Associations Between Physical Fitness Indices and Working Memory in Breast Cancer Survivors and Age-Matched Controls

PubMed Central

Mackenzie, Michael J.; Zuniga, Krystle E.; Raine, Lauren B.; Awick, Elizabeth A.; Hillman, Charles H.; Kramer, Arthur F.

2016-01-01

Abstract Background: This study examined the effects of cardiorespiratory fitness, heart rate recovery, and physical activity on working memory in breast cancer survivors and age-matched controls. Method: Using a case-control design, 32 women who had received a breast cancer diagnosis and completed primary treatment within the past 36-months (11 radiation only; 21 chemotherapy) and 30 age-matched women with no previous cancer diagnosis completed a n-back continuous performance task commonly used as an assessment of working memory. In addition, cardiorespiratory fitness and heart rate recovery were measured during a submaximal graded exercise test and physical activity was measured using 7-days of accelerometer monitoring. Results: Breast cancer survivors who had received chemotherapy had poorer heart rate recovery (p = .010) and engaged in less physical activity than women who had received radiation only (p = .004) or non-cancer controls (p = .029). Cancer treatment (radiation; chemotherapy) predicted differences in reaction times on the 1-back working memory task (p = .029). However, more rapid heart rate recovery predicted shorter reaction times on the 1-back task in the age-matched control group (p = .002). All participants with greater cardiorespiratory fitness displayed greater accuracy independent of disease status on the 1-back task (p = .017). No significant group differences in reaction times were observed for 2-back target trials between breast cancer survivors and controls. However, greater total physical activity predicted shorter reaction times in breast cancer survivors (radiation, chemotherapy) on the 2-back task (p = .014). In addition, all participants who exhibited more rapid heart rate recovery demonstrated better greater accuracy regardless of disease status (p = .013). Conclusion: These findings support differences in physical activty participation, heart rate recovery, and 1- and 2-back working memory reaction

Reductions in expression of growth regulating genes in skeletal muscle with age in wild type and myostatin null mice.

PubMed

Jones, Jennifer C; Kroscher, Kellie A; Dilger, Anna C

2014-03-28

Genes that decline in expression with age and are thought to coordinate growth cessation have been identified in various organs, but their expression in skeletal muscle is unknown. Therefore, our objective was to determine expression of these genes (Ezh2, Gpc3, Mdk, Mest, Mycn, Peg3, and Plagl1) in skeletal muscle from birth to maturity. We hypothesized that expression of these genes would decline with age in skeletal muscle but differ between sexes and between wild type and myostatin null mice. Female and male wild type and myostatin null mice (C57BL/6J background) were sacrificed by carbon dioxide asphyxiation followed by decapitation at d -7, 0, 21, 42, and 70 days of age. Whole bodies at d -7, all muscles from both hind limbs at d 0, and bicep femoris muscle from d 21, 42 and 70 were collected. Gene expression was determined by quantitative real-time PCR. In general, expression of these growth-regulating genes was reduced at d 21 compared with day 0 and d -7. Expression of Gpc3, Mest, and Peg3 was further reduced at d 42 and 70 compared with d 21, however the expression of Mycn increased from d 21 to d 42 and 70. Myostatin null mice, as expected, were heavier with increased biceps femoris weight at d 70. However, with respect to sex and genotype, there were few differences in expression. Expression of Ezh2 was increased at d 70 and expression of Mdk was increased at d 21 in myostatin null mice compared with wild type, but no other genotype effects were present. Expression of Mdk was increased in females compared to males at d 70, but no other sex effects were present. Overall, these data suggest the downregulation of these growth-regulating genes with age might play a role in the coordinated cessation of muscle growth similar to organ growth but likely have a limited role in the differences between sexes or genotypes.

DNA vaccines encoding proteins from wild-type and attenuated canine distemper virus protect equally well against wild-type virus challenge.

PubMed

Nielsen, Line; Jensen, Trine Hammer; Kristensen, Birte; Jensen, Tove Dannemann; Karlskov-Mortensen, Peter; Lund, Morten; Aasted, Bent; Blixenkrone-Møller, Merete

2012-10-01

Immunity induced by DNA vaccines containing the hemagglutinin (H) and nucleoprotein (N) genes of wild-type and attenuated canine distemper virus (CDV) was investigated in mink (Mustela vison), a highly susceptible natural host of CDV. All DNA-immunized mink seroconverted, and significant levels of virus-neutralizing (VN) antibodies were present on the day of challenge with wild-type CDV. The DNA vaccines also primed the cell-mediated memory responses, as indicated by an early increase in the number of interferon-gamma (IFN-γ)-producing lymphocytes after challenge. Importantly, the wild-type and attenuated CDV DNA vaccines had a long-term protective effect against wild-type CDV challenge. The vaccine-induced immunity induced by the H and N genes from wild-type CDV and those from attenuated CDV was comparable. Because these two DNA vaccines were shown to protect equally well against wild-type virus challenge, it is suggested that the genetic/antigenic heterogeneity between vaccine strains and contemporary wild-type strains are unlikely to cause vaccine failure.

Characteristics of the personal and environmental components of person-environment fit in very old age: a comparison between people with self-reported Parkinson's disease and matched controls.

PubMed

Slaug, Björn; Nilsson, Maria H; Iwarsson, Susanne

2013-12-01

To investigate differences and similarities in person-environment (P-E) fit problems between very old people with self-reported Parkinson's disease (PD) and matched controls. Data collected for the cross-national ENABLE-AGE Survey Study were used to identify people with self-reported PD (n = 20), and to select three matched controls per individual (n = 60). The matching criteria were age (mean = 82 years), sex, country, and type of housing. The data analysis targeted P-E fit (i.e. accessibility) problems, including studying the personal and environmental components separately. The personal component was analyzed in terms of functional limitations, and the environmental component in terms of physical environmental barriers. In comparison to the matched controls, the participants with PD had more functional limitations, used more mobility devices and were subjected to more P-E fit problems, though the number of environmental barriers did not differ from the controls. In the PD sample, P-E fit problems were significantly stronger associated with poor balance and incoordination, and the environmental barriers that generated the most severe P-E fit problems were more often located to the exterior surroundings of the housing compared to the controls. The novel contribution of this explorative study is the demonstration of the type of knowledge that can be generated by unfolding and comparing the composition of P-E fit (accessibility) problems among people with self-reported PD as compared with matched controls. The knowledge thereby generated can be used to develop more targeted rehabilitation approaches, efficient housing adaptation services and societal planning for people with neurodegenerative disorders.

Direct comparison of progenitor cells derived from adipose, muscle, and bone marrow from wild-type or craniosynostotic rabbits

PubMed Central

GM, Cooper; EL, Lensie; JJ, Cray; MR, Bykowski; GE, DeCesare; MA, Smalley; MP, Mooney; PG, Campbell; JE, Losee

2010-01-01

Background Reports have identified cells capable of osteogenic differentiation in bone marrow, muscle, and adipose tissues, but there are few direct comparisons of these different cell-types. Also, few have investigated the potential connection between a tissue-specific pathology and cells derived from seemingly unrelated tissues. Here, we compare cells isolated from wild-type rabbits or rabbits with nonsyndromic craniosynostosis, defined as the premature fusion of one or more of the cranial sutures. Methods Cells were derived from bone marrow, adipose, and muscle of 10 day-old wild-type rabbits (WT; n=17) or from age-matched rabbits with familial nonsyndromic craniosynostosis (CS; n=18). Cells were stimulated with bone morphogenetic protein 4 (BMP4) and alkaline phosphatase expression and cell proliferation were assessed. Results In WT rabbits, cells derived from muscle had more alkaline phosphatase activity than cells derived from either adipose or bone marrow. The cells derived from CS rabbit bone marrow and muscle were significantly more osteogenic than WT. Adipose-derived cells demonstrated no significant differences. While muscle-derived cells were most osteogenic in WT rabbits, bone marrow-derived cells were most osteogenic in CS rabbits. Conclusions Results suggest that cells from different tissues have different potentials for differentiation. Furthermore, cells derived from rabbits with craniosynostosis were different from wild-type derived cells. Interestingly, cells derived from the craniosynostotic rabbits were not uniformly more responsive compared with wild-type cells, suggesting that specific tissue-derived cells may react differently in individuals with craniosynostosis. PMID:20871482

Magnetic resonance imaging based morphologic evaluation of the pineal gland for suspected pineoblastoma in retinoblastoma patients and age-matched controls.

PubMed

Pham, Thi Thai Hien; Siebert, Eberhard; Asbach, Patrick; Willerding, Gregor; Erb-Eigner, Katharina

2015-12-15

The purpose of this study was to evaluate the morphologic magnetic resonance imaging (MRI) characteristics of the pineal gland in retinoblastoma (Rb) patients without and with pineoblastoma in comparison to age-matched controls to improve early identification of pineoblastomas (trilateral retinoblastoma, TRb). 80 patients with retinoblastoma and 80 age-matched controls who had undergone brain MRI were included in this retrospective institutional review board approved cohort study. Two readers analyzed the following MR characteristics of the pineal gland: signal intensity on T1- and T2-weighted images, enhancement pattern, delineation of the gland, presence of cystic component, size of pineal gland and size of pineal cysts, respectively. A third reader assessed all images for the presence or absence of pineoblastoma. 3 patients were positive (TRb cohort) and 77 negative for pineoblastoma (non-TRb cohort). The mean maximum diameter of the pineal gland was 6.4mm in Rb patients and 6.3mm in age-matched controls. The mean volume of the pineal gland in Rb patients was 93.1mm(3) and was 87.6mm(3) in age-matched controls. Considering all available MRI scans the mean maximum diameter of the pineal gland in TRb patients was 11.2mm and the mean volume in TRb patients was 453.3mm(3). The third reader identified pineoblastomas with a sensitivity of 100% (3 of 3) and a specificity of 94% (72 of 77). Our non-TRb patients did not show significant differences in the size of the pineal gland and pineal gland cysts compared to age-matched controls. The presented data can serve as a reference for the volume of normal pineal glands and pineal cysts in the diagnostic work-up of Rb patients with suspected pineoblastoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Chloroplast parameters differ in wild type and transgenic poplars overexpressing gsh1 in the cytosol.

PubMed

Ivanova, L A; Ronzhina, D A; Ivanov, L A; Stroukova, L V; Peuke, A D; Rennenberg, H

2009-07-01

Poplar mutants overexpressing the bacterial genes gsh1 or gsh2 encoding the enzymes of glutathione biosynthesis are among the best-characterised transgenic plants. However, this characterisation originates exclusively from laboratory studies, and the performance of these mutants under field conditions is largely unknown. Here, we report a field experiment in which the wild-type poplar hybrid Populus tremula x P. alba and a transgenic line overexpressing the bacterial gene gsh1 encoding gamma-glutamylcysteine synthetase in the cytosol were grown for 3 years at a relatively clean (control) field site and a field site contaminated with heavy metals. Aboveground biomass accumulation was slightly smaller in transgenic compared to wild-type plants; soil contamination significantly decreased biomass accumulation in both wild-type and transgenic plants by more than 40%. Chloroplasts parameters, i.e., maximal diameter, projection area and perimeter, surface area and volume, surface/volume ratio and a two-dimensional form coefficient, were found to depend on plant type, leaf tissue and soil contamination. The greatest differences between wild and transgenic poplars were observed at the control site. Under these conditions, chloroplast sizes in palisade tissue of transgenic poplar significantly exceeded those of the wild type. In contrast to the wild type, palisade chloroplast volume exceeded that of spongy chloroplasts in transgenic poplars at both field sites. Chlorophyll content per chloroplast was the same in wild and transgenic poplars. Apparently, the increase in chloroplast volume was not connected to changes in the photosynthetic centres. Chloroplasts of transgenic poplar at the control site were more elongated in palisade cells and close to spherical in spongy mesophyll chloroplasts. At the contaminated site, palisade and spongy cell chloroplasts of leaves from transgenic trees and the wild type were the same shape. Transgenic poplars also had a smaller chloroplast

Microvascular diabetes complications in Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAD]): an age- and duration-matched comparison with common type 1 diabetes.

PubMed

Cano, Aline; Molines, Laurent; Valéro, René; Simonin, Gilbert; Paquis-Flucklinger, Véronique; Vialettes, Bernard

2007-09-01

Some previous studies suggested that patients suffering from Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) might be relatively preserved from diabetic retinopathy and nephropathy. However, these data were not conclusive because either observations were only anecdotic or did not match with control type 1 diabetic populations. A group of 26 French diabetic patients with DIDMOAD was compared with a population of 52 patients with common type 1 diabetes matched for age at diabetes diagnosis (8.62 +/- 1.84 vs. 8.27 +/- 1.30 years; P = NS) and diabetes duration (12.88 +/- 1.58 vs. 12.87 +/- 1.13 years; P = NS) to study the quality of glycemic control and the incidence of microvascular complications. Glycemic control was significantly better in the DIDMOAD group than in the type 1 diabetic group (A1C: 7.72 +/- 0.21 vs. 8.99 +/- 0.25%, respectively; P = 0.002), with significant lower daily insulin requirements (0.71 +/- 0.07 vs. 0.88 +/- 0.04 UI x kg(-1) x day(-1), respectively; P = 0.0325). The prevalence of microvascular complications in the DIDMOAD group was half that observed in the type 1 diabetic group, but the difference was not significant. Diabetes in DIDMOAD patients is more easily controlled despite the presence of other handicaps. This better glycemic control could explain the trend to decreased microvascular diabetes complications observed in previous studies.

Sabin and wild type polioviruses from children who presented with acute flaccid paralysis in Nigeria.

PubMed

Adedeji, A O; Okonko, I O; Adu, F D

2012-09-01

Sensitive poliovirus surveillance to detect vaccine-derived-polioviruses will continue to increase in importance. Isolating and identifying poliovirus strains from children of pediatrics age in Nigeria. A total of 120 fecal samples were randomly collected from children under the age of five who presented with acute flaccid paralysis. Samples were tested by tissue culture technique and further characterized by intratypic differentiation testing using ELISA and PCR methods. The study confirmed the presence of 22(18.3%) enteroviral isolates comprising 19(86.4%) polioviruses and 3(13.6%) non-polio enteroviruses. These 19 polioviruses include: Sabin-type poliovirus-1 (15.8%), poliovirus-2 (10.5%), poliovirus-3 (10.5%) and wild-type poliovirus-1 (63.2%) isolates. It showed that poliovirus infection was higher in children ages 6-11 months (18.9%), females (18.4%), northern states (91.0%) with no vaccination record (75.0%). Wild-type poliovirus-1 was isolated from the stool samples of 12(54.6%) children from northern states and in all age groups except 18-23 months. No significant differences (P >0.05) between poliovirus infection and age (18.9% vs. 17.7%; 81.9% vs. 18.2%) and sex (18.3% vs. 18.4%). There was significant differences (P<0.05) between poliovirus infection and location (91.0% vs. 9.0%) and history of polio vaccination (75.0% vs. 0.0%). No wild-type poliovirus was found in those with complete vaccination. This study further confirms the presence of Sabin and wild-type poliovirus among children in Nigeria. The isolation of Sabin strain of poliovirus is advantageous to the polio eradication program as it is capable of inducing natural immunity in susceptible hosts. Transmission of wild-type poliovirus among children with incomplete vaccination poses a serious threat to polio eradication program in Nigeria. Environmental and serological surveillance with larger sample size are important for monitoring poliovirus circulation in Nigeria.

Environmental arsenic exposure and risk of diabetes type 2 in Ron Phibun subdistrict, Nakhon Si Thammarat Province, Thailand: unmatched and matched case–control studies

PubMed Central

Sripaoraya, Kwanyuen; Siriwong, Wattasit; Pavittranon, Sumol; Chapman, Robert S

2017-01-01

Background There are inconsistent findings on associations between low-to-moderate level of arsenic in water and diabetes risk from previous epidemiological reports. In Ron Phibun subdistrict, Nakhon Si Thammarat Province, Thailand, a low level of arsenic exposure among population was observed and increased diabetes mellitus (DM) rate was identified. Objectives We aimed to investigate the association between determinants (including low-level water arsenic exposure) of DM type 2 risk among residents of three villages of Ron Phibun subdistrict, Nakhon Si Thammarat Province. Materials and methods Secondary data from two previous community based-studies, conducted in 2000 and 2008, were utilized. Data on independent variables relating to arsenic exposure and sociodemographic characteristics were taken from questionnaires and worksheets for health-risk screening. Water samples collected during household visit were sent for analysis of arsenic level at certified laboratories. Diabetes cases (N=185) were those who had been diagnosed with DM type 2. Two groups of controls, one unmatched to cases (n=200) and one pair matched on age and gender (n=200), were selected for analysis as unmatched and matched case–control studies, respectively. A multiple imputation technique was used to impute missing values of independent variables. Multivariable logistic regression models, with independent variables for arsenic exposure and sociodemographic characteristics, were constructed. The unmatched and matched data sets were analyzed using unconditional and conditional logistic analyses, respectively. Results Older age, body mass index (BMI), having a history of illness in siblings and parents, and drinking were associated with increased DM type 2 risk. We found no convincing association between DM type 2 risk and water arsenic concentration in either study. Conclusion We did not observe meaningful association between diabetes risk and the low-to-moderate arsenic levels observed in

Comparison of MRI-defined back muscles volume between patients with ankylosing spondylitis and control patients with chronic back pain: age and spinopelvic alignment matched study.

PubMed

Bok, Doo Hee; Kim, Jihye; Kim, Tae-Hwan

2017-02-01

To compare MRI-defined back muscle volume between AS patients and age, and spinopelvic alignment matched control patients with chronic back pain. 51 male patients with AS were enrolled. Age and spinopelvic alignment matched controls (male) were found among non-AS patients with chronic back pain. After matching procedure, fully matched controls were found in 31 of 51 AS patients (60.8%), who represent AS patients without deformity. However, matched controls were not found in 20 of 51 AS patients (39.2%), who represent AS patients with deformity. MRI parameters of back muscle (paraspinal muscle and psoas muscle) at L4/5 disc level including cross-sectional area (CSA) and fat-free cross-sectional area (FCSA) were compared between AS patients and matched controls. Covariates, including BMI, self-reported physical activity, and the presence of chronic disease, which can influence back muscle volume, were also investigated. There were no statistical differences in age, body mass index, score of back pain (NRS), and spinopelvic alignment, and physical activity between matched AS patients and control patients except for duration of back pain. All MRI parameters for paraspinal muscle volume in matched AS patients (without deformity) were significantly less than those of control patients, and significantly larger than those of non-matched AS patients (with deformity). Body size adjusted MRI parameters (relative CSA and relative FCSA) of paraspinal muscle showed strong correlations with lumbar lordosis and sacral slope. Such relationship between paraspinal muscle and spinopelvic parameters remained significant even after multivariate adjustment. AS patients without deformity already have decreased paraspinal muscle volume compared with age and spinopelvic alignment matched non-AS patients with chronic back pain. Such decrease in paraspinal muscle volume was significantly associated with kyphotic deformity of AS patients even after multivariate adjustment. Although the result

Comparison of Conditioning Impairments in Children with Down Syndrome, Autistic Spectrum Disorders and Mental Age-Matched Controls

ERIC Educational Resources Information Center

Reed, P.; Staytom, L.; Stott, S.; Truzoli, R.

2011-01-01

Background: This study investigated the relative ease of learning across four tasks suggested by an adaptation of Thomas's hierarchy of learning in children with Down syndrome, autism spectrum disorders and mental age-matched controls. Methods: Learning trials were carried out to investigate observational learning, instrumental learning, reversal…

Clinical and sonographic risk factors and complications of shoulder dystocia - a case-control study with parity and gestational age matched controls.

PubMed

Parantainen, Jukka; Palomäki, Outi; Talola, Nina; Uotila, Jukka

2014-06-01

To examine the clinical risk factors and complications of shoulder dystocia today and to evaluate ultrasound methods predicting it. Retrospective, matched case-control study at a University Hospital with 5000 annual deliveries. The study population consisted of 152 deliveries complicated by shoulder dystocia over a period of 8.5 years (January 2004-June 2012) and 152 controls matched for gestational age and parity. The data was collected from the medical records of mothers and children and analyzed by conditional logistic regression. Incidences and odds ratios were calculated for risk factors and complications. Antenatal ultrasound data was analyzed when available by conditional logistic regression to test for significant differences between study groups. Birthweight (OR 12.1 for ≥4000 g; 95% CI 4.18-35.0) and vacuum extraction (OR 3.98; 95% CI 1.25-12.7) remained the most significant clinical risk factors. Only a trend of an association of pregestational or gestational diabetes was noticed (OR 1.87; 95% CI 0.997-3.495, probability of type II error 51%). Of the complications of shoulder dystocia the incidence of brachial plexus palsies was high (40%). Antenatal ultrasound method based on the difference between abdominal and biparietal diameters had a significant difference between cases and controls. The impact of diabetes as a risk factor has diminished, which may reflect improved screening and treatment. Antenatal ultrasound methods are showing some promise, but the predictive value of ultrasound alone is probably low. Copyright © 2014. Published by Elsevier Ireland Ltd.

Wild Type and PPAR KO Dataset

EPA Pesticide Factsheets

Data set 1 consists of the experimental data for the Wild Type and PPAR KO animal study and includes data used to prepare Figures 1-4 and Table 1 of the Das et al, 2016 paper.This dataset is associated with the following publication:Das, K., C. Wood, M. Lin, A.A. Starkov, C. Lau, K.B. Wallace, C. Corton, and B. Abbott. Perfluoroalky acids-induced liver steatosis: Effects on genes controlling lipid homeostasis. TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 378: 32-52, (2017).

Sensorimotor Control of Tracking Movements at Various Speeds for Stroke Patients as Well as Age-Matched and Young Healthy Subjects

PubMed Central

Ao, Di; Song, Rong; Tong, Kai-yu

2015-01-01

There are aging- and stroke-induced changes on sensorimotor control in daily activities, but their mechanisms have not been well investigated. This study explored speed-, aging-, and stroke-induced changes on sensorimotor control. Eleven stroke patients (affected sides and unaffected sides) and 20 control subjects (10 young and 10 age-matched individuals) were enrolled to perform elbow tracking tasks using sinusoidal trajectories, which included 6 target speeds (15.7, 31.4, 47.1, 62.8, 78.5, and 94.2 deg/s). The actual elbow angle was recorded and displayed on a screen as visual feedback, and three indicators, the root mean square error (RMSE), normalized integrated jerk (NIJ) and integral of the power spectrum density of normalized speed (IPNS), were used to investigate the strategy of sensorimotor control. Both NIJ and IPNS had significant differences among the four groups (P<0.01), and the values were ranked in the following order: young controls < age-matched controls aging-induced increase in reliance on feedback control. The RMSE increased with the increase in the target speed and the NIJ and IPNS initially declined and then remained steady for all four groups, which indicated a shift from feedback to feedforward control as the target speed increased. The feedback-feedforward trade-off induced by stroke, aging and speed might be explained by a change in the transmission delay and neuromotor noise. The findings in this study improve our understanding of the mechanism underlying the sensorimotor control and neurological changes caused by stroke and aging. PMID:26030289

Evolutionary significance of ageing in the wild.

PubMed

Kowald, Axel; Kirkwood, Thomas B L

2015-11-01

Human lifespan has risen dramatically over the last 150 years, leading to a significant increase in the fraction of aged people in the population. Until recently it was believed that this contrasted strongly with the situation in wild populations of animals, where the likelihood of encountering demonstrably senescent individuals was believed to be negligible. Over the recent years, however, a series of field studies has appeared that shows ageing can also be observed for many species in the wild. We discuss here the relevance of this finding for the different evolutionary theories of ageing, since it has been claimed that ageing in the wild is incompatible with the so-called non-adaptive (non-programmed) theories, i.e. those in which ageing is presumed not to offer a direct selection benefit. We show that a certain proportion of aged individuals in the population is fully compatible with the antagonistic pleiotropy and the disposable soma theories, while it is difficult to reconcile with the mutation accumulation theory. We also quantify the costs of ageing using life history data from recent field studies and a range of possible metrics. We discuss the merits and problems of the different metrics and also introduce a new metric, yearly death toll, that aims directly at quantifying the deaths caused by the ageing process. Copyright © 2015 Elsevier Inc. All rights reserved.

Association of young and advanced age of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

PubMed

Csermely, Gyula; Susánszky, Éva; Czeizel, Andrew E

2015-03-01

To analyze the possible association of maternal age with the risk of all congenital abnormalities (CAs) in a population-based large case-matched control data set. The Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with isolated CA and their 34,311 matched controls. First the distribution of maternal age groups in 24 CA-groups and their matched controls was compared. In the second step, young (19 years or less) and advanced (35 years or more) age groups were compared. Finally, the subgroups of neural-tube defects, congenital heart defects and abdominal wall's CA were evaluated separately. A higher risk of gastroschisis, congenital heart defects, particularly left-sided obstructive defects, undescended testis and clubfoot was found in the youngest age group (19 years or less) of cases. The higher proportion of pregnant women with advanced age (i.e. 35 years or more) showed only a borderline excess in cases with clubfoot. The so-called U-shaped risk of maternal age distribution was found in cases with clubfoot and in the total group of isolated CAs. The maternal age is a contributing factor to the origin of some isolated CAs mainly in young pregnant women.

Attention problems of very preterm children compared with age-matched term controls at school-age.

PubMed

de Kieviet, Jorrit F; van Elburg, Ruurd M; Lafeber, Harrie N; Oosterlaan, Jaap

2012-11-01

To clarify the severity, specificity, and neurocognitive underpinnings of attention problems in very preterm children. A sample of 66 preterm (<32 weeks gestation), mean (SD) age 7.5 (0.4) years, and 66 age-matched term controls participated. Symptoms of inattention were assessed using parent and teacher-rated questionnaires, and neurocognitive measures included speed and consistency in speed of information processing, lapses of attention (tau), alerting, orienting, and executive attention, as well as verbal and visuospatial working memory. Group differences were investigated using ANOVA, and Sobel tests were used to clarify the mediating role of neurocognitive impairments on attention problems. There was a large decrease in visuospatial working memory abilities (P < .001, d = .87), and medium increases in tau (P = .002, d = 0.55) as well as parent and teacher ratings of inattention (range d = 0.40-0.56) in very preterm children compared with term peers. Tau and visuospatial working memory were significant predictors of parent (R(2) = .161, P < .001 and R(2) = .071, P = .001; respectively) and teacher (R(2) = .152, P < .001 and R(2) = .064, P = .002; respectively) ratings of inattention, and completely explained the effects of very preterm birth on attention problems. Increased lapses of attention and poorer visuospatial working memory fully account for the attention problems in very premature children at school-age. Copyright © 2012 Mosby, Inc. All rights reserved.

Outcomes of hip arthroscopy in patients aged 50 years or older compared with a matched-pair control of patients aged 30 years or younger.

PubMed

Domb, Benjamin G; Linder, Dror; Finley, Zachary; Botser, Itamar B; Chen, Austin; Williamson, Joseph; Gupta, Asheesh

2015-02-01

Age has been suggested as a negative prognostic factor for hip arthroscopy. The purpose of this study was to compare patient characteristics and outcomes after hip arthroscopy in patients aged 50 years or older with a matched control group of patients aged 30 years or younger at a minimum postoperative follow-up of 2 years. Between September 2008 and March 2010, data were prospectively collected on all patients aged 50 years or older undergoing primary hip arthroscopy. Fifty-two patients met our inclusion and matching criteria, of whom all 52 (100%) were available for follow-up at a minimum of 2 years. This cohort was compared with a matched-pair control group of patients aged 30 years or younger who underwent similar procedures. The mean age of the study group was 54.8 years (range, 50 to 69 years), and that of the control group was 20.3 years (range, 13 to 30 years). The groups were matched at a 1:1 ratio, including 18 male patients (34.6%) and 34 female patients (65.4%) in each group, with a mean follow-up period of 32 months (range, 24 to 54 months). In the younger control group, the score improvement from preoperatively to 2 years' follow-up was 62.9 to 84.2 for the modified Harris Hip Score, 60.5 to 84.2 for the Non-Arthritic Hip Score, 63.1 to 86.5 for the Hip Outcome Score-Activities of Daily Living, and 42.2 to 72.7 for the Hip Outcome Score-Sport-Specific Subscale. In the older study group, the score improvement from preoperatively to 2 years' follow-up was 61.2 to 82.2 for the modified Harris Hip Score, 59.9 to 80.4 for the Non-Arthritic Hip Score, 63.9 to 83 for the Hip Outcome Score-Activities of Daily Living, and 41.2 to 64.6 for the Hip Outcome Score-Sport-Specific Subscale. All improvements in both groups were statistically significant at the 2-year postoperative follow-up (P < .001). There was no significant difference for all patient-reported outcome (PRO) scores at final follow-up between both groups. When we compared the change in PRO scores (�

Canine Length in Wild Male Baboons: Maturation, Aging and Social Dominance Rank

PubMed Central

Galbany, Jordi; Tung, Jenny; Altmann, Jeanne; Alberts, Susan C.

2015-01-01

Canines represent an essential component of the dentition for any heterodont mammal. In primates, like many other mammals, canines are frequently used as weapons. Hence, tooth size and wear may have significant implications for fighting ability, and consequently for social dominance rank, reproductive success, and fitness. We evaluated sources of variance in canine growth and length in a well-studied wild primate population because of the potential importance of canines for male reproductive success in many primates. Specifically, we measured maxillary canine length in 80 wild male baboons (aged 5.04–20.45 years) from the Amboseli ecosystem in southern Kenya, and examined its relationship with maturation, age, and social dominance rank. In our analysis of maturation, we compared food-enhanced baboons (those that fed part time at a refuse pit associated with a tourist lodge) with wild-feeding males, and found that food-enhanced males achieved long canines earlier than wild-feeding males. Among adult males, canine length decreased with age because of tooth wear. We found some evidence that, after controlling for age, longer canines were associated with higher adult dominance rank (accounting for 9% of the variance in rank), but only among relatively high-ranking males. This result supports the idea that social rank, and thus reproductive success and fitness, may depend in part on fighting ability mediated by canine size. PMID:25950700

Intake of key micronutrients and food groups in patients with late-stage age-related macular degeneration compared with age-sex-matched controls.

PubMed

Gopinath, Bamini; Liew, Gerald; Russell, Joanna; Cosatto, Victoria; Burlutsky, George; Mitchell, Paul

2017-08-01

Knowledge of the risk factor profile of patients presenting with late-stage age-related macular degeneration (AMD) could help identify the most frequent modifiable AMD precursors among people who are referred for treatment. We aimed to assess dietary behaviours by comparing adjusted mean intakes of micronutrients and major food groups (fruits, vegetables, fish) among patients with AMD and a sample of age-sex-matched controls. Cross-sectional analysis of 480 late AMD cases and 518 population-based age-sex-matched controls with no AMD signs. AMD cases (aged 60+ years) were those presenting for treatment to a hospital eye clinic in Sydney, Australia, during 2012-2015. The comparator group were obtained from a cohort study (Blue Mountains Eye Study; Sydney, Australia) during 2002-2009. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. AMD lesions were assessed from retinal photographs. After multivariable adjustment, patients with late-stage AMD compared with controls had significantly lower intakes of vitamin E (7.4 vs 9.8 mg/day; p<0.0001), beta-carotene (6232 vs 7738 μg/day; p<0.0001), vitamin C (161 vs 184 mg/day; p=0.0002) and folate (498.3 vs 602 μg/day; p<0.0001); but had higher intakes of zinc (13.0 vs 11.9 mg/day; p<0.0001). A significantly lower proportion of patients with late AMD met the recommended intake of vegetables than controls: 52.9% versus 64.5%; p=0.0002. This study showed significant differences in intakes of vitamins C and E, beta-carotene, folate and vegetables between patients with late-stage AMD and healthy controls, and thus has provided a better understanding of the nutritional intake of patients presenting with advanced AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Presbypropria: the effects of physiological ageing on proprioceptive control.

PubMed

Boisgontier, Matthieu P; Olivier, Isabelle; Chenu, Olivier; Nougier, Vincent

2012-10-01

Several changes in the human sensory systems, like presbycusis or presbyopia, are well-known to occur with physiological ageing. A similar change is likely to occur in proprioception, too, but there are strong and unexplained discrepancies in the literature. It was proposed that assessment of the attentional cost of proprioceptive control could provide information able to unify these previous studies. To this aim, 15 young adults and 15 older adults performed a position matching task in single and dual-task paradigms with different difficulty levels of the secondary task (congruent and incongruent Stroop-type tasks) to assess presumed age-related deficits in proprioceptive control. Results showed that proprioceptive control was as accurate and as consistent in older as in young adults for a single proprioceptive task. However, performing a secondary cognitive task and increasing the difficulty of this secondary task evidenced both a decreased matching performance and/or an increased attentional cost of proprioceptive control in older adults as compared to young ones. These results advocated for an impaired proprioception in physiological ageing.

Wild-derived mouse stocks: an underappreciated tool for aging research

PubMed Central

2008-01-01

Virtually all biomedical research makes use of a relatively small pool of laboratory-adapted, inbred, isogenic stocks of mice. Although the advantages of these models are many, there are a number of disadvantages as well. When studying a multifaceted process such as aging, the problems associated with using laboratory stocks are greatly inflated. On the other hand, wild-derived mouse stocks, loosely defined here as either wild-caught individuals or the recent progeny of wild-caught individuals, have much to offer to biogerontology research. Hence, the aims of this review are threefold: (1) to (re)acquaint readers with the pros and cons of using a typical inbred laboratory mouse model for aging research; (2) to reintroduce the notion of using wild-derived mouse stocks in aging research as championed by Austad, Miller and others for more than a decade, and (3) to provide an overview of recent advances in biogerontology using wild-derived mouse stocks. PMID:19424863

Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents.

PubMed

Nicaise, Charles; Prozzi, Deborah; Viaene, Eric; Moreno, Christophe; Gustot, Thierry; Quertinmont, Eric; Demetter, Pieter; Suain, Valérie; Goffin, Philippe; Devière, Jacques; Hols, Pascal

2008-10-01

Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed. Hyperammonemia in constitutive model or after acute or chronic induced liver failure can be controlled by the administration of L. plantarum with a significant effect on survival. The mechanism involved in this ammonia decrease implicates direct ammonia consumption in the gut.

Glio-vascular changes during ageing in wild-type and Alzheimer's disease-like APP/PS1 mice.

PubMed

Janota, C S; Brites, D; Lemere, C A; Brito, M A

2015-09-16

Vascular and glial involvement in the development of neurodegenerative disorders, such as Alzheimer's disease (AD), and age-related brain vulnerabilities have been suggested. Therefore, we sought to: (i) investigate which vascular and glial events are evident in ageing and/or AD, (ii) to establish the temporal evolution of vascular and glial changes in AD-like and wild-type (WT) mice and (iii) to relate them to amyloid-β (Aβ) peptide accumulation. We examined immunohistochemically hippocampi and cortex from APP/PS1dE9 and WT C57BL/6 mice along ageing and disease progression (young-adulthood, middle- and old-age). Ageing resulted in the increase in receptor for advanced glycation endproducts expression, as well as the entrance of thrombin and albumin in hippocampal parenchyma. In contrast, the loss of platelet-derived growth factor receptor-β (PDGFR-β) positive cells, in both regions, was only related to AD pathogenesis. Hypovascularization was affected by both ageing and AD in the hippocampus, but resulted from the interaction between both factors in the cortex. Astrogliosis was a result of AD in hippocampus and of both factors in cortex, while microgliosis was associated with fibrillar amyloid plaques in AD-like mice and with the interaction between both factors in each of the studied regions. In sum, these data show that senile plaques precede vascular and glial alterations only in hippocampus, whereas in cortex, vascular and glial alterations, namely the loss of PDGFR-β-positive cells and astrogliosis, accompanied the first senile plaques. Hence, this study points to vascular and glial events that co-exist in AD pathogenesis and age-related brain vulnerabilities. Copyright © 2015 Elsevier B.V. All rights reserved.

Type A personality, hostility, time urgency and unintentional injuries among Chinese undergraduates: a matched case–control study

PubMed Central

2013-01-01

Background Associations between type A behaviour pattern (TABP) and injuries are inconsistent. These inconsistencies may be due to different effects of various components of TABP, namely time urgency/impatience, hostility and competitive drive. It is important to examine the relationship between the global TABP, its two components, and unintentional injuries, among undergraduates in China. Methods On the basis of a previous cross-sectional study, we conducted a matched case–control study. 253 cases and an equal number of age-, gender-, and major-matched controls were included. The questionnaire solicited socio-demographic information, the experience of injuries, the scale of TABP, and other potential confounding factors. Besides the correlation between the global TABP and injuries, the influences of the two components of TABP on injuries were also evaluated. Conditional logistic regression was used to determine the crude odds ratios (ORs) and adjusted ORs of injury events. Results A dose–response relationship was apparent among students who rated themselves higher on the TABP scale (P-value for trend, 0.002), with a crude OR of 2.93 (95% CI: 0.93–9.19) for injuries comparing those with TABP to those with type B behaviour pattern (TBBP). After adjustment for potential confounding factors, TABP remained statistically significant, and the adjusted OR was 5.52 (95% CI: 1.43–21.27); from a comparison of students with TABP to those with TBBP. A dose–response relationship was also apparent between the hostility component and nonfatal injuries, both in crude analysis and after adjusting for other confounders. The relationship between time-hurry and injuries was not statistically significant, based on univariate and multivariate analyses. Conclusions Both the global TABP and the hostility component were associated with a dose response increase in the risk of non-fatal unintentional injuries among Chinese undergraduates. Further studies need to be conducted to

Molecular Evolution of a Type 1 Wild-Vaccine Poliovirus Recombinant during Widespread Circulation in China

PubMed Central

Liu, Hong-Mei; Zheng, Du-Ping; Zhang, Li-Bi; Oberste, M. Steven; Pallansch, Mark A.; Kew, Olen M.

2000-01-01

Type 1 wild-vaccine recombinant polioviruses were isolated from poliomyelitis patients in China from 1991 to 1993. We compared the sequences of 34 recombinant isolates over the 1,353-nucleotide (nt) genomic interval (nt 2480 to 3832) encoding the major capsid protein, VP1, and the protease, 2A. All recombinants had a 367-nt block of sequence (nt 3271 to 3637) derived from the Sabin 1 oral poliovirus vaccine strain spanning the 3′-terminal sequences of VP1 (115 nt) and the 5′ half of 2A (252 nt). The remaining VP1 sequences were closely (up to 99.5%) related to those of a major genotype of wild type 1 poliovirus endemic to China up to 1994. In contrast, the non-vaccine-derived sequences at the 3′ half of 2A were more distantly related (<90% nucleotide sequence match) to those of other contemporary wild polioviruses from China. The vaccine-derived sequences of the earliest (April 1991) isolates completely matched those of Sabin 1. Later isolates diverged from the early isolates primarily by accumulation of synonymous base substitutions (at a rate of ∼3.7 × 10−2 substitutions per synonymous site per year) over the entire VP1-2A interval. Distinct evolutionary lineages were found in different Chinese provinces. From the combined epidemiologic and evolutionary analyses, we propose that the recombinant virus arose during mixed infection of a single individual in northern China in early 1991 and that its progeny spread by multiple independent chains of transmission into some of the most populous areas of China within a year of the initiating infection. PMID:11070012

A case-control study of self-reported health, quality-of-life and general functioning among recent immigrants and age- and sex-matched Swedish-born controls.

PubMed

Löfvander, Monica; Rosenblad, Andreas; Wiklund, Tony; Bennström, Halina; Leppert, Jerzy

2014-12-01

To examine whether new immigrants had inferior quality-of-life, well-being and general functioning compared with Swedish age- and sex-matched controls. A prospective case-control study was designed including immigrants from non-European countries, 18-65 years of age, with recent Permanent Permits to Stay (PPS) in Sweden, and age- and sex-matched Swedish-born (SB) persons from the general population in Västmanland County, Sweden. The General Health Questionnaire (GHQ-12), the brief version of the World Health Organization Quality-of-Life (WHOQOL-BREF) Scale and the General Activity Functioning Assessment Scale (GAF) from DSM-IV were posted (SB), or applied in personal interviews (PPS) with interpreters. Differences between the PPS and SB groups were measured using McNemar's test and Wilcoxon signed-rank test conducted separately for observations at baseline, 6- and 12-month follow-up. There were 93 pairs (mean age 36 years). Persons from Somalia (67%) and Iraq (27%) dominated the PPS group. The differences between the groups were statistically significant for all time points for the Psychological health and Social relationship domains of WHOQOL-BREF, and for the baseline and 6-month follow-up time points of GHQ-12 where the PPS-group had a higher degree of well-being, health and quality-of-life than the SB. This tendency applied for both sexes in the immigrant group. These new immigrants did not have inferior physical or psychological health, quality-of-life, well-being or social functioning compared with their age- and sex-matched Swedish born pairs during a 1-year follow-up. Thus, there is reason to advocate immigrants' fast integration into society. © 2014 the Nordic Societies of Public Health.

Orthotopic transplantation of LH receptor knockout and wild-type ovaries.

PubMed

Chudgar, Daksha; Lei, Zhenmin; Rao, Ch V

2005-10-07

Luteinizing hormone (LH) receptor knockout animals have an ovarian failure due to an arrest in folliculogenesis at the antral stage. As a result, the animals have an infertility phenotype. The present study was undertaken to determine whether this phenotype could be reversed by orthotopic transplantation of wild-type ovaries. The results revealed that transplanting wild-type ovaries into null animals did not result in resumption of estrus cycles. Although the number of different types of follicles increased, none progressed to ovulation. The serum hormone profiles improved, reflecting the ovarian changes. The wild-type animals with null ovaries also failed to cycle and their ovaries and serum hormone levels were more like null animals with their own ovaries. Although the lack of rescue of null ovaries placed into wild-type animals was predicted, the failure of wild-type ovaries placed in null animals was not, which could be due to chronic exposure of transplanted tissue to high circulating LH levels and also possibly due to altered internal milieu in null animals. These findings may have implications for potential future considerations of grafting normal donor ovaries into women who have an ovarian failure resulting from inactivating LH receptor mutations.

On-going electroencephalographic rhythms related to cortical arousal in wild-type mice: the effect of aging.

