R; Smit, Jan W; Frolich, Marijke; Keenan, Daniel M; Veldhuis, Johannes D; Romijn, Johannes A

2009-01-01

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells.

First evidence of epithelial transport in tardigrades: a comparative investigation of organic anion transport.

PubMed

Halberg, Kenneth Agerlin; Møbjerg, Nadja

2012-02-01

We investigated transport of the organic anion Chlorophenol Red (CPR) in the tardigrade Halobiotus crispae using a new method for quantifying non-fluorescent dyes. We compared the results acquired from the tardigrade with CPR transport data obtained from Malpighian tubules of the desert locust Schistocerca gregaria. CPR accumulated in the midgut lumen of H. crispae, indicating that organic anion transport takes place here. Our results show that CPR transport is inhibited by the mitochondrial un-coupler DNP (1 mmol l(-1); 81% reduction), the Na(+)/K(+)-ATPase inhibitor ouabain (10 mmol l(-1); 21% reduction) and the vacuolar H(+)-ATPase inhibitor bafilomycin (5 μmol l(-1); 21% reduction), and by the organic anions PAH (10 mmol l(-1); 44% reduction) and probenecid (10 mmol l(-1); 61% reduction, concentration-dependent inhibition). Transport by locust Malpighian tubules exhibits a similar pharmacological profile, albeit with markedly higher concentrations of CPR being reached in S. gregaria. Immunolocalization of the Na(+)/K(+)-ATPase α-subunit in S. gregaria revealed that this transporter is abundantly expressed and localized to the basal cell membranes. Immunolocalization data could not be obtained from H. crispae. Our results indicate that organic anion secretion by the tardigrade midgut is transporter mediated with likely candidates for the basolateral entry step being members of the Oat and/or Oatp transporter families. From our results, we cautiously suggest that apical H(+) and possibly basal Na(+)/K(+) pumps provide the driving force for the transport; the exact coupling between electrochemical gradients generated by the pumps and transport of ions, as well as the nature of the apical exit step, are unknown. This study is, to our knowledge, the first to show active epithelial transport in tardigrades.

Seasonal variation in body mass, body temperature and thermogenesis in the Hwamei, Garrulax canorus.

PubMed

Wu, Mei-Xiu; Zhou, Li-Meng; Zhao, Li-Dan; Zhao, Zhi-Jun; Zheng, Wei-Hong; Liu, Jin-Song

2015-01-01

The basal thermogenesis of birds is beginning to be viewed as a highly flexible physiological trait influenced by environmental fluctuations, particularly changes in ambient temperature (Ta). Many birds living in regions with seasonal fluctuations in Ta typically respond to cold by increasing their insulation and adjusting their metabolic rate. To understand these metabolic adaptations, body temperature (Tb), metabolic rate (MR), thermal neutral zone (TNZ) and thermal conductance were measured within a range of temperatures from 5 to 40°C in free-living Hwamei, Garrulax canorus, in both winter and summer. Body mass was 61.2±0.3g in winter and 55.5±1.0g in summer, and mean Tb was 41.6±0.1°C in winter and 42.3±0.1°C in summer. TNZ was between 28.3 and 35.1°C in winter and between 28.7 and 33.2°C in summer. The mean basal metabolic rate (BMR) within TNZ was 203.32±11.81ml O2 h(-1) in winter and 168.99±6.45ml O2 h(-1) in summer. Minimum thermal conductance was 3.73±0.09joulesg(-1)h(-1)°C(-1) in winter and 3.26±0.06joulesg(-1)h(-1)°C(-1) in summer. Birds caught in winter had higher body mass, MR, and more variable TNZ than those in summer. The increased winter BMR indicates improved ability to cope with cold and maintenance of a high Tb. These results show that the Hwamei's metabolism is not constant, but exhibits pronounced seasonal phenotypic flexibility associated with maintenance of a high Tb. Copyright © 2014 Elsevier Inc. All rights reserved.

Sequestosome 1 (SQSTM1/p62) maintains protein folding capacity under endoplasmic reticulum stress in mouse hypothalamic organotypic culture.

PubMed

Tominaga, Takashi; Goto, Motomitsu; Onoue, Takeshi; Mizoguchi, Akira; Sugiyama, Mariko; Tsunekawa, Taku; Hagiwara, Daisuke; Morishita, Yoshiaki; Ito, Yoshihiro; Iwama, Shintaro; Suga, Hidetaka; Banno, Ryoichi; Arima, Hiroshi

2017-08-24

Sequestosome 1 (SQSTM1) also known as ubiquitin-binding protein p62 (p62) is a cargo protein involved in the degradation of misfolded proteins via selective autophagy. Disruption of autophagy and resulting accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress. ER stress is implicated in several neurodegenerative diseases and obesity. As knockout of p62 (p62KO) reportedly induces obesity in mice, we examined how p62 contributes to ER stress and the ensuing unfolded protein response (UPR) in hypothalamus using mouse organotypic cultures in the present study. Cultures from p62KO mice showed significantly reduced formation of LC3-GFP puncta, an index of autophagosome formation, in response to the chemical ER stressor thapsigargin compared to wild-type (WT) cultures. Hypothalamic cultures from p62KO mice exhibited higher basal expression of the UPR/ER stress markers CHOP mRNA and ATF4 mRNA than WT cultures. Thapsigargin enhanced CHOP, ATF4, and BiP mRNA as well as p-eIF2α protein expression in both WT and p62KO cultures, but all peak values were greater in p62KO cultures. A proteasome inhibitor increased p62 expression in WT cultures and upregulated the UPR/ER stress markers CHOP mRNA and ATF4 mRNA in both genotypes, but to a greater extent in p62KO cultures. Therefore, p62 deficiency disturbed autophagosome formation and enhanced both basal and chemically induced ER stress, suggesting that p62 serves to prevent ER stress in mouse hypothalamus by maintaining protein folding capacity. Copyright © 2017 Elsevier B.V. All rights reserved.

Cloud shading and fog drip influence the metabolism of a coastal pine ecosystem.