PubMed

Del Percio, Claudio; Drinkenburg, Wilhelmus; Lopez, Susanna; Infarinato, Francesco; Bastlund, Jesper Frank; Laursen, Bettina; Pedersen, Jan T; Christensen, Ditte Zerlang; Forloni, Gianluigi; Frasca, Angelisa; Noè, Francesco M; Bentivoglio, Marina; Fabene, Paolo Francesco; Bertini, Giuseppe; Colavito, Valeria; Kelley, Jonathan; Dix, Sophie; Richardson, Jill C; Babiloni, Claudio

2017-01-01

Resting state electroencephalographic (EEG) rhythms reflect the fluctuation of cortical arousal and vigilance in a typical clinical setting, namely the EEG recording for few minutes with eyes closed (i.e., passive condition) and eyes open (i.e., active condition). Can this procedure be back-translated to C57 (wild type) mice for aging studies? On-going EEG rhythms were recorded from a frontoparietal bipolar channel in 85 (19 females) C57 mice. Male mice were subdivided into 3 groups: 25 young (4.5-6 months), 18 middle-aged (12-15 months), and 23 old (20-24 months) mice to test the effect of aging. EEG power density was compared between short periods (about 5 minutes) of awake quiet behavior (passive) and dynamic exploration of the cage (active). Compared with the passive condition, the active condition induced decreased EEG power at 1-2 Hz and increased EEG power at 6-10 Hz in the group of 85 mice. Concerning the aging effects, the passive condition showed higher EEG power at 1-2 Hz in the old group than that in the others. Furthermore, the active condition exhibited a maximum EEG power at 6-8 Hz in the former group and 8-10 Hz in the latter. In the present conditions, delta and theta EEG rhythms reflected changes in cortical arousal and vigilance in freely behaving C57 mice across aging. These changes resemble the so-called slowing of resting state EEG rhythms observed in humans across physiological and pathological aging. The present EEG procedures may be used to enhance preclinical phases of drug discovery in mice for understanding the neurophysiological effects of new compounds against brain aging. Copyright © 2016 Elsevier Inc. All rights reserved.

Wild-Type and Non-Wild-Type Mycobacterium tuberculosis MIC Distributions for the Novel Fluoroquinolone Antofloxacin Compared with Those for Ofloxacin, Levofloxacin, and Moxifloxacin

PubMed Central

Yu, Xia; Wang, Guirong; Chen, Suting; Wei, Guomei; Shang, Yuanyuan; Dong, Lingling; Schön, Thomas; Moradigaravand, Danesh; Peacock, Sharon J.

2016-01-01

Antofloxacin (AFX) is a novel fluoroquinolone that has been approved in China for the treatment of infections caused by a variety of bacterial species. We investigated whether it could be repurposed for the treatment of tuberculosis by studying its in vitro activity. We determined the wild-type and non-wild-type MIC ranges for AFX as well as ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), using the microplate alamarBlue assay, of 126 clinical Mycobacterium tuberculosis strains from Beijing, China, of which 48 were OFX resistant on the basis of drug susceptibility testing on Löwenstein-Jensen medium. The MIC distributions were correlated with mutations in the quinolone resistance-determining regions of gyrA (Rv0006) and gyrB (Rv0005). Pharmacokinetic/pharmacodynamic (PK/PD) data for AFX were retrieved from the literature. AFX showed lower MIC levels than OFX but higher MIC levels than LFX and MFX on the basis of the tentative epidemiological cutoff values (ECOFFs) determined in this study. All strains with non-wild-type MICs for AFX harbored known resistance mutations that also resulted in non-wild-type MICs for LFX and MFX. Moreover, our data suggested that the current critical concentration of OFX for Löwenstein-Jensen medium that was recently revised by the World Health Organization might be too high, resulting in the misclassification of phenotypically non-wild-type strains with known resistance mutations as wild type. On the basis of our exploratory PK/PD calculations, the current dose of AFX is unlikely to be optimal for the treatment of tuberculosis, but higher doses could be effective. PMID:27324769

Determination of mutated genes in the presence of wild-type DNA by using molecular beacons as probe

NASA Astrophysics Data System (ADS)

Zhang, Yonghua; Ai, Junjie; Gu, Qiaorong; Gao, Qiang; Qi, Honglan; Zhang, Chengxiao

2017-03-01

Low-abundance mutations in the presence of wild-type DNA can be determined using molecular beacon (MB) as probe. A MB is generally used as DNA probe because it can distinguish single-base mismatched target DNA from fully matched target DNA. However, the probe can not determine low-abundance mutations in the presence of wild-type DNA. In this study, this limitation is addressed by enhancing the stability of unpaired base-containing dsDNA with a hydrogen-bonding ligand, which was added after hybridization of the MB to the target DNA. The ligand formed hydrogen bonds with unpaired bases and stabilized the unpaired base-containing dsDNA if target DNA is mutated one. As a result, more MBs were opened by the mutant genes in the presence of the ligand and a further increase in the fluorescence intensity was obtained. By contrast, fluorescence intensity did not change if target DNA is wild-type one. Consequent increase in the fluorescence intensity of the MB was regarded as a signal derived from mutant genes. The proposed method was applied in synthetic template systems to determine point mutation in DNA obtained from PCR analysis. The method also allows rapid and simple discrimination of a signal if it is originated in the presence of mutant gene or alternatively by a lower concentration of wild gene.

Prosody Perception and Production in Children with Hearing Loss and Age- and Gender-Matched Controls.

PubMed

Kalathottukaren, Rose Thomas; Purdy, Suzanne C; Ballard, Elaine

2017-04-01

Auditory development in children with hearing loss, including the perception of prosody, depends on having adequate input from cochlear implants and/or hearing aids. Lack of adequate auditory stimulation can lead to delayed speech and language development. Nevertheless, prosody perception and production in people with hearing loss have received less attention than other aspects of language. The perception of auditory information conveyed through prosody using variations in the pitch, amplitude, and duration of speech is not usually evaluated clinically. This study (1) compared prosody perception and production abilities in children with hearing loss and children with normal hearing; and (2) investigated the effect of age, hearing level, and musicality on prosody perception. Participants were 16 children with hearing loss and 16 typically developing controls matched for age and gender. Fifteen of the children with hearing loss were tested while using amplification (n = 9 hearing aids, n = 6 cochlear implants). Six receptive subtests of the Profiling Elements of Prosody in Speech-Communication (PEPS-C), the Child Paralanguage subtest of Diagnostic Analysis of Nonverbal Accuracy 2 (DANVA 2), and Contour and Interval subtests of the Montreal Battery of Evaluation of Amusia (MBEA) were used. Audio recordings of the children's reading samples were rated using a perceptual prosody rating scale by nine experienced listeners who were blinded to the children's hearing status. Thirty two children, 16 with hearing loss (mean age = 8.71 yr) and 16 age- and gender-matched typically developing children with normal hearing (mean age = 8.87 yr). Assessments were completed in one session lasting 1-2 hours in a quiet room. Test items were presented using a laptop computer through loudspeaker at a comfortable listening level. For children with hearing loss using hearing instruments, all tests were completed with hearing devices set at their everyday listening setting. All PEPS

Case-control study of infections with Salmonella enteritidis phage type 4 in England.

PubMed Central

Cowden, J. M.; Lynch, D.; Joseph, C. A.; O'Mahony, M.; Mawer, S. L.; Rowe, B.; Bartlett, C. L.

1989-01-01

OBJECTIVE--To determine the source of indigenous sporadic infection with Salmonella enteritidis phage type 4. DESIGN--Case-control study of primary sporadic cases identified by the Public Health Laboratory Service between 1 August and 30 September 1988. SETTING--PHLS Communicable Disease Surveillance Centre, Division of Enteric Pathogens, 11 PHLS laboratories, and 42 local authority environmental health departments in England. SUBJECTS--232 Patients (cases) with confirmed primary sporadic infection, for 160 of whom (88 female) (median age 30 years, age range 4 months to 85 years) data were obtained by questionnaire about consumption of fresh eggs, egg products, precooked chicken, and minced meat in the three days and one week before onset of the symptoms. Up to three controls, matched for neighbourhood, age, and sex (if aged greater than 11 years), were asked the same questions for the same calendar period. MAIN OUTCOME MEASURE--Association of primary sporadic infection with consumption of suspected food items. RESULTS--Illness due to S enteritidis phage type 4 was significantly associated with consumption of raw shell egg products (homemade mayonnaise, ice cream, and milk drinks containing eggs) (matched p = 0.02) and shop bought sandwiches containing mayonnaise (matched p = 0.00004) or eggs (matched p = 0.02). Illness was also significantly associated with eating lightly cooked eggs (unmatched p = 0.02), but not soft boiled eggs, and precooked hot chicken (matched p = 0.006). Reported consumption of eggs was not appreciably different between cases and controls before or after the median date of interview. CONCLUSIONS--Fresh shell eggs, egg products, and precooked hot chicken are vehicles of S enteritidis phage type 4 infection in indigenous sporadic cases. Public health education and reduction in contamination of eggs and infection of poultry with S enteritidis are needed to reduce the incidence of human infection. PMID:2508916

P300-based brain-computer interface (BCI) event-related potentials (ERPs): People with amyotrophic lateral sclerosis (ALS) vs. age-matched controls.

PubMed

McCane, Lynn M; Heckman, Susan M; McFarland, Dennis J; Townsend, George; Mak, Joseph N; Sellers, Eric W; Zeitlin, Debra; Tenteromano, Laura M; Wolpaw, Jonathan R; Vaughan, Theresa M

2015-11-01

Brain-computer interfaces (BCIs) aimed at restoring communication to people with severe neuromuscular disabilities often use event-related potentials (ERPs) in scalp-recorded EEG activity. Up to the present, most research and development in this area has been done in the laboratory with young healthy control subjects. In order to facilitate the development of BCI most useful to people with disabilities, the present study set out to: (1) determine whether people with amyotrophic lateral sclerosis (ALS) and healthy, age-matched volunteers (HVs) differ in the speed and accuracy of their ERP-based BCI use; (2) compare the ERP characteristics of these two groups; and (3) identify ERP-related factors that might enable improvement in BCI performance for people with disabilities. Sixteen EEG channels were recorded while people with ALS or healthy age-matched volunteers (HVs) used a P300-based BCI. The subjects with ALS had little or no remaining useful motor control (mean ALS Functional Rating Scale-Revised 9.4 (±9.5SD) (range 0-25)). Each subject attended to a target item as the items in a 6×6 visual matrix flashed. The BCI used a stepwise linear discriminant function (SWLDA) to determine the item the user wished to select (i.e., the target item). Offline analyses assessed the latencies, amplitudes, and locations of ERPs to the target and non-target items for people with ALS and age-matched control subjects. BCI accuracy and communication rate did not differ significantly between ALS users and HVs. Although ERP morphology was similar for the two groups, their target ERPs differed significantly in the location and amplitude of the late positivity (P300), the amplitude of the early negativity (N200), and the latency of the late negativity (LN). The differences in target ERP components between people with ALS and age-matched HVs are consistent with the growing recognition that ALS may affect cortical function. The development of BCIs for use by this population may begin

Measuring Animal Age with DNA Methylation: From Humans to Wild Animals.

PubMed

De Paoli-Iseppi, Ricardo; Deagle, Bruce E; McMahon, Clive R; Hindell, Mark A; Dickinson, Joanne L; Jarman, Simon N

2017-01-01

DNA methylation (DNAm) is a key mechanism for regulating gene expression in animals and levels are known to change with age. Recent studies have used DNAm changes as a biomarker to estimate chronological age in humans and these techniques are now also being applied to domestic and wild animals. Animal age is widely used to track ongoing changes in ecosystems, however chronological age information is often unavailable for wild animals. An ability to estimate age would lead to improved monitoring of (i) population trends and status and (ii) demographic properties such as age structure and reproductive performance. Recent studies have revealed new examples of DNAm age association in several new species increasing the potential for developing DNAm age biomarkers for a broad range of wild animals. Emerging technologies for measuring DNAm will also enhance our ability to study age-related DNAm changes and to develop new molecular age biomarkers.

Age structure changes and extraordinary lifespan in wild medfly populations.

PubMed

Carey, James R; Papadopoulos, Nikos T; Müller, Hans-Georg; Katsoyannos, Byron I; Kouloussis, Nikos A; Wang, Jane-Ling; Wachter, Kenneth; Yu, Wei; Liedo, Pablo

2008-06-01

The main purpose of this study was to test the hypotheses that major changes in age structure occur in wild populations of the Mediterranean fruit fly (medfly) and that a substantial fraction of individuals survive to middle age and beyond (> 3-4 weeks). We thus brought reference life tables and deconvolution models to bear on medfly mortality data gathered from a 3-year study of field-captured individuals that were monitored in the laboratory. The average time-to-death of captured females differed between sampling dates by 23.9, 22.7, and 37.0 days in the 2003, 2004, and 2005 field seasons, respectively. These shifts in average times-to-death provided evidence of changes in population age structure. Estimates indicated that middle-aged medflies (> 30 days) were common in the population. A surprise in the study was the extraordinary longevity observed in field-captured medflies. For example, 19 captured females but no reference females survived in the laboratory for 140 days or more, and 6 captured but no reference males survived in the laboratory for 170 days or more. This paper advances the study of aging in the wild by introducing a new method for estimating age structure in insect populations, demonstrating that major changes in age structure occur in field populations of insects, showing that middle-aged individuals are common in the wild, and revealing the extraordinary lifespans of wild-caught individuals due to their early life experience in the field.

Characterization of hearing loss in aged type II diabetics

PubMed Central

Frisina, Susan T.; Mapes, Frances; Kim, SungHee; Frisina, D. Robert; Frisina, Robert D.

2009-01-01

Presbycusis – age-related hearing loss – is the number one communicative disorder and a significant chronic medical condition of the aged. Little is known about how type II diabetes, another prevalent age-related medical condition, and presbycusis interact. The present investigation aimed to comprehensively characterize the nature of hearing impairment in aged type II diabetics. Hearing tests measuring both peripheral (cochlea) and central (brainstem and cortex) auditory processing were utilized. The majority of differences between the hearing abilities of the aged diabetics and their age-matched controls were found in measures of inner ear function. For example, large differences were found in pure-tone audiograms, wideband noise and speech reception thresholds, and otoacoustic emissions. The greatest deficits tended to be at low frequencies. In addition, there was a strong tendency for diabetes to affect the right ear more than the left. One possible interpretation is that as one develops presbycusis, the right ear advantage is lost, and this decline is accelerated by diabetes. In contrast, auditory processing tests that measure both peripheral and central processing showed fewer declines between the elderly diabetics and the control group. Consequences of elevated blood sugar levels as possible underlying physiological mechanisms for the hearing loss are discussed. PMID:16309862

Endoscopic detection rate of sessile serrated lesions in Lynch syndrome patients is comparable with an age- and gender-matched control population: case-control study with expert pathology review.

PubMed

Vleugels, Jasper L A; Sahin, Husna; Hazewinkel, Yark; Koens, Lianne; van den Berg, Jose G; van Leerdam, Monique E; Dekker, Evelien

2018-05-01

Carcinogenesis in Lynch syndrome involves fast progression of adenomas to colorectal cancer (CRC) because of microsatellite instability. The role of sessile serrated lesions (SSLs) and the serrated neoplasia pathway in these patients is unknown. The aim of this matched case-control study was to compare endoscopic detection rates and distribution of SSLs in Lynch syndrome patients with a matched control population. We collected data of Lynch syndrome patients with a proven germline mutation who underwent colonoscopy between January 2011 and April 2016 in 2 tertiary referral hospitals. Control subjects undergoing elective colonoscopy from 2011 and onward for symptoms or surveillance were selected from a prospectively collected database. Patients were matched 1:1 for age, gender, and index versus surveillance colonoscopy. An expert pathology review of serrated polyps was performed. The primary outcomes included the detection rates and distribution of SSLs. We identified 321 patients with Lynch syndrome who underwent at least 1 colonoscopy. Of these, 223 Lynch syndrome patients (mean age, 49.3; 59% women; index colonoscopy, 56%) were matched to 223 control subjects. SSLs were detected in 7.6% (95% confidence interval, 4.8-11.9) of colonoscopies performed in Lynch syndrome patients and in 6.7% (95% confidence interval, 4.1-10.8) of control subjects (P = .86). None of the detected SSLs in Lynch syndrome patients contained dysplasia. The detection rate of SSLs in Lynch syndrome patients undergoing colonoscopy is comparable with a matched population. These findings suggest that the role of the serrated neoplasia pathway in CRC development in Lynch syndrome seems to be comparable with that in the general population. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Proteome profiling of virus-host interactions of wild type and attenuated measles virus strains.

PubMed

Billing, Anja M; Kessler, Julia R; Revets, Dominique; Sausy, Aurélie; Schmitz, Stephanie; Barra, Claire; Muller, Claude P

2014-08-28

Quantitative gel-based proteomics (2D DIGE coupled to MALDI-TOF/TOF MS) has been used to investigate the effects of different measles virus (MV) strains on the host cell proteome. A549/hSLAM cells were infected either with wild type MV strains, an attenuated vaccine or a multiple passaged Vero cell adapted strain. By including interferon beta treatment as a control it was possible to distinguish between the classical antiviral response and changes induced specifically by the different strains. Of 38 differentially expressed proteins in total (p-value ≤0.05, fold change ≥2), 18 proteins were uniquely modulated following MV infection with up to 9 proteins specific per individual strain. Interestingly, wt strains displayed distinct protein patterns particularly during the late phase of infection. Proteins were grouped into cytoskeleton, metabolism, transcription/translation, immune response and mitochondrial proteins. Bioinformatics analysis revealed mostly changes in proteins regulating cell death and apoptosis. Surprisingly, wt strains affected the cytokeratin system much stronger than the vaccine strain. To our knowledge, this is the first study on the MV-host proteome addressing interstrain differences. In the present study we investigated the host cell proteome upon measles virus (MV) infection. The novelty about this study is the side-by side comparison of different strains from the same virus, which has not been done at the proteome level for any other virus including MV. We used different virus strains including a vaccine strain, wild type isolates derived from MV-infected patients as well as a Vero cell adapted strain, which serves as an intermediate between vaccine and wild type strain. We observed differences between vaccine and wild type strains as well as common features between different wild type strains. Perhaps one of the most surprising findings was that differences did not only occur between wild type and vaccine or Vero cell adapted strains but

Analysis of near infrared spectra for age-grading of wild populations of Anopheles gambiae.

PubMed

Krajacich, Benjamin J; Meyers, Jacob I; Alout, Haoues; Dabiré, Roch K; Dowell, Floyd E; Foy, Brian D

2017-11-07

Understanding the age-structure of mosquito populations, especially malaria vectors such as Anopheles gambiae, is important for assessing the risk of infectious mosquitoes, and how vector control interventions may impact this risk. The use of near-infrared spectroscopy (NIRS) for age-grading has been demonstrated previously on laboratory and semi-field mosquitoes, but to date has not been utilized on wild-caught mosquitoes whose age is externally validated via parity status or parasite infection stage. In this study, we developed regression and classification models using NIRS on datasets of wild An. gambiae (s.l.) reared from larvae collected from the field in Burkina Faso, and two laboratory strains. We compared the accuracy of these models for predicting the ages of wild-caught mosquitoes that had been scored for their parity status as well as for positivity for Plasmodium sporozoites. Regression models utilizing variable selection increased predictive accuracy over the more common full-spectrum partial least squares (PLS) approach for cross-validation of the datasets, validation, and independent test sets. Models produced from datasets that included the greatest range of mosquito samples (i.e. different sampling locations and times) had the highest predictive accuracy on independent testing sets, though overall accuracy on these samples was low. For classification, we found that intramodel accuracy ranged between 73.5-97.0% for grouping of mosquitoes into "early" and "late" age classes, with the highest prediction accuracy found in laboratory colonized mosquitoes. However, this accuracy was decreased on test sets, with the highest classification of an independent set of wild-caught larvae reared to set ages being 69.6%. Variation in NIRS data, likely from dietary, genetic, and other factors limits the accuracy of this technique with wild-caught mosquitoes. Alternative algorithms may help improve prediction accuracy, but care should be taken to either maximize

Locomotor differences in mice expressing wild-type human α-synuclein.

PubMed

Giraldo, Genesys; Brooks, Mieu; Giasson, Benoit I; Janus, Christopher

2018-05-01

Parkinson's disease manifests as a progressive movement disorder with underlying degeneration of dopaminergic neurons in the substantia nigra, consequent depletion of dopamine levels, and the accumulation of Lewy bodies in the brain. Because α-synuclein (α-Syn) protein is the major component of Lewy bodies, mouse models expressing wild-type or mutant SNCA/α-Syn genes provide a useful tool to investigate canonical characteristics of the disease. We evaluated a mouse model (denoted M20) that expresses human wild-type SNCA gene. The M20 mice showed abnormal locomotor behavior and reduced species-specific home cage activity. However, the direction of behavioral changes was task specific. In comparison with their control littermates, the M20 mice exhibited shorter grip endurance, and longer times to traverse elevated beams, but they descended the vertical pole faster and stayed longer on the accelerated rod than the control mice. The M20 mice were also impaired in burrowing and nest building activities. These results indicate a possible role of α-Syn in motor coordination and the motivation to perform species-specific behaviors in the presymptomatic model of synucleinopathy. Published by Elsevier Inc.

Transcript profiling reveals expression differences in wild-type and glabrous soybean lines

PubMed Central

2011-01-01

Background Trichome hairs affect diverse agronomic characters such as seed weight and yield, prevent insect damage and reduce loss of water but their molecular control has not been extensively studied in soybean. Several detailed models for trichome development have been proposed for Arabidopsis thaliana, but their applicability to important crops such as cotton and soybean is not fully known. Results Two high throughput transcript sequencing methods, Digital Gene Expression (DGE) Tag Profiling and RNA-Seq, were used to compare the transcriptional profiles in wild-type (cv. Clark standard, CS) and a mutant (cv. Clark glabrous, i.e., trichomeless or hairless, CG) soybean isoline that carries the dominant P1 allele. DGE data and RNA-Seq data were mapped to the cDNAs (Glyma models) predicted from the reference soybean genome, Williams 82. Extending the model length by 250 bp at both ends resulted in significantly more matches of authentic DGE tags indicating that many of the predicted gene models are prematurely truncated at the 5' and 3' UTRs. The genome-wide comparative study of the transcript profiles of the wild-type versus mutant line revealed a number of differentially expressed genes. One highly-expressed gene, Glyma04g35130, in wild-type soybean was of interest as it has high homology to the cotton gene GhRDL1 gene that has been identified as being involved in cotton fiber initiation and is a member of the BURP protein family. Sequence comparison of Glyma04g35130 among Williams 82 with our sequences derived from CS and CG isolines revealed various SNPs and indels including addition of one nucleotide C in the CG and insertion of ~60 bp in the third exon of CS that causes a frameshift mutation and premature truncation of peptides in both lines as compared to Williams 82. Conclusion Although not a candidate for the P1 locus, a BURP family member (Glyma04g35130) from soybean has been shown to be abundantly expressed in the CS line and very weakly expressed in the

Wild-type myoblasts rescue the ability of myogenin-null myoblasts to fuse in vivo.

PubMed

Myer, A; Wagner, D S; Vivian, J L; Olson, E N; Klein, W H

1997-05-15

Skeletal muscle is formed via a complex series of events during embryogenesis. These events include commitment of mesodermal precursor cells, cell migration, cell-cell recognition, fusion of myoblasts, activation of structural genes, and maturation. In mice lacking the bHLH transcription factor myogenin, myoblasts are specified and positioned correctly, but few fuse to form multinucleated fibers. This indicates that myogenin is critical for the fusion process and subsequent differentiation events of myogenesis. To further define the nature of the myogenic defects in myogenin-null mice, we investigated whether myogenin-null myoblasts are capable of fusing with wild-type myoblasts in vivo using chimeric mice containing mixtures of myogenin-null and wild-type cells. Chimeric embryos demonstrated that myogenin-null myoblasts readily fused in the presence of wild-type myoblasts. However, chimeric myofibers did not express wild-type levels of muscle-specific gene products, and myofibers with a high percentage of mutant nuclei appeared abnormal, suggesting that the wild-type nuclei could not fully rescue mutant nuclei in the myofibers. These data demonstrate that myoblast fusion can be uncoupled from complete myogenic differentiation and that myogenin regulates a specific subset of genes with diverse function. Thus, myogenin appears to control not only transcription of muscle structural genes but also the extracellular environment in which myoblast fusion takes place. We propose that myogenin regulates the expression of one or more extracellular or cell surface proteins required to initiate the muscle differentiation program.

Optimal case-control matching in practice.

PubMed

Cologne, J B; Shibata, Y

1995-05-01

We illustrate modern matching techniques and discuss practical issues in defining the closeness of matching for retrospective case-control designs (in which the pool of subjects already exists when the study commences). We empirically compare matching on a balancing score, analogous to the propensity score for treated/control matching, with matching on a weighted distance measure. Although both methods in principle produce balance between cases and controls in the marginal distributions of the matching covariates, the weighted distance measure provides better balance in practice because the balancing score can be poorly estimated. We emphasize the use of optimal matching based on efficient network algorithms. An illustration is based on the design of a case-control study of hepatitis B virus infection as a possible confounder and/or effect modifier of radiation-related primary liver cancer in atomic bomb survivors.

Incidence of type 2 diabetes after bariatric surgery: population-based matched cohort study.

PubMed

Booth, Helen; Khan, Omar; Prevost, Toby; Reddy, Marcus; Dregan, Alex; Charlton, Judith; Ashworth, Mark; Rudisill, Caroline; Littlejohns, Peter; Gulliford, Martin C

2014-12-01

The effect of currently used bariatric surgical procedures on the development of diabetes in obese people is not well defined. We aimed to assess the effect of bariatric surgery on development of type 2 diabetes in a large population of obese individuals. We did a matched cohort study of adults (age 20–100 years) identified from a UK-wide database of family practices, who were obese (BMI ≥30 kg/m2) and did not have diabetes. We enrolled 2167 patients who had undergone bariatric surgery between Jan 1, 2002, and April 30, 2014, and matched them--according to BMI, age, sex, index year, and HbA1c--with 2167 controls who had not had surgery. Procedures included laparoscopic gastric banding (n=1053), gastric bypass (795), and sleeve gastrectomy (317), with two procedures undefined. The primary outcome was development of clinical diabetes, which we extracted from electronic health records. Analyses were adjusted for matching variables, comorbidity, cardiovascular risk factors, and use of antihypertensive and lipid-lowering drugs. During a maximum of 7 years of follow-up (median 2·8 years [IQR 1·3–4·5]), 38 new diagnoses of diabetes were made in bariatric surgery patients and 177 were made in controls. By the end of 7 years of follow-up, 4·3% (95% CI 2·9–6·5) of bariatric surgery patients and 16·2% (13·3–19·6) of matched controls had developed diabetes. The incidence of diabetes diagnosis was 28·2 (95% CI 24·4–32·7) per 1000 person-years in controls and 5·7 (4·2–7·8) per 1000 person-years in bariatric surgery patients; the adjusted hazard ratio was 0·20 (95% CI 0·13–0·30, p<0·0001). This estimate was robust after varying the comparison group in sensitivity analyses, excluding gestational diabetes, or allowing for competing mortality risk. Bariatric surgery is associated with reduced incidence of clinical diabetes in obese participants without diabetes at baseline for up to 7 years after the procedure. UK National Institute for Health

Serum 25-hydroxyvitamin D concentrations in dogs with osteosarcoma do not differ from those of age- and weight-matched control dogs.

PubMed

Willcox, Jennifer L; Hammett-Stabler, Catherine; Hauck, Marlene L

2016-11-01

Vitamin D concentrations show an inverse correlation with incidence of certain tumors in people and dogs. Additionally, human osteosarcoma has been associated with dysregulation of vitamin D-dependent pathways. The study objective was to compare serum 25-hydroxyvitamin D 2 and 25-hydroxyvitamin D 3 in 20 dogs with osteosarcoma to age- and weight-matched control dogs. We hypothesized that dogs with osteosarcoma would have lower serum 25-hydroxyvitamin D than control dogs. The mean 25-hydroxyvitamin D 3 concentrations for dogs with osteosarcoma and matched-controls were 34.95 ng/mL and 33.85 ng/mL, respectively (P = 0.784). Based on these data, 25-hydroxyvitamin D insufficiency might not be important in the pathogenesis of canine osteosarcoma. Published by Elsevier Ltd.

Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells.

PubMed

Cawood, Ryan; Chen, Hannah H; Carroll, Fionnadh; Bazan-Peregrino, Miriam; van Rooijen, Nico; Seymour, Leonard W

2009-05-01

Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5x10(10) viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases.

Matched-pair analysis of a multi-institutional cohort reveals that epidermal growth factor receptor mutation is not a risk factor for postoperative recurrence of lung adenocarcinoma.

PubMed

Matsumura, Yuki; Suzuki, Hiroyuki; Ohira, Tetsuya; Shiono, Satoshi; Abe, Jiro; Sagawa, Motoyasu; Sakurada, Akira; Katahira, Masato; Machida, Yuichiro; Takahashi, Satomi; Okada, Yoshinori

2017-12-01

It is unclear whether epidermal growth factor receptor (EGFR) mutation status is a risk factor for postoperative recurrence of surgically resected lung adenocarcinoma (ADC). Therefore, we conducted a multi-institutional study employing matched-pair analysis to compare recurrence-free survival (RFS) and overall survival (OS) of patients with lung ADC according to EGFR mutation status. We collected the records of 909 patients who underwent surgical resection for lung ADC between 2005 and 2012 at five participating institutions and were also examined their EGFR mutation status. For each patient with an EGFR mutation, we selected one with the wild-type EGFR sequence and matched them according to institution, age, gender, smoking history, pathological stage (pStage), and adjuvant treatment. We compared RFS and OS of the matched cohort. The patients were allocated into groups (n=181 each) with mutated or wild-type EGFR sequences. Both cohorts had identical characteristics as follows: institution, median age (68 years), men (85, 47%), ever smokers (77, 43%), and pStage (IA, 108, 60%; IB, 48, 27%; II, 14, 8%; III, 11, 6%). The 3- and 5-year RFS rates of patients with mutated or wild-type EGFR sequence were 79%, 68% and 77%, 68%, respectively (p=0.557). The respective OS rates were 92%, 81%, and 89%, 79% (p=0.574). Matched-pair and multi-institutional analysis reveals that an EGFR mutation was not a significant risk factor for recurrence of patients with surgically resected lung adenocarcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Performance of Disease Risk Score Matching in Nested Case-Control Studies: A Simulation Study.

PubMed

Desai, Rishi J; Glynn, Robert J; Wang, Shirley; Gagne, Joshua J

2016-05-15

In a case-control study, matching on a disease risk score (DRS), which includes many confounders, should theoretically result in greater precision than matching on only a few confounders; however, this has not been investigated. We simulated 1,000 hypothetical cohorts with a binary exposure, a time-to-event outcome, and 13 covariates. Each cohort comprised 2 subcohorts of 10,000 patients each: a historical subcohort and a concurrent subcohort. DRS were estimated in the historical subcohorts and applied to the concurrent subcohorts. Nested case-control studies were conducted in the concurrent subcohorts using incidence density sampling with 2 strategies-matching on age and sex, with adjustment for additional confounders, and matching on DRS-followed by conditional logistic regression for 9 outcome-exposure incidence scenarios. In all scenarios, DRS matching yielded lower average standard errors and mean squared errors than did matching on age and sex. In 6 scenarios, DRS matching also resulted in greater empirical power. DRS matching resulted in less relative bias than did matching on age and sex at lower outcome incidences but more relative bias at higher incidences. Post-hoc analysis revealed that the effect of DRS model misspecification might be more pronounced at higher outcome incidences, resulting in higher relative bias. These results suggest that DRS matching might increase the statistical efficiency of case-control studies, particularly when the outcome is rare. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Constitutive expression of tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert mice.

PubMed

Canela, Andrés; Martín-Caballero, Juan; Flores, Juana M; Blasco, María A

2004-05-01

Here we describe a new mouse model with constitutive expression of the catalytic subunit of telomerase (Tert) targeted to thymocytes and peripheral T cells (Lck-Tert mice). Two independent Lck-Tert mouse lines showed higher incidences of spontaneous T-cell lymphoma than the corresponding age-matched wild-type controls, indicating that constitutive expression of Tert promotes lymphoma. Interestingly, T-cell lymphomas in Lck-Tert mice were more disseminated than those in wild-type controls and affected both lymphoid and nonlymphoid tissues, while nonlymphoid tissues were never affected with lymphoma in age-matched wild-type controls. Importantly, these roles of Tert constitutive expression in promoting tumor progression and dissemination were independent of the role of telomerase in telomere length maintenance, since telomere length distributions on a single-cell basis were identical in Lck-Tert and wild-type thymocytes. Finally, Tert constitutive expression did not interfere with telomere capping in Lck-Tert primary thymocytes, although it resulted in greater chromosomal instability upon gamma irradiation in Lck-Tert primary lymphocytes than in controls, suggesting that Tert overexpression may interfere with the cellular response to DNA damage.

Neuropsychological functioning in older people with type 2 diabetes: the effect of controlling for confounding factors.

PubMed

Asimakopoulou, K G; Hampson, S E; Morrish, N J

2002-04-01

Neuropsychological functioning was examined in a group of 33 older (mean age 62.40 +/- 9.62 years) people with Type 2 diabetes (Group 1) and 33 non-diabetic participants matched with Group 1 on age, sex, premorbid intelligence and presence of hypertension and cardio/cerebrovascular conditions (Group 2). Data statistically corrected for confounding factors obtained from the diabetic group were compared with the matched control group. The results suggested small cognitive deficits in diabetic people's verbal memory and mental flexibility (Logical Memory A and SS7). No differences were seen between the two samples in simple and complex visuomotor attention, sustained complex visual attention, attention efficiency, mental double tracking, implicit memory, and self-reported memory problems. These findings indicate minimal cognitive impairment in relatively uncomplicated Type 2 diabetes and demonstrate the importance of control and matching for confounding factors.

Racing performance of Standardbred trotting horses undergoing surgery of the carpal flexor sheath and age- and sex-matched control horses.

PubMed

Carmalt, James L; Johansson, Bengt C; Zetterström, Sandra M; McOnie, Rebecca C

2017-07-01

OBJECTIVE To determine factors affecting race speed in Swedish Standardbred horses undergoing surgery of the carpal flexor sheath (CFS), to investigate whether preoperative racing speed was associated with specific intraoperative findings and whether horses returned to racing, and to compare the performance of horses undergoing surgery of the CFS with that of age- and sex-matched control horses. ANIMALS 149 Swedish Standardbred trotters undergoing surgery of the CFS and 274 age- and sex-matched control horses. PROCEDURES Medical records of CFS horses were examined. Racing data for CFS and control horses were retrieved from official online records. Generalizing estimating equations were used to examine overall and presurgery racing speeds and the association of preoperative clinical and intraoperative findings with preoperative and postoperative speeds. Multivariable regression analysis was used to examine career earnings and number of career races. Kaplan-Meier survival analysis was used to compare career longevity between CFS and control horses. RESULTS CFS horses were significantly faster than control horses. The CFS horses that raced before surgery were slower as they approached the surgery date, but race speed increased after surgery. There were 124 of 137 (90.5%) CFS horses that raced after surgery. No intrathecal pathological findings were significantly associated with preoperative racing speed. Career longevity did not differ between CFS and control horses. CONCLUSIONS AND CLINICAL RELEVANCE Horses undergoing surgery of the CFS had a good prognosis to return to racing after surgery. Racing careers of horses undergoing surgery of the CFS were not significantly different from racing careers of control horses.

Heart rate autonomic regulation system at rest and during paced breathing among patients with CRPS as compared to age-matched healthy controls.

PubMed

Bartur, Gadi; Vatine, Jean-Jacques; Raphaely-Beer, Noa; Peleg, Sara; Katz-Leurer, Michal

2014-09-01

The objective of this study is to assess the autonomic nerve heart rate regulation system at rest and its immediate response to paced breathing among patients with complex regional pain syndrome (CRPS) as compared with age-matched healthy controls. Quasiexperimental. Outpatient clinic. Ten patients with CRPS and 10 age- and sex-matched controls. Participants underwent Holter ECG (NorthEast Monitoring, Inc., Maynard, MA, USA) recording during rest and biofeedback-paced breathing session. Heart rate variability (HRV), time, and frequency measures were assessed. HRV and time domain values were significantly lower at rest among patients with CRPS as compared with controls. A significant association was noted between pain rank and HRV frequency measures at rest and during paced breathing; although both groups reduced breathing rate significantly during paced breathing, HRV time domain parameters increased only among the control group. The increased heart rate and decreased HRV at rest in patients with CRPS suggest a general autonomic imbalance. The inability of the patients to increase HRV time domain values during paced breathing may suggest that these patients have sustained stress response with minimal changeability in response to slow-paced breathing stimuli. Wiley Periodicals, Inc.

Cyclists Have Greater Chondromalacia Index Than Age-Matched Controls at the Time of Hip Arthroscopy.

PubMed

Stone, Austin V; Howse, Elizabeth A; Mannava, Sandeep; Stubbs, Allston J

2016-10-01

To evaluate the clinical symptoms and intraoperative pathology associated with hip pain in the cyclist compared with a matched hip arthroscopy surgical group. In an institutional review board-approved study, we retrospectively reviewed a prospective database of 1,200 consecutive hip arthroscopy patients from 2008 to 2015. Adult patients were identified who reported cycling as a major component of their activity. Patients were age, gender, and body mass index matched to a control, noncycling group. Pain symptoms, preoperative examinations, radiographic and operative findings were compared. Primary outcome variables included the femoral and acetabular Outerbridge chondromalacia grade. Additional outcome measurements included the involved area and the chondromalacia index (CMI; the product of the Outerbridge chondromalacia grade and surface area [mm 2  × severity]). A total of 167 noncyclists were matched to the cycling group (n = 16). Cyclists had significantly greater femoral head chondromalacia grade (2.0 [95% confidence interval (CI), 1.5-2.5] v 1.4 [95% CI, 1.3-1.6], P = .043), femoral head chondromalacia area (242 mm 2 [95% CI, 191-293 mm 2 ] v 128 mm 2 [95% CI, 113-141 mm 2 ], P < .001), and femoral head CMI (486 [95% CI, 358-615] v 247 [95% CI, 208-286], P = .001) assessed intraoperatively. Hip pain in cyclists positively correlated with an increased acetabular center-edge angle (R = 0.261, P < .001) and an increased Tonnis grade (R = 0.305, P < .001). Cyclists were also more likely to have a coxalgic gait on physical examination (R = 0.250, P = .006). Cyclists had a greater degree of femoral chondromalacia than a matched group of noncyclists. Cycling activity positively correlated with the presence of femoral chondromalacia with clinically significant gait alterations. These data support the hypothesis that cyclists with hip pain have more chondral pathology than a similar group of other patients with hip pain. Ultimately, cyclists with hip pain

Issues Related to Obtaining Intelligence Quotient-Matched Controls in Autism Research

PubMed Central

Rao, Vanitha S.; Raman, Vijaya; Mysore, Ashok V.

2015-01-01

Background: Intelligence Quotient (IQ) is considered to be an index of global cognitive functioning and has traditionally been used as a fulcral measure in case-control studies in neuro-developmental disorders such as autism. Aim: The aim is to highlight the issues of “matching for IQ” with controls in autism research. Materials and Methods: Percentile scores on the Coloured Progressive Matrices of 20 children with autism in the age range of 5 to 12 years have been graphically compared with 21 age matched typically developing children. Results and Conclusions: The percentile scores of the so-called high functioning children with autism from special schools were well below that of typically developing children. There are many challenges when using IQ in case-control studies of autism. Alternative approaches need to be considered. PMID:25969598

Identification, Isolation, and Phylogenetic Analysis of Clostridium perfringens Type A and Type C from Wild Boar ( Sus scrofa ) in the People's Republic of China.

PubMed

Li, Meng; Zhang, Xu; Zhu, Lingwei; Wang, Haifeng; Zhao, Na; Luo, Jing; Wang, Chengmin; Wang, Yutian; Liu, Yanhua; Zhou, Wei; Zhang, Bikai; Guo, Huancheng; He, Hongxuan

2017-07-01

Clostridium perfringens is a Gram-positive, anaerobic, spore-forming bacterium that can induces gas gangrene or enteritis in poultry and humans and many other mammalian species. Here, we report an outbreak of C. perfringens type A and type C coinfection in wild boars ( Sus scrofa ). In February 2016, 10 dead wild boars, including two fresh carcasses, were found in Zhaosu County, Xinjiang Province, People's Republic of China. The two fresh carcasses were included in this study. Two strains of C. perfringens were isolated, identified, genotyped, and phylogenetically analyzed. Based on postmortem examination, bacterium isolation and identification, enterotoxin detection, and auxiliary tests, we made a diagnosis that the wild boar were killed by C. perfringens . Our findings provide the evidence that wild boar can be killed by C. perfringens intoxication. Wild boars are important reservoirs for many zoonotic agents. Therefore, more actions should be taken on the surveillance, prevention, and control of wild pig-borne diseases.

Functional Aspects of Gait in Essential Tremor: A Comparison with Age-Matched Parkinson's Disease Cases, Dystonia Cases, and Controls.

PubMed

Louis, Elan D; Rao, Ashwini K

2015-01-01

An understanding of the functional aspects of gait and balance has wide ramifications. Individuals with balance disorders often restrict physical activity, travel, and social commitments to avoid falling, and loss of balance confidence, itself, is a source of disability. We studied the functional aspects of gait in patients with essential tremor (ET), placing their findings within the context of two other neurological disorders (Parkinson's disease [PD] and dystonia) and comparing them with age-matched controls. We administered the six-item Activities of Balance Confidence (ABC-6) Scale and collected data on number of falls and near-falls, and use of walking aids in 422 participants (126 ET, 77 PD, 46 dystonia, 173 controls). Balance confidence was lowest in PD, intermediate in ET, and relatively preserved in dystonia compared with controls. This ordering reoccurred for each of the six ABC-6 items. The number of near-falls and falls followed a similar ordering. Use of canes, walkers, and wheelchairs was elevated in ET and even greater in PD. Several measures of balance confidence (ABC-6 items 1, 4, 5, and 6) were lower in torticollis cases than in those with blepharospasm, although the two groups did not differ with respect to falls or use of walking aids. Lower balance confidence, increased falls, and greater need for walking aids are variably features of a range of movement disorder patients compared to age-matched controls. While most marked among PD patients, these issues affected ET patients as well and, to a small degree, some patients with dystonia.

The vgll3 Locus Controls Age at Maturity in Wild and Domesticated Atlantic Salmon (Salmo salar L.) Males.

PubMed

Ayllon, Fernando; Kjærner-Semb, Erik; Furmanek, Tomasz; Wennevik, Vidar; Solberg, Monica F; Dahle, Geir; Taranger, Geir Lasse; Glover, Kevin A; Almén, Markus Sällman; Rubin, Carl J; Edvardsen, Rolf B; Wargelius, Anna

2015-11-01

Wild and domesticated Atlantic salmon males display large variation for sea age at sexual maturation, which varies between 1-5 years. Previous studies have uncovered a genetic predisposition for variation of age at maturity with moderate heritability, thus suggesting a polygenic or complex nature of this trait. The aim of this study was to identify associated genetic loci, genes and ultimately specific sequence variants conferring sea age at maturity in salmon. We performed a genome wide association study (GWAS) using a pool sequencing approach (20 individuals per river and phenotype) of male salmon returning to rivers as sexually mature either after one sea winter (2009) or three sea winters (2011) in six rivers in Norway. The study revealed one major selective sweep, which covered 76 significant SNPs in which 74 were found in a 370 kb region of chromosome 25. Genotyping other smolt year classes of wild and domesticated salmon confirmed this finding. Genotyping domesticated fish narrowed the haplotype region to four SNPs covering 2386 bp, containing the vgll3 gene, including two missense mutations explaining 33-36% phenotypic variation. A single locus was found to have a highly significant role in governing sea age at maturation in this species. The SNPs identified may be both used as markers to guide breeding for late maturity in salmon aquaculture and in monitoring programs of wild salmon. Interestingly, a SNP in proximity of the VGLL3 gene in humans (Homo sapiens), has previously been linked to age at puberty suggesting a conserved mechanism for timing of puberty in vertebrates.

Keeping children safe at home: protocol for three matched case–control studies of modifiable risk factors for falls

PubMed Central

Kendrick, Denise; Stewart, Jane; Clacy, Rose; Coffey, Frank; Cooper, Nicola; Coupland, Carol; Hayes, Mike; McColl, Elaine; Reading, Richard; Sutton, Alex; M L Towner, Elizabeth; Craig Watson, Michael

2012-01-01

Background Childhood falls result in considerable morbidity, mortality and health service use. Despite this, little evidence exists on protective factors or effective falls prevention interventions in young children. Objectives To estimate ORs for three types of medically attended fall injuries in young children in relation to safety equipment, safety behaviours and hazard reduction and explore differential effects by child and family factors and injury severity. Design Three multicentre case–control studies in UK hospitals with validation of parental reported exposures using home observations. Cases are aged 0–4 years with a medically attended fall injury occurring at home, matched on age and sex with community controls. Children attending hospital for other types of injury will serve as unmatched hospital controls. Matched analyses will use conditional logistic regression to adjust for potential confounding variables. Unmatched analyses will use unconditional logistic regression, adjusted for age, sex, deprivation and distance from hospital in addition to other confounders. Each study requires 496 cases and 1984 controls to detect an OR of 0.7, with 80% power, 5% significance level, a correlation between cases and controls of 0.1 and a range of exposure prevalences. Main outcome measures Falls on stairs, on one level and from furniture. Discussion As the largest in the field to date, these case control studies will adjust for potential confounders, validate measures of exposure and investigate modifiable risk factors for specific falls injury mechanisms. Findings should enhance the evidence base for falls prevention for young children. PMID:22628151

Genetic relationships and epidemiological links between wild type 1 poliovirus isolates in Pakistan and Afghanistan

PubMed Central

2012-01-01

Background/Aim Efforts have been made to eliminate wild poliovirus transmission since 1988 when the World Health Organization began its global eradication campaign. Since then, the incidence of polio has decreased significantly. However, serotype 1 and serotype 3 still circulate endemically in Pakistan and Afghanistan. Both countries constitute a single epidemiologic block representing one of the three remaining major global reservoirs of poliovirus transmission. In this study we used genetic sequence data to investigate transmission links among viruses from diverse locations during 2005-2007. Methods In order to find the origins and routes of wild type 1 poliovirus circulation, polioviruses were isolated from faecal samples of Acute Flaccid Paralysis (AFP) patients. We used viral cultures, two intratypic differentiation methods PCR, ELISA to characterize as vaccine or wild type 1 and nucleic acid sequencing of entire VP1 region of poliovirus genome to determine the genetic relatedness. Results One hundred eleven wild type 1 poliovirus isolates were subjected to nucleotide sequencing for genetic variation study. Considering the 15% divergence of the sequences from Sabin 1, Phylogenetic analysis by MEGA software revealed that active inter and intra country transmission of many genetically distinct strains of wild poliovirus type 1 belonged to genotype SOAS which is indigenous in this region. By grouping wild type 1 polioviruses according to nucleotide sequence homology, three distinct clusters A, B and C were obtained with multiple chains of transmission together with some silent circulations represented by orphan lineages. Conclusion Our results emphasize that there was a persistent transmission of wild type1 polioviruses in Pakistan and Afghanistan during 2005-2007. The epidemiologic information provided by the sequence data can contribute to the formulation of better strategies for poliomyelitis control to those critical areas, associated with high risk

Risk of Infection in Type 1 and Type 2 Diabetes Compared With the General Population: A Matched Cohort Study.

PubMed

Carey, Iain M; Critchley, Julia A; DeWilde, Stephen; Harris, Tess; Hosking, Fay J; Cook, Derek G

2018-03-01

We describe in detail the burden of infections in adults with diabetes within a large national population cohort. We also compare infection rates between patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM). A retrospective cohort study compared 102,493 English primary care patients aged 40-89 years with a diabetes diagnosis by 2008 ( n = 5,863 T1DM and n = 96,630 T2DM) with 203,518 age-sex-practice-matched control subjects without diabetes. Infection rates during 2008-2015, compiled from primary care and linked hospital and mortality records, were compared across 19 individual infection categories. These were further summarized as any requiring a prescription or hospitalization or as cause of death. Poisson regression was used to estimate incidence rate ratios (IRRs) between 1 ) people with diabetes and control subjects and 2 ) T1DM and T2DM adjusted for age, sex, smoking, BMI, and deprivation. Compared with control subjects without diabetes, patients with diabetes had higher rates for all infections, with the highest IRRs seen for bone and joint infections, sepsis, and cellulitis. IRRs for infection-related hospitalizations were 3.71 (95% CI 3.27-4.21) for T1DM and 1.88 (95% CI 1.83-1.92) for T2DM. A direct comparison of types confirmed higher adjusted risks for T1DM versus T2DM (death from infection IRR 2.19 [95% CI 1.75-2.74]). We estimate that 6% of infection-related hospitalizations and 12% of infection-related deaths were attributable to diabetes. People with diabetes, particularly T1DM, are at increased risk of serious infection, representing an important population burden. Strategies that reduce the risk of developing severe infections and poor treatment outcomes are under-researched and should be explored. © 2018 by the American Diabetes Association.

Activation Of Wild-Type Hras Suppresses The Earliest Stages Of Pancreatic Cancer.

PubMed

Weyandt, Jamie

2015-08-01

The RAS family of small GTPases is comprised of HRAS, NRAS, and KRAS. KRAS is invariably oncogenically mutated in pancreatic cancers, which is known to induce this disease. Beyond oncogenic KRAS, redox-dependent reactions have been implicated in the activation of the remaining wild-type RAS proteins in pancreatic cancer cell lines. These results suggest a possible involvement of wild-type RAS proteins in pancreatic cancer. To evaluate the impact of genetically suppressing wild-type RAS expression on pancreatic cancer. Hras homozygous null mice (Hras -/- ) were crossed into a Pdx-Cre; LSL-Kras G12D/+ (KC) murine background in which oncogenic Kras is activated in the pancreas to promote preinvasive pancreatic cancer. Tumor burden was then measured at different stages of disease. HRas -/- ;KC mice exhibited more precancerous lesions in the pancreas and more off-target skin papillomas compared to their wild-type counterparts, suggesting that Hras suppresses early oncogenic Kras-driven tumorigenesis, possibly at the time of initiation. Loss of Hras also reduced the survival of mice engineered to develop aggressive pancreatic cancer by the additional disruption of one allele of the tumor suppressor p53 (Trp53 R172H/+ ). However, this survival advantage was lost when both alleles of Trp53 were mutated, suggesting that wild-type Hras inhibits tumorigenesis in a p53-dependent fashion. Loss of wild-type Hras promotes the earliest stages of pancreatic tumorigenesis, and moreover results in more rapid progression of the disease. As such, mechanisms leading to activation of wild-type Ras proteins, including but not limited to redox-dependent reactions, may influence the development of pancreatic cancer. Copyright © 2015. Published by Elsevier B.V.

Evaluation of the Applicability of Different Age Determination Methods for Estimating Age of the Endangered African Wild Dog (Lycaon Pictus).

PubMed

Mbizah, Moreangels M; Steenkamp, Gerhard; Groom, Rosemary J

2016-01-01

African wild dogs (Lycaon pictus) are endangered and their population continues to decline throughout their range. Given their conservation status, more research focused on their population dynamics, population growth and age specific mortality is needed and this requires reliable estimates of age and age of mortality. Various age determination methods from teeth and skull measurements have been applied in numerous studies and it is fundamental to test the validity of these methods and their applicability to different species. In this study we assessed the accuracy of estimating chronological age and age class of African wild dogs, from dental age measured by (i) counting cementum annuli (ii) pulp cavity/tooth width ratio, (iii) tooth wear (measured by tooth crown height) (iv) tooth wear (measured by tooth crown width/crown height ratio) (v) tooth weight and (vi) skull measurements (length, width and height). A sample of 29 African wild dog skulls, from opportunistically located carcasses was analysed. Linear and ordinal regression analysis was done to investigate the performance of each of the six age determination methods in predicting wild dog chronological age and age class. Counting cementum annuli was the most accurate method for estimating chronological age of wild dogs with a 79% predictive capacity, while pulp cavity/tooth width ratio was also a reliable method with a 68% predictive capacity. Counting cementum annuli and pulp cavity/tooth width ratio were again the most accurate methods for separating wild dogs into three age classes (6-24 months; 25-60 months and > 60 months), with a McFadden's Pseudo-R2 of 0.705 and 0.412 respectively. The use of the cementum annuli method is recommended when estimating age of wild dogs since it is the most reliable method. However, its use is limited as it requires tooth extraction and shipping, is time consuming and expensive, and is not applicable to living individuals. Pulp cavity/tooth width ratio is a moderately

Evaluation of the Applicability of Different Age Determination Methods for Estimating Age of the Endangered African Wild Dog (Lycaon Pictus)

PubMed Central

Steenkamp, Gerhard; Groom, Rosemary J.

2016-01-01

African wild dogs (Lycaon pictus) are endangered and their population continues to decline throughout their range. Given their conservation status, more research focused on their population dynamics, population growth and age specific mortality is needed and this requires reliable estimates of age and age of mortality. Various age determination methods from teeth and skull measurements have been applied in numerous studies and it is fundamental to test the validity of these methods and their applicability to different species. In this study we assessed the accuracy of estimating chronological age and age class of African wild dogs, from dental age measured by (i) counting cementum annuli (ii) pulp cavity/tooth width ratio, (iii) tooth wear (measured by tooth crown height) (iv) tooth wear (measured by tooth crown width/crown height ratio) (v) tooth weight and (vi) skull measurements (length, width and height). A sample of 29 African wild dog skulls, from opportunistically located carcasses was analysed. Linear and ordinal regression analysis was done to investigate the performance of each of the six age determination methods in predicting wild dog chronological age and age class. Counting cementum annuli was the most accurate method for estimating chronological age of wild dogs with a 79% predictive capacity, while pulp cavity/tooth width ratio was also a reliable method with a 68% predictive capacity. Counting cementum annuli and pulp cavity/tooth width ratio were again the most accurate methods for separating wild dogs into three age classes (6–24 months; 25–60 months and > 60 months), with a McFadden’s Pseudo-R2 of 0.705 and 0.412 respectively. The use of the cementum annuli method is recommended when estimating age of wild dogs since it is the most reliable method. However, its use is limited as it requires tooth extraction and shipping, is time consuming and expensive, and is not applicable to living individuals. Pulp cavity/tooth width ratio is a

Natural Variation of Drug Susceptibility in Wild-Type Human Immunodeficiency Virus Type 1

PubMed Central

Parkin, N. T.; Hellmann, N. S.; Whitcomb, J. M.; Kiss, L.; Chappey, C.; Petropoulos, C. J.

2004-01-01

Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or “biological cutoffs,” for the PhenoSense HIV phenotypic drug susceptibility assay. Definition of the natural variation in drug susceptibility in wild-type human immunodeficiency virus (HIV) type 1 isolates is necessary to determine the prevalence of innate drug resistance and to assess the capability of the PhenoSense assay to reliably measure subtle reductions in drug susceptibility. The biological cutoffs for each drug, defined by the 99th percentile of the fold change in the 50% inhibitory concentration distributions or the mean fold change plus 2 standard deviations, were lower than those previously reported for other phenotypic assays and lower than the clinically relevant cutoffs previously defined for the PhenoSense assay. The 99th percentile fold change values ranged from 1.2 (tenofovir) to 1.8 (zidovudine) for nucleoside reverse transcriptase RT inhibitors (RTIs), from 3.0 (efavirenz) to 6.2 (delavirdine) for nonnucleoside RTIs, and from 1.6 (lopinavir) to 3.6 (nelfinavir) for protease inhibitors. To evaluate the potential role of intrinsic assay variability in the observed variations in the drug susceptibilities of wild-type isolates, 10 reference viruses with different drug susceptibility patterns were tested 8 to 30 times each. The median coefficients of variation in fold change for the reference viruses ranged from 12 to 18% for all drugs except zidovudine (32%), strongly suggesting that the observed differences in wild-type virus susceptibility to the different drugs is related to intrinsic virus variability rather than assay variability. The low biological cutoffs and assay variability suggest that the PhenoSense HIV assay may assist in defining clinically relevant susceptibility cutoffs for resistance to antiretroviral drugs. PMID:14742192

Antibody Affinity Against 2009 A/H1N1 Influenza and Pandemrix Vaccine Nucleoproteins Differs Between Childhood Narcolepsy Patients and Controls.

PubMed

Lind, Alexander; Freyhult, Eva; Ramelius, Anita; Olsson, Tomas; Arnheim-Dahlström, Lisen; Lamb, Favelle; Khademi, Mohsen; Ambati, Aditya; Maeurer, Markus; Lima Bomfim, Izaura; Fink, Katharina; Fex, Malin; Törn, Carina; Elding Larsson, Helena; Lernmark, Åke

2017-10-01

Increased narcolepsy incidence was observed in Sweden following the 2009 influenza vaccination with Pandemrix ® . A substitution of the 2009 nucleoprotein for the 1934 variant has been implicated in narcolepsy development. The aims were to determine (a) antibody levels toward wild-type A/H1N1-2009[A/California/04/2009(H1N1)] (NP-CA2009) and Pandemrix-[A/Puerto Rico/8/1934(H1N1)] (NP-PR1934) nucleoproteins in 43 patients and 64 age-matched controls; (b) antibody affinity in reciprocal competitive assays in 11 childhood narcolepsy patients compared with 21 age-matched controls; and (c) antibody levels toward wild-type A/H1N1-2009[A/California/04/2009(H1N1)] (H1N1 NS1), not a component of the Pandemrix vaccine. In vitro transcribed and translated 35 S-methionine-labeled H1N1 influenza A virus proteins were used in radiobinding reciprocal competition assays to estimate antibody levels and affinity (Kd). Childhood patients had higher NP-CA2009 (p = 0.0339) and NP-PR1934 (p = 0.0246) antibody levels compared with age-matched controls. These childhood controls had lower NP-CA2009 (p = 0.0221) and NP-PR1934 (p = 0.00619) antibodies compared with controls 13 years or older. In contrast, in patients 13 years or older, the levels of NP-PR1934 (p = 0.279) and NP-CA2009 (p = 0.0644) antibodies did not differ from the older controls. Childhood antibody affinity (Kd) against NP-CA2009 was comparable between controls (68 ng/mL) and patients (74 ng/mL; p = 0.21) with NP-CA2009 and NP-PR1934 displacement (controls: 165 ng/mL; patients: 199 ng/mL; p = 0.48). In contrast, antibody affinity against NP-PR1934 was higher in controls with either NP-PR1934 (controls: 9 ng/mL; patients: 20 ng/mL; p = 0.0031) or NP-CA2009 (controls: 14 ng/mL; patients: 23 ng/mL; p = 0.0048). A/H1N1-NS1 antibodies were detected in 0/43 of the narcolepsy patients compared with 3/64 (4.7%) controls (p = 0.272). Similarly, none (0/11) of the childhood

Modest increased sensitivity to radiation oncogenesis in ATM heterozygous versus wild-type mammalian cells

NASA Technical Reports Server (NTRS)

Smilenov, L. B.; Brenner, D. J.; Hall, E. J.

2001-01-01

Subpopulations that are genetically predisposed to radiation-induced cancer could have significant public health consequences. Individuals homozygous for null mutations at the ataxia telangiectasia gene are indeed highly radiosensitive, but their numbers are very small. Ataxia Telangiectasia heterozygotes (1-2% of the population) have been associated with somewhat increased radiosensitivity for some end points, but none directly related to carcinogenesis. Here, intralitter comparisons between wild-type mouse embryo fibroblasts and mouse embryo fibroblasts carrying ataxia telangiectasia mutated (ATM) null mutation indicate that the heterozygous cells are more sensitive to radiation oncogenesis than their normal, litter-matched, counterparts. From these data we suggest that Ataxia Telangiectasia heterozygotes could indeed represent a societally-significant radiosensitive human subpopulation.

Kinematic Movement Strategies in Primary School Children with 22q11.2 Deletion Syndrome Compared to Age- and IQ-Matched Controls during Visuo-Manual Tracking

ERIC Educational Resources Information Center

Van Aken, Katrijn; Swillen, Ann; Beirinckx, Marc; Janssens, Luc; Caeyenberghs, Karen; Smits-Engelsman, Bouwien

2010-01-01

The present study focused on the mechanism subserving the production of kinematic patterns in 21 children with 22q11.2DS (mean age=9.6 [plus or minus] 1.9; mean FSIQ=73.05 [plus or minus] 10.2) and 21 age- and IQ-matched control children (mean age=9.6 [plus or minus] 1.9; mean FSIQ=73.38 [plus or minus] 12.0) when performing a visuo-manual…

Wild-type cells rescue genotypically Math1-null hair cells in the inner ears of chimeric mice.

PubMed

Du, Xiaoping; Jensen, Patricia; Goldowitz, Daniel; Hamre, Kristin M

2007-05-15

The transcription factor Math1 has been shown to be critical in the formation of hair cells (HCs) in the inner ear. However, the influence of environmental factors in HC specification suggests that cell extrinsic factors are also crucial to their development. To test whether extrinsic factors impact development of Math1-null (Math1(beta-Gal/beta-Gal)) HCs, we examined neonatal (postnatal ages P0-P4.5) Math1-null chimeric mice in which genotypically mutant and wild-type cells intermingle to form the inner ear. We provide the first direct evidence that Math1-null HCs are able to be generated and survive in the conducive chimeric environment. beta-Galactosidase expression was used to identify genetically mutant cells while cells were phenotypically defined as HCs by morphological characteristics notably the expression of HC-specific markers. Genotypically mutant HCs were found in all sensory epithelia of the inner ear at all ages examined. Comparable results were obtained irrespective of the wild-type component of the chimeric mice. Thus, genotypically mutant cells retain the competence to differentiate into HCs. The implication is that the lack of the Math1 gene in HC precursors can be overcome by environmental influences, such as cell-cell interactions with wild-type cells, to ultimately result in the formation of HCs.

Child Maltreatment as a Risk Factor for Opioid Dependence: Comparison of Family Characteristics and Type and Severity of Child Maltreatment with a Matched Control Group

ERIC Educational Resources Information Center

Conroy, Elizabeth; Degenhardt, Louisa; Mattick, Richard P.; Nelson, Elliot C.

2009-01-01

Objective: To examine the prevalence, characteristics and risk factors for child maltreatment among opioid-dependent persons compared to a community sample of similar social disadvantage. Method: The study employed a case-control design. Cases had a history of opioid pharmacotherapy. Controls were frequency matched to cases with regard to age, sex…

Research on the ultrafast fluorescence property of thylakoid membranes of the wild-type and mutant rice

NASA Astrophysics Data System (ADS)

Ren, Zhao-Yu; Xu, Xiao-Ming; Wang, Shui-Cai; Xin, Yue-Yong; He, Jun-Fang; Hou, Xun

2003-10-01

A high yielding rice variety mutant (Oryza sativa L., Zhenhui 249) with low chlorophyll b (Chl b) has been discovered in natural fields. It has a quality character controlled by a pair of recessive genes (nuclear gene). The partial loss of Chl b in content affects the efficiency of light harvest in a light harvest complex (LHC), thus producing the difference of the exciting energy transfer and the efficiency of photochemistry conversion between the mutant and wild-type rice in photosynthetic unit. The efficiency of utilizing light energy is higher in the mutant than that in the wild-type rice relatively. For further discussion of the above-mentioned difference and learning about the mechanism of the increase in the photochemical efficiency of the mutant, the pico-second resolution fluorescence spectrum measurement with delay-frame-scanning single photon counting technique is adopted. Thylakoid membranes of the mutant and the wild-type rice are excited by an Ar+ laser with a pulse width of 120 ps, repetition rate of 4 MHz and wavelength of 514 nm. Compared with the time and spectrum property of exciting fluorescence, conclusions of those ultrafast dynamic experiments are: 1) The speeds of the exciting energy transferred in photo-system I are faster than that in photo-system II in both samples. 2) The speeds of the exciting energy transfer of mutant sample are faster than those of the wild-type. This might be one of the major reasons why the efficiency of photosynthesis is higher in mutant than that in the wild-type rice.

Assessing landowners' attitudes toward wild hogs and support for control options.

PubMed

Caplenor, Carlotta A; Poudyal, Neelam C; Muller, Lisa I; Yoest, Chuck

2017-10-01

Wild hogs (Sus scrofa) are an invasive species with destructive habits, particularly rooting and wallowing, which can directly impact agricultural crops, pasture land, and water quality. Considering wild hogs are widely dispersed across the landscape, they are extremely difficult to control. Disagreements can arise among different stakeholders over whether and how their populations should be managed. The purpose of this article was to examine Tennessee, United States landowners' attitudes toward wild hogs, to compare acceptability of control methods, and to evaluate factors significantly influencing public support for regulations to control wild hogs. Logistic regression was employed to analyze data collected from a statewide survey of rural landowners in the fall of 2015. Landowners had overwhelmingly negative attitudes towards wild hogs, and were concerned about their impact on the natural environment and rural economy. Although landowners showed support for controlling wild hogs, levels of acceptability for management options varied. Respondents favored active management and supported education and incentive-based control programs to control wild hogs. Cognitive concepts such as social and personal norms and awareness of consequences, as well as demographic characteristics, significantly predicted landowners' support for state regulations to control wild hogs in Tennessee. Findings increase our understanding of the human dimensions of wild hog management and that of other similarly invasive animals, and may guide resource managers in designing effective and socially acceptable management strategies to control wild hog populations in Tennessee and elsewhere. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hyperactivation of working memory related brain circuits in newly-diagnosed middle-aged type 2 diabetics

PubMed Central

He, Xiao-Song; Wang, Zhao-Xin; Zhu, You-Zhi; Wang, Nan; Hu, Xiaoping; Zhang, Da-Ren; Zhu, De-Fa; Zhou, Jiang-Ning

2014-01-01

Type 2 diabetes mellitus (T2DM) is well known for its adverse impacts on brain and cognition, which lead to multidimensional cognitive deficits and wildly-spread cerebral structure abnormalities. However, existing literatures are mainly focused on patients with advanced age or extended T2DM duration. Therefore, it remains unclear whether and how brain function would be affected at the initial onset stage of T2DM in relatively younger population. In current study, twelve newly-diagnosed middle-aged T2DM patients with no previous diabetic treatment history and twelve matched controls were recruited. Brain activations during a working memory task, the digit n-back paradigm (0-, 1- and 2-back), were obtained with functional magnetic resonance imaging (fMRI) and tested by repeated measures ANOVA. Whereas patients performed the n-back task comparably well as controls, significant load-by-group interactions of brain activation were found in the right dorsolateral prefrontal cortex (DLPFC), left middle/inferior frontal gyrus, and left parietal cortex, where patients exhibited hyperactivation in the 2-back but not the 0-back or 1-back condition compared to controls. Furthermore, the severity of chronic hyperglycemia, estimated by glycosylated hemoglobin (HbA1c) level, was entered into partial correlational analyses with task-related brain activations, while controlling for the real-time influence of glucose, estimated by instant plasma glucose level measured before scanning. Significant positive correlations were found between HbA1c and brain activations in the anterior cingulate cortex and bilateral DLPFC only in patients. Taken together, these findings suggest there might be a compensatory mechanism due to brain inefficiency related to chronic hyperglycemia at the initial onset stage of T2DM. PMID:24993663

Comorbidity is more common and occurs earlier in persons living with HIV than in HIV-uninfected matched controls, aged 50 years and older: A cross-sectional study.

PubMed

Maciel, Rafael Aguiar; Klück, Helena Moreira; Durand, Madeleine; Sprinz, Eduardo

2018-05-01

At present, data are limited on the comorbidity profiles associated with aging people with HIV in the developing world, where most such people live. The aim of this study was to compare the disease burden between older HIV-positive subjects and HIV-negative matched controls in Brazil. This was a cross-sectional analysis of the South Brazilian HIV Cohort. Individuals aged 50 years and older were enrolled at Hospital de Clínicas de Porto Alegre and matched with HIV-negative controls from the primary practice unit of the same hospital. Multimorbidity (the presence of two or more comorbid conditions) and the number of non-infectious comorbidities were compared. Poisson regression was used to identify factors associated with multimorbidity. A total of 208 HIV-positive subjects were matched to 208 HIV-negative controls. Overall, the median age was 57 years and 56% were male. The prevalence of multimorbidity was higher in HIV-positive subjects than in HIV-negative controls (63% vs. 43%, p<0.001), and the median number of comorbidities was 2, compared to 1 in controls (p<0.001). The duration of HIV infection (p=0.02) and time on treatment in years (p=0.015) were associated with greater multimorbidity in HIV-positive persons. In this large cohort from the developing world, multimorbidity was found to be more common in HIV-positive subjects than in HIV-negative controls. The duration of HIV and time on antiretrovirals were associated with multimorbidity. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

System-wide identification of wild-type SUMO-2 conjugation sites

PubMed Central

Hendriks, Ivo A.; D'Souza, Rochelle C.; Chang, Jer-Gung; Mann, Matthias; Vertegaal, Alfred C. O.

2015-01-01

SUMOylation is a reversible post-translational modification (PTM) regulating all nuclear processes. Identification of SUMOylation sites by mass spectrometry (MS) has been hampered by bulky tryptic fragments, which thus far necessitated the use of mutated SUMO. Here we present a SUMO-specific protease-based methodology which circumvents this problem, dubbed Protease-Reliant Identification of SUMO Modification (PRISM). PRISM allows for detection of SUMOylated proteins as well as identification of specific sites of SUMOylation while using wild-type SUMO. The method is generic and could be widely applied to study lysine PTMs. We employ PRISM in combination with high-resolution MS to identify SUMOylation sites from HeLa cells under standard growth conditions and in response to heat shock. We identified 751 wild-type SUMOylation sites on endogenous proteins, including 200 dynamic SUMO sites in response to heat shock. Thus, we have developed a method capable of quantitatively studying wild-type mammalian SUMO at the site-specific and system-wide level. PMID:26073453

Risk factors for oropharyngeal gonorrhoea in men who have sex with men: an age-matched case-control study.

PubMed

Cornelisse, Vincent J; Walker, Sandra; Phillips, Tiffany; Hocking, Jane S; Bradshaw, Catriona S; Lewis, David A; Prestage, Garrett Paul; Grulich, Andrew E; Fairley, Christopher K; Chow, Eric P F

2018-01-22

Oropharyngeal gonorrhoea is common among men who have sex with men (MSM). We aimed to clarify which oral sex practices were independent risk factors for oropharyngeal gonorrhoea: tongue kissing, receptive oro-penile sex (fellatio) or insertive oro-anal sex (rimming), and whether daily use of mouthwash and recent antibiotic use was protective. In 2015, we conducted an age-matched case-control study of MSM who attended the Melbourne Sexual Health Centre. Cases had tested positive for oropharyngeal gonorrhoea by nucleic acid amplification testing, and controls had tested negative. Questionnaire items included tongue kissing, oral sex practices, condom use, recent antibiotic use, mouthwash use and alcohol consumption. We identified 177 cases, age matched to 354 controls. In univariable analyses, cases were 1.90 times (95% CI 1.13 to 3.20) more likely than controls to have had casual sexual partners (CSP) in the preceding 3 months, were 2.17 times (95% CI 1.31 to 3.59) more likely to have kissed CSP and were 2.04 times (95% CI 1.26 to 3.30) more likely to have had receptive oro-penile sex with CSP. Oropharyngeal gonorrhoea was not associated with insertive oro-anal sex or mouthwash use. The number of CSP for tongue kissing and receptive oral sex and total CSP were highly correlated, and in multivariable analysis neither kissing nor receptive oro-penile sex was significantly associated with having oropharyngeal gonorrhoea, after adjusting for total number of CSP. The finding that oropharyngeal gonorrhoea was associated with a higher number of sexual partners but not specific sexual practices highlights the need for further research in the area of gonorrhoea transmission to define the probability of transmission from specific sex acts. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Differential proteomic and behavioral effects of long-term voluntary exercise in wild-type and APP-overexpressing transgenics.

PubMed

Rao, Shailaja Kishan; Ross, Jordan M; Harrison, Fiona E; Bernardo, Alexandra; Reiserer, Randall S; Reiserer, Ronald S; Mobley, James A; McDonald, Michael P

2015-06-01

Physical exercise may provide protection against the cognitive decline and neuropathology associated with Alzheimer's disease, although the mechanisms are not clear. In the present study, APP/PSEN1 double-transgenic and wild-type mice were allowed unlimited voluntary exercise for 7months. Consistent with previous reports, wheel-running improved cognition in the double-transgenic mice. Interestingly, the average daily distance run was strongly correlated with spatial memory in the water maze in wild-type mice (r(2)=.959), but uncorrelated in transgenics (r(2)=.013). Proteomics analysis showed that sedentary transgenic mice differed significantly from sedentary wild-types with respect to proteins involved in synaptic transmission, cytoskeletal regulation, and neurogenesis. When given an opportunity to exercise, the transgenics' deficiencies in cytoskeletal regulation and neurogenesis largely normalized, but abnormal synaptic proteins did not change. In contrast, exercise enhanced proteins associated with cytoskeletal regulation, oxidative phosphorylation, and synaptic transmission in wild-type mice. Soluble and insoluble Aβ40 and Aβ42 levels were significantly decreased in both cortex and hippocampus of active transgenics, suggesting that this may have played a role in the cognitive improvement in APP/PSEN1 mice. β-secretase was significantly reduced in active APP/PSEN1 mice compared to sedentary controls, suggesting a mechanism for reduced Aβ. Taken together, these data illustrate that exercise improves memory in wild-type and APP-overexpressing mice in fundamentally different ways. Copyright © 2015 Elsevier Inc. All rights reserved.

Efficient Reassignment of a Frequent Serine Codon in Wild-Type Escherichia coli.

PubMed

Ho, Joanne M; Reynolds, Noah M; Rivera, Keith; Connolly, Morgan; Guo, Li-Tao; Ling, Jiqiang; Pappin, Darryl J; Church, George M; Söll, Dieter

2016-02-19

Expansion of the genetic code through engineering the translation machinery has greatly increased the chemical repertoire of the proteome. This has been accomplished mainly by read-through of UAG or UGA stop codons by the noncanonical aminoacyl-tRNA of choice. While stop codon read-through involves competition with the translation release factors, sense codon reassignment entails competition with a large pool of endogenous tRNAs. We used an engineered pyrrolysyl-tRNA synthetase to incorporate 3-iodo-l-phenylalanine (3-I-Phe) at a number of different serine and leucine codons in wild-type Escherichia coli. Quantitative LC-MS/MS measurements of amino acid incorporation yields carried out in a selected reaction monitoring experiment revealed that the 3-I-Phe abundance at the Ser208AGU codon in superfolder GFP was 65 ± 17%. This method also allowed quantification of other amino acids (serine, 33 ± 17%; phenylalanine, 1 ± 1%; threonine, 1 ± 1%) that compete with 3-I-Phe at both the aminoacylation and decoding steps of translation for incorporation at the same codon position. Reassignments of different serine (AGU, AGC, UCG) and leucine (CUG) codons with the matching tRNA(Pyl) anticodon variants were met with varying success, and our findings provide a guideline for the choice of sense codons to be reassigned. Our results indicate that the 3-iodo-l-phenylalanyl-tRNA synthetase (IFRS)/tRNA(Pyl) pair can efficiently outcompete the cellular machinery to reassign select sense codons in wild-type E. coli.

Case-control study of dementia of the Alzheimer type

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

French, L.R.; Schuman, L.M.; Mortimer, J.A.

1985-03-01

A case-control study to assess factors of possible etiologic significance to dementia of the Alzheimer type was conducted with 78 male cases diagnosed in 1979-1982 at the Veterans Administration Medical Center in Minneapolis, Minnesota and age-race-sex-matched hospital and neighborhood controls (14 of 16 autopsied cases were histopathologically confirmed). Information was obtained on variables relevant to vital, genetic, and immunologic hypotheses, and on possible occupational and environmental exposures, drug use, psychologic stress, smoking, and alcohol consumption. The only major difference between patients with dementia of the Alzheimer type and controls was a significantly greater occurrence of antecedent head trauma in themore » patients (odds ratio = 4.50). This finding is consistent with the literature on posttraumatic dementia but its importance is presently unclear.« less

Analysis of Retinal Thinning Using Spectral-domain Optical Coherence Tomography Imaging of Sickle Cell Retinopathy Eyes Compared to Age- and Race-Matched Control Eyes.

PubMed

Lim, Jennifer I; Cao, Dingcai

2018-03-17

To determine whether the retina is thinner in sickle cell patients than in race- and age-matched controls, and, if it is thinner, whether there is any association with systemic diseases. Sickle cell and control (age- and race-matched) patients were prospectively enrolled from a university retina clinic into this observational study. Participants underwent visual acuity testing, slit-lamp biomicroscopy, dilated ophthalmoscopy, and spectral-domain optical coherence tomography imaging. Sickle cell retinal lesions, degree of vascular tortuosity, caliber of arteriovenous anastomosis, and stage of retinopathy were noted. Early Treatment Diabetic Retinopathy Study (ETDRS) subfield measurements were compared between sickle cell and control subjects and also among sickle cell hemoglobin subtypes. Associations between ETDRS subfield measurements and hemoglobin subtype, retinopathy stage, and systemic diseases were assessed. A total of 513 sickle cell eyes (260 patients) and 75 control eyes (39 patients) had median visual acuities of 20/20. ETDRS central (P = .002), inner (nasal P = .009, superior P = .021, temporal P < .001, inferior P = .017), and temporal outer (P = .012) subfield measurements were thinner in sickle cell eyes compared to control eyes. Hemoglobin SS eyes had significantly thinner inner ETDRS subfield measurements compared to SC and SThal eyes. Retinal thinning in all subfields was associated with age (P = .017) for sickle cell and control eyes. No association was found between retinal thinning and hydroxyurea use or arteriovenous anastomosis caliber. The macula is thinner in sickle cell eyes compared to control eyes; retinal thickness decreases with increasing age and sickle cell retinopathy stage and is most severe in hemoglobin SS subtypes. Copyright © 2018 Elsevier Inc. All rights reserved.

[Motor skills and safety of patients with bi- or trimalleolar ankle injury : Comparison with healthy, active, age-matched control subjects].

PubMed

Loudovici-Krug, Dana; Benkenstein, Monique; Derlien, Steffen; Best, Norman

2018-06-01

Do patients with bi- or trimalleolar ankle injury show differences in motor skills and safety in comparison with healthy, active, age-matched control subjects? Prospective controlled cross-sectional study. Inclusion of 17 patients with bi- or trimalleolar ankle injury (mean 1.5 years postsurgery) and 23 healthy, active subjects of comparable age (fitness studio). Measurement instruments: motor test procedures and questionnaires. Comparison of patients and control subjects by routine daily motor function: patients < controls with the "timed 'Up & Go' test" (TUG, p = 0.011), the chair rising test and a coordination test using a gymnastic hoop (CRT and GR p > 0.05), fear of falling: patients > controls (p = 0.003) and physical activity: patients < controls (p = 0.032). There were no significant motor deficits in activities of daily life between the patients and controls, only tendencies; however, the patients showed definite limitations with an increased fear of falling and a reduced physical activity compared with the healthy control group. The resulting differences should be positively influenced by appropriate enhancement of training or participation in sports courses. The aim is to achieve a similar quality of life by a perception of safety and trust in one's own motor skills.

Effectiveness of 7-valent pneumococcal conjugate vaccine in the prevention of invasive pneumococcal disease in children aged 7-59 months. A matched case-control study.

PubMed

Domínguez, Angela; Ciruela, Pilar; García-García, Juan José; Moraga, Fernando; de Sevilla, Mariona F; Selva, Laura; Coll, Francis; Muñoz-Almagro, Carmen; Planes, Ana María; Codina, Gemma; Jordán, Iolanda; Esteva, Cristina; Hernández, Sergi; Soldevila, Núria; Cardeñosa, Neus; Batalla, Joan; Salleras, Luis

2011-11-08

The aim of this study was to evaluate the effectiveness of the administration of the 7-valent pneumococcal conjugate vaccine in a region with an intermediate vaccination coverage. A matched case-control study was carried out in children aged 7-59 months with invasive pneumococcal disease (IPD) admitted to two university hospitals in Catalonia. Three controls matched for hospital, age, sex, date of hospitalization and underlying disease were selected for each case. Information on the vaccination status of cases and controls was obtained from the vaccination card, the child's health card, the hospital medical record or the vaccination register of the primary healthcare center where the child was attended for non-severe conditions. A conditional logistic regression analysis was made to control for the effect of possible confounding variables. The adjusted vaccination effectiveness of the complete vaccination schedule (3 doses at 2, 4 and 6 months and a fourth dose at 15 months, 2 doses at least two months apart in children aged 12-23 months or a single dose in children aged >24 months) in preventing IPD caused by vaccine serotypes was 93.7% (95% CI 51.8-99.2). It was not effective in preventing cases caused by non-vaccine serotypes. The results of this study carried out in a population with intermediate vaccination coverage confirm those of other observational studies showing high levels of effectiveness of routine 7-valent pneumococcal conjugate vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cochlear implantation in patients with autoimmune inner ear disease including cogan syndrome: a comparison with age- and sex-matched controls.

PubMed

Wang, Jenny R; Yuen, Heng W; Shipp, David B; Stewart, Suzanne; Lin, Vincent Y W; Chen, Joseph M; Nedzelski, Julian M

2010-12-01

Evaluate the characteristics and outcomes of patients with autoimmune inner ear disease (AIED) who have undergone cochlear implantation (CI) and compare post-CI performance in AIED to matched controls. Retrospective case control study. Study cohort was comprised of 25 adult implantees (AIED [n = 18], Cogan syndrome [n = 7]). The AIED group was defined by rapidly progressive bilateral sensorineural hearing loss leading to unusable hearing within weeks to months. Patients with Cogan syndrome, the archetypal inner ear autoimmune disease, were also examined and used for within-cohort comparison. Clinical and operative records were reviewed. Post-CI performance was assessed using open-set sentence tests. Age- and sex-matched individuals deafened by other postlingual causes were used as controls. Of 25 patients, 24 had uneventful, full electrode insertions. One AIED patient had partial insertion due to cochlear ossification and did not achieve open-set speech perception post-CI. Mean open-set sentence scores for study patients with uneventful insertions were 92.8%, 97.3%, and 96.4% at 6 months, 1 year, and ≥ 2 years, respectively. Compared to matched controls, patients deafened by autoimmune causes had significantly higher post-CI performance at all postoperative test intervals (P < .05). There was no significant difference in postimplantation performance between Cogan syndrome and AIED patients. To our knowledge this was the largest study of cochlear implantation in AIED and Cogan syndrome patients. In our experience, both groups generally attained high levels of post-CI speech perception and performed above average. Cochlear ossification affecting implantation in Cogan syndrome patients was not observed in our series, contrary to some reports.

KCa 3.1 upregulation preserves endothelium-dependent vasorelaxation during aging and oxidative stress.

PubMed

Choi, Shinkyu; Kim, Ji Aee; Li, Hai-Yan; Shin, Kyong-Oh; Oh, Goo Taeg; Lee, Yong-Moon; Oh, Seikwan; Pewzner-Jung, Yael; Futerman, Anthony H; Suh, Suk Hyo

2016-10-01

Endothelial oxidative stress develops with aging and reactive oxygen species impair endothelium-dependent relaxation (EDR) by decreasing nitric oxide (NO) availability. Endothelial KCa 3.1, which contributes to EDR, is upregulated by H2 O2 . We investigated whether KCa 3.1 upregulation compensates for diminished EDR to NO during aging-related oxidative stress. Previous studies identified that the levels of ceramide synthase 5 (CerS5), sphingosine, and sphingosine 1-phosphate were increased in aged wild-type and CerS2 mice. In primary mouse aortic endothelial cells (MAECs) from aged wild-type and CerS2 null mice, superoxide dismutase (SOD) was upregulated, and catalase and glutathione peroxidase 1 (GPX1) were downregulated, when compared to MAECs from young and age-matched wild-type mice. Increased H2 O2 levels induced Fyn and extracellular signal-regulated kinases (ERKs) phosphorylation and KCa 3.1 upregulation. Catalase/GPX1 double knockout (catalase(-/-) /GPX1(-/-) ) upregulated KCa 3.1 in MAECs. NO production was decreased in aged wild-type, CerS2 null, and catalase(-/-) /GPX1(-/-) MAECs. However, KCa 3.1 activation-induced, N(G) -nitro-l-arginine-, and indomethacin-resistant EDR was increased without a change in acetylcholine-induced EDR in aortic rings from aged wild-type, CerS2 null, and catalase(-/-) /GPX1(-/-) mice. CerS5 transfection or exogenous application of sphingosine or sphingosine 1-phosphate induced similar changes in levels of the antioxidant enzymes and upregulated KCa 3.1. Our findings suggest that, during aging-related oxidative stress, SOD upregulation and downregulation of catalase and GPX1, which occur upon altering the sphingolipid composition or acyl chain length, generate H2 O2 and thereby upregulate KCa 3.1 expression and function via a H2 O2 /Fyn-mediated pathway. Altogether, enhanced KCa 3.1 activity may compensate for decreased NO signaling during vascular aging. © 2016 The Authors. Aging Cell published by the Anatomical Society and

Exploratory biomarker analysis for treatment response in KRAS wild type metastatic colorectal cancer patients who received cetuximab plus irinotecan.