PubMed

Carbone, Mariah S; Park Williams, A; Ambrose, Anthony R; Boot, Claudia M; Bradley, Eliza S; Dawson, Todd E; Schaeffer, Sean M; Schimel, Joshua P; Still, Christopher J

2013-02-01

Assessing the ecological importance of clouds has substantial implications for our basic understanding of ecosystems and for predicting how they will respond to a changing climate. This study was conducted in a coastal Bishop pine forest ecosystem that experiences regular cycles of stratus cloud cover and inundation in summer. Our objective was to understand how these clouds impact ecosystem metabolism by contrasting two sites along a gradient of summer stratus cover. The site that was under cloud cover ~15% more of the summer daytime hours had lower air temperatures and evaporation rates, higher soil moisture content, and received more frequent fog drip inputs than the site with less cloud cover. These cloud-driven differences in environmental conditions translated into large differences in plant and microbial activity. Pine trees at the site with greater cloud cover exhibited less water stress in summer, larger basal area growth, and greater rates of sap velocity. The difference in basal area growth between the two sites was largely due to summer growth. Microbial metabolism was highly responsive to fog drip, illustrated by an observed ~3-fold increase in microbial biomass C with increasing summer fog drip. In addition, the site with more cloud cover had greater total soil respiration and a larger fractional contribution from heterotrophic sources. We conclude that clouds are important to the ecological functioning of these coastal forests, providing summer shading and cooling that relieve pine and microbial drought stress as well as regular moisture inputs that elevate plant and microbial metabolism. These findings are important for understanding how these and other seasonally dry coastal ecosystems will respond to predicted changes in stratus cover, rainfall, and temperature. © 2012 Blackwell Publishing Ltd.

Reversal of cardiac myocyte dysfunction as a unique mechanism of rescue by P2X4 receptors in cardiomyopathy.

PubMed

Shen, Jian-Bing; Shutt, Robin; Agosto, Mariela; Pappano, Achilles; Liang, Bruce T

2009-04-01

Binary cardiac transgenic (Tg) overexpression of P2X(4) receptors (P2X(4)R) improved the survival of the cardiomyopathic calsequestrin (CSQ) mice. Here we studied the mechanism of rescue using binary P2X(4)R/CSQ Tg and CSQ Tg mice as models. Cellular and intact heart properties were determined by simultaneous sarcomere shortening (SS) and Ca(2+) transients in vitro and echocardiography in vivo. Similar to a delay in death, binary mice exhibited a slowed heart failure progression with a greater left ventricular (LV) fractional shortening (FS) and thickness and a concomitant lesser degree of LV dilatation in both systole and diastole at 8 or 12 wk. By 16 wk, binary hearts showed similarly depressed FS and thinned out LV and equal enlargement of LV as did 12-wk-old CSQ hearts. Binary cardiac myocytes showed higher peak basal cell shortening (CS) and SS as well as greater basal rates of shortening and relaxation than did the CSQ myocytes at either 8 or 12 wk. Similar data were obtained in comparing the Ca(2+) transient. At 16 wk, binary myocytes were like the 12-wk-old CSQ myocytes with equally depressed CS, SS, and Ca(2+) transient. CSQ myocytes were longer than myocytes from wild-type and binary mice at 12 wk of age. At 16 wk, the binary myocyte length increased to that of the 12-wk-old CSQ myocyte, parallel to LV dilatation. The data suggest a unique mechanism, which involves a reversal of cardiac myocyte dysfunction and a delay in heart failure progression. It represents an example of targeting the abnormal failing myocyte in treating heart failure.

[Morphological pathology of classic Kaposi's sarcoma. Ultrastructural studies and reflections on histogenesis].

PubMed

Holzhausen, H J; Stiller, D; Sachs, M

1988-01-01

Histological and electron-microscopic studies were conducted into biopsy material from cases of what is called the classical type of idiopathic Kaposi's sarcoma without acquired immunodeficiency syndrome. Ultrastructural analysis was conducted, with the view to characterizing a possible progenitor cell from which the angioblastic and fibroblastic elements were likely to originate. The biopsy material had been obtained from two males, aged 86 or 83 years, who had been afflicted with the disease for 18 or 8 years. The nodular lesions were typical of Kaposi's sarcoma and were, histologically, made up of variable mixtures of vascular and spindle cell elements. The angiomatous structures were a capillary meshwork or sinusoidal patterns lined by atypical endothelial cells. The spindle cell areas contained large numbers of slit-like spaces which were without endothelial lining but were stuffed with erythrocytes. Flattened endothelioid cells were recordable from semi-thin-sections of some clefts. Haemosiderin was, typically, deposited in places. Electron microscopically, the endothelial cells of vascular channels exhibited varying amounts of characteristic organelles, such as Weibel-Palade bodies, microfilaments and pinocytotic vesicles as well as basal membranes. Cells with typical endothelial markers, too, were detectable in solid sprouts or in capillary-like differentiations with narrow or small lumina. The spindle cell tumour areas consisted of fibroblastic cells with plenty of rough endoplasmic reticulum and surrounded by material of basal membrane nature. Also visible were solid, sprout-type multilayer cell complexes surrounded by basal membranes which exhibited undifferentiated or primitive cellular forms, endothelioid and pericytic. Transitional forms from these complexes to the above vascular tumours or the spindle-cell formations were detectable. These ultrastructural findings might be interpreted to the effect that an angioblastically determined mesenchymal cell, a so-called endothelioblast, was thinkable and was discussed as the precursor cell of atypical vascular and spindle cell proliferation in Kaposi's sarcoma.

Behaviorally activated mRNA expression profiles produce signatures of learning and enhanced inhibition in aged rats with preserved memory.

PubMed

Haberman, Rebecca P; Colantuoni, Carlo; Koh, Ming Teng; Gallagher, Michela

2013-01-01

Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions.

Kv2.2: a novel molecular target to study the role of basal forebrain GABAergic neurons in the sleep-wake cycle.

PubMed

Hermanstyne, Tracey O; Subedi, Kalpana; Le, Wei Wei; Hoffman, Gloria E; Meredith, Andrea L; Mong, Jessica A; Misonou, Hiroaki

2013-12-01

The basal forebrain (BF) has been implicated as an important brain region that regulates the sleep-wake cycle of animals. Gamma-aminobutyric acidergic (GABAergic) neurons are the most predominant neuronal population within this region. However, due to the lack of specific molecular tools, the roles of the BF GABAergic neurons have not been fully elucidated. Previously, we have found high expression levels of the Kv2.2 voltage-gated potassium channel on approximately 60% of GABAergic neurons in the magnocellular preoptic area and horizontal limb of the diagonal band of Broca of the BF and therefore proposed it as a potential molecular target to study this neuronal population. In this study, we sought to determine the functional roles of the Kv2.2-expressing neurons in the regulation of the sleep-wake cycle. Sleep analysis between two genotypes and within each genotype before and after sleep deprivation. Animal sleep research laboratory. Adult mice. Wild-type and Kv2.2 knockout mice with C57/BL6 background. EEG/EMG recordings from the basal state and after sleep-deprivation which was induced by mild agitation for 6 h. Immunostaining of a marker of neuronal activity indicates that these Kv2.2-expressing neurons appear to be preferentially active during the wake state. Therefore, we tested whether Kv2.2-expressing neurons in the BF are involved in arousal using Kv2.2-deficient mice. BF GABAergic neurons exhibited augmented expression of c-Fos. These knockout mice exhibited longer consolidated wake bouts than wild-type littermates, and that phenotype was further exacerbated by sleep deprivation. Moreover, in-depth analyses of their cortical electroencephalogram revealed a significant decrease in the delta-frequency activity during the nonrapid eye movement sleep state. These results revealed the significance of Kv2.2-expressing neurons in the regulation of the sleep-wake cycle.

Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat.

PubMed

Vargas, Vladimir E; Gurung, Sunam; Grant, Benjamin; Hyatt, Kimberly; Singleton, Krista; Myers, Sarah M; Saunders, Debra; Njoku, Charity; Towner, Rheal; Myers, Dean A

2017-01-01

The effect of gestational hypoxia on the neonatal leptin surge, development of hypothalamic arcuate nuclei (ARH) projections and appetite that could contribute to the programming of offspring obesity is lacking. We examined the effect of 12% O2 from gestational days 15-19 in the Sprague-Dawley rat on post-weaning appetite, fat deposition by MRI, adipose tissue cytokine expression, the neonatal leptin surge, ARH response to exogenous leptin, and αMSH projections to the paraventricular nucleus (PVN) in response to a high fat (HFD) or control diet (CD) in male offspring. Normoxia (NMX) and Hypoxia (HPX) offspring exhibited increased food intake when fed a HFD from 5-8 weeks post-birth; HPX offspring on the CD had increased food intake from weeks 5-7 vs. NMX offspring on a CD. HPX offspring on a HFD remained hyperphagic through 23 weeks. Body weight were the same between offspring from HPX vs. NMX dams from 4-12 weeks of age fed a CD or HFD. By 14-23 weeks of age, HPX offspring fed the CD or HFD as well as male NMX offspring fed the HFD were heavier vs. NMX offspring fed the CD. HPX offspring fed a CD exhibited increased abdominal adiposity (MRI) that was amplified by a HFD. HPX offspring fed a HFD exhibited the highest abdominal fat cytokine expression. HPX male offspring had higher plasma leptin from postnatal day (PN) 6 through 14 vs. NMX pups. HPX offspring exhibited increased basal c-Fos labeled cells in the ARH vs. NMX pups on PN16. Leptin increased c-Fos staining in the ARH in NMX but not HPX offspring at PN16. HPX offspring had fewer αMSH fibers in the PVN vs. NMX offspring on PN16. In conclusion, gestational hypoxia impacts the developing ARH resulting in hyperphagia contributing to adult obesity on a control diet and exacerbated by a HFD.

Gestational hypoxia disrupts the neonatal leptin surge and programs hyperphagia and obesity in male offspring in the Sprague-Dawley rat

PubMed Central

Vargas, Vladimir E.; Gurung, Sunam; Grant, Benjamin; Hyatt, Kimberly; Singleton, Krista; Myers, Sarah M.; Saunders, Debra; Njoku, Charity; Towner, Rheal

2017-01-01

The effect of gestational hypoxia on the neonatal leptin surge, development of hypothalamic arcuate nuclei (ARH) projections and appetite that could contribute to the programming of offspring obesity is lacking. We examined the effect of 12% O2 from gestational days 15–19 in the Sprague-Dawley rat on post-weaning appetite, fat deposition by MRI, adipose tissue cytokine expression, the neonatal leptin surge, ARH response to exogenous leptin, and αMSH projections to the paraventricular nucleus (PVN) in response to a high fat (HFD) or control diet (CD) in male offspring. Normoxia (NMX) and Hypoxia (HPX) offspring exhibited increased food intake when fed a HFD from 5–8 weeks post-birth; HPX offspring on the CD had increased food intake from weeks 5–7 vs. NMX offspring on a CD. HPX offspring on a HFD remained hyperphagic through 23 weeks. Body weight were the same between offspring from HPX vs. NMX dams from 4–12 weeks of age fed a CD or HFD. By 14–23 weeks of age, HPX offspring fed the CD or HFD as well as male NMX offspring fed the HFD were heavier vs. NMX offspring fed the CD. HPX offspring fed a CD exhibited increased abdominal adiposity (MRI) that was amplified by a HFD. HPX offspring fed a HFD exhibited the highest abdominal fat cytokine expression. HPX male offspring had higher plasma leptin from postnatal day (PN) 6 through 14 vs. NMX pups. HPX offspring exhibited increased basal c-Fos labeled cells in the ARH vs. NMX pups on PN16. Leptin increased c-Fos staining in the ARH in NMX but not HPX offspring at PN16. HPX offspring had fewer αMSH fibers in the PVN vs. NMX offspring on PN16. In conclusion, gestational hypoxia impacts the developing ARH resulting in hyperphagia contributing to adult obesity on a control diet and exacerbated by a HFD. PMID:28957383

The Oncogenic Role of RhoGAPs in Basal-Like Breast Cancer

DTIC Science & Technology

2016-04-01

somatic mutations of RhoA in peripheral T cell lymphomas (PTCLs) (16-18) and in diffuse-type gastric carcinomas (19-21). Surprisingly, unlike Rac1...Diffuse-type gastric cancers exhibited mutations in the effector binding domain of RhoA, most commonly Y42C (19-21), which prevents binding to the...Impiombato A, Perez-Garcia A, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas . Nat Genet 2014;46

Ultrastructural characteristics of carcinogen-induced nondysplastic changes in tracheal epithelium.

PubMed Central

Klein-Szanto, A. J.; Topping, D. C.; Heckman, C. A.; Nettesheim, P.