PubMed

Kim, Seung Tae; Ahn, Tae Jin; Lee, Eunjin; Do, In-Gu; Lee, Su Jin; Park, Se Hoon; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Kim, Suk Hyeong; Lee, Jeeyun; Kim, Hee Cheol

2015-10-20

More than half of the patients selected based on KRAS mutation status fail to respond to the treatment with cetuximab in metastatic colorectal cancer (mCRC). We designed a study to identify additional biomarkers that could act as indicators for cetuximab treatment in mCRC. We investigated 58 tumor samples from wild type KRAS CRC patients treated with cetuximab plus irinotecan (CI). We conducted the genotyping for mutations in either BRAF or PIK3CA and profiled comprehensively the expression of 522 kinase genes. BRAF mutation was detected in 5.1 % (3/58) of patients. All 50 patients showed wild type PIK3CA. Gene expression patterns that categorized patients with or without the disease control to CI were compared by supervised classification analysis. PSKH1, TLK2 and PHKG2 were overexpressed significantly in patients with the disease control to IC. The higher expression value of PSKH1 (r = 0.462, p < 0.001) and TLK2 (r = 0.361, p = 0.005) had the significant correlation to prolonged PFS. The result of this work demonstrated that expression nature of kinase genes such as PSKH1, TLK2 and PHKG2 may be informative to predict the efficacy of CI in wild type KRAS CRC. Mutations in either BRAF or PIK3CA were rare subsets in wild type KRAS CRC.

Accelerated age-related olfactory decline among type 1 Usher patients.

PubMed

Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D

2016-06-22

Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin' Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome.

WILD PIGS: BIOLOGY, DAMAGE, CONTROL TECHINQUES AND MANAGEMENT

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

Mayer, John; Brisbin, I. Lehr

The existence of problems with wild pigs (Sus scrofa) is nothing new to the Western Hemisphere. Damage by these introduced animals was reported as far back as 1505 by the early Spanish colonies in the Caribbean, where wild pigs were killing the colonists cattle. Droves of these animals also ravaged cultivated crops of maize and sugarcane on islands in the West Indies during this same time period. These wild pigs reportedly were very aggressive and often attacked Spanish soldiers hunting rebellious Indians or escaped slaves on these islands, especially when these animals were cornered. The documentation of such impacts bymore » introduced populations of this species in the United States has subsequently increased in recent years, and continued up through the present (Towne and Wentworth. 1950, Wood and Barrett 1979, Mayer and Brisbin 1991, Dickson et al. 2001). In spite of a fairly constant history in this country since the early 1900s, wild pigs have had a dramatic recent increase in both distribution and numbers in the United States. Between 1989 and 2009, the number of states reporting the presence of introduced wild pigs went from 19 up to as many as 44. This increase, in part natural, but largely manmade, has caused an increased workload and cost for land and resource managers in areas where these new populations are found. This is the direct result of the damage that these introduced animals do. The cost of both these impacts and control efforts has been estimated to exceed a billion dollars annually (Pimentel 2007). The complexity of this problem has been further complicated by the widespread appeal and economic potential of these animals as a big game species (Tisdell 1982, Degner 1989). Wild pigs are a controversial problem that is not going away and will likely only get worse with time. Not only do they cause damage, but wild pigs are also survivors. They reproduce at a rate faster than any other mammal of comparable size, native or introduced; they can

Haematocrit, hypertension and smoking in patients with transient ischaemic attacks and in age and sex matched controls.

PubMed Central

Harrison, M J; Pollock, S; Thomas, D; Marshall, J

1982-01-01

The blood pressure, smoking habit and haemotocrit of 154 patients with transient ischaemic attacks and 191 age-and sex-matched neurological controls were studied. Regression analysis revealed that the haematocrit value was related to both systolic and diastolic blood pressure, and to smoking. Smoking elevated the haematocrit by 1.9 +/- 0.59 in males and by 2.18 +/- 0.68 in females. When these associations were allowed for there was still evidence of a higher haematocrit in patients with transient ischaemic attacks (plus 1.44 +/- 0.56 in males and 0.75 +/- 0.75 in females p less than 0.02). The role of an elevated haematocrit in the pathogenesis of cerebrovascular disease and its management are briefly discussed. PMID:7119818

Anthelmintic effect of Psidium guajava and Tagetes erecta on wild-type and Levamisole-resistant Caenorhabditis elegans strains.

PubMed

Piña-Vázquez, Denia M; Mayoral-Peña, Zyanya; Gómez-Sánchez, Maricela; Salazar-Olivo, Luis A; Arellano-Carbajal, Fausto

2017-04-18

Psidium guajava and Tagetes erecta have been used traditionally to treat gastrointestinal parasites, but their active metabolites and mechanisms of action remain largely unknown. To evaluate the anthelmintic potential of Psidium guajava and Tagetes erecta extracts on Levamisole-sensitive and Levamisole-resistant strains of the model nematode Caenorhabditis elegans. Aqueous extracts of Psidium guajava (PGE) and Tagetes erecta (TEE) were assayed on locomotion and egg-laying behaviors of the wild-type (N2) and Levamisole-resistant (CB193) strains of Caenorhabditis elegans. Both extracts paralyzed wild-type and Levamisole-resistant nematodes in a dose-dependent manner. In wild-type worms, TEE 25mg/mL induced a 75% paralysis after 8h of treatment and PGE 25mg/mL induced a 100% paralysis after 4h of treatment. PGE exerted a similar paralyzing effect on N2 wild-type and CB193 Levamisole-resistant worms, while TEE only partially paralyzed CB193 worms. TEE 25mg/mL decreased N2 egg-laying by 65% with respect to the untreated control, while PGE did it by 40%. Psidium guajava leaves and Tagetes erecta flower-heads possess hydrosoluble compounds that block the motility of Caenorhabditis elegans by a mechanism different to that of the anthelmintic drug Levamisole. Effects are also observable on oviposition, which was diminished in the wild-type worms. The strong anthelmintic effects in crude extracts of these plants warrants future work to identify their active compounds and to elucidate their molecular mechanisms of action. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Wild-type Measles Virus in Brain Tissue of Children with Subacute Sclerosing Panencephalitis, Argentina

PubMed Central

Barrero, Paola Roxana; Grippo, Jorge; Viegas, Mariana

2003-01-01

We studied eight children who had measles at 6 to 10 months of age during the 1998 Argentine measles outbreak and in whom subacute sclerosing panencephalitis developed 4 years later. We report the genetic characterization of brain tissue–associated measles virus samples from three patients. Phylogenetic relationships clustered these viruses with the wild-type D6 genotype isolated during the 1998 outbreak. The children received measles vaccine; however, vaccinal strains were not found. PMID:14609476

Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response.

PubMed

Heritage, Mandy L; Murphy, Therese L; Bridle, Kim R; Anderson, Gregory J; Crawford, Darrell H G; Fletcher, Linda M

2009-08-01

Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe(-/-)). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe(-/-) mice. Hfe(-/-) and C57BL/6 (wild-type) mice were pair-fed either an alcohol liquid diet or control diet for up to 8 weeks. The mRNA levels of hepcidin and ferroportin were measured at the mRNA level by RT-PCR and protein expression of hypoxia inducible factor-1 alpha (HIF-1alpha) was measured by western blot. Hamp1 mRNA expression was significantly decreased and duodenal ferroportin expression was increased in alcohol-fed wild-type mice at 8 weeks. Time course experiments showed that the decrease in hepcidin mRNA was not immediate, but was significant by 4 weeks. Consistent with the genetic defect, Hamp1 mRNA was decreased and duodenal ferroportin mRNA expression was increased in Hfe(-/-) mice fed on the control diet compared with wild-type animals and alcohol further exacerbated these effects. HIF-1alpha protein levels were elevated in alcohol-fed wild-type animals compared with controls. Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia.

Statin Use and Fatal Prostate Cancer: A Matched Case-Control Study

PubMed Central

Marcella, Stephen W.; David, Alice; Ohman-Strickland, Pamela A.; Carson, Jeffery; Rhoads, George G.

2015-01-01

Background Statins are one of the most commonly prescribed medications in medical practice and prostate cancer is the most common male malignancy. While there has been no consistent evidence that statins affect cancer incidence, including prostate cancer, several reports suggest they may decrease the rate of advanced prostate cancer. However, no study has examined statin use and prostate cancer mortality specifically. We report here a population-based case-control investigation that examines this association. Methods We conducted a matched case-control study. Cases were residents of New Jersey ages 55 – 79 who died from prostate cancer between 1997–2000. We individually matched population-based controls by five-year age-group and race. Medication data were obtained identically for cases and controls from blinded medical chart review. We used conditional logistic regression to adjust for confounders. Results We identified 718 cases and obtained cooperation from 77% of their spouses (N=553). After review of medical records, 387 were eligible and 380 were matched to a control. The unadjusted odds ratio was 0.49 (95% CI, 0.34–0.70) which decreased to 0.37 (p<0.0001) after adjustment for education, waist size, BMI, comorbidities, and anti-hypertensive medication. There was little difference between lipophilic and hydrophilic statins but more risk reduction was noted for hi-potency statins (73%, p<0.0001) as compared to low-potency statins (31%, p=0.32). Conclusion Statin use is associated with substantial protection against prostate cancer death, adding to the epidemiologic evidence for an inhibitory effect on prostate cancer. PMID:22180145

TGFbeta type II receptor signaling controls Schwann cell death and proliferation in developing nerves.

PubMed

D'Antonio, Maurizio; Droggiti, Anna; Feltri, M Laura; Roes, Jürgen; Wrabetz, Lawrence; Mirsky, Rhona; Jessen, Kristján R

2006-08-16

During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF) beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGFbeta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGFbeta signaling did not appear to affect other processes in which TGFbeta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death.

Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption

PubMed Central

Siddiqui, Sana; Lustig, Ana; Carter, Arnell; Sankar, Mathavi; Daimon, Caitlin M.; Premont, Richard T.; Etienne, Harmonie; van Gastel, Jaana; Azmi, Abdelkrim; Janssens, Jonathan; Becker, Kevin G.; Zhang, Yongqing; Wood, William; Lehrmann, Elin; Martin, James G.; Martin, Bronwen; Taub, Dennis D.; Maudsley, Stuart

2017-01-01

Recent research has proposed that GIT2 (G protein-coupled receptor kinase interacting protein 2) acts as an integrator of the aging process through regulation of ‘neurometabolic’ integrity. One of the commonly accepted hallmarks of the aging process is thymic involution. At a relatively young age, 12 months old, GIT2−/− mice present a prematurely distorted thymic structure and dysfunction compared to age-matched 12 month-old wild-type control (C57BL/6) mice. Disruption of thymic structure in GIT2−/− (GIT2KO) mice was associated with a significant reduction in the expression of the cortical thymic marker, Troma-I (cytokeratin 8). Double positive (CD4+CD8+) and single positive CD4+ T cells were also markedly reduced in 12 month-old GIT2KO mice compared to age-matched control wild-type mice. Coincident with this premature thymic disruption in GIT2KO mice was the unique generation of a novel cervical ‘organ’, i.e. ‘parathymic lobes’. These novel organs did not exhibit classical peripheral lymph node-like characteristics but expressed high levels of T cell progenitors that were reflexively reduced in GIT2KO thymi. Using signaling pathway analysis of GIT2KO thymus and parathymic lobe transcriptomic data we found that the molecular signaling functions lost in the dysfunctional GIT2KO thymus were selectively reinstated in the novel parathymic lobe – suggestive of a compensatory effect for the premature thymic disruption. Broader inspection of high-dimensionality transcriptomic data from GIT2KO lymph nodes, spleen, thymus and parathymic lobes revealed a systemic alteration of multiple proteins (Dbp, Tef, Per1, Per2, Fbxl3, Ddit4, Sin3a) involved in the multidimensional control of cell cycle clock regulation, cell senescence, cellular metabolism and DNA damage. Altered cell clock regulation across both immune and non-immune tissues therefore may be responsible for the premature ‘aging’ phenotype of GIT2KO mice. PMID:28260693

Outcomes of Arthroscopic Rotator Cuff Repair in Patients Who Are 70 Years of Age or Older Versus Under 70 Years of Age: A Sex- and Tear Size-Matched Case-Control Study.

PubMed

Gwark, Ji-Yong; Sung, Chang-Meen; Na, Jae-Boem; Park, Hyung Bin

2018-05-19

To compare the structural and clinical outcomes after arthroscopic rotator cuff repair (ARCR) of a case group aged 70 and above with those of a control group younger than 70, with the 2 groups matched for sex and tear size. The case group, comprising 53 patients 70 or older, and the control group, comprising 159 patients younger than 70, all received ARCR to 1 shoulder with symptomatic full-thickness rotator cuff tear. The case and the control subjects, who were matched for sex and tear size to minimize bias related to tendon healing, received ARCR during the same period. The mean age was 71.8 ± 2.6 years in the case group and 59.3 ± 7.1 years in the control group. The minimum follow-up period was 1 year in both groups. Cuff integrity was evaluated using ultrasonography. Structural and clinical outcomes of the 2 groups were compared. Regarding structural outcomes, the complete healing, partial-thickness retear, and full-thickness retear rates were 66% (35/53), 15% (8/53), and 19% (10/53) in the case group, and 68% (108/159), 19% (30/159), and 13% (21/159), respectively, in the control group. The 2 groups had no significantly different retear rates (P = .52). Regarding clinical outcomes, the mean improvements in range of motion, pain, muscle strength, and age- and sex-matched Constant scores were not significantly different between the 2 groups (P > .37). The preoperative tear size was significantly associated with retear in both studied groups (P = .02). The clinical and structural outcomes of ARCR in patients 70 or older with symptomatic full-thickness rotator cuff tear are comparable with those in patients younger than 70 with at least 1-year follow-up. Preoperative tear size, a biological factor, is a strong predictor for retear. Level III, a retrospective comparative (case-control) study. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Pulmonary Tuberculosis Is Associated With Biomass Fuel Use Among Rural Women in Pakistan: An Age- and Residence-Matched Case-Control Study.

PubMed

Rabbani, Unaib; Sahito, Ambreen; Nafees, Asaad Ahmed; Kazi, Ambreen; Fatmi, Zafar

2017-04-01

Facility-based, age- and residential area-matched case-control study was conducted in Sindh, Pakistan to determine association between biomass fuel use for cooking and pulmonary tuberculosis (TB). Cases were women with pulmonary TB, and controls were those suffering from other diseases. Current users of biomass fuel were at higher risk of pulmonary TB (adjusted matched odds ratio [mOR] = 3.0; 95% CI = 1.1-4.9) compared with nonusers. In comparison with former biomass users (women not using biomass for >10 years), recent biomass users (women who switched from biomass to nonbiomass ≤10 years ago), and current (lifetime) users were at a higher risk in a dose-response manner (adjusted mOR = 2.8, 95% CI = 0.9-8.2 and adjusted mOR = 3.9, 95% CI = 1.4-10.7, respectively). Population attributable fraction for TB related to biomass fuel use was 40.6% (95% CI = 35.5%-45.7%). This study strengthens the evidence that biomass fuel use for cooking is associated with pulmonary TB and risk increases with duration of exposure.

Stability of Iowa mutant and wild type Aβ-peptide aggregates

NASA Astrophysics Data System (ADS)

Alred, Erik J.; Scheele, Emily G.; Berhanu, Workalemahu M.; Hansmann, Ulrich H. E.

2014-11-01

Recent experiments indicate a connection between the structure of amyloid aggregates and their cytotoxicity as related to neurodegenerative diseases. Of particular interest is the Iowa Mutant, which causes early-onset of Alzheimer's disease. While wild-type Amyloid β-peptides form only parallel beta-sheet aggregates, the mutant also forms meta-stable antiparallel beta sheets. Since these structural variations may cause the difference in the pathological effects of the two Aβ-peptides, we have studied in silico the relative stability of the wild type and Iowa mutant in both parallel and antiparallel forms. We compare regular molecular dynamics simulations with such where the viscosity of the samples is reduced, which, we show, leads to higher sampling efficiency. By analyzing and comparing these four sets of all-atom molecular dynamics simulations, we probe the role of the various factors that could lead to the structural differences. Our analysis indicates that the parallel forms of both wild type and Iowa mutant aggregates are stable, while the antiparallel aggregates are meta-stable for the Iowa mutant and not stable for the wild type. The differences result from the direct alignment of hydrophobic interactions in the in-register parallel oligomers, making them more stable than the antiparallel aggregates. The slightly higher thermodynamic stability of the Iowa mutant fibril-like oligomers in its parallel organization over that in antiparallel form is supported by previous experimental measurements showing slow inter-conversion of antiparallel aggregates into parallel ones. Knowledge of the mechanism that selects between parallel and antiparallel conformations and determines their relative stability may open new avenues for the development of therapies targeting familial forms of early-onset Alzheimer's disease.

Defining wild-type life span in Caenorhabditis elegans.

PubMed

Gems, D; Riddle, D L

2000-05-01

The nematode Caenorhabditis elegans reproduces predominantly as a self-fertilizing hermaphrodite, and this drives laboratory populations to be homozygous at all genetic loci. Passaging of stocks can lead to fixation of spontaneous mutations, especially when the latter do not result in a selective disadvantage under laboratory conditions. Life span may be such a trait, since a comparison of six wild-type N2 lines derived from a common ancestor (but maintained separately in several laboratories) revealed four variants with median adult life spans ranging from 12.0 +/- 0.8 to 17.0 +/- 0.6 days at 20 degrees C. Fertility was also reduced in the two shortest-lived strains. We determined which life span most closely corresponds to that of the authentic wild type by two means. Firstly, N2 hermaphrodites were compared with seven C. elegans wild isolates. The latter were found to resemble only the longest-lived N2 strain. Comparison of male life spans of six lines also revealed additional strain variation. Secondly, life spans of F1 progeny issuing from crosses between N2 variants showed that short life spans were recessive, indicating that they result from loss-of-function mutations. We infer that the longest-lived N2 variant best resembles the original N2 isolate. This is the N2 male stock currently distributed by the Caenorhabditis Genetics Center.

The relative age effect in soccer: a match-related perspective.

PubMed

Vaeyens, Roel; Philippaerts, Renaat M; Malina, Robert M

2005-07-01

Asymmetries in the distributions of birth dates in senior professional and youth soccer players have been interpreted as evidence for systematic discrimination against individuals born shortly before the cut-off date in assigning youth to specific age groups. This concept is known as the "relative age effect". The results of a longitudinal study of birth date distritubions of 2757 semi-professional and amateur senior soccer players in Belgium are presented. Records for competitive games were available in official statistics provided by the Royal Belgian Football Association. The chi-square statistic was used to examine differences between observed and expected birth date distributions. Regression analyses indicated a shift of bias when two different start dates were compared. Players born in the early part of the new age band (January to March) were over-represented compared with players born late in the new selection period (October to December). However, players with birthdays at the start of the old selection year (August) were still represented. In a retrospective analysis of 2138 players, variables indicative of match involvement, number of selections for matches, and time played were examined in relation to the relative age effect. The group of semi-professional and amateur senior soccer players born in the first quarter of the selected age band received more playing opportunities. Comparisons of birth date distributions (traditional approach to relative age effect) with match-related variables gave similar, though not entirely consistent, results. However, there were no differences for the mean number of selections and for playing minutes between players born at the start or the end of the selection year. Our findings suggest that match-based variables may provide a more reliable indication of the relative age effect in soccer.

Statin use and fatal prostate cancer: a matched case-control study.

PubMed

Marcella, Stephen W; David, Alice; Ohman-Strickland, Pamela A; Carson, Jeffery; Rhoads, George G

2012-08-15

Statins are some of the most commonly prescribed medications in medical practice, and prostate cancer is the most common malignancy among men. Although there has been no consistent evidence that statins affect cancer incidence, including prostate cancer, several reports suggest they may decrease the rate of advanced prostate cancer. However, no study to date has specifically examined statin use and prostate cancer mortality. The authors conducted this population-based case-control investigation to examine this association. This was a matched case-control study. Cases were residents of New Jersey ages 55 to 79 years who died from prostate cancer between 1997 and 2000. The cases were matched individually to population-based controls by 5-year age group and race. Medication data were obtained identically for cases and controls from blinded medical chart review. Conditional logistic regression was used to adjust for confounders. In total, 718 cases were identified, and cooperation was obtained from 77% of their spouses (N = 553). After a review of medical records, 387 men were eligible, and 380 were matched to a control. The unadjusted odds ratio was 0.49 (95% confidence interval, 0.34-0.70) and decreased to 0.37 (P < .0001) after adjusting for education, waist size, body mass index, comorbidities, and antihypertensive medication. There was little difference between lipophilic and hydrophilic statins, but more risk reduction was noted for high-potency statins (73%; P < .0001) compared with low-potency statins (31%; P = .32). Statin use was associated with substantial protection against prostate cancer death, adding to the epidemiologic evidence for an inhibitory effect on prostate cancer. Copyright © 2011 American Cancer Society.

To dance or not to dance? A comparison of balance, physical fitness and quality of life in older Irish set dancers and age-matched controls.

PubMed

Shanahan, J; Coman, L; Ryan, F; Saunders, J; O'Sullivan, K; Ni Bhriain, O; Clifford, A M

2016-12-01

The objective of this study is to determine if older adults regularly participating in Irish set dancing have superior balance, physical fitness and quality of life compared to age-matched controls. This study used a community-based, observational cross-sectional design. Regular set dancers (n = 39) and age-matched controls (n = 33) were recruited. Participants were assessed using the physical activity scale for the elderly (physical activity levels), mini-BESTest (balance) and senior fitness test (battery of functional fitness tests). Quality of life was also assessed using the EuroQol EQ visual analogue scale. When controlling for between-group differences in levels of physical activity (ANCOVA analysis), the dancers had significantly better balance, functional capacity and quality of life (all P < 0.05) compared to controls. No differences between the groups were observed in other measures of functional fitness. The findings of this study suggest regular participation in set dancing is associated with health benefits for older adults. These results may inform future studies prospectively examining the role of set dancing for falls prevention, emotional well-being and cognitive function in community-dwelling older adults. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Academic abilities and glycaemic control in children and young people with Type 1 diabetes mellitus.

PubMed

Semenkovich, K; Patel, P P; Pollock, A B; Beach, K A; Nelson, S; Masterson, J J; Hershey, T; Arbeláez, A M

2016-05-01

To determine if children and young people aged < 23 years with Type 1 diabetes differ in academic ability from age-matched control subjects without Type 1 diabetes and whether academic scores are related to glycaemic control. Using a cross-sectional study design, we administered cognitive and academic tests (Woodcock-Johnson III Spatial Relations, General Information, Letter-Word Recognition, Calculation and Spelling tests) to young people with Type 1 diabetes (n=61) and control subjects (n=26) aged 9-22 years. The groups did not differ in age or gender. Participants with Type 1 diabetes had a disease duration of 5-17.7 years. History of glycaemic control (HbA1c , diabetic ketoacidosis and severe hypoglycaemic episodes) was obtained via medical records and interviews. The participants with Type 1 diabetes had a lower mean estimated verbal intelligence (IQ) level compared with those in the control group (P=0.04). Greater exposure to hyperglycaemia over time was associated with lower spelling abilities within the group with Type 1 diabetes (P=0.048), even after controlling for age, gender, socio-economic status, blood glucose level at time of testing and verbal IQ (P=0.01). History of severe hypoglycaemia or ketoacidosis was not associated with differences in academic abilities. In children and young people, Type 1 diabetes was associated with a lower verbal IQ. Moreover, increased exposure to hyperglycaemia was associated with lower spelling performance. These results imply that hyperglycaemia can affect cognitive function and/or learning processes that may affect academic achievement. © 2015 Diabetes UK.

Recipient-donor age matching in liver transplantation: a single-center experience.

PubMed

Pagano, D; Grosso, G; Vizzini, G; Spada, M; Cintorino, D; Malaguarnera, M; Donati, M; Mistretta, A; Gridelli, B; Gruttadauria, S

2013-09-01

The aim of this study was to investigate whether donor age was a predictor of outcomes in liver transplantation, representing an independent risk factor as well as its impact related to recipient age-matching. We analyzed prospectively collected data from 221 adult liver transplantations performed from January 2006 to September 2009. Compared with recipients who received grafts from donors <60 years old, transplantation from older donors was associated with significantly higher rates of graft rejection (9.5% vs 3.5%; P = .05) and worse graft survival (P = .021). When comparing recipient and graft survivals according to age matching, we observed significantly worse values for age-mismatched (P values .029 and .037, respectively) versus age-matched patients. After adjusting for covariates in a multivariate model, age mismatch was an independent risk factor for patient death (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.1-4.17; P = .027) and graft loss (HR 3.86, 95% CI 1.02-15.47; P = .046). The results of this study suggest to that optimized donor allocation takes into account both donor and recipient ages maximize survival of liver-transplanted patients. Copyright © 2013 Elsevier Inc. All rights reserved.

A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice.

PubMed

Clopath, Claudia; Badura, Aleksandra; De Zeeuw, Chris I; Brunel, Nicolas

2014-05-21

Mechanisms of cerebellar motor learning are still poorly understood. The standard Marr-Albus-Ito theory posits that learning involves plasticity at the parallel fiber to Purkinje cell synapses under control of the climbing fiber input, which provides an error signal as in classical supervised learning paradigms. However, a growing body of evidence challenges this theory, in that additional sites of plasticity appear to contribute to motor adaptation. Here, we consider phase-reversal training of the vestibulo-ocular reflex (VOR), a simple form of motor learning for which a large body of experimental data is available in wild-type and mutant mice, in which the excitability of granule cells or inhibition of Purkinje cells was affected in a cell-specific fashion. We present novel electrophysiological recordings of Purkinje cell activity measured in naive wild-type mice subjected to this VOR adaptation task. We then introduce a minimal model that consists of learning at the parallel fibers to Purkinje cells with the help of the climbing fibers. Although the minimal model reproduces the behavior of the wild-type animals and is analytically tractable, it fails at reproducing the behavior of mutant mice and the electrophysiology data. Therefore, we build a detailed model involving plasticity at the parallel fibers to Purkinje cells' synapse guided by climbing fibers, feedforward inhibition of Purkinje cells, and plasticity at the mossy fiber to vestibular nuclei neuron synapse. The detailed model reproduces both the behavioral and electrophysiological data of both the wild-type and mutant mice and allows for experimentally testable predictions. Copyright © 2014 the authors 0270-6474/14/347203-13$15.00/0.

Age-Related Brain Activation Changes during Rule Repetition in Word-Matching.

PubMed

Methqal, Ikram; Pinsard, Basile; Amiri, Mahnoush; Wilson, Maximiliano A; Monchi, Oury; Provost, Jean-Sebastien; Joanette, Yves

2017-01-01

Objective: The purpose of this study was to explore the age-related brain activation changes during a word-matching semantic-category-based task, which required either repeating or changing a semantic rule to be applied. In order to do so, a word-semantic rule-based task was adapted from the Wisconsin Sorting Card Test, involving the repeated feedback-driven selection of given pairs of words based on semantic category-based criteria. Method: Forty healthy adults (20 younger and 20 older) performed a word-matching task while undergoing a fMRI scan in which they were required to pair a target word with another word from a group of three words. The required pairing is based on three word-pair semantic rules which correspond to different levels of semantic control demands: functional relatedness, moderately typical-relatedness (which were considered as low control demands), and atypical-relatedness (high control demands). The sorting period consisted of a continuous execution of the same sorting rule and an inferred trial-by-trial feedback was given. Results: Behavioral performance revealed increases in response times and decreases of correct responses according to the level of semantic control demands (functional vs. typical vs. atypical) for both age groups (younger and older) reflecting graded differences in the repetition of the application of a given semantic rule. Neuroimaging findings of significant brain activation showed two main results: (1) Greater task-related activation changes for the repetition of the application of atypical rules relative to typical and functional rules, and (2) Changes (older > younger) in the inferior prefrontal regions for functional rules and more extensive and bilateral activations for typical and atypical rules. Regarding the inter-semantic rules comparison, only task-related activation differences were observed for functional > typical (e.g., inferior parietal and temporal regions bilaterally) and atypical > typical (e

Ultrasound Characteristics of the Achilles Tendon in Tophaceous Gout: A Comparison with Age- and Sex-matched Controls.

PubMed

Carroll, Matthew; Dalbeth, Nicola; Allen, Bruce; Stewart, Sarah; House, Tony; Boocock, Mark; Frampton, Christopher; Rome, Keith

2017-10-01

To investigate the frequency and distribution of characteristics of the Achilles tendon (AT) in people with tophaceous gout using musculoskeletal ultrasound (US). Twenty-four participants with tophaceous gout and 24 age- and sex-matched controls without gout or other arthritis were recruited. All participants underwent a greyscale and power Doppler US examination. The AT was divided into 3 anatomical zones (insertion, pre-insertional, and proximal to the mid-section). The following US characteristics were assessed: tophus, tendon echogenicity, tendon vascularity, tendon morphology, entheseal characteristics, bursal morphology, and calcaneal bone profile. The majority of the participants with tophaceous gout were middle-aged men (n = 22, 92%) predominately of European ethnicity (n = 14, 58%). Tophus deposition was observed in 73% (n = 35) of tendons in those with gout and in none of the controls (p < 0.01). Intratendinous hyperechoic spots (p < 0.01) and intratendinous power Doppler signal (p < 0.01) were more frequent in participants with gout compared to controls. High prevalence of entheseal calcifications, calcaneal bone cortex irregularities, and calcaneal enthesophytes were observed in both gout participants and controls, without differences between groups. Intratendinous structural damage was rare. Hyperechoic spots were significantly more common at the insertion compared to the zone proximal to the mid-section (p < 0.01), but between-zone differences were not observed for other features. US features of urate deposition, tophus, and vascularization are present throughout the AT in patients with tophaceous gout. Despite crystal deposition, intratendinous structural changes are infrequent. Many characteristics observed in the AT in people with tophaceous gout, particularly at the calcaneal enthesis, are not disease-specific.

Gene expression patterns in the hippocampus during the development and aging of Glud1 (Glutamate Dehydrogenase 1) transgenic and wild type mice.

PubMed

Wang, Xinkun; Patel, Nilam D; Hui, Dongwei; Pal, Ranu; Hafez, Mohamed M; Sayed-Ahmed, Mohamed M; Al-Yahya, Abdulaziz A; Michaelis, Elias K

2014-03-04

Extraneuronal levels of the neurotransmitter glutamate in brain rise during aging. This is thought to lead to synaptic dysfunction and neuronal injury or death. To study the effects of glutamate hyperactivity in brain, we created transgenic (Tg) mice in which the gene for glutamate dehydrogenase (Glud1) is over-expressed in neurons and in which such overexpression leads to excess synaptic release of glutamate. In this study, we analyzed whole genome expression in the hippocampus, a region important for learning and memory, of 10 day to 20 month old Glud1 and wild type (wt) mice. During development, maturation and aging, both Tg and wt exhibited decreases in the expression of genes related to neurogenesis, neuronal migration, growth, and process elongation, and increases in genes related to neuro-inflammation, voltage-gated channel activity, and regulation of synaptic transmission. Categories of genes that were differentially expressed in Tg vs. wt during development were: synaptic function, cytoskeleton, protein ubiquitination, and mitochondria; and, those differentially expressed during aging were: synaptic function, vesicle transport, calcium signaling, protein kinase activity, cytoskeleton, neuron projection, mitochondria, and protein ubiquitination. Overall, the effects of Glud1 overexpression on the hippocampus transcriptome were greater in the mature and aged than the young. Glutamate hyperactivity caused gene expression changes in the hippocampus at all ages. Some of these changes may result in premature brain aging. The identification of these genomic expression differences is important in understanding the effects of glutamate dysregulation on neuronal function during aging or in neurodegenerative diseases.

Memory and phonological awareness in children with Benign Rolandic Epilepsy compared to a matched control group.

PubMed

Northcott, Ellen; Connolly, Anne M; Berroya, Anna; McIntyre, Jenny; Christie, Jane; Taylor, Alan; Bleasel, Andrew F; Lawson, John A; Bye, Ann M E

2007-06-01

In a previous study we demonstrated children with Benign Rolandic Epilepsy have normal intelligence and language ability. However, difficulties in verbal and visual memory and aspects of phonological awareness were found compared to normative data. To address the methodological limitations related to the use of normative data, we compared the same cohort of children with Benign Rolandic Epilepsy to a matched control group. Controls (n=40) matched on age and gender to the Benign Rolandic Epilepsy cohort underwent neuropsychological assessment. The life functioning of the control group was assessed using a modified version of the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). The study confirmed the previous findings of memory and phonological awareness difficulties. In addition, the children with Benign Rolandic Epilepsy had significantly lower IQ scores than the matched control group. Paired sample t-tests showed that on 8 of 11 QOLCE scales, children with Benign Rolandic Epilepsy were rated by parents as having poorer life functioning compared to matched controls, including lower parental ratings on the subscales of memory and language. Benign Rolandic Epilepsy has an excellent seizure prognosis, but this study further emphasizes potential cognitive difficulties. Using an age and gender matched control group, the previous findings of memory and phonological awareness difficulties were validated. These problems in cognition were also identified by parents of children with Benign Rolandic Epilepsy as problematic and impacting upon the child's quality of life.

Fat-free mass is not lower 24 months postbariatric surgery than nonoperated matched controls

PubMed Central

Strain, Gladys Witt; Ebel, Faith; Honohan, Jamie; Gagner, Michel; Dakin, Gregory F.; Pomp, Alfons; Gallagher, Dympna

2017-01-01

Objective Concerns about an excessive loss of fat-free mass (FFM) after bariatric surgery prompted this comparison of operated versus matched nonoperated controls regarding FFM. Setting University Hospital and University Research Unit in an urban medical center. Methods Body composition with bioelectric impedance (Tanita 310, Tanita Corp, Arlington Heights, IL) was measured approximately 2 years after bariatric surgery in weight stable patients and nonoperated weight stable controls matched for body mass index (BMI), gender, and age. t tests provided comparisons. Analysis of variance was used to compare FFM changes for 4 procedures. Levene’s test evaluated variance. Results Patients (n = 252; 24.7 ± 15 mo after surgery) and nonoperated controls (n = 252) were matched for gender (71.8% female), age (44.5 ± 11.0 yr), and BMI (32.8 ± 7.0 kg/m2). Patients had different surgical procedures: 107 gastric bypasses (RYGBs), 62 biliopancreatic diversions with duodenal switch (BPD/DSs), 40 adjustable gastric bands (AGBs), and 43 sleeve gastrectomies (LSGs). FFM percentage was significantly higher in the operated patients than controls, 66% versus 62%, P < .0001. For 3 procedures, the FFM was significantly higher; however, AGBs changed only 7.3 BMI units and FFM was not significantly different from their matched controls, 59.8% versus 58.2%. Across surgical groups, FFM percentage differed, P < .0001 (RYGB 66.5 ± 9.2%, BPD/DS 74.0 ± 9.3%, AGB 59.8 ± 7.0%, LSG 59.6 ± 9.3%). Variance was not different (P = .17). Conclusion Weight-reduced bariatric surgery patients have greater FFM compared with nonoperated matched controls. These findings support surgically assisted weight loss as a physiologic process and in general patients do not suffer from excessive FFM depletion after bariatric procedures. PMID:27387700

Fat-free mass is not lower 24 months postbariatric surgery than nonoperated matched controls.

PubMed

Strain, Gladys Witt; Ebel, Faith; Honohan, Jamie; Gagner, Michel; Dakin, Gregory F; Pomp, Alfons; Gallagher, Dympna

2017-01-01

Concerns about an excessive loss of fat-free mass (FFM) after bariatric surgery prompted this comparison of operated versus matched nonoperated controls regarding FFM. University Hospital and University Research Unit in an urban medical center. Body composition with bioelectric impedance (Tanita 310, Tanita Corp, Arlington Heights, IL) was measured approximately 2 years after bariatric surgery in weight stable patients and nonoperated weight stable controls matched for body mass index (BMI), gender, and age. t tests provided comparisons. Analysis of variance was used to compare FFM changes for 4 procedures. Levene's test evaluated variance. Patients (n = 252; 24.7±15 mo after surgery) and nonoperated controls (n = 252) were matched for gender (71.8% female), age (44.5±11.0 yr), and BMI (32.8±7.0 kg/m 2 ). Patients had different surgical procedures: 107 gastric bypasses (RYGBs), 62 biliopancreatic diversions with duodenal switch (BPD/DSs), 40 adjustable gastric bands (AGBs), and 43 sleeve gastrectomies (LSGs). FFM percentage was significantly higher in the operated patients than controls, 66% versus 62%, P<.0001. For 3 procedures, the FFM was significantly higher; however, AGBs changed only 7.3 BMI units and FFM was not significantly different from their matched controls, 59.8% versus 58.2%. Across surgical groups, FFM percentage differed, P<.0001 (RYGB 66.5±9.2%, BPD/DS 74.0±9.3%, AGB 59.8±7.0%, LSG 59.6±9.3%). Variance was not different (P = .17). Weight-reduced bariatric surgery patients have greater FFM compared with nonoperated matched controls. These findings support surgically assisted weight loss as a physiologic process and in general patients do not suffer from excessive FFM depletion after bariatric procedures. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Accelerated age-related olfactory decline among type 1 Usher patients

PubMed Central

Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D.

2016-01-01

Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin’ Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome. PMID:27329700

The Impact of Cetuximab Plus AKT- or mTOR- Inhibitor in a Patient-Derived Colon Cancer Cell Model with Wild-Type RAS and PIK3CA Mutation.

PubMed

Kim, Ju Sun; Kim, Jung Eun; Kim, Kyung; Lee, Jeeyun; Park, Joon Oh; Lim, Ho Yeong; Park, Young Suk; Kang, Won Ki; Kim, Seung Tae

2017-01-01

Background: Anti-EGFR therapies have been recommended for advanced colorectal cancer (CRC) with wild-type RAS and PIK3CA mutation. However, PIK3CA mutations are a poor prognostic marker and a negative predictor of response to anti-EGFR therapies in RAS wild-type CRC. Therefore, new and advanced treatment strategies are needed for personalized medical treatment of patients with wild-type RAS and PIK3CA mutation. Methods: Patient-derived tumor cells were collected from the ascites of a refractory colon cancer patient with wild-type RAS and PIK3CA mutation. We performed a cell viability assay for cetuximab, AZD5363 (AKT inhibitor), and everolimus (mTOR inhibitor) using PDCs. We also evaluated combinations of cetuximab plus AZD5363 or everolimus in a cell viability assay. Results: Based on cellular proliferation by MTT assay, tumor cells were significantly inhibited by 1uM cetuximab (control vs. cetuximab, mean growth = 100.0% vs 58.07%, p = 0.0103), 1uM AZD5363 (control vs. AZD5363, mean growth = 100.0% vs 58.22%, p = 0.0123), and 1uM everolimus (control vs. everolimus, mean growth = 100.0% vs 52.17%, p = 0.0011). Tumor cell growth was more profoundly reduced by combinations of cetuximab plus AZD5363 (control vs. cetuximab plus AZD5363, mean growth = 100.0% vs 25.00%, p < 0.0001) or everolimus (control vs. cetuximab+everolimus, mean growth = 100.0% vs 28.24%, p < 0.0001). Conclusions: Taken together, these results indicate that RAS wild-type and PIK3CA mutant PDCs originating from CRC are considerably inhibited by treatment with cetuximab plus AZD5363 or everolimus, with downregulation of the AKT and ERK pathways. These combinations may be considered as new options for advanced CRC patients with wild-type RAS and PIK3CA mutation in the context of clinical trials.

Responses of sympathetic nervous system to cold exposure in vibration syndrome subjects and age-matched healthy controls.

PubMed

Nakamoto, M

1990-01-01

Plasma norepinephrine and epinephrine in vibration syndrome subjects and age-matched healthy controls were measured for the purpose of estimating the responsibility of the sympathetic nervous system to cold exposure. In preliminary experiment, it was confirmed that cold air exposure of the whole body was more suitable than one-hand immersion in cold water. In the main experiment, 195 subjects were examined. Sixty-five subjects had vibration syndrome with vibration-induced white finger (VWF + group) and 65 subjects had vibration syndrome without VWF (VWF- group) and 65 controls had no symptoms (control group). In the three groups, plasma norepinephrine levels increased during cold air exposure of whole body at 7 degrees +/- 1.5 degrees C. Blood pressure increased and skin temperature decreased during cold exposure. Percent increase of norepinephrine in the VWF+ group was the highest while that in VWF- group followed and that in the control group was the lowest. This whole-body response of the sympathetic nervous system to cold conditions reflected the VWF which are characteristic symptoms of vibration syndrome. Excluding the effects of shivering and a cold feeling under cold conditions, it was confirmed that the sympathetic nervous system in vibration syndrome is activated more than in the controls. These results suggest that vibration exposure to hand and arm affects the sympathetic nervous system.

Sister chromatid exchange in children of Seventh-Day Adventists and matched controls.

PubMed

Hermansen, R; Waksvik, H; Fønnebø, V

1991-03-01

The low risk of cancer in Seventh-Day Adventists (SDAs) has been suggested to be due to genetic selection. To investigate this claim we examined the sister chromatid exchange (SCE) frequency in peripheral blood lymphocytes in 16 SDA children in Tromsø, all aged 0.5-8 years and 16 controls matched for sex and age. In 12 of 16 pairs, the SDA children had a lower SCE frequency than the controls. The mean difference was 4.06 (95% confidence interval -17.02-8.89, P = 0.51). There was no sex difference, and no correlation between age and SCE frequency. The genetic starting point with regard to SCE frequency seems to be the same for SDA children and controls.

Role of matching in case-control studies of antimicrobial resistance.

PubMed

Cerceo, Elizabeth; Lautenbach, Ebbing; Linkin, Darren R; Bilker, Warren B; Lee, Ingi

2009-05-01

Of 57 case-control studies of antimicrobial resistance, matching was used in 23 (40%). Matched variables differed substantially across studies. Of these 23 matched case-control studies, 12 (52%) justified the use of matching, and 9 (39%) noted the strengths or limitations of this approach. Analysis that accounted for matching was performed in only 52% of the case-control studies.

Rotavirus A genotype G1P[8]: a novel method to distinguish wild-type strains from the Rotarix vaccine strain.

PubMed

Rose, Tatiana L; Miagostovich, Marize P; Leite, José Paulo G

2010-12-01

Rotaviruses are important enteric pathogens for humans and animals. Group A rotaviruses (RV-A) are the most common agents of severe gastroenteritis in infants and young children and vaccination is the most effective method to reduce RV-A-associated diseases. G1P[8], the most prevalent RV-A genotype worldwide, is included in the RV-A vaccine Rotarix®. The discrimination between wild-type G1P[8] and vaccine G1P[8] strains is an important topic in the study of RV-A epidemiology to manage outbreaks and to define control measures for vaccinated children. In this study, we developed a novel method to segregate the wild-type and vaccine strains using restriction endonucleases. The dsRNA from the Rotarix® vaccine was sequenced and the NSP3 gene was selected as the target gene. The vaccine strain has a restriction pattern that is different than that of wild-type RV-A G1P[8] isolates after digestion with the restriction endonuclease BspHI. This pattern could be used as a marker for the differentiation of wild-type G1P[8] strains from the vaccine strain.