1980-01-01

Nondysplastic hypotrophic and metaplastic epithelial alterations induced by dimethylbenz(a)anthracene in isogenic tracheal transplants were studied by light and electron microscopy 3--24 months after cessation of a 4-week carcinogen exposure. Hypotrophic epithelium observed at all time points was characterized by the presence of nonciliated cells that adopted either cuboidal or squamous shapes, forming simple or bistratified epithelia. Most of these cells, as well as some metaplastic cells, exhibited features of mucin-secreting cells. The metaplastic epithelia showed nonkeratinizing squamous metaplasia, closely related to transitional metaplasia, and keratinizing squamous metaplasia, which presented either an atrophic or an acanthotic epithelium. Although many of these epithelia showed morphologic features of normal stratified epithelia, several nonkeratinizing squamous metaplasias and acanthotic keratinizing squamous metaplasias exhibited some irregularities, probably representing very early atypical ultrastructural features (ie, perinuclear concentration of tonofilament bundles, the presence of dark and clear basal epithelial cells, interruptions and alterations of the basal lamina). These features were not observed in a group of early squamous metaplasias studied for comparative purposes 2 weeks after cessation of dimethylbenz(a)anthracene exposure, which were characterized by a combination of degenerative phenomena and increased cell proliferation. Images Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 14 Figure 15 Figure 6 Figure 7 PMID:6766047

Chromosome numbers in antlions (Myrmeleontidae) and owlflies (Ascalaphidae) (Insecta, Neuroptera).

PubMed

Kuznetsova, Valentina G; Khabiev, Gadzhimurad N; Krivokhatsky, Victor A

2015-01-01

A short review of main cytogenetic features of insects belonging to the sister neuropteran families Myrmeleontidae (antlions) and Ascalaphidae (owlflies) is presented, with a particular focus on their chromosome numbers and sex chromosome systems. Diploid male chromosome numbers are listed for 37 species, 21 genera from 9 subfamilies of the antlions as well as for seven species and five genera of the owlfly subfamily Ascalaphinae. The list includes data on five species whose karyotypes were studied in the present work. It is shown here that antlions and owlflies share a simple sex chromosome system XY/XX; a similar range of chromosome numbers, 2n = 14-26 and 2n = 18-22 respectively; and a peculiar distant pairing of sex chromosomes in male meiosis. Usually the karyotype is particularly stable within a genus but there are some exceptions in both families (in the genera Palpares and Libelloides respectively). The Myrmeleontidae and Ascalaphidae differ in their modal chromosome numbers. Most antlions exhibit 2n = 14 and 16, and Palparinae are the only subfamily characterized by higher numbers, 2n = 22, 24, and 26. The higher numbers, 2n = 20 and 22, are also found in owlflies. Since the Palparinae represent a basal phylogenetic lineage of the Myrmeleontidae, it is hypothesized that higher chromosome numbers are ancestral for antlions and were inherited from the common ancestor of Myrmeleontidae + Ascalaphidae. They were preserved in the Palparinae (Myrmeleontidae), but changed via chromosomal fusions toward lower numbers in other subfamilies.

Physiological plasticity related to zonation affects hsp70 expression in the reef-building coral Pocillopora verrucosa

PubMed Central

Poli, Davide; Fabbri, Elena; Goffredo, Stefano; Airi, Valentina

2017-01-01

This study investigates for the first time the transcriptional regulation of a stress-inducible 70-kDa heat shock protein (hsp70) in the scleractinian coral Pocillopora verrucosa sampled at three locations and two depths (3 m and 12 m) in Bangka Island waters (North Sulawesi, Indonesia). Percentage of coral cover indicated reduced habitat suitability with depth and at the Tanjung Husi (TA) site, which also displayed relatively higher seawater temperatures. Expression of the P. verrucosa hsp70 transcript evaluated under field conditions followed a depth-related profile, with relatively higher expression levels in 3-m collected nubbins compared to the 12-m ones. Expression levels of metabolism-related transcripts ATP synthase and NADH dehydrogenase indicated metabolic activation of nubbins to cope with habitat conditions of the TA site at 3 m. After a 14-day acclimatization to common and fixed temperature conditions in the laboratory, corals were subjected for 7 days to an altered thermal regime, where temperature was elevated at 31°C during the light phase and returned to 28°C during the dark phase. Nubbins collected at 12 m were relatively more sensitive to thermal stress, as they significantly over-expressed the selected transcripts. Corals collected at 3 m appeared more resilient, as they showed unaffected mRNA expressions. The results indicated that local habitat conditions may influence transcription of stress-related genes in P. verrucosa. Corals exhibiting higher basal hsp70 levels may display enhanced tolerance towards environmental stressors. PMID:28199351

The relationship of thioredoxin-1 and cisplatin resistance: its impact on ROS and oxidative metabolism in lung cancer cells.

PubMed

Wangpaichitr, Medhi; Sullivan, Elizabeth J; Theodoropoulos, George; Wu, Chunjing; You, Min; Feun, Lynn G; Lampidis, Theodore J; Kuo, Macus T; Savaraj, Niramol

2012-03-01

Elimination of cisplatin-resistant lung cancer cells remains a major obstacle. We have shown that cisplatin-resistant tumors have higher reactive oxygen species (ROS) levels and can be exploited for targeted therapy. Here, we show that increased secretion of the antioxidant thioredoxin-1 (TRX1) resulted in lowered intracellular TRX1 and contributed to higher ROS in cisplatin-resistant tumors in vivo and in vitro. By reconstituting TRX1 protein in cisplatin-resistant cells, we increased sensitivity to cisplatin but decreased sensitivity to elesclomol (ROS inducer). Conversely, decreased TRX1 protein in parental cells reduced the sensitivity to cisplatin but increased sensitivity to elesclomol. Cisplatin-resistant cells had increased endogenous oxygen consumption and mitochondrial activity but decreased lactic acid production. They also exhibited higher levels of argininosuccinate synthetase (ASS) and fumarase mRNA, which contributed to oxidative metabolism (OXMET) when compared with parental cells. Restoring intracellular TRX1 protein in cisplatin-resistant cells resulted in lowering ASS and fumarase mRNAs, which in turn sensitized them to arginine deprivation. Interestingly, cisplatin-resistant cells also had significantly higher basal levels of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Overexpressing TRX1 lowered ACC and FAS proteins expressions in cisplatin-resistant cells. Chemical inhibition and short interfering RNA of ACC resulted in significant cell death in cisplatin-resistant compared with parental cells. Conversely, TRX1 overexpressed cisplatin-resistant cells resisted 5-(tetradecyloxy)-2-furoic acid (TOFA)-induced death. Collectively, lowering TRX1 expression through increased secretion leads cisplatin-resistant cells to higher ROS production and increased dependency on OXMET. These changes raise an intriguing therapeutic potential for future therapy in cisplatin-resistant lung cancer.

The Relationship of Thioredoxin-1 and Cisplatin Resistance: Its Impact on ROS and Oxidative Metabolism in Lung Cancer Cells

PubMed Central

Wangpaichitr, Medhi; Theodoropoulos, George; Wu, Chunjing; You, Min; Feun, Lynn G.; Kuo, Macus T.; Savaraj, Niramol

2012-01-01

Elimination of cisplatin resistant (CR) lung cancer cells remains a major obstacle. We have shown that CR tumors have higher reactive oxygen species (ROS) levels and can be exploited for targeted therapy. Here we show that increased secretion of the antioxidant thioredoxin-1 (TRX1) resulted in lowered intracellular TRX1, and contributed to higher ROS in CR tumors in vivo and in vitro. By reconstitutingTRX1 protein in CR cells, we increased sensitivity to cisplatin but decreased sensitivity to elesclomol (ROS inducer). Conversely, decreased TRX1 protein in parental cells reduced the sensitivity to cisplatin but increased sensitivity to elesclomol. CR cells had increased endogenous oxygen consumption and mitochondrial activity but decreased lactic acid production. They also exhibited higher levels of argininosuccinate synthetase (ASS) and fumarase (FH) mRNA which contributed to oxidative metabolism (OXMET) when compared to parental cells. Restoring intracellular TRX1 protein in CR cells resulted in lowering ASS and FH mRNAs which in turn sensitized them to arginine deprivation. Interestingly, CR cells also possessed significantly higher basal levels of acetyl-CoA-carboxylase (ACC) and fatty acid synthase (FAS). Over-expressing TRX1 lowered ACC and FAS proteins expressions in CR cells. Chemical inhibition and siRNA of ACC resulted in significant cell death in CR compared to parental cells. Conversely, TRX1 over-expressed CR cells resisted to TOFA-induced death. Collectively, lowering TRX1 expression through increased secretion leads CR cells to higher ROS production and increase in dependency on OXMET. These changes raise an intriguing therapeutic potential for future therapy in cisplatin resistant lung cancer. PMID:22248473

Insulin and GH secretion in adolescent girls with irregular cycles: polycystic vs multifollicular ovaries.

PubMed

Villa, P; Rossodivita, A; Fulghesu, A M; Cucinelli, F; Barini, A; Apa, R; Belosi, C; Lanzone, A

2003-04-01

In the present study insulin (I) and GH secretion was studied in a group of twenty-five young adolescent girls (mean age: 15 +/- 0.23 yr) with cycle irregularity associated to clinical signs of hyperandrogenism in comparison with that observed in eleven normal matched subjects with regular menses. All patients underwent basal hormone measurements and, on two consecutive days, an oral glucose tolerance test (OGTT) and a GHRH iv test. Therefore, all subjects had a transabdominal US scan for the measurement of ovarian volume and the characterization of ovarian morphology. On the basis of the US examination we found patients with polycystic ovaries (PCO-like group) and subjects with multifollicular ovaries (MFO group). PCO-like group exhibited T (p<0.01) and LH (p<0.05) plasma levels higher than control group and the highest free androgen index (FAI) values (13 +/- 0.87). All patients with irregular menses showed plasma concentrations of AUC for I (AUC-I) significantly higher in respect to control group (7359.4 +/- 709 vs 5447 +/- 431 microIU/ml x 180 min, p<0.01) as well as both PCO-like group and MFO group did (p<0.001 and p<0.01) respectively. MFO group showed higher values of the AUC for GH (AUC-GH) (2809 +/- 432 ng/ml x 120 min) in respect to controls (1708 +/- 208 ng/ml x 120 min, p<0.05) and PCO-like subjects (p<0.001), who on the contrary showed the lowest AUC-GH values (618 +/- 119 ng/ml x 120 min). In conclusion, PCO-like patients associated hyperinsulinemia with a blunted GH secretion while MFO patients had higher GH secretion associated with higher AUC-I values in a way suggesting an immature and still developing reproductive system.

Altered insulin response to an acute bout of exercise in pediatric obesity.

PubMed

Tran, Brian D; Leu, Szu-Yun; Oliver, Stacy; Graf, Scott; Vigil, Diana; Galassetti, Pietro

2014-11-01

Pediatric obesity typically induces insulin resistance, often later evolving into type 2 diabetes. While exercise, enhancing insulin sensitivity, is broadly used to prevent this transition, it is unknown whether alterations in the exercise insulin response pattern occur in obese children. Therefore, we measured exercise insulin responses in 57 healthy weight (NW), 20 overweight (OW), and 56 obese (Ob) children. Blood samples were drawn before and after 30 min of intermittent (2 min on, 1 min off) cycling at ~80% VO2max. In a smaller group (14 NW, 6 OW, 15 Ob), a high-fat meal was ingested 45 min preexercise. Baseline glycemia was similar and increased slightly and similarly in all groups during exercise. Basal insulin (pmol/L) was significantly higher in Ob vs. other groups; postexercise, insulin increased in NW (+7± 3) and OW (+5 ± 8), but decreased in Ob (-15±5, p < .0167 vs. NW). This insulin drop in Ob was disproportionately more pronounced in the half of Ob children with higher basal insulin (Ob-H). In all groups, high-fat feeding caused a rapid rise in insulin, promptly corrected by exercise. In Ob, however, insulin rose again 30 min postexercise. Our data indicates a distinct pattern of exercise-induced insulin modulation in pediatric obesity, possibly modulated by basal insulin concentrations.

Increased lung neutrophil apoptosis and inflammation resolution in nonresponding pneumonia.

PubMed

Moret, I; Lorenzo, M J; Sarria, B; Cases, E; Morcillo, E; Perpiñá, M; Molina, J M; Menéndez, R

2011-11-01

Neutrophil activation state and its relationship with an inflammatory environment in community-acquired pneumonia (CAP) remain insufficiently elucidated. We aimed to evaluate the neutrophil apoptosis and cytokine pattern in CAP patients after 72 h of treatment, and their impact on infection resolution. Apoptosis of blood and bronchoalveolar lavage (BAL) neutrophils was measured in nonresponding CAP (NCAP), in responding CAP (blood only) and in patients without infection (control). Pro-inflammatory (interleukin (IL)-6, IL-8) and anti-inflammatory (IL-10) cytokines were measured. Main outcomes were clinical stability and days of hospitalisation. Basal neutrophil apoptosis was higher in the BAL and blood of NCAP, whereas spontaneous apoptosis (after 24 h culture) was lower. Cytokines in NCAP were higher than in responding CAP and control: IL-6 was increased in BAL and blood, IL-8 in BAL and IL-10 in blood. An increased basal apoptosis (≥20%) in BAL of NCAP was associated with lower systemic IL-10 (p<0.01), earlier clinical stability (p=0.05) and shorter hospital stay (p=0.02). A significant correlation was found for systemic IL-6 and IL-10 with days to reach stability and length of stay. After 72 h of treatment, an increased basal alveolar neutrophil apoptosis might contribute to downregulation of inflammation and to faster clinical stability.