Impedance-matching system for a flexible surface-coil-type resonator

NASA Astrophysics Data System (ADS)

Hirata, Hiroshi; Ono, Mitsuhiro

1997-09-01

This article describes an impedance-matching system for a flexible surface-coil-type resonator (FSCR) used in electron paramagnetic resonance (EPR) experiments. To design the matching system, the input impedance of the FSCR was formulated using transmission line theory, and then the parameters of a matching circuit using varicap diodes were calculated. Experimental measurements of input impedance showed the validity of the formulation and the usefulness of the matching system. The matching circuit made by the varicap diodes 1SV186 offered the tunable bandwidth of 50 MHz for the prototype FSCR. Such a matching system also offers the possibility of remotely tuning EPR resonators electronically.

Wild-type presenilin 1 protects against Alzheimer disease mutation-induced amyloid pathology.

PubMed

Wang, Runsheng; Wang, Baiping; He, Wanxia; Zheng, Hui

2006-06-02

Mutations in presenilin 1 (PS1) lead to dominant inheritance of early onset familial Alzheimer disease (FAD). These mutations are known to alter the gamma-secretase cleavage of the amyloid precursor protein, resulting in increased ratio of Abeta42/Abeta40 and accelerated amyloid plaque pathology in transgenic mouse models. To investigate the factors that drive the Abeta42/Abeta40 ratio and amyloid pathogenesis and to investigate the possible interactions between wild-type and FAD mutant PS1, which are co-expressed in transgenic animals, we expressed the PS1 M146V knock-in allele either on wild-type PS1 (PS1M146V/+) or PS1 null (PS1M146V/-) background and crossed these alleles with the Tg2576 APP transgenic mice. Introduction of the PS1 M146V mutation on Tg2576 background resulted in earlier onset of plaque pathology. Surprisingly, removing the wild-type PS1 in the presence of the PS1 M146V mutation (PS1M146V/-) greatly exacerbated the amyloid burden; and this was attributed to a reduction of gamma-secretase activity rather than an increase in Abeta42. Our findings establish a protective role of the wild-type PS1 against the FAD mutation-induced amyloid pathology through a partial loss-of-function mechanism.

Serum transthyretin levels in senile systemic amyloidosis: effects of age, gender and ethnicity

PubMed Central

Buxbaum, Joel; Koziol, James; Connors, Lawreen H.

2017-01-01

Serum transthyretin (TTR) levels are reduced in familial amyloidotic polyneuropathy (FAP). A single study of patients with senile systemic amyloidosis (SSA) in Sweden found that those individuals also had a significantly lower mean serum TTR concentration than age- and gender-matched controls. To determine if the same phenomenon prevailed in an ethnically more heterogeneous population, we compared the serum TTR levels, as determined by ELISA, in 45 documented SSA patients with congestive heart failure, 20 AL patients with congestive heart failure and population controls. Serum TTR concentrations in the controls were influenced in a statistically significant manner by age, gender and ethnicity. Although it is unlikely that such differences are clinically relevant, they must be considered when assessing the meaning of serum TTR concentrations in any clinically defined population. The serum concentrations in patients with SSA did not differ from age, gender and ethnically matched controls or from a group of AL patients with significant clinical cardiac involvement. We also compared TTR concentrations in 12 African-Americans carrying the TTR V122I allele with those in 826 African-Americans who were homozygous wild type at the TTR locus. The TTR V122I carriers had significantly lower serum TTR concentrations than appropriate controls even though the majority of such individuals had not reached the age of clinical or anatomic risk, i.e. over 60. Thus, as in carriers of other TTR mutations the serum TTR level is lower than normal, despite having a much later appearance of clinical disease. PMID:19065297

A Ten-Week Biochemistry Lab Project Studying Wild-Type and Mutant Bacterial Alkaline Phosphatase

ERIC Educational Resources Information Center

Witherow, D. Scott

2016-01-01

This work describes a 10-week laboratory project studying wild-type and mutant bacterial alkaline phosphatase, in which students purify, quantitate, and perform kinetic assays on wild-type and selected mutants of the enzyme. Students also perform plasmid DNA purification, digestion, and gel analysis. In addition to simply learning important…

Structures and Free Energy Landscapes of the Wild-Type and A30P Mutant-Type α-Synuclein Proteins with Dynamics

PubMed Central

2013-01-01

The genetic missense A30P mutation of the wild-type α-synuclein protein results in the replacement of the 30th amino acid residue from alanine (Ala) to proline (Pro) and was initially found in the members of a German family who developed Parkinson’s disease. Even though the structures of these proteins have been measured before, detailed understanding about the structures and their relationships with free energy landscapes is lacking, which is of interest to provide insights into the pathogenic mechanism of Parkinson’s disease. We report the secondary and tertiary structures and conformational free energy landscapes of the wild-type and A30P mutant-type α-synuclein proteins in an aqueous solution environment via extensive parallel tempering molecular dynamics simulations along with thermodynamic calculations. In addition, we present the residual secondary structure component transition stabilities at the atomic level with dynamics in terms of free energy change calculations using a new strategy that we reported most recently. Our studies yield new interesting results; for instance, we find that the A30P mutation has local as well as long-range effects on the structural properties of the wild-type α-synuclein protein. The helical content at Ala18-Gly31 is less prominent in comparison to the wild-type α-synuclein protein. The β-sheet structure abundance decreases in the N-terminal region upon A30P mutation of the wild-type α-synuclein, whereas the NAC and C-terminal regions possess larger tendencies for β-sheet structure formation. Long-range intramolecular protein interactions are less abundant upon A30P mutation, especially between the NAC and C-terminal regions, which is linked to the less compact and less stable structures of the A30P mutant-type rather than the wild-type α-synuclein protein. Results including the usage of our new strategy for secondary structure transition stabilities show that the A30P mutant-type α-synuclein tendency toward

Structures and free energy landscapes of the wild-type and A30P mutant-type α-synuclein proteins with dynamics.

PubMed

Wise-Scira, Olivia; Aloglu, Ahmet Kemal; Dunn, Aquila; Sakallioglu, Isin Tuna; Coskuner, Orkid

2013-03-20

The genetic missense A30P mutation of the wild-type α-synuclein protein results in the replacement of the 30th amino acid residue from alanine (Ala) to proline (Pro) and was initially found in the members of a German family who developed Parkinson's disease. Even though the structures of these proteins have been measured before, detailed understanding about the structures and their relationships with free energy landscapes is lacking, which is of interest to provide insights into the pathogenic mechanism of Parkinson's disease. We report the secondary and tertiary structures and conformational free energy landscapes of the wild-type and A30P mutant-type α-synuclein proteins in an aqueous solution environment via extensive parallel tempering molecular dynamics simulations along with thermodynamic calculations. In addition, we present the residual secondary structure component transition stabilities at the atomic level with dynamics in terms of free energy change calculations using a new strategy that we reported most recently. Our studies yield new interesting results; for instance, we find that the A30P mutation has local as well as long-range effects on the structural properties of the wild-type α-synuclein protein. The helical content at Ala18-Gly31 is less prominent in comparison to the wild-type α-synuclein protein. The β-sheet structure abundance decreases in the N-terminal region upon A30P mutation of the wild-type α-synuclein, whereas the NAC and C-terminal regions possess larger tendencies for β-sheet structure formation. Long-range intramolecular protein interactions are less abundant upon A30P mutation, especially between the NAC and C-terminal regions, which is linked to the less compact and less stable structures of the A30P mutant-type rather than the wild-type α-synuclein protein. Results including the usage of our new strategy for secondary structure transition stabilities show that the A30P mutant-type α-synuclein tendency toward

Identifying patients with chronic hepatitis B at high risk of type 2 diabetes mellitus: a cross-sectional study with pair-matched controls.

PubMed

Shen, Yi; Zhang, Jian; Cai, Hui; Shao, Jian-Guo; Zhang, You-Yi; Liu, Yan-Mei; Qin, Gang; Qin, Yan

2015-03-19

The presence of diabetes mellitus (DM) is associated with increased liver morbidity and mortality risk in patients with chronic hepatitis B (CHB). Aim of this study was to identify factors associated with type 2 diabetes mellitus (T2DM) in CHB patients. A cross-sectional study with pair-matched controls was conducted in Nantong Third People's Hospital, Nantong University, China. From January 2008 to December 2012, a total of 1783 CHB patients were screened for study subjects, among whom 207 patients with T2DM were enrolled as cases and 207 sex- and age-matched non-DM patients as controls. Demographic, anthropometric, lifestyle, clinical, and laboratory data were obtained from each subject. In the univariate model, thirteen variables showed marked differences between the DM group and non-DM group. Patients with longer duration of CHB (≥15 years) and alcoholic steatosis showed the highest likelihood of T2DM (odds ratio = 5.39 and 4.95; 95% confidence intervals 2.76-10.53 and 1.65-14.91). In the multivariate adjusted analysis, three CHB-related factors, namely high viral load, long duration of illness, and presence of cirrhosis, contributed to substantially increase the likelihood of T2DM, in addition to the other five risk factors including family history of DM, low education level, elevated triglycerides (TG), gamma-glutamyl transferase (GGT) levels, and presence of alcoholic steatosis. Our findings suggest that high viral load, long duration of CHB, presence of cirrhosis, alcoholic steatosis and several other factors may be potential risk factors for development of T2DM in CHB patients. It is of vital importance to monitor glucose in high-risk CHB patients and aggressively intervene on modifiable risk factors.

Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A

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

Huang Shurong; Risques, Rosa Ana; Martin, George M.

2008-01-01

LMNA mutations are responsible for a variety of genetic disorders, including muscular dystrophy, lipodystrophy, and certain progeroid syndromes, notably Hutchinson-Gilford Progeria. Although a number of clinical features of these disorders are suggestive of accelerated aging, it is not known whether cells derived from these patients exhibit cellular phenotypes associated with accelerated aging. We examined a series of isogenic skin fibroblast lines transfected with LMNA constructs bearing known pathogenic point mutations or deletion mutations found in progeroid syndromes. Fibroblasts overexpressing mutant lamin A exhibited accelerated rates of loss of telomeres and shortened replicative lifespans, in addition to abnormal nuclear morphology. Tomore » our surprise, these abnormalities were also observed in lines overexpressing wild-type lamin A. Copy number variants are common in human populations; those involving LMNA, whether arising meiotically or mitotically, might lead to progeroid phenotypes. In an initial pilot study of 23 progeroid cases without detectable WRN or LMNA mutations, however, no cases of altered LMNA copy number were detected. Nevertheless, our findings raise a hypothesis that changes in lamina organization may cause accelerated telomere attrition, with different kinetics for overexpession of wild-type and mutant lamin A, which leads to rapid replicative senescence and progroid phenotypes.« less

The causes and prognoses of different types of fractures in wild koalas submitted to wildlife hospitals.

PubMed

Henning, Joerg; Hannon, Christabel; McKinnon, Allan; Larkin, Rebecca; Allavena, Rachel

2015-12-01

Fractures are a major problem in wild koalas of great veterinary and conservation importance as their occurrence in different locations of the body might result in varying healing success. The aim of this study was to determine the fracture types (defined by location of the fracture) occurring in wild koalas, temporal patterns, possible causes and risk factors of fracture types, and the prognosis for successfully releasing kolas with healed fracture types into the wild. Data from a total of 2031 wild koalas submitted to wildlife hospitals in South-East Queensland, Australia, over a period of 13 years were analysed. Approximately 56.7% of koalas experienced head fractures, 13.4% had torso fractures, 14.9% had limb fractures and 15% had combination fractures. A total of 84.1% of fractures were caused by vehicle collisions, 9.1% by dog attacks, 3.3% by falls from trees, 1.3% by train collisions, 0.2% by livestock trampling and 1.8% due to unknown causes. Multinominal logistic regression was used to identify risk factors (cause of fracture, age category, sex, year, three-year admission period and season of fracture event) by fracture type. The type of fracture was associated with both the cause of the fracture and the season when it occurred: for example torso fractures (compared to combination fractures) were associated with dog attacks (OR=10.98; 95% CI6.03, 20.01) and falls from trees (OR=4.79; 95% CI2.26, 10.19) relative to vehicle collisions. More submissions of koalas with head fractures due to vehicle collisions occurred in spring compared to autumn and winter, coinciding with the breeding season of koalas and increased animal movement. Prognosis for koalas with fractures was poor, with approximately 63.8% of koalas admitted dead on arrival, 34.2% euthanised, and only 2.0% of koalas able to be released. Given this data, further research into mitigation strategies to decrease the risk of fractures and to increase the observed low recovery rate should be

Differential induction of Toll-like receptors & type 1 interferons by Sabin attenuated & wild type 1 polioviruses in human neuronal cells.

PubMed

Mohanty, Madhu C; Deshpande, Jagadish M

2013-01-01

Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains) do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV) and Sabin attenuated type 1 poliovirus (Sabin PV) in cultured human neuronal cells. By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs) and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH) infected with Sabin PV and wild PV. Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5) m-RNA in neuronal cells at the beginning of infection (up to 4 h) as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.

Ablation of the Sam68 RNA Binding Protein Protects Mice from Age-Related Bone Loss

PubMed Central

Richard, Stéphane; Torabi, Nazi; Franco, Gladys Valverde; Tremblay, Guy A; Chen, Taiping; Vogel, Gillian; Morel, Mélanie; Cléroux, Patrick; Forget-Richard, Alexandre; Komarova, Svetlana; Tremblay, Michel L; Li, Wei; Li, Ailian; Gao, Yun Jing; Henderson, Janet E

2005-01-01

The Src substrate associated in mitosis of 68 kDa (Sam68) is a KH-type RNA binding protein that has been shown to regulate several aspects of RNA metabolism; however, its physiologic role has remained elusive. Herein we report the generation of Sam68-null mice by homologous recombination. Aged Sam68−/− mice preserved their bone mass, in sharp contrast with 12-month-old wild-type littermates in which bone mass was decreased up to approximately 75%. In fact, the bone volume of the 12-month-old Sam68−/− mice was virtually indistinguishable from that of 4-month-old wild-type or Sam68−/− mice. Sam68−/− bone marrow stromal cells had a differentiation advantage for the osteogenic pathway. Moreover, the knockdown of Sam68 using short hairpin RNA in the embryonic mesenchymal multipotential progenitor C3H10T1/2 cells resulted in more pronounced expression of the mature osteoblast marker osteocalcin when differentiation was induced with bone morphogenetic protein-2. Cultures of mouse embryo fibroblasts generated from Sam68+/+ and Sam68−/− littermates were induced to differentiate into adipocytes with culture medium containing pioglitazone and the Sam68−/− mouse embryo fibroblasts shown to have impaired adipocyte differentiation. Furthermore, in vivo it was shown that sections of bone from 12-month-old Sam68−/− mice had few marrow adipocytes compared with their age-matched wild-type littermate controls, which exhibited fatty bone marrow. Our findings identify endogenous Sam68 as a positive regulator of adipocyte differentiation and a negative regulator of osteoblast differentiation, which is consistent with Sam68 being a modulator of bone marrow mesenchymal cell differentiation, and hence bone metabolism, in aged mice. PMID:16362077

Comprehensive Endocrine-Metabolic Evaluation of Patients with Alström Syndrome Compared to BMI-Matched Controls.

PubMed

Han, Joan C; Reyes-Capo, Daniela P; Liu, Chia-Ying; Reynolds, James C; Turkbey, Evrim; Turkbey, Ismail Baris; Bryant, Joy; Marshall, Jan D; Naggert, Jürgen K; Gahl, William A; Yanovski, Jack A; Gunay-Aygun, Meral

2018-04-27

Alström syndrome (AS), a monogenic form of obesity, is caused by recessive mutations in the centrosome- and basal body-associated gene, ALMS1. AS is characterized by retinal dystrophy, sensory hearing loss, cardiomyopathy, childhood obesity, and metabolic derangements. We sought to characterize the endocrine and metabolic features of AS while accounting for obesity as a confounder by comparing patients with AS to BMI-matched controls. We evaluated 38 patients with AS (age 2-38y) who were matched with 76 controls (age 2-48y) by age, sex, race, and BMI. Fasting biochemistries, mixed meal test (MMT), indirect calorimetry, DEXA, and MRI/MRS were performed. Frequent abnormalities in AS included 76% obesity, 37% type 2 diabetes (T2DM), 29% hypothyroidism (1/3-central, 2/3-primary), 3% central adrenal insufficiency, 57% adult hypogonadism (1/3-central, 2/3-primary), and 25% female hyperandrogenism. AS and controls had similar BMI-Z, body fat, waist circumference, abdominal visceral fat, muscle fat, resting energy expenditure (adjusted for lean mass), free fatty acids, glucagon, prolactin, ACTH, and cortisol. Compared to controls, AS were shorter and had lower IGF1 concentrations (p's≤0.001). AS had significantly greater fasting and MMT insulin resistance indices, higher MMT glucose, insulin, and C-peptide values, higher hemoglobin A1c, and higher prevalence of T2DM (p's<0.001). AS had significantly higher triglycerides, lower HDL-cholesterol, and a 10-fold greater prevalence of metabolic syndrome (p's<0.001). AS demonstrated significantly greater liver triglyceride accumulation and higher transaminases (p's<0.001). Severe insulin resistance and T2DM are the hallmarks of AS. However, patients with AS may present with multiple other endocrinopathies affecting growth and development.

MTBDRplus and MTBDRsl Assays: Absence of Wild-Type Probe Hybridization and Implications for Detection of Drug-Resistant Tuberculosis

PubMed Central

Georghiou, Sophia B.; Catanzaro, Donald; Rodrigues, Camilla; Crudu, Valeriu; Victor, Thomas C.; Garfein, Richard S.; Catanzaro, Antonino; Rodwell, Timothy C.

2016-01-01

Accurate identification of drug-resistant Mycobacterium tuberculosis is imperative for effective treatment and subsequent reduction in disease transmission. Line probe assays rapidly detect mutations associated with resistance and wild-type sequences associated with susceptibility. Examination of molecular-level performance is necessary for improved assay result interpretation and for continued diagnostic development. Using data collected from a large, multisite diagnostic study, probe hybridization results from line probe assays, MTBDRplus and MTBDRsl, were compared to those of sequencing, and the diagnostic performance of each individual mutation and wild-type probe was assessed. Line probe assay results classified as resistant due to the absence of wild-type probe hybridization were compared to those of sequencing to determine if novel mutations were inhibiting wild-type probe hybridization. The contribution of absent wild-type probe hybridization to the detection of drug resistance was assessed via comparison to a phenotypic reference standard. In our study, mutation probes demonstrated significantly higher specificities than wild-type probes and wild-type probes demonstrated marginally higher sensitivities than mutation probes, an ideal combination for detecting the presence of resistance conferring mutations while yielding the fewest number of false-positive results. The absence of wild-type probe hybridization without mutation probe hybridization was determined to be primarily the result of failure of mutation probe hybridization and not the result of novel or rare mutations. Compared to phenotypic culture-based drug susceptibility testing, the absence of wild-type probe hybridization without mutation probe hybridization significantly contributed to the detection of phenotypic rifampin and fluoroquinolone resistance with negligible increases in false-positive results. PMID:26763971

DNA barcoding of wild edible mushrooms consumed by the ethnic tribes of India.

PubMed

Khaund, Polashree; Joshi, S R

2014-10-15

Wild edible mushrooms are consumed by the tribes of Meghalaya in the North-Eastern region of India, as part of their ethnic cuisine because of their favored organoleptic characteristics and traditionally known health benefits. Majority of these mushrooms have not yet been characterized in detail and are slowly shrinking in their natural habitats owing to anthropogenic factors and climate change. In the present study, representative specimens of ten morphologically distinct groups of wild edible mushrooms available in the traditional markets and their respective forest habitats, were subjected to multi-loci molecular characterization using SSU, ITS, RPB1 and RPB2 markers. The species identities inferred for the ten mushroom types using the SSU marker matched their morphological description in the case of four morphological groups only whereas the ITS marker successfully resolved the species identity for nine out of the ten mushroom groups under study. Both the protein coding gene markers RPB1 and RPB2 successfully resolved the species identity for three out of the ten morphologically distinct groups. Finally the most likely identity of the wild edible mushrooms under study has been suggested by matching their unique morphological characteristics with the generated DNA barcoding data. The present molecular characterization reveals the ten widely consumed wild mushroom types of Meghalaya, India to be Gomphus floccosus, Lactarius deliciosus, Lactarius volemus, Cantharellus cibarius, Tricholoma viridiolivaceum, Inocybe aff. sphaerospora, Laccaria vinaceoavellanea, Albatrellus ellisii, Ramaria maculatipes and Clavulina cristata. The final species identity generated by the ITS marker matched more accurately with the morphological characteristics/appearance of the specimens indicating the ITS region as a reliable barcode for identifying wild edible mushrooms. Copyright © 2014 Elsevier B.V. All rights reserved.

Antibody responses to avian influenza viruses in wild birds broaden with age

PubMed Central

Manvell, Ruth J.; Schulenburg, Bodo; Shell, Wendy; Wikramaratna, Paul S.; Perrins, Christopher; Sheldon, Ben C.; Brown, Ian H.; Pybus, Oliver G.

2016-01-01

For viruses such as avian influenza, immunity within a host population can drive the emergence of new strains by selecting for viruses with novel antigens that avoid immune recognition. The accumulation of acquired immunity with age is hypothesized to affect how influenza viruses emerge and spread in species of different lifespans. Despite its importance for understanding the behaviour of avian influenza viruses, little is known about age-related accumulation of immunity in the virus's primary reservoir, wild birds. To address this, we studied the age structure of immune responses to avian influenza virus in a wild swan population (Cygnus olor), before and after the population experienced an outbreak of highly pathogenic H5N1 avian influenza in 2008. We performed haemagglutination inhibition assays on sampled sera for five avian influenza strains and show that breadth of response accumulates with age. The observed age-related distribution of antibody responses to avian influenza strains may explain the age-dependent mortality observed during the highly pathogenic H5N1 outbreak. Age structures and species lifespan are probably important determinants of viral epidemiology and virulence in birds. PMID:28003449

Cdx mutant axial progenitor cells are rescued by grafting to a wild type environment.

PubMed

Bialecka, Monika; Wilson, Valerie; Deschamps, Jacqueline

2010-11-01

Cdx transcription factors are required for axial extension. Cdx genes are expressed in the posterior growth zone, a region that supplies new cells for axial elongation. Cdx2(+/-)Cdx4(-/-) (Cdx2/4) mutant embryos show abnormalities in axis elongation from E8.5, culminating in axial truncation at E10.5. These data raised the possibility that the long-term axial progenitors of Cdx mutants are intrinsically impaired in their ability to contribute to posterior growth. We investigated whether we could identify cell-autonomous defects of the axial progenitor cells by grafting mutant cells into a wild type growth zone environment. We compared the contribution of GFP labeled mutant and wild type progenitors grafted to unlabeled wild type recipients subsequently cultured over the period during which Cdx2/4 defects emerge. Descendants of grafted cells were scored for their contribution to differentiated tissues in the elongating axis and to the posterior growth zone. No difference between the contribution of descendants from wild type and mutant grafted progenitors was detected, indicating that rescue of the Cdx mutant progenitors by the wild type recipient growth zone is provided non-cell autonomously. Recently, we showed that premature axial termination of Cdx mutants can be partly rescued by stimulating canonical Wnt signaling in the posterior growth zone. Taken together with the data shown here, this suggests that Cdx genes function to maintain a signaling-dependent niche for the posterior axial progenitors. Copyright © 2010 Elsevier Inc. All rights reserved.

A positively gravitropic mutant mirrors the wild-type protonemal response in the moss Ceratodon purpureus

NASA Technical Reports Server (NTRS)

Wagner, T. A.; Cove, D. J.; Sack, F. D.

1997-01-01

Wild-type Ceratodon purpureus (Hedw.) Brid. protonemata grow up in the dark by negative gravitropism. When upright wild-type protonemata are reoriented 90 degrees, they temporarily grow down soon after reorientation ("initial reversal") and also prior to cytokinesis ("mitotic reversal"). A positively gravitropic mutant designated wrong- way response (wwr-1) has been isolated by screening ultraviolet light-mutagenized Ceratodon protonemata. Protonemata of wwr-l reoriented from the vertical to the horizontal grow down with kinetics comparable to those of the wild-type. Protonemata of wwr-1 also show initial and mitotic reversals where they temporarily grow up. Thus, the direction of gravitropism, initial reversal, and mitotic reversal are coordinated though each are opposite in wwr-1 compared to the wild-type. Normal plastid zonation is still maintained in dark-grown wwr-1 apical cells, but the plastids are more numerous and plastid sedimentation is more pronounced. In addition, wwr-1 apical cells are wider and the tips greener than in the wild-type. These data suggest that a functional WWR gene product is not necessary for the establishment of some gravitropic polarity, for gravitropism, or for the coordination of the reversals. Thus, the WWR protein may normally transduce information about cell orientation.

Modeling the competition between antenna size mutant and wild type microalgae in outdoor mass culture.

PubMed

de Mooij, Tim; Schediwy, Kira; Wijffels, René H; Janssen, Marcel

2016-12-20

Under high light conditions, microalgae are oversaturated with light which significantly reduces the light use efficiency. Microalgae with a reduced pigment content, antenna size mutants, have been proposed as a potential solution to increase the light use efficiency. The goal of this study was to investigate the competition between antenna size mutants and wild type microalgae in mass cultures. Using a kinetic model and literature-derived experimental data from wild type Chlorella sorokiniana, the productivity and competition of wild type cells and antenna size mutants were simulated. Cultivation was simulated in an outdoor microalgal raceway pond production system which was assumed to be limited by light only. Light conditions were based on a Mediterranean location (Tunisia) and a more temperate location (the Netherlands). Several wild type contamination levels were simulated in each mutant culture separately to predict the effect on the productivity over the cultivation time of a hypothetical summer season of 100days. The simulations demonstrate a good potential of antenna size reduction to increase the biomass productivity of microalgal cultures. However, it was also found that after a contamination with wild type cells the mutant cultures will be rapidly overgrown resulting in productivity loss. Copyright © 2016 Elsevier B.V. All rights reserved.

Mini-dystrophin restores L-type calcium currents in skeletal muscle of transgenic mdx mice

PubMed Central

Friedrich, O; Both, M; Gillis, J M; Chamberlain, J S; Fink, RHA

2004-01-01

L-type calcium currents (iCa) were recorded using the two-microelectrode voltage-clamp technique in single short toe muscle fibres of three different mouse strains: (i) C57/SV129 wild-type mice (wt); (ii) mdx mice (an animal model for Duchenne muscular dystrophy; and (iii) transgenically engineered mini-dystrophin (MinD)-expressing mdx mice. The activation and inactivation properties of iCa were examined in 2- to 18-month-old animals. Ca2+ current densities at 0 mV in mdx fibres increased with age, but were always significantly smaller compared to age-matched wild-type fibres. Time-to-peak (TTP) of iCa was prolonged in mdx fibres compared to wt fibres. MinD fibres always showed similar TTP and current amplitudes compared to age-matched wt fibres. In all three genotypes, the voltage-dependent inactivation and deactivation of iCa were similar. Intracellular resting calcium concentration ([Ca2+]i) and the distribution of dihydropyridine binding sites were also not different in young animals of all three genotypes, whereas iCa was markedly reduced in mdx fibres. We conclude, that dystrophin influences L-type Ca2+ channels via a direct or indirect linkage which may be disrupted in mdx mice and may be crucial for proper excitation–contraction coupling initiating Ca2+ release from the sarcoplasmic reticulum. This linkage seems to be fully restored in the presence of mini-dystrophin. PMID:14594987

Risk factors for achilles tendon rupture: A matched case control study.

PubMed

Noback, Peter C; Jang, Eugene S; Cuellar, Derly O; Seetharaman, Mani; Malagoli, Emiliano; Greisberg, Justin K; Vosseller, J Turner

2017-10-01

The purpose of this study was to elucidate whether body mass index (BMI), activity level, and other risk factors predispose patients to Achilles tendon ruptures. A retrospective review of 279 subjects was performed (93 with Achilles tendon rupture, matched 1:2 with 186 age/sex matched controls with ankle sprains). Demographic variables and risk factors for rupture were tabulated and compared. The rupture group mean BMI was 27.77 (95% CI, 26.94-28.49), and the control group mean BMI was 26.66 (95% CI, 26.06-27.27). These populations were found to be statistically equivalent (p=0.047 and p<0.001 by two one-sided t-test). A significantly higher proportion of those suffering ruptures reported regular athletic activity at baseline (74%) versus controls (59%, p=0.013). There was no clinically significant difference found in BMI between patients with ruptures and controls. Furthermore, it was found that patients who sustained ruptures were also more likely to be active at baseline than their ankle sprain counterparts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice.

PubMed

Schlegel, Victoria; Thieme, Markus; Holzmann, Carsten; Witt, Martin; Grittner, Ulrike; Rolfs, Arndt; Wree, Andreas

2016-11-09

Niemann-Pick Type C1 (NPC1) is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1 nih Npc1 -/- mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1 -/- animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.

Wild-Type Measles Viruses with Non-Standard Genome Lengths

PubMed Central

Bankamp, Bettina; Liu, Chunyu; Rivailler, Pierre; Bera, Jayati; Shrivastava, Susmita; Kirkness, Ewen F.; Bellini, William J.; Rota, Paul A.

2014-01-01

The length of the single stranded, negative sense RNA genome of measles virus (MeV) is highly conserved at 15,894 nucleotides (nt). MeVs can be grouped into 24 genotypes based on the highly variable 450 nucleotides coding for the carboxyl-terminus of the nucleocapsid protein (N-450). Here, we report the genomic sequences of 2 wild-type viral isolates of genotype D4 with genome lengths of 15,900 nt. Both genomes had a 7 nt insertion in the 3′ untranslated region (UTR) of the matrix (M) gene and a 1 nt deletion in the 5′ UTR of the fusion (F) gene. The net gain of 6 nt complies with the rule-of-six required for replication competency of the genomes of morbilliviruses. The insertions and deletion (indels) were confirmed in a patient sample that was the source of one of the viral isolates. The positions of the indels were identical in both viral isolates, even though epidemiological data and the 3 nt differences in N-450 between the two genomes suggested that the viruses represented separate chains of transmission. Identical indels were found in the M-F intergenic regions of 14 additional genotype D4 viral isolates that were imported into the US during 2007–2010. Viral isolates with and without indels produced plaques of similar size and replicated efficiently in A549/hSLAM and Vero/hSLAM cells. This is the first report of wild-type MeVs with genome lengths other than 15,894 nt and demonstrates that the length of the M-F UTR of wild-type MeVs is flexible. PMID:24748123

Gravitropism of hypocotyls of wild-type and starch-deficient Arabidopsis seedlings in spaceflight studies

NASA Technical Reports Server (NTRS)

Kiss, J. Z.; Edelmann, R. E.; Wood, P. C.

1999-01-01

The major purpose of this spaceflight project was to investigate the starch-statolith hypothesis for gravity perception, and a secondary goal was to study plant growth and development under spaceflight conditions. This research was based on our ground studies of gravity perception in the wild type and three starch-deficient (one starchless and two reduced starch) mutants of Arabidopsis thaliana (L.) Heynh. Dark-grown seedlings that developed in microgravity were given one of several (30 min, 60 min, or 90 min) 1-g stimuli by an on-board centrifuge, and additional controls for seedling development also were performed. These latter control experiments included a morphological study of plants that developed in space in microgravity (F microg), in space on a centrifuge (F 1g), on the ground (G 1g), and on a rotating clinostat on the ground. Since elevated levels of ethylene were reported in the spacecraft atmosphere, additional controls for morphology and gravitropism with added ethylene also were performed. While exogenous ethylene reduced the absolute magnitude of the response in all four strains of Arabidopsis, this gas did not appear to change the relative graviresponsiveness among the strains. The relative response of hypocotyls of microgravity-grown seedlings to the stimuli provided by the in-flight centrifuge was: wild type > starch-deficient mutants. Although the protoplast pressure model for gravity perception cannot be excluded, these results are consistent with a statolith-based model for perception in plants.

The short-term effect of flavonoid-rich dark chocolate on retinal vessel diameter in glaucoma patients and age-matched controls.

PubMed

Terai, Naim; Gedenk, Alexandra; Spoerl, Eberhard; Pillunat, Lutz E; Stodtmeister, Richard

2014-08-01

To investigate the effect of flavonoid-rich dark chocolate and non-flavonoid-rich white chocolate on retinal vessel diameter in glaucoma patients and age-matched controls. Thirty glaucoma patients and 30 age-matched subjects were assigned to dark or white chocolate by randomization with forced equal distribution. The number in each of the four groups was 15. Measured parameters included systemic blood pressure (BP), blood glucose levels, static retinal vessel analysis, as measured by central retinal artery equivalent (CRAE) (which relates to the diameter of the central retinal artery), central retinal vein equivalent (CRVE) (which relates to the diameter of central retinal vein) and the arterio-venous ratio (AVR), which represents the CRAE/CRVE ratio, dynamic retinal vessel analysis as measured by the change in vessel diameter in response to flicker light stimulation. Three recording cycles from each were averaged. Blood pressure parameters (systolic BP, diastolic BP and pulse), IOP and blood glucose levels did not differ significantly between both groups before and after consumption of white or dark chocolate. Static vessel analysis did not show any significant changes in CRAE, CRVE or AVR before and after dark or white chocolate in both groups (p > 0.05). Mean dilatation of the venules in the control group was 3.2 ± 0.9 % before dark chocolate and 4.2 ± 1.4 % after dark chocolate intake, which was statistically significantly different (p = 0.01). Mean dilatation of the arterioles in the control group was 2.8 ± 1.8 % before dark chocolate and 3.5 ± 1.8 % after dark chocolate intake with a trend to statistical significance (p = 0.14), but not reaching the significance level. Mean diameter changes in the glaucoma group did not show any significant differences after dark chocolate consumption. The present study showed a significant improvement of venous vasodilatation 2 hr after dark chocolate intake in the control group, but not in the glaucoma group. This

Intake of Wild Blueberry Powder Improves Episodic-Like and Working Memory during Normal Aging in Mice.

PubMed

Beracochea, Daniel; Krazem, Ali; Henkouss, Nadia; Haccard, Guillaume; Roller, Marc; Fromentin, Emilie

2016-08-01

The number of Americans older than 65 years old is projected to more than double in the next 40 years. Cognitive changes associated to aging can affect an adult's day-to-day functioning. Among these cognitive changes, reasoning, episodic memory, working memory, and processing speed decline gradually over time. Early memory changes include a decline in both working and episodic memory. The aim of the present study was to determine whether chronic (up to 75 days) daily administration of wild blueberry extract or a wild blueberry full spectrum powder would help prevent memory failure associated with aging in tasks involving various forms of memory. Both blueberry ingredients were used in a study comparing young mice (6 months old) to aged mice (18 months old). At this age, mice exhibit memory decline due to aging, which is exacerbated first by a loss in working and contextual (episodic-like) memory. Contextual memory (episodic-like memory) was evaluated using the contextual serial discrimination test. Working and spatial memory were evaluated using the Morris-Water maze test and the sequential alternation test. Statistical analysis was performed using an ANOVA with the Bonferroni post-hoc test. Supplementation with wild blueberry full spectrum powder and wild blueberry extract resulted in significant improvement of contextual memory, while untreated aged mice experienced a decline in such memory. Only the wild blueberry full spectrum powder significantly contributed to an improvement of spatial and working memory versus untreated aged mice. These improvements of cognitive performance may be related to brain oxidative status, acetylcholinesterase activity, neuroprotection, or attenuation of immunoreactivity. Georg Thieme Verlag KG Stuttgart · New York.

Recovery of deficient homologous recombination in Brca2-depleted mouse cells by wild-type Rad51 expression.

PubMed

Lee, Shauna A; Roques, Céline; Magwood, Alissa C; Masson, Jean-Yves; Baker, Mark D

2009-02-01

The BRCA2 tumor suppressor is important in maintaining genomic stability. BRCA2 is proposed to control the availability, cellular localization and DNA binding activity of the central homologous recombination protein, RAD51, with loss of BRCA2 resulting in defective homologous recombination. Nevertheless, the roles of BRCA2 in regulating RAD51 and how other proteins implicated in RAD51 regulation, such as RAD52 and RAD54 function relative to BRCA2 is not known. In this study, we tested whether defective homologous recombination in Brca2-depleted mouse hybridoma cells could be rectified by expression of mouse Rad51 or the Rad51-interacting mouse proteins, Rad52 and Rad54. In the Brca2-depleted cells, defective homologous recombination can be restored by over-expression of wild-type mouse Rad51, but not mouse Rad52 or Rad54. Correction of the homologous recombination defect requires Rad51 ATPase activity. A sizeable fraction ( approximately 50%) of over-expressed wild-type Rad51 is nuclear localized. The restoration of homologous recombination in the presence of a low (i.e., non-functional) level of Brca2 by wild-type Rad51 over-expression is unexpected. We suggest that Rad51 may access the nuclear compartment in a Brca2-independent manner and when Rad51 is over-expressed, the normal requirement for Brca2 control over Rad51 function in homologous recombination is dispensable. Our studies support loss of Rad51 function as a critical underlying factor in the homologous recombination defect in the Brca2-depleted cells.

Nested case-control studies: should one break the matching?

PubMed

Borgan, Ørnulf; Keogh, Ruth

2015-10-01

In a nested case-control study, controls are selected for each case from the individuals who are at risk at the time at which the case occurs. We say that the controls are matched on study time. To adjust for possible confounding, it is common to match on other variables as well. The standard analysis of nested case-control data is based on a partial likelihood which compares the covariates of each case to those of its matched controls. It has been suggested that one may break the matching of nested case-control data and analyse them as case-cohort data using an inverse probability weighted (IPW) pseudo likelihood. Further, when some covariates are available for all individuals in the cohort, multiple imputation (MI) makes it possible to use all available data in the cohort. In the paper we review the standard method and the IPW and MI approaches, and compare their performance using simulations that cover a range of scenarios, including one and two endpoints.

Changes in fatty acid content and composition between wild type and CsHMA3 overexpressing Camelina sativa under heavy-metal stress.

PubMed

Park, Won; Feng, Yufeng; Kim, Hyojin; Suh, Mi Chung; Ahn, Sung-Ju

2015-09-01

Under heavy-metal stress, CsHMA3 overexpressing transgenic Camelina plants displayed not only a better quality, but also a higher quantity of unsaturated fatty acids in their seeds compared with wild type. Camelina sativa L. belongs to the Brassicaceae family and is frequently used as a natural vegetable oil source, as its seeds contain a high content of fatty acids. In this study, we observed that, when subjected to heavy metals (Cd, Co, Zn and Pb), the seeds of CsHMA3 (Heavy-Metal P1B-ATPase 3) transgenic lines retained their original golden yellow color and smooth outline, unlike wild-type seeds. Furthermore, we investigated the fatty acids content and composition of wild type and CsHMA3 transgenic lines after heavy metal treatments compared to the control. The results showed higher total fatty acid amounts in seeds of CsHMA3 transgenic lines compared with those in wild-type seeds under heavy-metal stresses. In addition, the compositions of unsaturated fatty acids-especially 18:1 (oleic acid), 18:2 (linoleic acid; only in case of Co treatment), 18:3 (linolenic acid) and 20:1 (eicosenoic acid)-in CsHMA3 overexpressing transgenic lines treated with heavy metals were higher than those of wild-type seeds under the same conditions. Furthermore, reactive oxygen species (ROS) contents in wild-type leaves and roots when treated with heavy metal were higher than in CsHMA3 overexpressing transgenic lines. These results indicate that overexpression of CsHMA3 affects fatty acid composition and content-factors that are responsible for the fuel properties of biodiesel-and can alleviate ROS accumulation caused by heavy-metal stresses in Camelina. Due to these factors, we propose that CsHMA3 transgenic Camelina can be used for phytoremediation of metal-contaminated soil as well as for oil production.

Wild type measles virus attenuation independent of type I IFN.

PubMed

Druelle, Johan; Sellin, Caroline I; Waku-Kouomou, Diane; Horvat, Branka; Wild, Fabian T

2008-02-03

Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt). The adaptation of a measles virus isolate (G954-PBL) by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13) differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene). While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the alpha/beta IFN system.

Wild type measles virus attenuation independent of type I IFN

PubMed Central

Druelle, Johan; Sellin, Caroline I; Waku-Kouomou, Diane; Horvat, Branka; Wild, Fabian T

2008-01-01

Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt). Results The adaptation of a measles virus isolate (G954-PBL) by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13) differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene). While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system. PMID:18241351

Male and Female Mice Lacking Neuroligin-3 Modify the Behavior of Their Wild-Type Littermates.

PubMed

Kalbassi, Shireene; Bachmann, Sven O; Cross, Ellen; Roberton, Victoria H; Baudouin, Stéphane J

2017-01-01

In most mammals, including humans, the postnatal acquisition of normal social and nonsocial behavior critically depends on interactions with peers. Here we explore the possibility that mixed-group housing of mice carrying a deletion of Nlgn3 , a gene associated with autism spectrum disorders, and their wild-type littermates induces changes in each other's behavior. We have found that, when raised together, male Nlgn3 knockout mice and their wild-type littermates displayed deficits in sociability. Moreover, social submission in adult male Nlgn3 knockout mice correlated with an increase in their anxiety. Re-expression of Nlgn3 in parvalbumin-expressing cells in transgenic animals rescued their social behavior and alleviated the phenotype of their wild-type littermates, further indicating that the social behavior of Nlgn3 knockout mice has a direct and measurable impact on wild-type animals' behavior. Finally, we showed that, unlike male mice, female mice lacking Nlgn3 were insensitive to their peers' behavior but modified the social behavior of their littermates. Altogether, our findings show that the environment is a critical factor in the development of behavioral phenotypes in transgenic and wild-type mice. In addition, these results reveal that the social environment has a sexually dimorphic effect on the behavior of mice lacking Nlgn3 , being more influential in males than females.