Rotational movement (circling) in normal humans: sex difference and relationship to hand, foot and eye preference.

PubMed

Bracha, H S; Seitz, D J; Otemaa, J; Glick, S D

1987-05-19

An endogenous asymmetry in striatal dopaminergic function has been identified in rats, and related to spontaneous and drug-induced circling (rotation, turning). We have developed an electronic device for measuring in humans the same kinds of rotational movements observed in rats. Our data indicate that, without being aware of the type of information being obtained, normal men and women rotate preferentially to the left or to the right during a routine day. Women had higher average rates of rotation than men. Males that were consistently right-sided (left-hemisphere dominant) for hand, foot and eye dominance rotated more to the right than to the left, whereas left-hemisphere dominant females rotated more to the left than to the right. Subjects tested on two occasions, 6 weeks apart, exhibited consistent (significantly correlated) rotational preferences--this was much more evident in left-hemisphere dominant than in mixed dominance individuals. In view of similar animal data, the device used in this study may become a useful and objective means for obtaining quantitative information regarding the status of basal ganglia function in humans.

Disorders of sexual development and associated changes in the pituitary-gonadal axis in dogs.

PubMed

Buijtels, J J C W M; de Gier, J; Kooistra, H S; Grinwis, G C M; Naan, E C; Zijlstra, C; Okkens, A C

2012-10-15

Normal sexual differentiation depends on completion of chromosomal sex determination, gonadal differentiation, and development of the phenotypic sex. An irregularity in any of these three steps can lead to a disorder in sexual development (DSD). We examined nine dogs with DSD by abdominal ultrasonography, laparotomy, histologic examination of the gonads, and reproductive tract, cytogenetic analysis, and mRNA expression of the SRY gene. We also determined the plasma concentrations of luteinizing hormone (LH), estradiol-17β, and testosterone before and after administration of gonadotropin-releasing hormone (GnRH) and compared these results with those obtained in anestrous bitches and male control dogs. The gonads of three dogs with DSD contained both testicular and ovarian tissue, while in the other six only testicular tissue was found. Each of the dogs had a uterus. Based on gynecologic examination, cytogenetic analysis, and the histology of the gonads, seven of the nine dogs appeared to be XX sex reversals. Three of these were XX true hermaphrodites and four were XX males; the other two dogs had incomplete XY gonadal dysgenesis. All seven XX sex-reversed dogs were found to be negative for the SRY gene by polymerase chain reaction. The basal plasma luteinizing hormone (LH) concentration was significantly higher in dogs with DSD than in anestrous bitches but not significantly different from that in male dogs. The basal plasma LH concentration increased significantly after GnRH administration in all dogs with DSD. The basal plasma estradiol concentration was significantly higher in dogs with DSD than in anestrous bitches but not significantly different from that in male dogs. The basal plasma testosterone concentration was lower in dogs with DSD than in male dogs. In all dogs with DSD both the basal and GnRH-induced plasma testosterone concentrations were above the upper limit of their respective ranges in the anestrous bitches. In conclusion, the secretion of LH and estradiol in these dogs with DSD, all of which had testicular tissue in their gonads, was similar to that in male control dogs. These results indicate that the basal and/or GnRH-stimulated plasma testosterone concentration might be used to detect the presence of testicular tissue in dogs with DSD. Copyright © 2012 Elsevier Inc. All rights reserved.

SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis

PubMed Central

Kim, Bo Ram; Van de Laar, Emily; Tarumi, Shintaro; Hasenoeder, Stefan; Wang, Dennis; Virtanen, Carl; Bandarchi, Bizhan; Pham, Nhu An; Lee, Sharon; Keshavjee, Shaf; Tsao, Ming-Sound; Moghal, Nadeem

2016-01-01

Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting in progressive premalignant epithelial changes ranging from squamous metaplasia to dysplasia. These changes can regress naturally, even with chronic smoking. However, for unknown reasons, dysplasias have higher progression rates than earlier stages. We used primary human tracheobronchial basal cells to investigate how copy number gains in SOX2 and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling, which is activated by smoking, to initiate the squamous injury response in basal cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K signaling levels are high during dysplasia, while SOX9 is not expressed. By contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and basal cells transiently enter a SOX2LoSOX9Hi state, with SOX9 promoting proliferation and preventing squamous differentiation. Transient reduction in SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal cells in a SOX2HiSOX9Lo state with active PI3K signaling, which sustains the squamous injury response while precluding normal mucociliary differentiation. Surprisingly, we find that, although later in invasive carcinoma SOX9 is generally expressed at low levels, its expression is higher in a subset of SQCCs with less squamous identity and worse clinical outcome. We propose that early pathogenesis of most SQCCs involves stabilization of the squamous injury state in stem cells through copy number gains at 3q, with the pro-proliferative activity of SOX9 possibly being exploited in a subset of SQCCs in later stages. PMID:27880766

Proton magnetic resonance spectroscopy of late-life major depressive disorder.

PubMed

Chen, Cheng-Sheng; Chiang, I-Chan; Li, Chun-Wei; Lin, Wei-Chen; Lu, Chia-Ying; Hsieh, Tsyh-Jyi; Liu, Gin-Chung; Lin, Hsiu-Fen; Kuo, Yu-Ting

2009-06-30

The primary goal of this study was to examine the biochemical abnormalities of late-life major depression by using 3-tesla (3-T) proton magnetic resonance spectroscopy ((1)H-MRS). The antidepressant effects on the biochemical abnormalities were investigated as well. Study participants were 27 elderly patients with major depressive disorders (among which 9 were on antidepressant medication) and 19 comparison elderly subjects. (1)H-MRS spectra were acquired from voxels that were placed in the left frontal white matter, left periventricular white matter, and left basal ganglia. Ratios of N-acetylaspartate (NAA), choline (Cho) and myo-inositol to creatine were calculated. Patients with late-life major depressive disorder had a significantly lower NAA/creatine ratio in the left frontal white matter, and higher Cho/creatine and myo-inositol/creatine ratios in the left basal ganglia when compared with the control subjects. The myo-inositol correlated with global cognitive function among the patients. The biochemical abnormalities in late-life major depressive disorder were found on the left side of the frontal white matter and the basal ganglia. Neuron degeneration in the frontal white matter and second messenger system dysfunction or glial dysfunction in the basal ganglia are suggested to be associated with late-life depression.

Molecular dynamics simulations of cesium adsorption on illite nanoparticles.

PubMed

Lammers, Laura N; Bourg, Ian C; Okumura, Masahiko; Kolluri, Kedarnath; Sposito, Garrison; Machida, Masahiko

2017-03-15

The charged surfaces of micaceous minerals, especially illite, regulate the mobility of the major radioisotopes of Cs ( 134 Cs, 135 Cs, 137 Cs) in the geosphere. Despite the long history of Cs adsorption studies, the nature of the illite surface sites remains incompletely understood. To address this problem, we present atomistic simulations of Cs competition with Na for three candidate illite adsorption sites - edge, basal plane, and interlayer. Our simulation results are broadly consistent with affinities and selectivities that have been inferred from surface complexation models. Cation exchange on the basal planes is thermodynamically ideal, but exchange on edge surfaces and within interlayers shows complex, thermodynamically non-ideal behavior. The basal planes are weakly Cs-selective, while edges and interlayers have much higher affinity for Cs. The dynamics of NaCs exchange are rapid for both cations on the basal planes, but considerably slower for Cs localized on edge surfaces. In addition to new insights into Cs adsorption and exchange with Na on illite, we report the development of a methodology capable of simulating fully-flexible clay mineral nanoparticles with stable edge surfaces using a well-tested interatomic potential model. Copyright © 2016 Elsevier Inc. All rights reserved.

Diffusion of Chlorinated Organic Contaminants into Aquitards: Enhanced by the Flocculation of Clay?

NASA Astrophysics Data System (ADS)

Ayral, D.; Otero, M.; Demond, A. H.; Goltz, M. N.; Huang, J.

2011-12-01

Waste organic contaminants stored in low permeability subsurface layers serve as long-term sources for dissolved phase contaminant plumes. Current models consider the movement into and out of aquitards or other low permeability layers to occur through transverse diffusion. Yet, field evidence suggests higher transport rates of contaminants than can be accounted for by diffusion alone. Waste organic liquids contain both organic liquid solvents as well as surface-active solutes. Measurements using montmorillonite in contact with pure chlorinated organic liquids such as trichloroethylene (TCE) showed that the basal spacing is similar to the case of montmorillonite in contact with air, thus suggesting that these fluids have similar flocculation effects. On the other hand, the basal spacing increased in contact with aqueous surfactant solutions. Measurements of the basal spacing in contact with a TCE waste gave the same results as with pure TCE, suggesting that effect on basal spacing is dominated by the organic solvent matrix rather than by the surfactant content. Since flocculation can lead to cracking, this behavior suggests that aquitards underlying aquifers contaminated with chlorinated organic wastes may develop cracks, thus enhancing the transport into low permeability layers.

Ovarian response markers lead to appropriate and effective use of corifollitropin alpha in assisted reproduction.

PubMed

La Marca, Antonio; D'Ippolito, Giovanni

2014-02-01

Corifollitropin alpha is a highly effective gonadotrophin, which maintains multifollicular growth for a week. The advantages of its administration include ease of use of the drug, making the treatment more patient friendly, resulting in a lower level of distress for the patient. At the same time, the pregnancy rate resulting from its use in IVF/intracytoplasmic sperm injection cycles is similar to that found when daily recombinant FSH is administered. The ovarian response to corifollitropin alpha is dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There is a general trend towards a higher ovarian response with an increasing AFC and the number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome following corifollitropin alpha is very similar to the rate reported in literature for young women undergoing IVF, the risk of overstimulation may be reduced by avoiding maximal ovarian stimulation in women anticipated to be hyperresponders. High basal anti-Müllerian hormone and/or AFC can identify women with enhanced functional ovarian reserve at risk of overstimulation, and the risk is even higher if maximally stimulated with corifollitropin alpha or high dose of daily recombinant FSH. Corifollitropin alpha is a highly effective gonadotrophin which maintains multifollicular growth for a week. The ovarian response to corifollitropin was demonstrated to be dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There was a general trend toward a higher ovarian response with an increasing AFC and the mean number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome (OHSS) following corifollitropin alpha is very similar to the rate of OHSS reported in literature for young women undergoing IVF, the risk of overstimulation may be reduced by avoiding maximal ovarian stimulation in women anticipated to be hyperresponders. Increasing evidence demonstrates that anti-Müllerian hormone and AFC exhibit a very good diagnostic performance in the prediction of hyperresponse. High basal anti-Müllerian hormone and/or AFC can identify women with enhanced functional ovarian reserve who are at risk of overstimulation if stimulated in IVF cycles and the risk is even higher if maximally stimulated with corifollitropin alpha or high dose of daily recombinant FSH. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Pregnancy - identifying fertile days

MedlinePlus

... mean ovulation is near. TAKING YOUR BASAL BODY TEMPERATURE After you ovulate, your body temperature will rise and stay at a higher level ... can use a special thermometer to take your temperature in the morning before you get out of ...

Large basal crevasses as a proxy for historic subglacial flooding events on Byrd Glacier

NASA Astrophysics Data System (ADS)

Child, S. F.; Stearns, L. A.; van der Veen, C. J.; Hamilton, G. S.

2016-12-01

Active networks of subglacial lakes have recently been found beneath the Antarctic Ice Sheet. On Byrd Glacier, East Antarctica, a subglacial lake outburst event in 2005/07 led to a short-lived glacier acceleration. Due to the sparse record of historical observations, it is unclear how frequently these outburst events occur, and the role they play in the dynamics of Antarctic outlet glaciers. Crevasses form when the tensile stress is greater than the fracture strength of ice. High extensional strain rates often exist at the grounding line where grounded ice begins to float. We hypothesize that the formation of anomalously large basal crevasses coincides with the higher strain rates observed during flooding events. In this study, we use the location of large basal crevasses ( 330 m tall), located along the floating portion of the Byrd Glacier flowline, to create a timeline of past flooding events. We first model crevasse formation to demonstrate that basal crevasses likely form at the grounding line. To do this, we use linear elastic fracture mechanics (LEFM) to estimate crevasse heights based on strain rates during known flood (300-350 m) and non-flood (100-150 m) time periods at Byrd Glacier's grounding line. Basal crevasse locations and heights are determined directly from radar echograms (2011/12 CReSIS radar data and 1974/75 SPRI NSF TUD radar data) along the Byrd Glacier flowline. We also use the locations of large surface depressions to infer the presence of basal crevasses. When crevasses penetrate a threshold proportion of the ice column, the overlying ice is no longer supported and a surface depression forms. We identify 22 large basal crevasses through these combined methods; the oldest crevasse likely formed 600 years ago. This research provides a framework of Antarctic subglacial flooding frequency and the effects that subglacial water drainage events have on outlet glacier dynamics.