Male and Female Mice Lacking Neuroligin-3 Modify the Behavior of Their Wild-Type Littermates

PubMed Central

Kalbassi, Shireene; Cross, Ellen

2017-01-01

Abstract In most mammals, including humans, the postnatal acquisition of normal social and nonsocial behavior critically depends on interactions with peers. Here we explore the possibility that mixed-group housing of mice carrying a deletion of Nlgn3, a gene associated with autism spectrum disorders, and their wild-type littermates induces changes in each other’s behavior. We have found that, when raised together, male Nlgn3 knockout mice and their wild-type littermates displayed deficits in sociability. Moreover, social submission in adult male Nlgn3 knockout mice correlated with an increase in their anxiety. Re-expression of Nlgn3 in parvalbumin-expressing cells in transgenic animals rescued their social behavior and alleviated the phenotype of their wild-type littermates, further indicating that the social behavior of Nlgn3 knockout mice has a direct and measurable impact on wild-type animals’ behavior. Finally, we showed that, unlike male mice, female mice lacking Nlgn3 were insensitive to their peers’ behavior but modified the social behavior of their littermates. Altogether, our findings show that the environment is a critical factor in the development of behavioral phenotypes in transgenic and wild-type mice. In addition, these results reveal that the social environment has a sexually dimorphic effect on the behavior of mice lacking Nlgn3, being more influential in males than females. PMID:28795135

Adeno-Associated Virus Type 2 Wild-Type and Vector-Mediated Genomic Integration Profiles of Human Diploid Fibroblasts Analyzed by Third-Generation PacBio DNA Sequencing

PubMed Central

Hüser, Daniela; Gogol-Döring, Andreas; Chen, Wei

2014-01-01

ABSTRACT Genome-wide analysis of adeno-associated virus (AAV) type 2 integration in HeLa cells has shown that wild-type AAV integrates at numerous genomic sites, including AAVS1 on chromosome 19q13.42. Multiple GAGY/C repeats, resembling consensus AAV Rep-binding sites are preferred, whereas rep-deficient AAV vectors (rAAV) regularly show a random integration profile. This study is the first study to analyze wild-type AAV integration in diploid human fibroblasts. Applying high-throughput third-generation PacBio-based DNA sequencing, integration profiles of wild-type AAV and rAAV are compared side by side. Bioinformatic analysis reveals that both wild-type AAV and rAAV prefer open chromatin regions. Although genomic features of AAV integration largely reproduce previous findings, the pattern of integration hot spots differs from that described in HeLa cells before. DNase-Seq data for human fibroblasts and for HeLa cells reveal variant chromatin accessibility at preferred AAV integration hot spots that correlates with variant hot spot preferences. DNase-Seq patterns of these sites in human tissues, including liver, muscle, heart, brain, skin, and embryonic stem cells further underline variant chromatin accessibility. In summary, AAV integration is dependent on cell-type-specific, variant chromatin accessibility leading to random integration profiles for rAAV, whereas wild-type AAV integration sites cluster near GAGY/C repeats. IMPORTANCE Adeno-associated virus type 2 (AAV) is assumed to establish latency by chromosomal integration of its DNA. This is the first genome-wide analysis of wild-type AAV2 integration in diploid human cells and the first to compare wild-type to recombinant AAV vector integration side by side under identical experimental conditions. Major determinants of wild-type AAV integration represent open chromatin regions with accessible consensus AAV Rep-binding sites. The variant chromatin accessibility of different human tissues or cell types will

Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope

PubMed Central

Cremolini, Chiara; Aprile, Giuseppe; Lonardi, Sara; Orlandi, Armando; Mennitto, Alessia; Berenato, Rosa; Antoniotti, Carlotta; Casagrande, Mariaelena; Marsico, Valentina; Marmorino, Federica; Cardellino, Giovanni Gerardo; Bergamo, Francesca; Tomasello, Gianluca; Formica, Vincenzo; Longarini, Raffaella; Giommoni, Elisa; Caporale, Marta; Di Bartolomeo, Maria; Loupakis, Fotios; de Braud, Filippo

2015-01-01

Background. No prospective trials have specifically addressed the efficacy and safety of panitumumab in elderly patients with metastatic colorectal cancer (CRC). We aimed at assessing the efficacy and safety of single agent panitumumab in “frail” elderly patients diagnosed with metastatic RAS and BRAF wild-type CRC. Materials and Methods. Forty elderly patients (aged ≥75 years) with metastatic RAS-BRAF wild-type CRC received off-label prescriptions of single-agent panitumumab at seven Italian institutions. Treatment was administered as first line in patients with absolute contraindication to any chemotherapy or as second-line treatment after failure of a fluoropyrimidine-based treatment, in the presence of contraindication to irinotecan. The outcome measures included objective response rate (ORR), as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results. The median PFS and OS were 6.4 months (95% confidence interval [CI]: 4.9–8 months) and 14.3 months (95% CI: 10.9–17.7 months), respectively. ORR was 32.5%, and DCR was 72.5%. Dose reductions related to adverse events (AEs) were reported in 9 (23%) patients, but no permanent treatment discontinuation caused by was reported. The most frequent grade 3 AE was skin rash, with an incidence of 20%. Conclusion. Panitumumab is effective and well-tolerated in frail elderly patients with RAS-BRAF wild-type metastatic CRC and deemed unfit for chemotherapy. A randomized study is needed to confirm these data. Implications for Practice: Treatment of elderly patients with metastatic colorectal cancer represents a difficult challenge in clinical practice. A significant proportion of frail elderly patients do not receive treatment, reflecting ongoing uncertainty of clinical benefit and toxicity of chemotherapy. Unfit condition in this cohort of patients further limits antineoplastic prescription and consequently patient survival. RAS and BRAF wild-type status could

Alcohol Habits in Patients with Long-Term Musculoskeletal Pain: Comparison with a Matched Control Group from the General Population

ERIC Educational Resources Information Center

Thelin Bronner, Kerstin Birgitta; Wennberg, Peter; Kallmen, Hakan; Schult, Marie-Louise Birgitta

2012-01-01

This prospective study aimed to describe alcohol habits in patients with chronic pain compared with those in a matched control group from the general Swedish population. In total, 100 consecutive patients enrolled were matched against 100 individuals in a control group on the basis of age and sex. Alcohol habits were measured using the Alcohol Use…

Massive outbreak of poliomyelitis caused by type-3 wild poliovirus in Angola in 1999.

PubMed Central

Valente, F.; Otten, M.; Balbina, F.; Van de Weerdt, R.; Chezzi, C.; Eriki, P.; Van-Dúnnen, J.; Bele, J. M.

2000-01-01

The largest outbreak of poliomyelitis ever recorded in Africa (1093 cases) occurred from 1 March to 28 May 1999 in Luanda, Angola, and in surrounding areas. The outbreak was caused primarily by a type-3 wild poliovirus, although type-1 wild poliovirus was circulating in the outbreak area at the same time. Infected individuals ranged in age from 2 months to 22 years; 788 individuals (72%) were younger than 3 years. Of the 590 individuals whose vaccination status was known, 23% had received no vaccine and 54% had received fewer than three doses of oral poliovirus vaccine (OPV). The major factors that contributed to this outbreak were as follows: massive displacement of unvaccinated persons to urban settings; low routine OPV coverage; inaccessible populations during the previous three national immunization days (NIDs); and inadequate sanitation. This outbreak indicates the urgent need to improve accessibility to all children during NIDs and the dramatic impact that war can have by displacing persons and impeding access to routine immunizations. The period immediately after an outbreak provides an enhanced opportunity to eradicate poliomyelitis. If continuous access in all districts for acute flaccid paralysis surveillance and supplemental immunizations cannot be assured, the current war in Angola may threaten global poliomyelitis eradication. PMID:10812730

Allanite age-dating: Non-matrix-matched standardization in quadrupole LA-ICP-MS

NASA Astrophysics Data System (ADS)

Burn, M.; Lanari, P.; Pettke, T.; Engi, M.

2014-12-01

Allanite Th-U-Pb age-dating has recently been found to be powerful in unraveling the timing of geological processes such as the metamorphic dynamics in subduction zones and crystallization velocity of magmas. However, inconsistencies among analytical techniques have raised doubts about the accuracy of allanite age data. Spot analysis techniques such as LA-ICP-MS are claimed to be crucially dependent on matrix-matched standards, the quality of which is variable. We present a new approach in LA-ICP-MS data reduction that allows non-matrix-matched standardization via well constrained zircon reference materials as primary standards. Our data were obtained using a GeoLas Pro 193 nm ArF excimer laser ablation system coupled to an ELAN DRC-e quadrupole ICP-MS. We use 32 μm and 24 μm spot sizes; laser operating conditions of 9 Hz repetition rate and 2.5 J/cm2 fluence have proven advantageous. Matrix dependent downhole fractionation evolution is empirically determined by analyzing 208Pb/232Th and 206Pb/238U and applied prior to standardization. The new data reduction technique was tested on three magmatic allanite reference materials (SISSb, CAPb, TARA); within error these show the same downhole fractionation evolution for all allanite types and in different analytical sessions, provided measurement conditions remain the same. Although the downhole evolution of allanite and zircon differs significantly, a link between zircon and allanite matrix is established by assuming CAPb and TARA to be fixed at the corresponding reference ages. Our weighted mean 208Pb/232Th ages are 30.06 ± 0.22 (2σ) for SISSb, 275.4 ± 1.3 (2σ) for CAPb, and 409.9 ± 1.8 (2σ) for TARA. Precision of single spot age data varies between 1.5 and 8 % (2σ), dependent on spot size and common lead concentrations. Quadrupole LA-ICP-MS allanite age-dating has thus similar uncertainties as do other spot analysis techniques. The new data reduction technique is much less dependent on quality and homogeneity

Wild poliovirus type 1 and type 3 importations--15 countries, Africa, 2008-2009.

PubMed

2009-04-17

The Global Polio Eradication Initiative began in 1988; by 2006, indigenous transmission of wild poliovirus (WPV) type 2 infection had been interrupted globally, and indigenous transmission of type 1 and 3 (WPV1 and WPV3) infection had been interrupted in all but four countries worldwide (Afghanistan, India, Nigeria, and Pakistan). Despite this success in controlling indigenous transmission, during 2002-2006, 20 previously polio-free countries in Africa and Asia had importations of WPV1 originating from Nigeria, and three polio-free countries in Africa had WPV1 importations originating from India. By the end of 2007, control efforts in all countries except Angola, Chad, Democratic Republic of the Congo (DRC), Niger, and Sudan had stopped transmission of WPV1 caused by these importations. However, during 2008-2009, multiple importations of WPV from countries with ongoing transmission resumed in Africa. This report describes 32 WPV importations into 15 African countries, resulting in 96 polio cases during January 2008-March 2009 and persistent WPV transmission in five previously polio-free African countries. As with the 2002-2006 resurgence, all of the importations originated from Nigeria or India, but more rapid WPV identification and response resulted in substantially fewer polio cases than reported during 2002-2006. Sensitive surveillance and continued rapid response supplemental immunization activities (SIAs) are key to limiting further WPV spread, interrupting the outbreaks, and allowing the polio prevention focus in Africa to return to eradicating polio in countries with persistent WPV transmission.

Differentiation between probiotic and wild-type Bacillus cereus isolates by antibiotic susceptibility test and Fourier transform infrared spectroscopy (FT-IR).

PubMed

Mietke, Henriette; Beer, W; Schleif, Julia; Schabert, G; Reissbrodt, R

2010-05-30

Animal feed often contains probiotic Bacillus strains used as feed additives. Spores of the non-pathogenic B. cereus var. toyoi (product name Toyocerin) are used. Distinguishing between toxic wild-type Bacillus cereus strains and this probiotic strain is essential for evaluating the quality and risk of feed. Bacillus cereus CIP 5832 (product name Paciflor was used as probiotic strain until 2001. The properties of the two probiotic strains are quite similar. Differentiating between probiotic strains and wild-type B. cereus strains is not easy. ss-lactam antibiotics such as penicillin and cefamandole exhibit an inhibition zone in the agar diffusion test of probiotic B. cereus strains which are not seen for wild-type strains. Therefore, performing the agar diffusion test first may make sense before FT-IR testing. When randomly checking these strains by Fourier transform infrared spectroscopy (FT-IR), the probiotic B. cereus strains were separated from wild-type B. cereus/B. thuringiensis/B. mycoides/B. weihenstephanensis strains by means of hierarchical cluster analysis. The discriminatory information was contained in the spectral windows 3000-2800 cm(-1) ("fatty acid region"), 1200-900 cm(-1) ("carbohydrate region") and 900-700 cm(-1) ("fingerprint region"). It is concluded that FT-IR spectroscopy can be used for the rapid quality control and risk analysis of animal feed containing probiotic B. cereus strains. (c) 2010 Elsevier B.V. All rights reserved.

MATCH: An Atom- Typing Toolset for Molecular Mechanics Force Fields

PubMed Central

Yesselman, Joseph D.; Price, Daniel J.; Knight, Jennifer L.; Brooks, Charles L.

2011-01-01

We introduce a toolset of program libraries collectively titled MATCH (Multipurpose Atom-Typer for CHARMM) for the automated assignment of atom types and force field parameters for molecular mechanics simulation of organic molecules. The toolset includes utilities for the conversion from multiple chemical structure file formats into a molecular graph. A general chemical pattern-matching engine using this graph has been implemented whereby assignment of molecular mechanics atom types, charges and force field parameters is achieved by comparison against a customizable list of chemical fragments. While initially designed to complement the CHARMM simulation package and force fields by generating the necessary input topology and atom-type data files, MATCH can be expanded to any force field and program, and has core functionality that makes it extendable to other applications such as fragment-based property prediction. In the present work, we demonstrate the accurate construction of atomic parameters of molecules within each force field included in CHARMM36 through exhaustive cross validation studies illustrating that bond increment rules derived from one force field can be transferred to another. In addition, using leave-one-out substitution it is shown that it is also possible to substitute missing intra and intermolecular parameters with ones included in a force field to complete the parameterization of novel molecules. Finally, to demonstrate the robustness of MATCH and the coverage of chemical space offered by the recent CHARMM CGENFF force field (Vanommeslaeghe, et al., JCC., 2010, 31, 671–690), one million molecules from the PubChem database of small molecules are typed, parameterized and minimized. PMID:22042689

Effects of age and spa treatment on match running performance over two consecutive games in highly trained young soccer players.

PubMed

Buchheit, Martin; Horobeanu, Cosmin; Mendez-Villanueva, Alberto; Simpson, Ben M; Bourdon, Pitre C

2011-03-01

The aim of this study was to examine the effect of age and spa treatment (i.e. combined sauna, cold water immersion, and jacuzzi) on match running performance over two consecutive matches in highly trained young soccer players. Fifteen pre- (age 12.8 ± 0.6 years) and 13 post- (15.9 ± 1 y) peak height velocity (PHV) players played two matches (Matches 1 and 2) within 48 h against the same opposition, with no specific between-match recovery intervention (control). Five post-PHV players also completed another set of two consecutive matches, with spa treatment implemented after the first match. Match running performance was assessed using a global positioning system with very-high-intensity running (> 16.1-19.0 km · h(-1)), sprinting distance (>19 km · h(-1)), and peak match speed determined. Match 2 very-high-intensity running was "possibly" impaired in post-PHV players (-9 ± 33%; ± 90% confidence limits), whereas it was "very likely" improved for the pre-PHV players (+27 ± 22%). The spa treatment had a beneficial impact on Match 2 running performance, with a "likely" rating for sprinting distance (+30 ± 67%) and "almost certain" for peak match speed (+6.4 ± 3%). The results suggest that spa treatment is an effective recovery intervention for post-PHV players, while its value in pre-PHV players is questionable.

Lipid biosensor interactions with wild type and matrix deletion HIV-1 Gag proteins.

PubMed

Barklis, Eric; Staubus, August O; Mack, Andrew; Harper, Logan; Barklis, Robin Lid; Alfadhli, Ayna

2018-05-01

The matrix (MA) domain of the HIV-1 precursor Gag protein (PrGag) has been shown interact with the HIV-1 envelope (Env) protein, and to direct PrGag proteins to plasma membrane (PM) assembly sites by virtue of its affinity to phosphatidylinositol-4,5-bisphosphate (PI[4,5]P2). Unexpectedly, HIV-1 viruses with large MA deletions (ΔMA) have been shown to be conditionally infectious as long as they are matched with Env truncation mutant proteins or alternative viral glycoproteins. To characterize the interactions of wild type (WT) and ΔMA Gag proteins with PI(4,5)P2 and other acidic phospholipids, we have employed a set of lipid biosensors as probes. Our investigations showed marked differences in WT and ΔMA Gag colocalization with biosensors, effects on biosensor release, and association of biosensors with virus-like particles. These results demonstrate an alternative approach to the analysis of viral protein-lipid associations, and provide new data as to the lipid compositions of HIV-1 assembly sites. Copyright © 2018 Elsevier Inc. All rights reserved.

Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.

PubMed

Wang, Tina; Tsui, Brian; Kreisberg, Jason F; Robertson, Neil A; Gross, Andrew M; Yu, Michael Ku; Carter, Hannah; Brown-Borg, Holly M; Adams, Peter D; Ideker, Trey

2017-03-28

Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1 df/df dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers.

Heart Failure Due to Age-Related Cardiac Amyloid Disease Associated With Wild-Type Transthyretin: A Prospective, Observational Cohort Study

PubMed Central

Connors, Lawreen H.; Sam, Flora; Skinner, Martha; Salinaro, Francesco; Sun, Fangui; Ruberg, Frederick L.; Berk, John L.; Seldin, David C.

2015-01-01

Background Heart failure due to wild-type transthyretin amyloidosis (ATTRwt) is an under-appreciated cause of morbidity and mortality in the aging population. The aims of this study were to examine features of disease and characterize outcomes in a large ATTRwt cohort. Methods and Results Over 20 years, 121 patients with ATTRwt were enrolled in a prospective observational study. Median age at enrollment was 75.6 years (range, 62.6–87.8); 97% of patients were Caucasian. The median survival, measured from biopsy diagnosis, was 46.69 months (95% CI, 41.95–56.77); 78% of deaths were due to cardiac causes. By Kaplan-Meier analysis, 5-year survival was 35.7% (95% CI, 25–46). Impaired functional capacity (mean VO2 max of 13.5 mL/kg/min) and atrial fibrillation (67%) were common clinical features. Multivariate predictors of reduced survival were elevated serum brain natriuretic peptide (BNP, 482 ± 337 pg/mL) and uric acid (8.2 ± 2.6 mg/dL), decreased left ventricular ejection fraction (LVEF, 50% median ranging 10-70%), and increased relative wall thickness (RWT, 0.75 ± 0.19). Conclusions In this series of patients with biopsy-proven ATTRwt amyloidosis, poor functional capacity and atrial arrhythmias were common clinical features. Elevated BNP and uric acid, decreased LVEF, and increased RWT were associated with limited survival of only 35.7% at 5 years for the group as a whole. These data establish the natural history of ATTRwt, provide statistical basis for the design of future interventional clinical trials, and highlight the need for more sensitive diagnostic tests and disease-specific treatments for this disease. PMID:26660282

Female fibromyalgia patients: lower resting metabolic rates than matched healthy controls.

PubMed

Lowe, John C; Yellin, Jackie; Honeyman-Lowe, Gina

2006-07-01

Many features of fibromyalgia and hypothyroidism are virtually the same, and thyroid hormone treatment trials have reduced or eliminated fibromyalgia symptoms. These findings led the authors to test the hypothesis that fibromyalgia patients are hypometabolic compared to matched controls. Resting metabolic rate (RMR) was measured by indirect calorimetry and body composition by bioelectrical impedance for 15 fibromyalgia patients and 15 healthy matched controls. Measured resting metabolic rate (mRMR) was compared to percentages of predicted RMR (pRMR) by fat-free weight (FFW) (Sterling-Passmore: SP) and by sex, age, height, and weight (Harris-Benedict: HB). Patients had a lower mRMR (4,306.31+/-1077.66 kJ vs 5,411.59+/-695.95 kJ, p=0.0028) and lower percentages of pRMRs (SP: -28.42+/-15.82% vs -6.83+/-12.55%, p<0.0001. HB: -29.20+/-17.43% vs -9.13+/-9.51%, p=0.0008). Whereas FFW, age, weight, and body mass index (BMI) best accounted for variability in controls' RMRs, age and fat weight (FW) did for patients. In the patient group, TSH level accounted for 28% of the variance in pain distribution, and free T3 (FT3) accounted for 30% of the variance in pressure-pain threshold. Patients had lower mRMR and percentages of pRMRs. The lower RMRs were not due to calorie restriction or low FFW. Patients' normal FFW argues against low physical activity as the mechanism. TSH, FT4, and FT3 levels did not correlate with RMRs in either group. This does not rule out inadequate thyroid hormone regulation because studies show these laboratory values do not reliably predict RMR.

Disturbed eating behavior and eating disorders in preteen and early teenage girls with type 1 diabetes: a case-controlled study.

PubMed

Colton, Patricia; Olmsted, Marion; Daneman, Denis; Rydall, Anne; Rodin, Gary

2004-07-01

To compare the prevalence of eating disturbances in preteen and early teenage girls with type 1 diabetes to their nondiabetic peers. A cross-sectional, case-controlled study of 101 girls with type 1 diabetes, ages 9-14 years, and 303 age-matched, female nondiabetic control subjects was conducted. Participants completed a Children's Eating Disorder Examination interview. Socioeconomic status, BMI, and diabetes-related variables were assessed. Groups were compared using chi(2) analyses. Binge eating; the use of intense, excessive exercise for weight control; the combination of two disturbed eating-related behaviors; and subthreshold eating disorders were all more common in girls with type 1 diabetes. Metabolic control was not related to eating behavior in this study population. Eating disturbances, though mostly mild, were significantly more common in preteen and early teenage girls with type 1 diabetes. Screening and prevention programs for this high-risk group should begin in the preteen years.

Strain-specific reverse transcriptase PCR assay: means to distinguish candidate vaccine from wild-type strains of respiratory syncytial virus.

PubMed Central

Zheng, H; Peret, T C; Randolph, V B; Crowley, J C; Anderson, L J

1996-01-01

Candidate live-virus vaccines for respiratory syncytial virus are being developed and are beginning to be evaluated in clinical trials. To distinguish candidate vaccine strains from wild-type strains isolated during these trials, we developed PCR assays specific to two sets of candidate vaccine strains. The two sets were a group A strain (3A), its three attenuated, temperature-sensitive variant strains, a group B strain (2B), and its four attenuated, temperature-sensitive variant strains. The PCR assays were evaluated by testing 18 group A wild-type strains, the 3A strains, 9 group B wild-type strains, and the 2B strains. PCR specific to group A wild-type strains amplified only group A wild-type strains, and 3A-specific PCR amplified only 3A strains. PCR specific to group B wild-type strains amplified all group A and group B strains but gave a 688-bp product for group B wild-type strains, a 279-bp product for 2B strains, a 547-bp product for all group A strains, and an additional 688-bp product for some group A strains, including 3A strains. These types of PCR assays can, in conjunction with other methods, be used to efficiently distinguish candidate vaccine strains from other respiratory syncytial virus strains. PMID:8789010

The wild type as concept and in experimental practice: A history of its role in classical genetics and evolutionary theory.

PubMed

Holmes, Tarquin

2017-06-01

Wild types in genetics are specialised strains of laboratory experimental organism which principally serve as standards against which variation is measured. As selectively inbred lineages highly isolated from ancestral wild populations, there appears to be little wild or typical about them. I will nonetheless argue that they have historically been successfully used as stand-ins for nature, allowing knowledge produced in the laboratory to be extrapolated to the natural world. In this paper, I will explore the 19th century origins of the wild type concept, the theoretical and experimental innovations which allowed concepts and organisms to move from wild nature to laboratory domestication c. 1900 (resulting in the production of standardised lab strains), and the conflict among early geneticists between interactionist and atomist accounts of wild type, which would eventually lead to the conceptual disintegration of wild types and the triumph of genocentrism and population genetics. I conclude by discussing how the strategy of using wild type strains to represent nature in the lab has nonetheless survived the downfall of the wild type concept and continues to provide, significant limitations acknowledged, an epistemically productive means of investigating heredity and evolutionary variation. Copyright © 2017 Elsevier Ltd. All rights reserved.

A radiographic study of permanent molar development in wild Virunga mountain gorillas of known chronological age from Rwanda.

PubMed

Kralick, Alexandra E; Loring Burgess, M; Glowacka, Halszka; Arbenz-Smith, Keely; McGrath, Kate; Ruff, Christopher B; Chan, King Chong; Cranfield, Michael R; Stoinski, Tara S; Bromage, Timothy G; Mudakikwa, Antoine; McFarlin, Shannon C

2017-05-01

While dental development is important to life history investigations, data from wild known-aged great apes are scarce. We report on the first radiographic examination of dental development in wild Virunga mountain gorillas, using known-age skeletal samples recovered in Rwanda. In 43 individuals (0.0-14.94 years), we collected radiographs of mandibular molars, and where possible, cone beam CT scans. Molar crown and root calcification status was assessed using two established staging systems, and age prediction equations generated using polynomial regression. Results were compared to available data from known-age captive and wild chimpanzees. Mountain gorillas generally fell within reported captive chimpanzee distributions or exceeded them, exhibiting older ages at equivalent radiographic stages of development. Differences reflect delayed initiation and/or an extended duration of second molar crown development, and extended first and second molar root development, in mountain gorillas compared to captive chimpanzees. However, differences in the duration of molar root development were less evident compared to wild chimpanzees. Despite sample limitations, our findings extend the known range of variation in radiographic estimates of molar formation timing in great apes, and provide a new age prediction technique based on wild specimens. However, mountain gorillas do not appear accelerated in radiographic assessment of molar formation compared to chimpanzees, as they are for other life history traits. Future studies should aim to resolve the influence of species differences, wild versus captive environments, and/or sampling phenomena on patterns observed here, and more generally, how they relate to variation in tooth size, eruption timing, and developmental life history. © 2017 Wiley Periodicals, Inc.

Incidence, prevalence and seasonal onset variation of Addison's disease among persons with type 1 diabetes mellitus: nationwide, matched cohort studies.

PubMed

Chantzichristos, Dimitrios; Persson, Anders; Eliasson, Björn; Miftaraj, Mervete; Franzén, Stefan; Svensson, Ann-Marie; Johannsson, Gudmundur

2018-01-01

We determined the incidence and prevalence of Addison's disease (AD) among persons with or without type 1 diabetes mellitus (T1DM) in nationwide, matched cohort studies. Persons with T1DM were identified from the Swedish National Diabetes Register and each was matched for age, sex, year and county to five controls randomly selected from the general population. Persons with AD were identified from the Swedish National Inpatient Register. Baseline demographics and seasonal onset variation of AD were presented by descriptive statistics. Prevalence and incidence were estimated by proportions and incidence rates, respectively. Times to AD were analyzed using the Cox proportional hazard model. Between 1998 and 2013, 66 persons with T1DM were diagnosed with AD at a mean age (s.d.) of 36.4 (13.0) years among 36 514 persons with T1DM, while 32 were diagnosed with AD at a mean age of 42.7 (15.2) years among 182 570 controls. The difference in mean age at diagnosis of AD between the groups was 6.3 years ( P value = 0.036). The incidence of AD for a person with or without T1DM was therefore 193 and 18 per million person-years, respectively. The adjusted relative risk increase of developing AD in T1DM was 10.8 (95% CI: 7.1-16.5). The highest incidence of AD was observed during February-March and September-October. The prevalence of AD in persons with or without T1DM in December 2012 was 3410 and 208 per million, respectively. The odds ratio for AD in persons with T1DM vs controls was 16.5 (95% CI: 11.1-24.5). The risk to develop AD among persons with T1DM is more than 10 times higher than in persons without T1DM. Persons with T1DM develop AD at a younger age. The incidence of AD may have a seasonal pattern. © 2018 European Society of Endocrinology.

Abuse and deliberate self-poisoning in women: a matched case-control study.

PubMed

Coll, X; Law, F; Tobías, A; Hawton, K; Tomàs, J

2001-10-01

Controlled studies have shown deliberate self-harm to be more common in abused populations, but no controlled studies have shown abuse to be more common in self-harming populations. This is the first controlled study to determine whether abuse experiences (sexual, physical, and psychological) occurred more commonly in women who take overdoses than in controls. The design was a matched (1:1) case-control study set in a district general hospital in England. The subjects were 36 women admitted following deliberate self-poisoning. They were matched with the next non-overdose admission to the same hospital on six variables (sex, age, ethnicity, social class, marital status, and geographical locality). The main outcome measures used were modified versions of standardized self-report questionnaires of sexual, physical, and psychological abuse, together with measures of parenting style and general psychopathology. Women who had taken an overdose were more likely (odds ratio 15.0, 95% confidence interval 2.0 to 113.6) to have been sexually abused, and somewhat more likely to have been psychologically (1.02, 1.00 to 1.05) but not physically abused. They also had higher measures of psychopathology (GHQ-30: 1.19, 1.07 to 1.31), were more likely to have been abused at a younger age, exposed to the "affectionless control" style of parenting by their mothers, and to have harmed themselves in other ways. The management of women presenting to hospital after self-poisoning should include assessment of abuse experiences, and instigation of appropriate treatment in those with significant sequelae of abuse.

BACHD rats expressing full-length mutant huntingtin exhibit differences in social behavior compared to wild-type littermates

PubMed Central

Manfré, Giuseppe; Novati, Arianna; Faccini, Ilaria; Rossetti, Andrea C.; Bosch, Kari; Molteni, Raffaella; Riva, Marco A.; Van der Harst, Johanneke E.; Homberg, Judith R.

2018-01-01

Background Huntington disease (HD) is a devastating inherited neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms without any cure to slow down or stop the progress of the disease. The BACHD rat model for HD carrying the human full-length mutant huntingtin protein (mHTT) with 97 polyQ repeats has been recently established as a promising model which reproduces several HD-like features. While motor and cognitive functions have been characterized in BACHD rats, little is known about their social phenotype. Objective This study focuses especially on social behavior since evidence for social disturbances exists in human patients. Our objective was to compare social behavior in BACHD and wild-type (WT) rats at different ages, using two different measures of sociability. Methods Animals were tested longitudinally at the age of 2, 4 and 8 months in the social interaction test to examine different parameters of sociability. A separate cohort of 7 month old rats was tested in the three chamber social test to measure both sociability and social novelty. Gene expression analyses in 8 months old animals were performed by real time qRT-PCR to evaluate a potential involvement of D1 and D2 dopaminergic receptors and the contribution of Brain-derived neurotrophic factor (BDNF) to the observed behavioral alterations. Results In the social interaction test, BACHD rats showed age-dependent changes in behaviour when they were-re introduced to their cagemate after a 24 hours-period of individual housing. The time spent on nape attacks increased with aging. Furthermore, a significant higher level of pinning at 2 months of age was shown in the BACHD rats compared to wild-types, followed by a reduction at 4 and 8 months. On the other hand, BACHD rats exhibited a decreased active social behaviour compared to wild-types, reflected by genotype-effects on approaching, following and social nose contact. In the three chamber social test, BACHD rats

Synergistic effects of acyclovir and 3, 19-isopropylideneandrographolide on herpes simplex virus wild types and drug-resistant strains.

PubMed

Priengprom, Thongkoon; Ekalaksananan, Tipaya; Kongyingyoes, Bunkerd; Suebsasana, Supawadee; Aromdee, Chantana; Pientong, Chamsai

2015-03-11

An andrographolide analogue, 3, 19-isopropylideneandrographolide (IPAD), exerts an inhibitory effect on replication of wild-type herpes simplex virus serotype 1 (HSV-1). In this study, we examined the anti-viral activity of IPAD on HSV wild types (HSV-1 strain KOS and HSV-2 clinical isolate) and HSV-1 drug-resistant strains (DRs). Synergistic effects of IPAD with acyclovir (ACV) were also evaluated. MTT and cytopathic effect (CPE) reduction assays were performed to determine cytotoxicity and anti-viral activities, respectively. A combination assay was used to determine synergistic effects of IPAD and ACV. Presence of viral DNA and protein in experimental cells was investigated using the polymerase chain reaction and western blotting, respectively. A non-cytotoxic concentration of IPAD (20.50 μM) completely inhibited CPE formation induced by HSV wild types and HSV-1 DRs after viral entry into the cells. The anti-HSV activities included inhibition of viral DNA and protein synthesis. The minimum inhibitory concentrations of ACV for HSV wild types and HSV-1 DRs were 20.20 and 2,220.00 μM, respectively. Combination of ACV with IPAD showed synergistic effects in inhibition of CPE formation, viral DNA and protein synthesis by HSV wild types as well as HSV-1 DRs. For the synergistic effects on HSV wild types and HSV-1 DRs, the effective concentrations of ACV were reduced. These results showed the inhibitory potential of IPAD on HSV wild types and HSV-1 DRs and suggested that IPAD could be used in combination with ACV for treatment of HSV-1 DRs infections.

Do age-specific survival patterns of wild boar fit current evolutionary theories of senescence?

PubMed

Gamelon, Marlène; Focardi, Stefano; Gaillard, Jean-Michel; Gimenez, Olivier; Bonenfant, Christophe; Franzetti, Barbara; Choquet, Rémi; Ronchi, Francesca; Baubet, Eric; Lemaître, Jean-François

2014-12-01

Actuarial senescence is widespread in age-structured populations. In growing populations, the progressive decline of Hamiltonian forces of selection with age leads to decreasing survival. As actuarial senescence is overcompensated by a high fertility, actuarial senescence should be more intense in species with high reproductive effort, a theoretical prediction that has not been yet explicitly tested across species. Wild boar (Sus scrofa) females have an unusual life-history strategy among large mammals by associating both early and high reproductive effort with potentially long lifespan. Therefore, wild boar females should show stronger actuarial senescence than similar-sized related mammals. Moreover, being polygynous and much larger than females, males should display higher senescence rates than females. Using a long-term monitoring (18 years) of a wild boar population, we tested these predictions. We provided clear evidence of actuarial senescence in both sexes. Wild boar females had earlier but not stronger actuarial senescence than similar-sized ungulates. Both sexes displayed similar senescence rates. Our study indicates that the timing of senescence, not the rate, is associated with the magnitude of fertility in ungulates. This demonstrates the importance of including the timing of senescence in addition to its rate to understand variation in senescence patterns in wild populations. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Type, number or both? A population-based matched case-control study on the risk of fall injuries among older people and number of medications beyond fall-inducing drugs.

PubMed

Laflamme, Lucie; Monárrez-Espino, Joel; Johnell, Kristina; Elling, Berty; Möller, Jette

2015-01-01

Drug use is a modifiable risk factor for fall-related injuries in older people. Whereas the injurious effect of polypharmacy is established, that of low numbers of medications has not been fully ascertained. Neither do we know whether it is the number per se or the type of medications that actually matters. We assessed this question for fall injuries leading to hospitalization. National register-based, population-based, matched case-control study. Community dwellers aged 65+ years living in Sweden between March 2006 and December 2009. Cases (n = 64,399) were identified in the national inpatient register and four controls per case were randomly matched by gender, date of birth and residential area. The association between number of prescribed medications, assessed through linkage with the Swedish prescribed drug register, and the risk of injurious falls was estimated with odds ratios with 95% confidence intervals using conditional logistic regression, adjusted for demographic and health status. The number of medications was associated with an increased risk of fall injury in a dose-response fashion, even after adjustment for marital status, comorbidity and number of fall-risk-inducing drugs (FRIDs). Using ten or more medications was associated with an almost two-fold higher risk (adjusted OR: 1.76, 95% CI: 1.66 to 1.88). When stratified by use (or not) of at least one FRID, the association weakened slightly among both non-users (adjusted OR: 1.50, 95% CI: 1.34 to 1.67) and users (adjusted OR: 1.67, 95% CI: 1.58 to 1.77). In older people, not only large but also small numbers of medications may affect the risk for them to sustain injurious falls. Although the mechanisms lying behind this are complex, the finding challenges the prevention strategies targeting either specific types of medications (FRIDs) or high numbers of them.

Early Alzheimer's disease-type pathology in the frontal cortex of wild mountain gorillas (Gorilla beringei beringei).

PubMed

Perez, Sylvia E; Sherwood, Chet C; Cranfield, Michael R; Erwin, Joseph M; Mudakikwa, Antoine; Hof, Patrick R; Mufson, Elliott J

2016-03-01

Amyloid beta (Aβ) and tau pathology have been described in the brains of captive aged great apes, but the natural progression of these age-related pathologies from wild great apes, including the gorilla, is unknown. In our previous study of Western lowland gorillas (Gorilla gorilla gorilla) who were housed in American Zoos and Aquariums-accredited facilities, we found an age-related increase in Aβ-positive plaques and vasculature, tau-positive astrocytes, oligodendrocyte coiled bodies, and neuritic clusters in the neocortex as well as hippocampus in older animals. Here, we demonstrate that aged wild mountain gorillas (Gorilla beringei beringei), who spent their entire lives in their natural habitat, also display an age-related increase in amyloid precursor protein (APP) and/or Aβ-immunoreactive blood vessels and plaques, but very limited tau pathology, in the frontal cortex. These results indicate that Aβ and tau lesions are age-related events that occur in the brain of gorillas living in captivity and in the wild. Copyright © 2016 Elsevier Inc. All rights reserved.

Involvement of overexpressed wild-type BRAF in the growth of malignant melanoma cell lines.

PubMed

Tanami, Hideaki; Imoto, Issei; Hirasawa, Akira; Yuki, Yasuhiro; Sonoda, Itaru; Inoue, Jun; Yasui, Kohichiro; Misawa-Furihata, Akiko; Kawakami, Yutaka; Inazawa, Johji

2004-11-18

Comparative genomic hybridization (CGH) using 40 cell lines derived from malignant melanomas (MMs) revealed frequent amplification at 7q33-q34 containing BRAF gene, which often is mutated in MM. We found this gene to be amplified to a remarkable degree in the MM cell lines that exhibited high-level gains at 7q33-q34 in CGH. Among 40 cell lines, the eight lines that revealed neither BRAF nor NRAS mutations showed even higher levels of BRAF mRNA expression than the 32 mutated lines, although DNA amplification at 7q33-q34 was not detected in every lines overexpressing BRAF. MM cells that carried wild-type BRAF and NRAS showed constitutive overexpression of B-Raf protein and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), even after serum starvation. Not only downregulation of the endogenously overexpressed wild-type B-Raf by antisense oligonucleotide but also a treatment with an inhibitor of mitogen-activated protein kinase kinase (MAPKK, MEK) reduced phosphorylated ERK1/2 and cell growth, whereas the exogenously expressed wild-type B-Raf promoted cell growth in MM cells. Our results provide the evidence that overexpression of wild-type B-Raf, in part but not always as a result of gene amplification, is one of the mechanisms underlying constitutive activation of the MAPK pathway that stimulates growth of MM cells.

Terpenoid Metabolism in Wild-Type and Transgenic Arabidopsis PlantsW⃞

PubMed Central

Aharoni, Asaph; Giri, Ashok P.; Deuerlein, Stephan; Griepink, Frans; de Kogel, Willem-Jan; Verstappen, Francel W. A.; Verhoeven, Harrie A.; Jongsma, Maarten A.; Schwab, Wilfried; Bouwmeester, Harro J.

2003-01-01

Volatile components, such as terpenoids, are emitted from aerial parts of plants and play a major role in the interaction between plants and their environment. Analysis of the composition and emission pattern of volatiles in the model plant Arabidopsis showed that a range of volatile components are released, primarily from flowers. Most of the volatiles detected were monoterpenes and sesquiterpenes, which in contrast to other volatiles showed a diurnal emission pattern. The active terpenoid metabolism in wild-type Arabidopsis provoked us to conduct an additional set of experiments in which transgenic Arabidopsis overexpressing two different terpene synthases were generated. Leaves of transgenic plants constitutively expressing a dual linalool/nerolidol synthase in the plastids (FaNES1) produced linalool and its glycosylated and hydroxylated derivatives. The sum of glycosylated components was in some of the transgenic lines up to 40- to 60-fold higher than the sum of the corresponding free alcohols. Surprisingly, we also detected the production and emission of nerolidol, albeit at a low level, suggesting that a small pool of its precursor farnesyl diphosphate is present in the plastids. Transgenic lines with strong transgene expression showed growth retardation, possibly as a result of the depletion of isoprenoid precursors in the plastids. In dual-choice assays with Myzus persicae, the FaNES1-expressing lines significantly repelled the aphids. Overexpression of a typical cytosolic sesquiterpene synthase resulted in the production of only trace amounts of the expected sesquiterpene, suggesting tight control of the cytosolic pool of farnesyl diphosphate, the precursor for sesquiterpenoid biosynthesis. This study further demonstrates the value of Arabidopsis for studies of the biosynthesis and ecological role of terpenoids and provides new insights into their metabolism in wild-type and transgenic plants. PMID:14630967

Effects of fibre type and kefir, wine lemon, and pineapple marinades on texture and sensory properties of wild boar and deer longissimus muscle.

PubMed

Żochowska-Kujawska, J; Lachowicz, K; Sobczak, M

2012-12-01

Fibre type percentage and changes in textural parameters, sensory properties as well as mean fibre cross sectional area (CSA), fibre shape, endomysium and perimysium thickness of wild boar and deer longissimus (L) muscle subjected to ageing with kefir, dry red wine, lemon and pineapple juice marinades for 4 days were studied. Among the non-marinated and non-aged samples of muscles it was found that wild boar meat with its higher percentage of red fibres, higher CSA, thicker connective tissue as compared with deer meat, was harder, more springy and stringy. Muscles ageing, regardless of methods, resulted in a decrease in both the CSA and thickness of the connective tissue, and improve in fibre shape. As a consequence ageing caused a reduction in hardness, cohesiveness, springiness, and stringiness as well as in augmentation of tenderness, juiciness and general attractiveness of the muscles studied. As demonstrated by obtained data, regardless of ageing methods, deer L muscle contained more white fibres compared to wild boar muscle, were more susceptible to tenderization. The highest structural and textural changes, but the worst general attractiveness was found in muscles marinated with pineapple juice addition. Insignificantly lower changes in both quality traits were found in muscles aged with kefir marinade which at the same time were characterized by the high tenderness, the highest juiciness and general attractiveness. Copyright © 2012 Elsevier Ltd. All rights reserved.

Wild-type MIC distributions for aminoglycoside and cyclic polypeptide antibiotics used for treatment of Mycobacterium tuberculosis infections.

PubMed

Juréen, P; Angeby, K; Sturegård, E; Chryssanthou, E; Giske, C G; Werngren, J; Nordvall, M; Johansson, A; Kahlmeter, G; Hoffner, S; Schön, T

2010-05-01

The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug-resistant tuberculosis, underscoring the need for accurate and reproducible drug susceptibility testing (DST). The epidemiological cutoff value (ECOFF) separating wild-type susceptible strains from non-wild-type strains is an important but rarely used tool for indicating susceptibility breakpoints against Mycobacterium tuberculosis. In this study, we established wild-type MIC distributions on Middlebrook 7H10 medium for amikacin, kanamycin, streptomycin, capreomycin, and viomycin using 90 consecutive clinical isolates and 21 resistant strains. Overall, the MIC variation between and within runs did not exceed +/-1 MIC dilution step, and validation of MIC values in Bactec 960 MGIT demonstrated good agreement. Tentative ECOFFs defining the wild type were established for all investigated drugs, including amikacin and viomycin, which currently lack susceptibility breakpoints for 7H10. Five out of seven amikacin- and kanamycin-resistant isolates were classified as susceptible to capreomycin according to the current critical concentration (10 mg/liter) but were non-wild type according to the ECOFF (4 mg/liter), suggesting that the critical concentration may be too high. All amikacin- and kanamycin-resistant isolates were clearly below the ECOFF for viomycin, and two of them were below the ECOFF for streptomycin, indicating that these two drugs may be considered for treatment of amikacin-resistant strains. Pharmacodynamic indices (peak serum concentration [Cmax]/MIC) were more favorable for amikacin and viomycin compared to kanamycin and capreomycin. In conclusion, our data emphasize the importance of establishing wild-type MIC distributions for improving the quality of drug susceptibility testing against Mycobacterium tuberculosis.

Vaccination Against Porcine Circovirus-2 Reduces Severity of Tuberculosis in Wild Boar.

PubMed

Risco, David; Bravo, María; Martínez, Remigio; Torres, Almudena; Gonçalves, Pilar; Cuesta, Jesús; García-Jiménez, Waldo; Cerrato, Rosario; Iglesias, Rocío; Galapero, Javier; Serrano, Emmanuel; Gómez, Luis; Fernández-Llario, Pedro; Hermoso de Mendoza, Javier

2018-03-09

Tuberculosis (TB) in wild boar (Sus scrofa) may be affected by coinfections with other pathogens, such as porcine circovirus type 2 (PCV2). Therefore, sanitary measures focused on controlling PCV2 could be useful in reducing the impact of TB in this wild suid. The aim of this study was to explore whether vaccination against PCV2 targeting young animals affects TB prevalence and TB severity in wild boar. The study was conducted on a game estate in mid-western Spain. Seventy animals of ages ranging from 4 to 8 months were captured, individually identified, vaccinated against PCV2 and released, forming a vaccinated group. Not-captured animals cohabiting with the vaccinated wild boar constituted the control group. Animals from both groups were hunted between 2013 and 2016 and a TB diagnosis based on pathological assessment and microbiological culture was made in all of them. The effect of PCV2 vaccination on TB prevalence and severity was explored using generalized lineal models. Whereas TB prevalence was similar in vaccinated and control groups (54.55 vs. 57.78%), vaccinated animals showed less probabilities to develop generalized TB lesions. Furthermore, mean TB severity score was significantly lower in vaccinated animals (1.55 vs. 2.42) suggesting a positive effect of PCV2 vaccination.

High dietary cholesterol masks type 2 diabetes-induced osteopenia and changes in bone microstructure in rats.

PubMed

Lapmanee, Sarawut; Charoenphandhu, Narattaphol; Aeimlapa, Ratchaneevan; Suntornsaratoon, Panan; Wongdee, Kannikar; Tiyasatkulkovit, Wacharaporn; Kengkoom, Kanchana; Chaimongkolnukul, Khuanjit; Seriwatanachai, Dutmanee; Krishnamra, Nateetip

2014-10-01

Type 2 diabetes mellitus (T2DM) often occurs concurrently with high blood cholesterol or dyslipidemia. Although T2DM has been hypothesized to impair bone microstructure, several investigations showed that, when compared to age-matched healthy individuals, T2DM patients had normal or relatively high bone mineral density (BMD). Since cholesterol and lipids profoundly affect the function of osteoblasts and osteoclasts, it might be cholesterol that obscured the changes in BMD and bone microstructure in T2DM. The present study, therefore, aimed to determine bone elongation, epiphyseal histology, and bone microstructure in non-obese T2DM Goto-Kakizaki rats treated with normal (GK-ND) and high cholesterol diet. We found that volumetric BMD was lower in GK-ND rats than the age-matched wild-type controls. In histomorphometric study of tibial metaphysis, T2DM evidently suppressed osteoblast function as indicated by decreases in osteoblast surface, mineral apposition rate, and bone formation rate in GK-ND rats. Meanwhile, the osteoclast surface and eroded surface were increased in GK-ND rats, thus suggesting an activation of bone resorption. T2DM also impaired bone elongation, presumably by retaining the chondrogenic precursor cells in the epiphyseal resting zone. Interestingly, several bone changes in GK rats (e.g., increased osteoclast surface) disappeared after high cholesterol treatment as compared to wild-type rats fed high cholesterol diet. In conclusion, high cholesterol diet was capable of masking the T2DM-induced osteopenia and changes in several histomorphometric parameters that indicated bone microstructural defect. Cholesterol thus explained, in part, why a decrease in BMD was not observed in T2DM, and hence delayed diagnosis of the T2DM-associated bone disease.

Comparison of Serum Protein Electrophoresis Values in Wild and Captive Whooping Cranes ( Grus americana ).

PubMed

Hausmann, Jennifer C; Cray, Carolyn; Hartup, Barry K

2015-09-01

Protein electrophoresis of serum samples from endangered, wild whooping cranes ( Grus americana ) was performed to help assess the health of the only self-sustaining, migratory population in North America. Serum samples from wild adult cranes (n = 22) were taken at Aransas National Wildlife Refuge, Texas, USA during winter. Wild juvenile cranes (n = 26) were sampled at Wood Buffalo National Park, Northwest Territories, Canada, in midsummer. All captive crane samples were acquired from the International Crane Foundation, Baraboo, WI, USA. Captive adult cranes (n = 30) were sampled during annual examinations, and archived serum samples from captive juvenile cranes (n = 19) were selected to match the estimated age of wild juveniles. Wild juveniles had significantly lower concentrations of all protein fractions than wild adults, except for prealbumin and γ globulins. All protein fraction concentrations for wild juveniles were significantly lower compared with captive juveniles, except for prealbumin and γ globulins, which were higher. Wild adults had significantly greater γ globulin concentrations than captive adults. Captive juveniles had significantly lower prealbumin and albumin concentrations and albumin : globulin ratios than captive adults. The higher γ globulin concentrations in wild versus captive cranes are likely because of increased antigenic exposure and immune stimulation. Protein fraction concentrations vary significantly with age and natural history in this species. Reference intervals for serum protein electrophoresis results from captive adult whooping cranes are provided in this study.

Psychosocial Health of Disease-Free Breast Cancer Survivors Compared with Matched Non-cancer Controls.

PubMed

Park, Boyoung; Lee, Moo Hyun; Kong, Sun-Young; Lee, Eun Sook

2018-04-05

The present study investigated the psychosocial health of disease-free breast cancer survivors who receive health examinations compared to matched non-cancer controls in a community setting. We used baseline data from the Health Examinee cohort, which is composed of subjects participating in health. The disease-free breast cancer survivors were defined as those who were ≥2 years from initial diagnosis of breast cancer who had completed treatment. Females without a history of cancer were randomly selected at 1:4 ratio by 5-year age groups, education, and household income as a comparison group. We analyzed results from the Psychosocial Well-being Index-Short Form (PWI-SF) as a psychosocial health measurement. A total of 347 survivors of breast cancer and 1,388 matched controls were included. Total scores on the PWI-SF were lower in breast cancer survivors than matched non-cancer controls (p=0.006), suggesting a lower level of psychosocial stress in breast cancer survivors. In comparison to the control group, prevalence of drinking, smoking and obesity were lower, while exercising for ≥150 min/wk was higher in breast cancer survivors (p < 0.05). These findings suggest that breast cancer survivors have better health behaviors than their non-cancer controls. After adjusting for other sociodemographic variables, breast cancer survivors were 36% less likely to be included in the stress group (odds ratio, 0.64; 95% confidence interval, 0.42 to 0.98). The disease-free breast cancer survivors resuming daily life demonstrated better psychosocial health status compared to matched non-cancer controls.

Host genotype and age shape the leaf and root microbiomes of a wild perennial plant

DOE PAGES

Wagner, Maggie R.; Lundberg, Derek S.; del Rio, Tijana G.; ...

2016-07-12

Bacteria living on and in leaves and roots influence many aspects of plant health, so the extent of a plant's genetic control over its microbiota is of great interest to crop breeders and evolutionary biologists. Laboratory-based studies, because they poorly simulate true environmental heterogeneity, may misestimate or totally miss the influence of certain host genes on the microbiome. Here we report a large-scale field experiment to disentangle the effects of genotype, environment, age and year of harvest on bacterial communities associated with leaves and roots of Boechera stricta (Brassicaceae), a perennial wild mustard. Host genetic control of the microbiome ismore » evident in leaves but not roots, and varies substantially among sites. Microbiome composition also shifts as plants age. Furthermore, a large proportion of leaf bacterial groups are shared with roots, suggesting inoculation from soil. Our results demonstrate how genotype-by-environment interactions contribute to the complexity of microbiome assembly in natural environments.« less

Haploinsufficiency of the Myc regulator Mtbp extends survival and delays tumor development in aging mice.

PubMed

Grieb, Brian C; Boyd, Kelli; Mitra, Ramkrishna; Eischen, Christine M

2016-10-30

Alterations of specific genes can modulate aging. Myc, a transcription factor that regulates the expression of many genes involved in critical cellular functions was shown to have a role in controlling longevity. Decreased expression of Myc inhibited many of the deleterious effects of aging and increased lifespan in mice. Without altering Myc expression, reduced levels of Mtbp, a recently identified regulator of Myc, limit Myc transcriptional activity and proliferation, while increased levels promote Myc-mediated effects. To determine the contribution of Mtbp to the effects of Myc on aging, we studied a large cohort of Mtbp heterozygous mice and littermate matched wild-type controls. Mtbp haploinsufficiency significantly increased longevity and maximal survival in mice. Reduced levels of Mtbp did not alter locomotor activity, litter size, or body size, but Mtbp heterozygous mice did exhibit elevated markers of metabolism, particularly in the liver. Mtbp +/- mice also had a significant delay in spontaneous cancer development, which was most prominent in the hematopoietic system, and an altered tumor spectrum compared to Mtbp +/+ mice. Therefore, the data suggest Mtbp is a regulator of longevity in mice that mimics some, but not all, of the properties of Myc in aging.

Factors contributing to outbreaks of wild poliovirus type 1 infection involving persons aged ≥15 years in the Democratic Republic of the Congo, 2010-2011, informed by a pre-outbreak poliovirus immunity assessment.

PubMed

Alleman, Mary M; Wannemuehler, Kathleen A; Weldon, William C; Kabuayi, Jean Pierre; Ekofo, Felly; Edidi, Samuel; Mulumba, Audry; Mbule, Albert; Ntumbannji, Renée N; Coulibaly, Tiekoura; Abiola, Nadine; Mpingulu, Minlangu; Sidibe, Kassim; Oberste, M Steven

2014-11-01

The Democratic Republic of the Congo (DRC) experienced atypical outbreaks of wild poliovirus type 1 (WPV1) infection during 2010-2011 in that they affected persons aged ≥15 years in 4 (Bandundu, Bas Congo, Kasaï Occidental, and Kinshasa provinces) of the 6 provinces with outbreaks. Analyses of cases of WPV1 infection with onset during 2010-2011 by province, age, polio vaccination status, and sex were conducted. The prevalence of antibodies to poliovirus (PV) types 1, 2, and 3 was assessed in sera collected before the outbreaks from women attending antenatal clinics in 3 of the 4 above-mentioned provinces. Of 193 cases of WPV1 infection during 2010-2011, 32 (17%) occurred in individuals aged ≥15 years. Of these 32 cases, 31 (97%) occurred in individuals aged 16-29 years; 9 (28%) were notified in Bandundu, 17 (53%) were notified in Kinshasa, and 22 (69%) had an unknown polio vaccination status. In the seroprevalence assessment, PV type 1 and 3 seroprevalence was lower among women aged 15-29 years in Bandundu and Kinshasa, compared with those in Kasaï Occidental. Seropositivity to PVs was associated with increasing age, more pregnancies, and a younger age at first pregnancy. This spatiotemporal analysis strongly suggests that the 2010-2011 outbreaks of WPV1 infection affecting young adults were caused by a PV type 1 immunity gap in Kinshasa and Bandundu due to insufficient exposure to PV type 1 through natural infection or vaccination. Poliovirus immunity gaps in this age group likely persist in DRC. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Comparison of polysomnographic data in age-, sex- and Axis I psychiatric diagnosis matched HIV-seropositive and HIV-seronegative insomnia patients.

PubMed

Low, Yinghui; Goforth, Harold W; Omonuwa, Toma; Preud'homme, Xavier; Edinger, Jack; Krystal, Andrew

2012-12-01

There is a high prevalence of insomnia in HIV-seropositive patients. Insomnia is associated with poorer disease outcomes, cognitive impairment and HIV-associated dementia. However there is limited data characterizing the type of sleep disturbances, and the cause. Previous studies report conflicting results, and observed changes in the distribution of REM and SWS were hypothesized to result from co-morbid mood disorders, although this is not established. We carried out this study to determine if there are differences in polysomnographic (PSG) sleep data in age-, sex- and Axis I diagnoses- matched HIV-seropositive and HIV-seronegative patients. Eighteen HIV-seropositive insomniacs were matched to HIV-seronegative insomniacs based on age, sex and Axis I diagnoses. Participants spent 2 consecutive nights in a sleep lab recording of PSG data. Multivariate analysis revealed an overall significant match-by-variable interaction (p=0.0126). Follow-up analysis show that compared to HIV-seronegative insomnia controls, HIV-seropositive insomniacs have significantly longer SOL, 8% decreased sleep efficiency, and 8-10% decreased time spent in REM sleep (p's<0.05). This study provides preliminary evidence that even after accounting for differences in age, sex and psychiatric diagnoses, HIV-seropositive patients with insomnia have significantly worse sleep than HIV-seronegative patients with insomnia. Unlike what previous authors have proposed, our results do not support the view that comorbid psychiatric disorders like depression are responsible for the observed differences in PSG findings and the greater incidence of insomnia, in HIV-seropositive patients when compared with other groups of insomnia patients. This suggests the presence of other etiologies including neuronal damage, psychosocial stressors, or comorbid medical conditions. Further studies are needed to determine the extent to which these play a role in insomnia in the HIV-seropositive population. Copyright © 2012

Genetic recombination of tick-borne flaviviruses among wild-type strains.

PubMed

Norberg, Peter; Roth, Anette; Bergström, Tomas

2013-06-05

Genetic recombination has been suggested to occur in mosquito-borne flaviviruses. In contrast, tick-borne flaviviruses have been thought to evolve in a clonal manner, although recent studies suggest that recombination occurs also for these viruses. We re-analyzed the data and found that previous conclusions on wild type recombination were probably falsely drawn due to misalignments of nucleotide sequences, ambiguities in GenBank sequences, or different laboratory culture histories suggestive of recombination events in laboratory. To evaluate if reliable predictions of wild type recombination of tick-borne flaviviruses can be made, we analyzed viral strains sequenced exclusively for this study, and other flavivirus sequences retrieved from GenBank. We detected genetic signals supporting recombination between viruses within the three clades of TBEV-Eu, TBEV-Sib and TBEV-Fe, respectively. Our results suggest that the tick-borne encephalitis viruses may undergo recombination under natural conditions, but that geographic barriers restrict most recombination events to involve only closely genetically related viruses. Copyright © 2013 Elsevier Inc. All rights reserved.

Wild-Type MIC Distributions for Aminoglycoside and Cyclic Polypeptide Antibiotics Used for Treatment of Mycobacterium tuberculosis Infections▿

PubMed Central

Juréen, P.; Ängeby, K.; Sturegård, E.; Chryssanthou, E.; Giske, C. G.; Werngren, J.; Nordvall, M.; Johansson, A.; Kahlmeter, G.; Hoffner, S.; Schön, T.

2010-01-01

The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug-resistant tuberculosis, underscoring the need for accurate and reproducible drug susceptibility testing (DST). The epidemiological cutoff value (ECOFF) separating wild-type susceptible strains from non-wild-type strains is an important but rarely used tool for indicating susceptibility breakpoints against Mycobacterium tuberculosis. In this study, we established wild-type MIC distributions on Middlebrook 7H10 medium for amikacin, kanamycin, streptomycin, capreomycin, and viomycin using 90 consecutive clinical isolates and 21 resistant strains. Overall, the MIC variation between and within runs did not exceed ±1 MIC dilution step, and validation of MIC values in Bactec 960 MGIT demonstrated good agreement. Tentative ECOFFs defining the wild type were established for all investigated drugs, including amikacin and viomycin, which currently lack susceptibility breakpoints for 7H10. Five out of seven amikacin- and kanamycin-resistant isolates were classified as susceptible to capreomycin according to the current critical concentration (10 mg/liter) but were non-wild type according to the ECOFF (4 mg/liter), suggesting that the critical concentration may be too high. All amikacin- and kanamycin-resistant isolates were clearly below the ECOFF for viomycin, and two of them were below the ECOFF for streptomycin, indicating that these two drugs may be considered for treatment of amikacin-resistant strains. Pharmacodynamic indices (peak serum concentration [Cmax]/MIC) were more favorable for amikacin and viomycin compared to kanamycin and capreomycin. In conclusion, our data emphasize the importance of establishing wild-type MIC distributions for improving the quality of drug susceptibility testing against Mycobacterium tuberculosis. PMID:20237102

Effects of gene deletion of the tissue inhibitor of the matrix metalloproteinase-type 1 (TIMP-1) on left ventricular geometry and function in mice

NASA Technical Reports Server (NTRS)

Roten, L.; Nemoto, S.; Simsic, J.; Coker, M. L.; Rao, V.; Baicu, S.; Defreyte, G.; Soloway, P. J.; Zile, M. R.; Spinale, F. G.

2000-01-01

Alterations in the expression and activity of the matrix metalloproteinases (MMPs) and the tissue inhibitors of the MMPs (TIMPs) have been implicated in tissue remodeling in a number of disease states. One of the better characterized TIMPs, TIMP-1, has been shown to bind to active MMPs and to regulate the MMP activational process. The goal of this study was to determine whether deletion of the TIMP-1 gene in mice, which in turn would remove TIMP-1 expression in LV myocardium, would produce time-dependent effects on LV geometry and function. Age-matched sibling mice (129Sv) deficient in the TIMP-1 gene (TIMP-1 knock-out (TIMP-1 KO), n=10) and wild-type mice (n=10) underwent comparative echocardiographic studies at 1 and 4 months of age. LV catheterization studies were performed at 4 months and the LV harvested for histomorphometric studies. LV end-diastolic volume and mass increased (18+/-4 and 38+/-3%, respectively, P<0.05) at 4 months in the TIMP-1 KO group; a significant increase compared to wild-type controls (P<0.05). At 4 months, LV and end-diastolic wall stress was increased by over two-fold in the TIMP-1 KO compared to wild type (P<0.05). However, LV systolic pressure and ejection performance were unchanged in the two groups of mice. LV myocyte cross-sectional area was unchanged in the TIMP-1 KO mice compared to controls, but myocardial fibrillar collagen content was reduced. Changes in LV geometry occurred in TIMP-1 deficient mice and these results suggest that constitutive TIMP-1 expression participates in the maintenance of normal LV myocardial structure. Copyright 2000 Academic Press.

Combining matched and unmatched control groups in case-control studies.

PubMed

le Cessie, Saskia; Nagelkerke, Nico; Rosendaal, Frits R; van Stralen, Karlijn J; Pomp, Elisabeth R; van Houwelingen, Hans C

2008-11-15

Multiple control groups in case-control studies are used to control for different sources of confounding. For example, cases can be contrasted with matched controls to adjust for multiple genetic or unknown lifestyle factors and simultaneously contrasted with an unmatched population-based control group. Inclusion of different control groups for a single exposure analysis yields several estimates of the odds ratio, all using only part of the data. Here the authors introduce an easy way to combine odds ratios from several case-control analyses with the same cases. The approach is based upon methods used for meta-analysis but takes into account the fact that the same cases are used and that the estimated odds ratios are therefore correlated. Two ways of estimating this correlation are discussed: sandwich methodology and the bootstrap. Confidence intervals for the pooled estimates and a test for checking whether the odds ratios in the separate case-control studies differ significantly are derived. The performance of the method is studied by simulation and by applying the methods to a large study on risk factors for thrombosis, the MEGA Study (1999-2004), wherein cases with first venous thrombosis were included with a matched control group of partners and an unmatched population-based control group.

Real-world surgical outcomes of a gelatin-hemostatic matrix in women requiring a hysterectomy: a matched case-control study.

PubMed

Obermair, Helena; Janda, Monika; Obermair, Andreas

2016-09-01

The aim of this study was to compare adverse events and surgical outcomes of hysterectomy with or without use of a gelatin-hemostatic matrix (SURGIFLO(®) ). Prospective case-control study (Canadian Task Force classification II2) of total hysterectomy (Piver Type 1) provided by surgeons in Australia between November 2005 and May 2015. Data were collected via SurgicalPerformance, a web-based data project which aims to provide confidential feedback to surgeons about their surgical outcomes. Of 2440 records of women who received a hysterectomy, 1351 were eligible for these analyses; 107 received SURGIFLO(®) hemostatic matrix to prevent postoperative blood loss and 1244 did not. Patients with or without SURGIFLO(®) differed in age, Charlson comorbidity index, and American Society of Anesthesiologists physical status classification system score (ASA), and also differed in clinical outcomes. After matching for patient's age and ASA at surgery, patients with and without SURGIFLO(®) had comparable baseline characteristics. Matched patients with and without SURGIFLO(®) had comparable clinical outcomes including risk of developing vault hematoma, return to the operating room, transfusion of red cells, surgical site infection (pelvis), readmission within 30 days and unplanned ICU admission. In a sample matched by age and ASA, SURGIFLO(®) neither prevented nor caused additional adverse events in women undergoing hysterectomy. Surgeons used SURGIFLO(®) more commonly among women who were older, had more comorbidities and a higher ASA score. This indicates that it may be most useful in complicated surgery or cases. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Impact of bariatric surgery on clinical depression. Interrupted time series study with matched controls.

PubMed

Booth, Helen; Khan, Omar; Prevost, A Toby; Reddy, Marcus; Charlton, Judith; Gulliford, Martin C

2015-03-15

Obesity is associated with depression. This study aimed to evaluate whether clinical depression is reduced after bariatric surgery (BS). Obese adults who received BS procedures from 2002 to 2014 were sampled from the UK Clinical Practice Research Datalink. An interrupted time series design, with matched controls, was conducted from three years before, to a maximum of seven years after surgery. Controls were matched for body mass index (BMI), age, gender and year of procedure. Clinical depression was defined as a medical diagnosis recorded in year, or an antidepressant prescribed in year to a participant ever diagnosed with depression. Adjusted odds ratios (AOR) were estimated. There were 3045 participants (mean age 45.9; mean BMI 44.0kg/m(2)) who received BS, including laparoscopic gastric banding in 1297 (43%), gastric bypass in 1265 (42%), sleeve gastrectomy in 477 (16%) and six undefined. Before surgery, 36% of BS participants, and 21% of controls, had clinical depression; between-group AOR, 2.02, 95%CI 1.75-2.33, P<0.001. In the second post-operative year 32% had depression; AOR, compared to time without surgery, 0.83 (0.76-0.90, P<0.001). By the seventh year, the prevalence of depression increased to 37%; AOR 0.99 (0.76-1.29, P=0.959). Despite matching there were differences in depression between BS and control patients, representing the highly selective nature of BS. Depression is frequent among individuals selected to undergo bariatric surgery. Bariatric surgery may be associated with a modest reduction in clinical depression over the initial post-operative years but this is not maintained. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Biomass productivities in wild type and pigment mutant of Cyclotella sp. (Diatom).

PubMed

Huesemann, Michael H; Hausmann, Tom S; Bartha, Richard; Aksoy, M; Weissman, Joseph C; Benemann, John R

2009-06-01

Microalgae are expected to play a significant role in greenhouse gas mitigation because they can utilize CO(2) from power plant flue gases directly while producing a variety of renewable carbon-neutral biofuels. In order for such a microalgal climate change mitigation strategy to become economically feasible, it will be necessary to significantly improve biomass productivities. One approach to achieve this objective is to reduce, via mutagenesis, the number of light-harvesting pigments, which, according to theory, should significantly improve the light utilization efficiency, primarily by increasing the light intensity at which photosynthesis saturates (I(s)). Employing chemical (ethylmethylsulfonate) and UV mutagenesis of a wild-type strain of the diatom Cyclotella, approximately 10,000 pigment mutants were generated, and two of the most promising ones (CM1 and CM1-1) were subjected to further testing in both laboratory cultures and outdoor ponds. Measurements of photosynthetic oxygen production rates as a function of light intensity (i.e., P-I curves) of samples taken from laboratory batch cultures during the exponential and linear growth phase indicated that the light intensity at which photosynthesis saturates (I(s)) was two to three times greater in the pigment mutant CM1-1 than in the wild type, i.e., 355-443 versus 116-169 mumol/m(2) s, respectively. While theory, i.e., the Bush equation, predicts that such a significant gain in I(s) should increase light utilization efficiencies and thus biomass productivities, particularly at high light intensities, no improvements in biomass productivities were observed in either semi-continuous laboratory cultures or outdoor ponds. In fact, the maximum biomass productivity in semi-continuous laboratory culture was always greater in the wild type than in the mutant, namely 883 versus 725 mg/L day, respectively, at low light intensity (200 micromol/m(2) s) and 1,229 versus 1,043 mg/L day, respectively, at high light

Molecular Characterization of Wild Type Measles Virus from Adult Patients in Northern China, 2014.

PubMed

Xu, Wen; Zhang, Ming-Xiang; Qin, En-Qiang; Yan, Ying-Chun; Li, Feng-Yi; Xu, Zhe; Tian, Xia; Fan, Rong; Tu, Bo; Chen, Wei-Wei; Zhao, Min

2016-04-01

In this study, we studied the N and H genes from wild type measles viruses (MeVs) isolated during the 2013-2014 outbreak. Clinical samples were collected, and the genotyping, phylogenetic analysis were performed. The vaccination rate of the study population was 4%. Genotype H1a was the predominant genotype. Wild type viruses were classified into clusters A and B, C and may have different origins. N-450 sequences from wild type viruses were highly homologous with, and likely evolved from MeVs circulating in Tianjing and Henan in 2012. MVs/Shenyang.CHN/18.14/3 could have evolved from MeVs from Liaoning, Beijing, Hebei, Heilongjiang, Henan, Jilin, and Tianjin. Our data suggested that one or more of the same viruses circulated between Beijing, Shenyang, Hong Kong, Taiwan and Berlin. Important factors contributing to outbreaks could include weak vaccination coverage, poor vaccination strategies, and migration of adult workers between cities, countries, and from rural areas to urban areas. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The neuropathology observed in wild-type mice inoculated with human poliovirus mirrors human paralytic poliomyelitis.

PubMed

Ford, Dayton J; Ropka, Stacie L; Collins, George H; Jubelt, Burk

2002-09-01

Human paralytic poliomyelitis results from the destruction of spinal cord anterior horn motor neurons by human poliovirus (PV). CNS disease pathology similar to human poliomyelitis has been observed in experimentally infected chimpanzees, monkeys and wild-type mice. In this study we present a detailed examination of the clinical and histopathological features in the wild-type mouse after intracranial (i.c.) and novel intramuscular (i.m.) injection of poliovirus. Either route of poliovirus administration results in a clinical disease characterized predominately by flaccid paralysis. The observed histopathological features are compared with the histopathology reported for human paralytic poliomyelitis, experimentally infected chimpanzees, monkeys and transgenic mice expressing the human poliovirus receptor (hPVR). The observation of flaccid paralysis and anterior horn motor neuron destruction mirrors what is observed in human paralytic poliomyelitis. Our results suggest that the neuropathology observed in the wild-type mouse model is similar to what has been observed in both the human disease and in other experimental animal models, with the possible exception of the transgenic mouse model. The observed neuropathology of the wild-type mouse model more closely reflects what has been observed in human poliomyelitis, as well as in experimentally infected chimpanzees and monkeys, than does the hPVR transgenic mouse model. The previously reported poliovirus-induced white matter demyelinating disease was not observed.

Cost-effectiveness of first-line treatments for patients with KRAS wild-type metastatic colorectal cancer

PubMed Central

Ewara, E.M.; Zaric, G.S.; Welch, S.; Sarma, S.

2014-01-01

Background Combinations of chemotherapy regimens and monoclonal antibodies have been demonstrated to improve clinical outcomes in patients with metastatic colorectal cancer (mcrc). Although these combination treatment strategies are safe and effective in first-line treatment for mcrc, little is known about their economic consequences and resource allocation implications. In the present study, we evaluated the cost-effectiveness of bevacizumab plus folfiri, cetuximab plus folfiri, and panitumumab plus folfiri for patients with KRAS wild-type mcrc. Methods A Markov model simulated the lifetime patient outcomes and costs of each first-line treatment strategy and subsequent lines of treatment from the perspective of the health care payer in Ontario. The model was parameterized using data from the Ontario Cancer Registry, Ontario health administrative databases, and published randomized control trials. Patient outcomes were measured in quality-adjusted life years (qalys), and costs were measured in monetary terms. Costs and outcomes were both discounted at 5% and expressed in 2012 Canadian dollars. Results For mcrc patients with KRAS wild-type disease, the treatment strategy of bevacizumab plus folfiri was found to dominate the other two first-line treatment strategies. Sensitivity analyses revealed that the incremental cost-effectiveness ratio values were sensitive to the effectiveness of treatment, the costs of bevacizumab and cetuximab, and health utility values. Conclusions Evidence from Ontario showed that bevacizumab plus folfiri is the cost-effective first-line treatment strategy for patients with KRAS wild-type mcrc. The panitumumab plus folfiri and cetuximab plus folfiri options were both dominated, but the cetuximab plus folfiri strategy must be further investigated given that, in the sensitivity analyses, the cost-effectiveness of that strategy was found to be superior to that of bevacizumab plus folfiri under certain ranges of parameter values. PMID:25089105

Erlotinib for Patients with EGFR Wild-Type Metastatic NSCLC: a Retrospective Biomarkers Analysis.

PubMed

Inno, Alessandro; Di Noia, Vincenzo; Martini, Maurizio; D'Argento, Ettore; Di Salvatore, Mariantonietta; Arena, Vincenzo; Schinzari, Giovanni; Orlandi, Armando; Larocca, Luigi Maria; Cassano, Alessandra; Barone, Carlo

2018-03-20

Erlotinib is approved for the treatment of patients with EGFR mutation positive, metastatic NSCLC. It is also approved as second/third line therapy for EGFR mutation negative patients, but in this setting the benefit of erlotinib is modest and there is no validated biomarker for selecting EGFR wild-type patients who may benefit the most from the treatment. We retrospectively assessed EGFR and K-RAS mutational status, and EGFR, c-MET and IGF1-R expression in tumor samples of 72 patients with metastatic NSCLC treated with erlotinib after at least one prior line of chemotherapy, from 2008 to 2012. We analyzed the association between biomarkers and outcome (RR, PFS, and OS). EGFR mutated patients achieved a better RR (56% vs 8%, p = .002), PFS (10 vs 3 months, HR 0.53, p = 0.48) and OS (20 vs 6 months, HR 0.55, p = .07), compared to EGFR wild-type patients. Among 63 EGFR wild-type patients, those with EGFR high-expression had a better outcome in terms of RR (40% vs 2%, p = .002), PFS (7.5 vs 2 months, HR 0.45, p = .007) and OS (30 vs 5 months, HR 0.34, p < .001) compared to patients with EGFR intermediate or low/negative-expression. IGF1-R expression, c-MET expression and K-RAS mutational status did not significantly affect the outcome; however, no patients with K-RAS mutation or c-MET high-expression achieved an objective response. In patients with metastatic, chemo-refractory EGFR wild-type NSCLC, EGFR high-expression may represent a positive predictor of activity for erlotinib, whereas K-RAS mutation and c-MET high-expression may predict lack of activity. These findings deserve further prospective evaluation.

Effects of age, maturity and body dimensions on match running performance in highly trained under-15 soccer players.

PubMed

Buchheit, Martin; Mendez-Villanueva, Alberto

2014-01-01

The aim of the present study was to compare, in 36 highly trained under-15 soccer players, the respective effects of age, maturity and body dimensions on match running performance. Maximal sprinting (MSS) and aerobic speeds were estimated. Match running performance was analysed with GPS (GPSport, 1 Hz) during 19 international friendly games (n = 115 player-files). Total distance and distance covered >16 km h(-1) (D > 16 km h(-1)) were collected. Players advanced in age and/or maturation, or having larger body dimensions presented greater locomotor (Cohen's d for MSS: 0.5-1.0, likely to almost certain) and match running performances (D > 16 km h(-1): 0.2-0.5, possibly to likely) than their younger, less mature and/or smaller teammates. These age-, maturation- and body size-related differences were of larger magnitude for field test measures versus match running performance. Compared with age and body size (unclear to likely), maturation (likely to almost certainly for all match variables) had the greatest impact on match running performance. The magnitude of the relationships between age, maturation and body dimensions and match running performance were position-dependent. Within a single age-group in the present player sample, maturation had a substantial impact on match running performance, especially in attacking players. Coaches may need to consider players' maturity status when assessing their on-field playing performance.

Family with sequence similarity 83, member B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild-type epidermal growth factor receptor.

PubMed

Yamaura, Takumi; Ezaki, Junji; Okabe, Naoyuki; Takagi, Hironori; Ozaki, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Fukuhara, Mitsuro; Muto, Satoshi; Matsumura, Yuki; Hasegawa, Takeo; Hoshino, Mika; Osugi, Jun; Shio, Yutaka; Waguri, Satoshi; Tamura, Hirosumi; Imai, Jun-Ichi; Ito, Emi; Yanagisawa, Yuka; Honma, Reiko; Watanabe, Shinya; Suzuki, Hiroyuki

2018-02-01

Lung adenocarcinoma (ADC) patients with tumors that harbor no targetable driver gene mutation, such as epidermal growth factor receptor ( EGFR ) gene mutations, have unfavorable prognosis, and thus, novel therapeutic targets are required. Family with sequence similarity 83, member B ( FAM83B ) is a biomarker for squamous cell lung cancer. FAM83B has also recently been shown to serve an important role in the EGFR signaling pathway. In the present study, the molecular and clinical impact of FAM83B in lung ADC was investigated. Matched tumor and adjacent normal tissue samples were obtained from 216 patients who underwent complete lung resection for primary lung ADC and were examined for FAM83B expression using cDNA microarray analysis. The associations between FAM83B expression and clinicopathological parameters, including patient survival, were examined. FAM83B was highly expressed in tumors from males, smokers and in tumors with wild-type EGFR . Multivariate analyses further confirmed that wild-type EGFR tumors were significantly positively associated with FAM83B expression. In survival analysis, FAM83B expression was associated with poor outcomes in disease-free survival and overall survival, particularly when stratified against tumors with wild-type EGFR . Furthermore, FAM83B knockdown was performed to investigate its phenotypic effect on lung ADC cell lines. Gene silencing by FAM83B RNA interference induced growth suppression in the HLC-1 and H1975 lung ADC cell lines. FAM83B may be involved in lung ADC tumor proliferation and can be a predictor of poor survival. FAM83B is also a potential novel therapeutic target for ADC with wild-type EGFR .

Angiotensin II Type 1 Receptor-Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin.

PubMed

Uneda, Kazushi; Wakui, Hiromichi; Maeda, Akinobu; Azushima, Kengo; Kobayashi, Ryu; Haku, Sona; Ohki, Kohji; Haruhara, Kotaro; Kinguchi, Sho; Matsuda, Miyuki; Ohsawa, Masato; Minegishi, Shintaro; Ishigami, Tomoaki; Toya, Yoshiyuki; Atobe, Yoshitoshi; Yamashita, Akio; Umemura, Satoshi; Tamura, Kouichi

2017-07-27

The kidney is easily affected by aging-associated changes, including glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Particularly, renal tubulointerstitial fibrosis is a final common pathway in most forms of progressive renal disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP), which was originally identified as a molecule that binds to AT1R, is highly expressed in the kidney. Previously, we have shown that ATRAP suppresses hyperactivation of AT1R signaling, but does not affect physiological AT1R signaling. We hypothesized that ATRAP has a novel functional role in the physiological age-degenerative process, independent of modulation of AT1R signaling. ATRAP-knockout mice were used to study the functional involvement of ATRAP in the aging. ATRAP-knockout mice exhibit a normal age-associated appearance without any evident alterations in physiological parameters, including blood pressure and cardiovascular and metabolic phenotypes. However, in ATRAP-knockout mice compared with wild-type mice, the following takes place: (1) age-associated renal function decline and tubulointerstitial fibrosis are more enhanced; (2) renal tubular mitochondrial abnormalities and subsequent increases in the production of reactive oxygen species are more advanced; and (3) life span is 18.4% shorter (median life span, 100.4 versus 123.1 weeks). As a key mechanism, age-related pathological changes in the kidney of ATRAP-knockout mice correlated with decreased expression of the prosurvival gene, Sirtuin1 . On the other hand, chronic angiotensin II infusion did not affect renal sirtuin1 expression in wild-type mice. These results indicate that ATRAP plays an important role in inhibiting kidney aging, possibly through sirtuin1-mediated mechanism independent of blocking AT1R signaling, and further protecting normal life span. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Influence of different types of compression garments on exercise-induced muscle damage markers after a soccer match.

PubMed

Marqués-Jiménez, Diego; Calleja-González, Julio; Arratibel-Imaz, Iñaki; Delextrat, Anne; Uriarte, Fernando; Terrados, Nicolás

2018-01-01

There is not enough evidence of positive effects of compression therapy on the recovery of soccer players after matches. Therefore, the objective was to evaluate the influence of different types of compression garments in reducing exercise-induced muscle damage (EIMD) during recovery after a friendly soccer match. Eighteen semi-professional soccer players (24 ± 4.07 years, 177 ± 5 cm; 71.8 ± 6.28 kg and 22.73 ± 1.81 BMI) participated in this study. A two-stage crossover design was chosen. Participants acted as controls in one match and were assigned to an experimental group (compression stockings group, full-leg compression group, shorts group) in the other match. Participants in experimental groups played the match wearing the assigned compression garments, which were also worn in the 3 days post-match, for 7 h each day. Results showed a positive, but not significant, effect of compression garments on attenuating EIMD biomarkers response, and inflammatory and perceptual responses suggest that compression may improve physiological and psychological recovery.

Interaction of root gravitropism and phototropism in Arabidopsis wild-type and starchless mutants.

PubMed

Vitha, S; Zhao, L; Sack, F D

2000-02-01

Root gravitropism in wild-type Arabidopsis and in two starchless mutants, pgm1-1 and adg1-1, was evaluated as a function of light position to determine the relative strengths of negative phototropism and of gravitropism and how much phototropism affects gravitropic measurements. Gravitropism was stronger than phototropism in some but not all light positions in wild-type roots grown for an extended period, indicating that the relationship between the two tropisms is more complex than previously reported. Root phototropism significantly influenced the time course of gravitropic curvature and the two measures of sensitivity. Light from above during horizontal exposure overestimated all three parameters for all three genotypes except the wild-type perception time. At the irradiance used (80 micromol m(-2) s(-1)), the shortest periods of illumination found to exaggerate gravitropism were 45 min of continuous illumination and 2-min doses of intermittent illumination. By growing roots in circumlateral light or by gravistimulating in the dark, corrected values were obtained for each gravitropic parameter. Roots of both starchless mutants were determined to be about three times less sensitive than prior estimates. This study demonstrates the importance of accounting for phototropism in the design of root gravitropism experiments in Arabidopsis.

Interaction of root gravitropism and phototropism in Arabidopsis wild-type and starchless mutants

NASA Technical Reports Server (NTRS)

Vitha, S.; Zhao, L.; Sack, F. D.

2000-01-01

Root gravitropism in wild-type Arabidopsis and in two starchless mutants, pgm1-1 and adg1-1, was evaluated as a function of light position to determine the relative strengths of negative phototropism and of gravitropism and how much phototropism affects gravitropic measurements. Gravitropism was stronger than phototropism in some but not all light positions in wild-type roots grown for an extended period, indicating that the relationship between the two tropisms is more complex than previously reported. Root phototropism significantly influenced the time course of gravitropic curvature and the two measures of sensitivity. Light from above during horizontal exposure overestimated all three parameters for all three genotypes except the wild-type perception time. At the irradiance used (80 micromol m(-2) s(-1)), the shortest periods of illumination found to exaggerate gravitropism were 45 min of continuous illumination and 2-min doses of intermittent illumination. By growing roots in circumlateral light or by gravistimulating in the dark, corrected values were obtained for each gravitropic parameter. Roots of both starchless mutants were determined to be about three times less sensitive than prior estimates. This study demonstrates the importance of accounting for phototropism in the design of root gravitropism experiments in Arabidopsis.

Root graviresponsiveness and cellular differentiation in wild-type and a starchless mutant of Arabidopsis thaliana

NASA Technical Reports Server (NTRS)

Moore, R.

1989-01-01

Primary roots of a starchless mutant of Arabidopsis thaliana L. are strongly graviresponsive despite lacking amyloplasts in their columella cells. The ultrastructures of calyptrogen and peripheral cells in wild-type as compared to mutant seedlings are not significantly different. The largest difference in cellular differentiation in caps of mutant and wild-type roots is the relative volume of plastids in columella cells. Plastids occupy 12.3% of the volume of columella cells in wild-type seedlings, but only 3.69% of columella cells in mutant seedlings. These results indicate that: (1) amyloplasts and starch are not necessary for root graviresponsiveness; (2) the increase in relative volume of plastids that usually accompanies differentiation of columella cells is not necessary for root graviresponsiveness; and (3) the absence of starch and amyloplasts does not affect the structure of calyptrogen (i.e. meristematic) and secretory (i.e. peripheral) cells in root caps. These results are discussed relative to proposed models for root gravitropism.

Indirect Estimates of Jaw Muscle Tension in Children with Suspected Hypertonia, Children with Suspected Hypotonia, and Matched Controls

ERIC Educational Resources Information Center

Connaghan, Kathryn P.; Moore, Christopher A.

2013-01-01

Purpose: In this study, the authors compared indirect estimates of jaw-muscle tension in children with suspected muscle-tone abnormalities with age- and gender-matched controls. Method: Jaw movement and muscle activation were measured in children (ages 3 years, 11 months, to 10 years) with suspected muscle-tone abnormalities (Down syndrome or…

Annual report for 2004 wild horse research and field activities

USGS Publications Warehouse

Ransom, Jason; Singer, Francis J.; Zeigenfuss, Linda; Coates-Markle, Linda

2005-01-01

The Bureau of Land Management (BLM) and U.S. Geological Survey-Biological Resources Discipline (USGS/BRD) continued wild horse research in 2004, investigating the strategic research elements of fertility control and population estimation. Fertility control research was focused on the individual-based porcine zonae pellucid (PZP) field trials at the Pryor Mountain Wild Horse Range (WHR), Little Rock Cliffs WHR, and McCullough Peaks Wild Horse Management Area (WHMA). Aerial population estimation research was conducted on a number of western wild horse herds to test different survey techniques as applied to various habitat types and population sizes.