Can basal magma oceans generate magnetic fields?

NASA Astrophysics Data System (ADS)

Stegman, D. R.; Ziegler, L. B.; Davies, C.

2015-12-01

Earth's magnetic field is very old, with recent data now showing the field possibly extended back to 4.1 billion years ago (Tarduno et al., Science, 2015). Yet, based upon our current knowledge there are difficulties in sustained a core dynamo over most of Earth's history. Moreover, recent estimates of thermal and electrical conductivity of liquid iron at core conditions from mineral physics experiments indicate that adiabatic heat flux is approximately 15 TW, nearly 3 times larger than previously thought, exacerbating difficulties for driving a core dynamo by convective core cooling alone throughout Earth history. A long-lived basal magma ocean in the lowermost mantle has been proposed to exist in the early Earth, surviving perhaps into the Archean. While the modern, solid lower mantle is an electromagnetic insulator, electrical conductivities of silicate melts are known to be higher, though as yet they are unconstrained for lowermost mantle conditions. Here we explore the geomagnetic consequences of a basal magma ocean layer for a range of possible electrical conductivities. For the highest electrical conductivities considered, we find a basal magma ocean could be a primary dynamo source region. This would suggest the proposed three magnetic eras observed in paleomagnetic data originate from distinct sources for dynamo generation: from 4.5-2.45 Ga within a basal magma ocean, from 2.25-0.4 Ga within a superadiabatically cooled liquid core, and from 0.4-present within a quasi-adiabatic core that includes a solidifying inner core. We have extended this work by developing a new code, Dynamantle, which is a model with an entropy-based approach, similar to those commonly used in core dynamics models. We present new results using this code to assess the conditions under which basal magma oceans can generate positive ohmic dissipation. This is more generally useful than just considering the early Earth, but also for many silicate exoplanets in which basal magma oceans are even more likely to exist.

Phase-sensitive radar on thick Antarctic ice - how well does it work?

NASA Astrophysics Data System (ADS)

Binder, Tobias; Eisen, Olaf; Helm, Veit; Humbert, Angelika; Steinhage, Daniel

2016-04-01

Phase-sensitive radar (pRES) has become one of the mostly used tools to determine basal melt rates as well as vertical strain in ice sheets. Whereas most applications are performed on ice shelves, only few experiments were conducted on thick ice in Greenland or Antarctica. The technical constrains on an ice shelf to deduce basal melt rates are less demanding than on inland ice of more than 2 km thickness. First, the ice itself is usually only several 100s of meters thick; and, second, the reflection coefficient at the basal interface between sea water and ice is the second strongest one possible. Although the presence of marine ice with higher conductivities might increase attenuation in the lower parts, most experiments on shelves were successful. To transfer this technology to inland regions, either for the investigation of basal melt rates of subglacial hydrological networks or for determining vertical strain rates in basal regions, a reliable estimate of the current system performance is necessary. To this end we conducted an experiment at and in the vicinity of the EPICA deep ice core drill site EDML in Dronning Maud Land, Antarctica. That site has been explored in extraordinary detail with different geophysical methods and provides an already well-studied ice core and borehole, in particular with respect to physical properties like crystal orientation fabric, dielectric properties and matching of internal radar horizons with conductivity signals. We present data from a commercially available pRES system initially recorded in January 2015 and repeated measurements in January 2016. The pRES data are matched to existing and already depth-calibrated airborne radar data. Apart from identifying prominent internal layers, e.g. the one originating from the deposits of the Toba eruption at around 75 ka, we put special focus on the identification of the basal reflection at multiple polarizations. We discuss the potential uncertainty estimates and requirements to unambiguously identify the basal melt rate on thick grounded ice in Antarctica.

Estrogen Regulation of Duodenal Bicarbonate Secretion and Sex-Specific Protection of Human Duodenum

PubMed Central

Tuo, Biguang; Wen, Guorong; Wei, Jinqi; Liu, Xuemei; Wang, Xue; Zhang, Yalin; Wu, Huichao; Dong, Xiao; Chow, Jimmy Y.C.; Vallon, Volker; Dong, Hui

2011-01-01

BACKGROUND & AIMS The reason that women have a lower prevalence of duodenal ulcer is not clear. We investigated whether estrogen regulates human duodenal bicarbonate secretion (DBS) and whether this process accounts for sex differences in the prevalence of duodenal ulcer. METHODS We performed an epidemiological study to correlate duodenal ulcer prevalence with sex and age. Proximal DBS was measured from healthy subjects. Estrogen receptor expression was examined in human duodenal mucosa by immunoblot and immunohistochemical analyses. RESULTS Among women, the prevalence of duodenal ulcer was significantly lower than among men. The reduced prevalence was greatest among premenopausal women (20–49 years), who were 3.91–5.09-fold less likely to develop duodenal ulcers than age-matched men; the difference was reduced to ≤1.32-fold among subjects 60 years or older. Premenopausal (20–29 years), but not post-menopausal (60–69 years) women, had significantly higher basal and acid-stimulated DBS than the age-matched men. Basal and acid-stimulated DBS in premenopausal women (20–29 years) were significantly higher than in post-menopausal women (60–69 years), whereas there were no significant differences in basal or acid-stimulated DBS between men that were 20–29 years old or 60–69 years old. Serum levels of estradiol changed in parallel with basal and acid-stimulated DBS during the physiological menstrual cycle in premenopausal women. 17β-estradiol-stimulated DBS was independent of age or sex. Estrogen receptors- and - were detected on plasma membrane and in cytosol of human duodenal epithelial cells. CONCLUSIONS Estrogen regulates human DBS, which could reduce the risk for duodenal ulcer in women and contribute to sex differences in prevalence of duodenal ulcer. PMID:21699784