Bayes and empirical Bayes methods for reduced rank regression models in matched case-control studies.

PubMed

Satagopan, Jaya M; Sen, Ananda; Zhou, Qin; Lan, Qing; Rothman, Nathaniel; Langseth, Hilde; Engel, Lawrence S

2016-06-01

Matched case-control studies are popular designs used in epidemiology for assessing the effects of exposures on binary traits. Modern studies increasingly enjoy the ability to examine a large number of exposures in a comprehensive manner. However, several risk factors often tend to be related in a nontrivial way, undermining efforts to identify the risk factors using standard analytic methods due to inflated type-I errors and possible masking of effects. Epidemiologists often use data reduction techniques by grouping the prognostic factors using a thematic approach, with themes deriving from biological considerations. We propose shrinkage-type estimators based on Bayesian penalization methods to estimate the effects of the risk factors using these themes. The properties of the estimators are examined using extensive simulations. The methodology is illustrated using data from a matched case-control study of polychlorinated biphenyls in relation to the etiology of non-Hodgkin's lymphoma. © 2015, The International Biometric Society.

Individualized behavioral assessments and maternal ratings of mastery motivation in mental age-matched toddlers with and without motor delay.

PubMed

Wang, Pei-Jung; Morgan, George A; Hwang, Ai-Wen; Liao, Hua-Fang

2013-01-01

Mastery motivation is a precursor of future developmental outcomes. Evidence about whether toddlers with motor delay have lower mastery motivation is inconclusive. The purpose of this study was to examine differences between mental age-matched toddlers with and without motor delay on various mastery motivation indicators. A mental age- and sex-matched case-control study was performed. Twenty-two children with motor delay, aged 23 to 47 months, and 22 children who were developing typically, aged 15 to 29 months, were recruited. Persistence and mastery pleasure were measured with behavioral tasks that were moderately challenging for each child and with maternal ratings using the Dimensions of Mastery Questionnaire (DMQ). The DMQ was rated by each child's mother based on her perception of her child's motivation. Two types of structured tasks (a puzzle and a cause-effect toy selected to be moderately challenging for each child) were administered in a laboratory setting and recorded on videos. Paired t tests or Wilcoxon signed rank tests were used to examine group differences in persistence and mastery pleasure (α=.007, 2-tailed). Children with motor delay were rated lower on DMQ persistence than the typically developing group, but they did not show significantly lower persistence on the structured tasks. There were no significant differences in mastery pleasure between the 2 groups on either measure. Large within-sample variability on the tasks and small sample size makes subgroup analysis (eg, different severities) difficult. Toddlers with motor delay did not show lower persistence and pleasure when given tasks that were moderately challenging; however, their mothers tended to view them as having lower motivation. Clinicians and parents should provide appropriately challenging tasks to increase children's success and motivation.

The art of matching brain tissue from patients and controls for postmortem research.

PubMed

Bao, Ai-Min; Swaab, Dick F

2018-01-01

The quality of postmortem research depends strongly on a thorough clinical investigation and documentation of the patient's disorder and therapies. In addition, a systematic and professional neuropathologic investigation of both cases and controls is absolutely crucial. In the experience of the Netherlands Brain Bank (NBB), about 20% of clinical neurologic diagnoses, despite being made in first-rate clinics, have to be revised or require an extra diagnosis after a complete and thorough review by the NBB. The neuropathology examination may reveal for instance that the "controls" already have preclinical neurodegenerative alterations. In postmortem studies the patient and control groups must be matched for as many of the known confounding factors as possible. This is necessary to make the groups as similar as possible, except for the topic being investigated. Confounding factors are present before, during, and after death. They are respectively: (1) genetic background, systemic diseases, duration and gravity of illness, medicines and addictive compounds used, age, sex, gender identity, sexual orientation, circadian and seasonal fluctuations, lateralization; (2) agonal state, stress of dying; and (3) postmortem delay, freezing procedures, fixation and storage time. Consequently, a brain bank should have a large number of controls at its disposal for appropriate matching. If matching fails for some confounders, then their influence may be determined by statistical methods such as analysis of variance or regression models. Copyright © 2018 Elsevier B.V. All rights reserved.

A Caenorhabditis elegans Wild Type Defies the Temperature–Size Rule Owing to a Single Nucleotide Polymorphism in tra-3

PubMed Central

Kammenga, Jan E; Doroszuk, Agnieszka; Riksen, Joost A. G; Hazendonk, Esther; Spiridon, Laurentiu; Petrescu, Andrei-Jose; Tijsterman, Marcel; Plasterk, Ronald H. A; Bakker, Jaap

2007-01-01

Ectotherms rely for their body heat on surrounding temperatures. A key question in biology is why most ectotherms mature at a larger size at lower temperatures, a phenomenon known as the temperature–size rule. Since temperature affects virtually all processes in a living organism, current theories to explain this phenomenon are diverse and complex and assert often from opposing assumptions. Although widely studied, the molecular genetic control of the temperature–size rule is unknown. We found that the Caenorhabditis elegans wild-type N2 complied with the temperature–size rule, whereas wild-type CB4856 defied it. Using a candidate gene approach based on an N2 × CB4856 recombinant inbred panel in combination with mutant analysis, complementation, and transgenic studies, we show that a single nucleotide polymorphism in tra-3 leads to mutation F96L in the encoded calpain-like protease. This mutation attenuates the ability of CB4856 to grow larger at low temperature. Homology modelling predicts that F96L reduces TRA-3 activity by destabilizing the DII-A domain. The data show that size adaptation of ectotherms to temperature changes may be less complex than previously thought because a subtle wild-type polymorphism modulates the temperature responsiveness of body size. These findings provide a novel step toward the molecular understanding of the temperature–size rule, which has puzzled biologists for decades. PMID:17335351

Mitochondrial pathways governing stress resistance, life, and death in the fungal aging model Podospora anserina.

PubMed

Osiewacz, Heinz D; Brust, Diana; Hamann, Andrea; Kunstmann, Birgit; Luce, Karin; Müller-Ohldach, Mathis; Scheckhuber, Christian Q; Servos, Jörg; Strobel, Ingmar

2010-06-01

Work from more than 50 years of research has unraveled a number of molecular pathways that are involved in controlling aging of the fungal model system Podospora anserina. Early research revealed that wild-type strain aging is linked to gross reorganization of the mitochondrial DNA. Later it was shown that aging of P. anserina does also take place, although at a slower pace, when the wild-type specific mitochondrial DNA rearrangements do not occur. Now it is clear that a network of different pathways is involved in the control of aging. Branches of these pathways appear to be connected and constitute a hierarchical system of responses. Although cross talk between the individual pathways seems to be fundamental in the coordination of the overall system, the precise underlying interactions remain to be unraveled. Such a systematic approach aims at a holistic understanding of the process of biological aging, the ultimate goal of modern systems biology.

GPER Mediates Functional Endothelial Aging in Renal Arteries.

PubMed

Meyer, Matthias R; Rosemann, Thomas; Barton, Matthias; Prossnitz, Eric R

2017-01-01

Aging is associated with impaired renal artery function, which is partly characterized by arterial stiffening and a reduced vasodilatory capacity due to excessive generation of reactive oxygen species by NADPH oxidases (Nox). The abundance and activity of Nox depends on basal activity of the heptahelical transmembrane receptor GPER; however, whether GPER contributes to age-dependent functional changes in renal arteries is unknown. This study investigated the effect of aging and Nox activity on renal artery tone in wild-type and GPER-deficient (Gper-/-) mice (4 and 24 months old). In wild-type mice, aging markedly impaired endothelium-dependent, nitric oxide (NO)-mediated relaxations to acetylcholine, which were largely preserved in renal arteries of aged Gper-/- mice. The Nox inhibitor gp91ds-tat abolished this difference by greatly enhancing relaxations in wild-type mice, while having no effect in Gper-/- mice. Contractions to angiotensin II and phenylephrine in wild-type mice were partly sensitive to gp91ds-tat but unaffected by aging. Again, deletion of GPER abolished effects of Nox inhibition on contractile responses. In conclusion, basal activity of GPER is required for the age-dependent impairment of endothelium-dependent, NO-mediated relaxation in the renal artery. Restoration of relaxation by a Nox inhibitor in aged wild-type but not Gper-/- mice strongly supports a role for Nox-derived reactive oxygen species as the underlying cause. Pharmacological blockers of GPER signaling may thus be suitable to inhibit functional endothelial aging of renal arteries by reducing Nox-derived oxidative stress and, possibly, the associated age-dependent deterioration of kidney function. © 2017 S. Karger AG, Basel.

Clinical effects of internal fixation for ulnar styloid fractures associated with distal radius fractures: A matched case-control study.

PubMed

Sawada, Hideyoshi; Shinohara, Takaaki; Natsume, Tadahiro; Hirata, Hitoshi

2016-11-01

Ulnar styloid fractures are often associated with distal radius fractures. However, controversy exists regarding whether to treat ulnar styloid fractures. This study aimed to evaluate clinical effects of internal fixation for ulnar styloid fractures after distal radius fractures were treated with the volar locking plate system. We used prospectively collected data of distal radius fractures. 111 patients were enrolled in this study. A matched case-control study design was used. We selected patients who underwent fixation for ulnar styloid fractures (case group). Three control patients for each patient of the case group were matched on the basis of age, sex, and fracture type of distal radius fractures from among patients who did not undergo fixation for ulnar styloid fractures (control group). The case group included 16 patients (7 men, 9 women; mean age: 52.6 years; classification of ulnar styloid fractures: center, 3; base, 11; and proximal, 2). The control group included 48 patients (15 men, 33 women; mean age: 61.1 years; classification of ulnar styloid fractures: center, 10; base, 31; and proximal, 7). For radiographic examination, the volar tilt angle, radial inclination angle, and ulnar variance length were measured, and the union of ulnar styloid fractures was judged. For clinical examination, the range of motions, grip strength, Hand20 score, and Numeric Rating Scale score were evaluated. There was little correction loss for each radiological parameter of fracture reduction, and these parameters were not significantly different between the groups. The bone-healing rate of ulnar styloid fractures was significantly higher in the case group than in the control group, but the clinical results were not significantly different. We revealed that there was no need to fix ulnar styloid fractures when distal radius fractures were treated via open reduction and internal fixation with a volar locking plate system. Copyright © 2016 The Japanese Orthopaedic Association

Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

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

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron

2011-11-15

Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemicalmore » changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and

Impairment of Vision in a Mouse Model of Usher Syndrome Type III.

PubMed

Tian, Guilian; Lee, Richard; Ropelewski, Philip; Imanishi, Yoshikazu

2016-03-01

The purpose of this study was to obtain an Usher syndrome type III mouse model with retinal phenotype. Speed congenic method was used to obtain Clrn1 exon 1 knockout (Clrn1-/-) and Clrn1N48K knockin (Clrn1N48K/N48K) mice under A/J background. To study the retinal functions of these mice, we measured scotopic and photopic ERG responses. To observe if there are any structural abnormalities, we conducted light and transmission electron microscopy of fixed retinal specimens. In 3-month-old Clrn1-/- mice, scotopic b-wave amplitude was reduced by more than 25% at the light intensities from -2.2 to 0.38 log cd·s/m2, but scotopic a-wave amplitudes were comparable to those of age-matched wild type mice at all the light intensities tested. In 9-month-old Clrn1-/- mice, scotopic b-wave amplitudes were further reduced by more than 35%, and scotopic a-wave amplitude also showed a small decline as compared with wild type mice. Photopic ERG responses were comparable between Clrn1-/- and wild type mice. Those electrophysiological defects were not associated with a loss of rods. In Clrn1N48K/N48K mice, both a- and b-wave amplitudes were not discernable from those of wild type mice aged up to 10 months. Mutations that are Clrn1-/- biallelic cause visual defects when placed under A/J background. The absence of apparent rod degeneration suggests that the observed phenotype is due to functional defects, and not due to loss of rods. Biallelic Clrn1N48K/N48K mutations did not cause discernible visual defects, suggesting that Clrn1- allele is more severely dysfunctional than ClrnN48K allele.

Immune mechanisms induced by an HSV-1 mutant strain: Discrepancy analysis of the immune system gene profile in comparison with a wild-type strain.

PubMed

Zhang, Xiaolong; Jiang, Quanlong; Xu, Xingli; Wang, Yongrong; Liu, Lei; Lian, Yaru; Li, Hao; Wang, Lichun; Zhang, Ying; Jiang, Guorun; Zeng, Jieyuan; Zhang, Han; Han, Jing-Dong Jackie; Li, Qihan

2018-04-25

Herpes simplex virus is a prevalent pathogen of humans of various age groups. The fact that no prophylactic or therapeutic vaccine is currently available suggests a significant need to further investigate the immune mechanisms induced by the virus and various vaccine candidates. We previously generated an HSV-1 mutant strain, M3, with partial deletions in ul7, ul41 and LAT that produced an attenuated phenotype in mice. In the present study, we performed a comparative analysis to characterize the immune responses induced by M3 versus wild-type HSV-1 in a mouse model. Infection with wild-type HSV-1 triggered an inflammatory-dominated response and adaptive immunity suppression and was accompanied by severe pathological damage. In contrast, infection with M3 induced a systematic immune response involving full activation of both innate and adaptive immunity and was accompanied by no obvious pathological changes. Furthermore, the immune response induced by M3 protected mice from lethal challenge with wild-type strains of HSV-1 and restrained virus proliferation and impaired latency. These data are useful for further HSV-1 vaccine development using a mutant strain construction strategy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Spontaneous hepatic repopulation in transgenic mice expressing mutant human α1-antitrypsin by wild-type donor hepatocytes

PubMed Central

Ding, Jianqiang; Yannam, Govardhana R.; Roy-Chowdhury, Namita; Hidvegi, Tunda; Basma, Hesham; Rennard, Stephen I.; Wong, Ronald J.; Avsar, Yesim; Guha, Chandan; Perlmutter, David H.; Fox, Ira J.; Roy-Chowdhury, Jayanta

2011-01-01

α1-Antitrypsin deficiency is an inherited condition that causes liver disease and emphysema. The normal function of this protein, which is synthesized by the liver, is to inhibit neutrophil elastase, a protease that degrades connective tissue of the lung. In the classical form of the disease, inefficient secretion of a mutant α1-antitrypsin protein (AAT-Z) results in its accumulation within hepatocytes and reduced protease inhibitor activity, resulting in liver injury and pulmonary emphysema. Because mutant protein accumulation increases hepatocyte cell stress, we investigated whether transplanted hepatocytes expressing wild-type AAT might have a competitive advantage relative to AAT-Z–expressing hepatocytes, using transgenic mice expressing human AAT-Z. Wild-type donor hepatocytes replaced 20%–98% of mutant host hepatocytes, and repopulation was accelerated by injection of an adenovector expressing hepatocyte growth factor. Spontaneous hepatic repopulation with engrafted hepatocytes occurred in the AAT-Z–expressing mice even in the absence of severe liver injury. Donor cells replaced both globule-containing and globule-devoid cells, indicating that both types of host hepatocytes display impaired proliferation relative to wild-type hepatocytes. These results suggest that wild-type hepatocyte transplantation may be therapeutic for AAT-Z liver disease and may provide an alternative to protein replacement for treating emphysema in AAT-ZZ individuals. PMID:21505264

Spontaneous hepatic repopulation in transgenic mice expressing mutant human α1-antitrypsin by wild-type donor hepatocytes.

PubMed

Ding, Jianqiang; Yannam, Govardhana R; Roy-Chowdhury, Namita; Hidvegi, Tunda; Basma, Hesham; Rennard, Stephen I; Wong, Ronald J; Avsar, Yesim; Guha, Chandan; Perlmutter, David H; Fox, Ira J; Roy-Chowdhury, Jayanta

2011-05-01

α1-Antitrypsin deficiency is an inherited condition that causes liver disease and emphysema. The normal function of this protein, which is synthesized by the liver, is to inhibit neutrophil elastase, a protease that degrades connective tissue of the lung. In the classical form of the disease, inefficient secretion of a mutant α1-antitrypsin protein (AAT-Z) results in its accumulation within hepatocytes and reduced protease inhibitor activity, resulting in liver injury and pulmonary emphysema. Because mutant protein accumulation increases hepatocyte cell stress, we investigated whether transplanted hepatocytes expressing wild-type AAT might have a competitive advantage relative to AAT-Z-expressing hepatocytes, using transgenic mice expressing human AAT-Z. Wild-type donor hepatocytes replaced 20%-98% of mutant host hepatocytes, and repopulation was accelerated by injection of an adenovector expressing hepatocyte growth factor. Spontaneous hepatic repopulation with engrafted hepatocytes occurred in the AAT-Z-expressing mice even in the absence of severe liver injury. Donor cells replaced both globule-containing and globule-devoid cells, indicating that both types of host hepatocytes display impaired proliferation relative to wild-type hepatocytes. These results suggest that wild-type hepatocyte transplantation may be therapeutic for AAT-Z liver disease and may provide an alternative to protein replacement for treating emphysema in AAT-ZZ individuals.

Potent hydroxyl radical-scavenging activity of drought-induced type-2 metallothionein in wild watermelon.

PubMed

Akashi, Kinya; Nishimura, Noriyuki; Ishida, Yoshinori; Yokota, Akiho

2004-10-08

Wild watermelon (Citrullus lanatus sp.) has the ability to tolerate severe drought/high light stress conditions despite carrying out normal C3-type photosynthesis. Here, mRNA differential display was employed to isolate drought-responsive genes in the leaves of wild watermelon. One of the isolated genes, CLMT2, shared significant homology with type-2 metallothionein (MT) sequences from other plants. The second-order rate constant for the reaction between a recombinant CLMT2 protein and hydroxyl radicals was estimated to be 1.2 x 10(11) M(-1) s(-1), demonstrating that CLMT2 had an extraordinary high activity for detoxifying hydroxyl radicals. Moreover, hydroxyl radical-catalyzed degradation of watermelon genomic DNA was effectively suppressed by CLMT2 in vitro. This is the first demonstration of a plant MT with antioxidant properties. The results suggest that CLMT2 induction contributes to the survival of wild watermelon under severe drought/high light stress conditions. Copyright 2004 Elsevier Inc.

Ala67Thr mutation in the poliovirus receptor CD155 is a potential risk factor for vaccine and wild-type paralytic poliomyelitis.

PubMed

Kindberg, Elin; Ax, Cecilia; Fiore, Lucia; Svensson, Lennart

2009-05-01

Poliovirus infections can be asymptomatic or cause severe paralysis. Why some individuals develop paralytic poliomyelitis is unknown, but a role for host genetic factors has been suggested. To investigate if a polymorphism, Ala67Thr, in the poliovirus receptor, which has been found to facilitate increased resistance against poliovirus-induced cell lysis and apoptosis, is associated with increased risk of paralytic poliomyelitis, poliovirus receptor genotyping was undertaken among Italian subjects with vaccine-associated (n = 9), or with wild-type paralytic poliomyelitis (n = 6), and control subjects (n = 71), using RFLP-PCR and pyrosequencing. Heterozygous poliovirus receptor Ala67Thr genotype was found in 13.3% of the patients with paresis and in 8.5% of the controls (Odds Ratio = 1.667). The frequency of Ala67Thr among the controls is in agreement with earlier published data. It is concluded that the Ala67Thr mutation in the poliovirus receptor is a possible risk factor for the development of vaccine-associated or paralytic poliomyelitis associated with wild-type virus. Copyright 2009 Wiley-Liss, Inc.

ELECTROPHORETIC MOBILITIES OF ESCHERICHIA COLI 0157:H7 AND WILD-TYPE ESCHERICHIA COLI STRAINS

EPA Science Inventory

The electrophoretic mobility (EPM) of a number of human-virulent and "wild-type" Escherichia coli strains in phosphate buffered water was measured. The impact of pH, ionic strength, cation type (valence) and concentration, and bacterial strain on the EPM was investigated. Resul...

Conversion between parallel and antiparallel β -sheets in wild-type and Iowa mutant Aβ40 fibrils

NASA Astrophysics Data System (ADS)

Xi, Wenhui; Hansmann, Ulrich H. E.

2018-01-01

Using a variant of Hamilton-replica-exchange, we study for wild type and Iowa mutant Aβ40 the conversion between fibrils with antiparallel β-sheets and such with parallel β-sheets. We show that wild type and mutant form distinct salt bridges that in turn stabilize different fibril organizations. The conversion between the two fibril forms leads to the release of small aggregates that in the Iowa mutant may shift the equilibrium from fibrils to more toxic oligomers.

Comparison of lateral abdominal muscle thickness between weightlifters and matched controls.

PubMed

Sitilertpisan, Patraporn; Pirunsan, Ubon; Puangmali, Aatit; Ratanapinunchai, Jonjin; Kiatwattanacharoen, Suchart; Neamin, Hudsaleark; Laskin, James J

2011-11-01

To compare lateral abdominal muscle thickness between weightlifters and matched controls. A case control study design. University laboratory. 16 female Thai national weightlifters and 16 matched controls participated in this study. Ultrasound imaging with a 12-MHz linear array was used to measure the resting thickness of transversus abdominis (TrA), internal oblique (IO) and total thickness (Total) of lateral abdominal muscle (LAM) on the right side of abdominal wall. The absolute muscle thickness and the relative contribution of each muscle to the total thickness were determined. Weightlifters had significantly thicker absolute TrA and IO muscles than matched controls (p < 0.01). Further, the relative thickness of the IO was significantly greater in weightlifters than matched controls (p < 0.05). The findings of this study suggest that routine Olympic style weight training among female weightlifters appears to result in preferential hypertrophy or adaptation of the IO muscle. Copyright © 2011 Elsevier Ltd. All rights reserved.

Glycemic control and high-density lipoprotein characteristics in adolescents with type 1 diabetes.

PubMed

Medina-Bravo, Patricia; Medina-Urrutia, Aída; Juárez-Rojas, Juan Gabriel; Cardoso-Saldaña, Guillermo; Jorge-Galarza, Esteban; Posadas-Sánchez, Rosalinda; Coyote-Estrada, Ninel; Nishimura-Meguro, Elisa; Posadas-Romero, Carlos

2013-09-01

Recent evidence suggests that high-density lipoprotein (HDL) physicochemical characteristics and functional capacity may be more important that HDL-C levels in predicting coronary heart disease. There is little data regarding HDL subclasses distribution in youth with type 1 diabetes. To assess the relationships between glycemic control and HDL subclasses distribution, composition, and function in adolescents with type 1 diabetes. This cross-sectional study included 52 adolescents with type 1 diabetes aged 12-16 years and 43 age-matched non-diabetic controls. Patients were divided into two groups: one in fair control [hemoglobin A1c (HbA1c) < 9.6%] and the second group with poor glycemic control (HbA1c ≥ 9.6%). In all participants, we determined HDL subclasses distribution, composition, and the ability of plasma and of isolated HDL to promote cellular cholesterol efflux. Levels of soluble adhesion molecules were also measured. Although both groups of patients and the control group had similar HDL-C levels, linear regression analyses showed that compared with non-diabetic subjects, the poor control group had a lower proportion of HDL2b subclass (p = 0.029), triglyceride enriched (p = 0.045), and cholesteryl ester depleted (p = 0.028) HDL particles. Despite these HDL changes, cholesterol efflux was comparable among the three groups. The poor control group also had significantly higher intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 plasma concentrations. In adolescents with type 1 diabetes, poor glycemic control is associated with abnormalities in HDL subclasses distribution and HDL lipid composition, however, in spite of these HDL changes, the ability of HDL to promote cholesterol efflux remains comparable to that of healthy subjects. © 2012 John Wiley & Sons A/S.

Ecological Value of Native Plant Cultivars Versus Wild-Type Native Plants for Promoting Hemipteran Diversity in Suburban Areas.

PubMed

Poythress, J C; Affolter, James M

2018-04-14

Because of concerns over recent declines in overall biodiversity in suburban areas, homeowners are attempting to improve the ecological functioning of their landscapes by incorporating native plants. Native plants are important for supporting native herbivorous insects, but it is unknown whether the native plants that are commercially available, typically cultivated varieties (cultivars) of a single genotype, are equally effective as food sources as the local, wild-type plants. We compared the hemipteran communities feeding on cultivars and wild-propagated plants for four species of native perennials commonly used as ornamentals. Of 65 hemipteran species collected, 35 exhibited a preference for some plant species over others, indicating a high degree of host-plant specialization. Moreover, the insect community associated with cultivars was distinct from the insect community associated with wild-type plants for each plant species, with three to four insect species accounting for most of the observed difference. Total insect abundance and insect biomass differed between cultivars and wild-propagated plants, but the direction of the difference changed over time and was not consistent among plant species. Species richness and a diversity index (the Q statistic) did not differ between cultivars and wild-type plants. These data suggest that abundance and diversity of hemipteran insects does not depend on the source of the plant material per se, but rather on the particular characteristics of cultivars that distinguish them from the wild type.

The Effect of Microporous Polysaccharide Hemospheres on Wound Healing and Scarring in Wild-Type and db/db Mice.

PubMed

Miller, Kyle J; Cao, Wei; Ibrahim, Mohamed M; Levinson, Howard

2017-04-01

Hemostasis, the initial phase of wound healing, sets the stage for tissue repair. Microporous polysaccharide hemosphere powder (MPH) is an FDA-approved hemostatic agent that may impact the wound-healing process. This study examined the role of MPH in murine wild-type and diabetic (db/db) wound-healing models and a foreign body response scarring model. The powder was topically applied to excisional wounds in wild-type C57BL/6 mice and db/db mice. The effect of MPH on scarring was evaluated by applying it to the expanded polytetrafluoroethylene tube implantation model. In wild-type mice, topically applied MPH increased epithelial thickness. Levels of α-smooth muscle actin (α-SMA) were decreased in MPH-treated wild-type wounds, whereas Rho-associated protein kinase 2 (ROCK2) and transforming growth factor β levels were increased. In db/db mice, topical wound MPH application decreased epithelial thickness and delayed wound closure. The db/db wounds displayed an increased collagen index. The ROCK2 was increased in a similar manner to wild-type mice, whereas α-SMA and transforming growth factor β levels were decreased. The MPH-treated expanded polytetrafluoroethylene tube mice showed increased α-SMA levels and depressed ROCK2 levels. There were no changes in histologic parameters of the foreign body response. The results suggest that MPH does not adversely impact wound healing in wild-type mice, both topically and around implants, but prolongs time to closure and diminishes thickness in db/db wounds. The MPH application alters contractile proteins in all wound models. These changes could have downstream effects on the wound healing process, and further investigation into the use of MPH in altered or impaired states of wound healing is warranted.

Prenatal Methamphetamine Exposure and Inhibitory Control among Young School-Age Children

PubMed Central

Derauf, Chris; LaGasse, Linda L.; Smith, Lynne M.; Newman, Elana; Shah, Rizwan; Neal, Charles; Arria, Amelia; Huestis, Marilyn A.; Grotta, Sheri Della; Dansereau, Lynne M.; Lin, Hai; Lester, Barry M.

2012-01-01

Objective To examine the association between prenatal methamphetamine exposure and inhibitory control in 66 month old children followed since birth in the multicenter, longitudinal Infant Development, Environment and Lifestyle Study. Study design The sample included 137 children with prenatal methamphetamine exposure and 130 comparison children, matched for race, birth weight, maternal education and type of insurance. Inhibitory control, an executive function related to emotional and cognitive control, was assessed using a computerized Stroop-like task developed for young children. Hierarchical linear modeling tested the relationship between the extent (heavy, some and no use) of prenatal methamphetamine exposure and accuracy and reaction time outcomes, adjusting for prenatal exposure to alcohol, tobacco and marijuana, age, sex, socioeconomic status, caregiver IQ and psychological symptoms, child protective services report of physical or sexual abuse, and site. Results In adjusted analyses, heavy prenatal methamphetamine exposure was related to reduced accuracy in both the incongruent and mixed conditions on the Stroop task. Caregiver psychological symptoms and Child Protective Services (CPS) report of physical or sexual abuse were associated with reduced accuracy in the incongruent and mixed, and incongruent conditions, respectively. Conclusions Heavy prenatal methamphetamine exposure, along with caregiver psychological distress and child maltreatment, is related to subtle deficits in inhibitory control during the early school-aged years. PMID:22424953

Joint dysfunction and functional decline in middle age myostatin null mice.

PubMed

Guo, Wen; Miller, Andrew D; Pencina, Karol; Wong, Siu; Lee, Amanda; Yee, Michael; Toraldo, Gianluca; Jasuja, Ravi; Bhasin, Shalender

2016-02-01

Since its discovery as a potent inhibitor for muscle development, myostatin has been actively pursued as a drug target for age- and disease-related muscle loss. However, potential adverse effects of long-term myostatin deficiency have not been thoroughly investigated. We report herein that male myostatin null mice (mstn(-/-)), in spite of their greater muscle mass compared to wild-type (wt) mice, displayed more significant functional decline from young (3-6months) to middle age (12-15months) than age-matched wt mice, measured as gripping strength and treadmill endurance. Mstn(-/-) mice displayed markedly restricted ankle mobility and degenerative changes of the ankle joints, including disorganization of bone, tendon and peri-articular connective tissue, as well as synovial thickening with inflammatory cell infiltration. Messenger RNA expression of several pro-osteogenic genes was higher in the Achilles tendon-bone insertion in mstn(-/-) mice than wt mice, even at the neonatal age. At middle age, higher plasma concentrations of growth factors characteristic of excessive bone remodeling were found in mstn(-/-) mice than wt controls. These data collectively indicate that myostatin may play an important role in maintaining ankle and wrist joint health, possibly through negative regulation of the pro-osteogenic WNT/BMP pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Interaction of older donor age and survival after weight-matched pediatric heart transplantation.

PubMed

Westbrook, Thomas C; Morales, David L S; Khan, Muhammad S; Bryant, Roosevelt; Castleberry, Chesney; Chin, Clifford; Zafar, Farhan

2017-05-01

Donors are matched for weight in pediatric heart transplantation (PHT), yet age differences are not considered in this decision. In this study we attempt to identify the effect of age differences in weight-matched patients and the effect these differences have on post-transplant survival. The United Network of Organ Sharing (UNOS) database was queried for the period from October 1987 to March 2014 for all pediatric heart transplant patients. Transplants with donor-to-recipient (D-R) weight ratios of 0.8 to 1.5 were identified (weight-matched). D-R age differences were categorized as: donors 5 years younger than recipients (DR+5). A total of 4,408 patients were identified as weight-matched transplants. Of these transplants, 681 were D>R+5, 3,596 were D=R±5 and 131 were DR+5 transplants were found to be associated with decreased post-transplant survival compared with D=R±5 (p = 0.002). Rates of acute rejection were similar among all groups but post-transplant coronary allograft vasculopathy (CAV) was more prevalent in D>R+5 than D=R±5 patients (28% and 18%, respectively; p < 0.001). Increasing age difference by each year was associated with decreasing median post-transplant survival time (p < 0.001; hazard ratio 1.018, range 1.011 to 1.025). The overall negative association with mortality was due to the adolescent cohort (11 to 17 years), specifically D>R+5 transplants, utilizing organs from donors >25 of age. In PHT, increasing D-R age difference decreases survival; however, this effect is driven by recipients 11 to 17 years old and donors >25 years old. Allocation of younger donor organs to adolescent recipients should be a priority. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

MT-PCR panel detection of canine parvovirus (CPV-2): Vaccine and wild-type CPV-2 can be difficult to differentiate in canine diagnostic fecal samples.

PubMed

Meggiolaro, Maira N; Ly, Anna; Rysnik-Steck, Benjamin; Silva, Carolina; Zhang, Joshua; Higgins, Damien P; Muscatello, Gary; Norris, Jacqueline M; Krockenberger, Mark; Šlapeta, Jan

2017-06-01

Canine parvovirus (CPV-2) remains an important cause of devastating enteritis in young dogs. It can be successfully prevented with live attenuated CPV-2 vaccines when given at the appropriate age and in the absence of maternal antibody interference. Rapid diagnosis of parvoviral enteritis in young dogs is essential to ensuring suitable barrier nursing protocols within veterinary hospitals. The current diagnostic trend is to use multiplexed PCR panels to detect an array of pathogens commonly responsible for diarrhea in dogs. The multiplexed PCR assays do not distinguish wild from vaccine CPV-2. They are highly sensitive and detect even a low level of virus shedding, such as those caused by the CPV-2 vaccine. The aim of this study was to identify the CPV-2 subtypes detected in diagnostic specimens and rule out occult shedding of CPV-2 vaccine strains. For a total of 21 samples that tested positive for CPV-2 in a small animal fecal pathogens diagnostic multiplexed tandem PCR (MT-PCR) panel during 2014-2016 we partially characterized the VP2 gene of CPV-2. Vaccine CPV-2 strain, wild type CPV-2a subtypes and vaccine-like CPV-2b subtypes were detected. High copy number was indicative of wild-type CPV-2a presence, but presence of vaccine-like CPV-2b had a variable copy number in fecal samples. A yardstick approach to a copy number or C t -value to discriminate vaccine strain from a wild type virus of CPV-2 can be, in some cases, potentially misleading. Therefore, discriminating vaccine strain from a wild type subtype of CPV-2 remains ambitious. Copyright © 2017 Elsevier Ltd. All rights reserved.

Porcine reproductive and respiratory syndrome virus and porcine circovirus type 2 infections in wild boar (Sus scrofa) in southwestern Germany.

PubMed

Hammer, Ralf; Ritzmann, Mathias; Palzer, Andreas; Lang, Christiane; Hammer, Birgit; Pesch, Stefan; Ladinig, Andrea

2012-01-01

Samples were collected from 203 wild boars (Sus scrofa) hunted in Baden-Wurtemburg, Germany from November-January 2008 and 2009. Samples from the lung and tonsil were analyzed by quantitative polymerase chain reaction (qPCR) for porcine reproductive and respiratory syndrome virus (PRRSV) type 1 (European type) and type 2 (American type). A qPCR to detect porcine circovirus type 2 (PCV2)-specific genome was performed on tissue homogenates including lung, tonsils, and inguinal lymph nodes. Serum samples were tested for antibodies against PRRSV and PCV2 by enzyme-linked immunosorbent assay (ELISA). No PRRSV was detected in any of the 203 samples and one sample had detectable antibodies against PRRSV. We detected PCV2 in organ materials from 103 wild boars with a prevalence of 50.7%. The number of wild boars positive for PCV2 by PCR varied according to the population density of wild boars among woodlands. More positive samples were detected in woodlands with a high density of wild boars. We found no correlation between the number of PCV2-positive wild boars and the density of domestic pigs in the surrounding area. The number of wild boars positive for antibodies against PCV2 by the INGEZIM Circovirus IgG/IgM test kit was low (53 sera positive for IgG- and three sera positive for IgM-antibodies) in comparison to the higher positive results from the INGEZIM CIRCO IgG test kit (102 positive and 12 inconclusive results).

De novo establishment of wild-type song culture in the zebra finch.

PubMed

Fehér, Olga; Wang, Haibin; Saar, Sigal; Mitra, Partha P; Tchernichovski, Ofer

2009-05-28

Culture is typically viewed as consisting of traits inherited epigenetically, through social learning. However, cultural diversity has species-typical constraints, presumably of genetic origin. A celebrated, if contentious, example is whether a universal grammar constrains syntactic diversity in human languages. Oscine songbirds exhibit song learning and provide biologically tractable models of culture: members of a species show individual variation in song and geographically separated groups have local song dialects. Different species exhibit distinct song cultures, suggestive of genetic constraints. Without such constraints, innovations and copying errors should cause unbounded variation over multiple generations or geographical distance, contrary to observations. Here we report an experiment designed to determine whether wild-type song culture might emerge over multiple generations in an isolated colony founded by isolates, and, if so, how this might happen and what type of social environment is required. Zebra finch isolates, unexposed to singing males during development, produce song with characteristics that differ from the wild-type song found in laboratory or natural colonies. In tutoring lineages starting from isolate founders, we quantified alterations in song across tutoring generations in two social environments: tutor-pupil pairs in sound-isolated chambers and an isolated semi-natural colony. In both settings, juveniles imitated the isolate tutors but changed certain characteristics of the songs. These alterations accumulated over learning generations. Consequently, songs evolved towards the wild-type in three to four generations. Thus, species-typical song culture can appear de novo. Our study has parallels with language change and evolution. In analogy to models in quantitative genetics, we model song culture as a multigenerational phenotype partly encoded genetically in an isolate founding population, influenced by environmental variables and taking

Molecular control of copper homeostasis in filamentous fungi: increased expression of a metallothionein gene during aging of Podospora anserina.

PubMed

Averbeck, N B; Borghouts, C; Hamann, A; Specke, V; Osiewacz, H D

2001-01-01

The lifespan of the ascomycete Podospora anserina was previously demonstrated to be significantly increased in a copper-uptake mutant, suggesting that copper is a potential stressor involved in degenerative processes. In order to determine whether changes in copper stress occur in the cells during normal aging of cultures, we cloned and characterized a gene coding for a component of the molecular machinery involved in the control of copper homeostasis. This gene, PaMt1, is a single-copy gene that encodes a metallothionein of 26 amino acids. The coding sequence of PaMt1 is interrupted by a single intron. The deduced amino acid sequence shows a high degree of sequence identity to metallothioneins of the filamentous ascomycete Neurospora crassa and the basidiomycete Agaricus bisporus, and to the N-terminal portion of mammalian metallothioneins. Levels of PaMt1 transcript increase in response to elevated amounts of copper in the growth medium and during aging of wild-type cultures. In contrast, in the long-lived mutant grisea, transcript levels first increase but then decrease again. The ability of wild-type cultures to respond to exogenous copper stress via the induction of PaMt1 transcription is not affected as they grow older.

Arginase-II Promotes Tumor Necrosis Factor-α Release From Pancreatic Acinar Cells Causing β-Cell Apoptosis in Aging.

PubMed

Xiong, Yuyan; Yepuri, Gautham; Necetin, Sevil; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

2017-06-01

Aging is associated with glucose intolerance. Arginase-II (Arg-II), the type-II L -arginine-ureahydrolase, is highly expressed in pancreas. However, its role in regulation of pancreatic β-cell function is not known. Here we show that female (not male) mice deficient in Arg-II (Arg-II -/- ) are protected from age-associated glucose intolerance and reveal greater glucose induced-insulin release, larger islet size and β-cell mass, and more proliferative and less apoptotic β-cells compared with the age-matched wild-type (WT) controls. Moreover, Arg-II is mainly expressed in acinar cells and is upregulated with aging, which enhances p38 mitogen-activated protein kinase (p38 MAPK) activation and release of tumor necrosis factor-α (TNF-α). Accordingly, conditioned medium of isolated acinar cells from old WT (not Arg-II -/- ) mice contains higher TNF-α levels than the young mice and stimulates β-cell apoptosis and dysfunction, which are prevented by a neutralizing anti-TNF-α antibody. In acinar cells, our study demonstrates an age-associated Arg-II upregulation, which promotes TNF-α release through p38 MAPK leading to β-cell apoptosis, insufficient insulin secretion, and glucose intolerance in female rather than male mice. © 2017 by the American Diabetes Association.

Age-dependent increment of hydroxymethylation in the brain cortex in the triple-transgenic mouse model of Alzheimer's disease.

PubMed

Cadena-del-Castillo, Carla; Valdes-Quezada, Christian; Carmona-Aldana, Francisco; Arias, Clorinda; Bermúdez-Rattoni, Federico; Recillas-Targa, Félix

2014-01-01

Alzheimer's disease (AD) is a complex disorder whose etiology is associated with environmental and genetic factors. Recently there have been several attempts to analyze the role of epigenetic alterations in the origin and progression of this neurodegenerative condition. To evaluate the potential participation of the methylation status of the genome that may contribute to AD progression, we have studied the levels and distribution of the 5-methylcytosine and 5-hydroxymethylcytosine in different brain regions at different ages. We analyzed and quantified the immunosignal of these two epigenetic marks in young versus old wild-type mice and in the triple-transgenic mouse model of AD (3xTg-AD). The results show a decline in global 5-methylcytosine mark over time in all studied brain regions concomitant with a significant and widespread increase in 5-hydroxymethylcytosine mark in the aged transgenic mice in contrast to the age-matched controls. These differences in the methylation pattern of brain DNA in the 3xTg-AD that accumulates along age indicates abnormal formation of permissive chromatin structure associated with the increase in AD-related markers.

Identifying the integrated neural networks involved in capsaicin-induced pain using fMRI in awake TRPV1 knockout and wild-type rats

PubMed Central

Yee, Jason R.; Kenkel, William; Caccaviello, John C.; Gamber, Kevin; Simmons, Phil; Nedelman, Mark; Kulkarni, Praveen; Ferris, Craig F.

2015-01-01

In the present study, we used functional MRI in awake rats to investigate the pain response that accompanies intradermal injection of capsaicin into the hindpaw. To this end, we used BOLD imaging together with a 3D segmented, annotated rat atlas and computational analysis to identify the integrated neural circuits involved in capsaicin-induced pain. The specificity of the pain response to capsaicin was tested in a transgenic model that contains a biallelic deletion of the gene encoding for the transient receptor potential cation channel subfamily V member 1 (TRPV1). Capsaicin is an exogenous ligand for the TRPV1 receptor, and in wild-type rats, activated the putative pain neural circuit. In addition, capsaicin-treated wild-type rats exhibited activation in brain regions comprising the Papez circuit and habenular system, systems that play important roles in the integration of emotional information, and learning and memory of aversive information, respectively. As expected, capsaicin administration to TRPV1-KO rats failed to elicit the robust BOLD activation pattern observed in wild-type controls. However, the intradermal injection of formalin elicited a significant activation of the putative pain pathway as represented by such areas as the anterior cingulate, somatosensory cortex, parabrachial nucleus, and periaqueductal gray. Notably, comparison of neural responses to capsaicin in wild-type vs. knock-out rats uncovered evidence that capsaicin may function in an antinociceptive capacity independent of TRPV1 signaling. Our data suggest that neuroimaging of pain in awake, conscious animals has the potential to inform the neurobiological basis of full and integrated perceptions of pain. PMID:25745388

Structures of the E46K Mutant-Type α-Synuclein Protein and Impact of E46K Mutation on the Structures of the Wild-Type α-Synuclein Protein

PubMed Central

2013-01-01

The E46K genetic missense mutation of the wild-type α-synuclein protein was recently identified in a family of Spanish origin with hereditary Parkinson’s disease. Detailed understanding of the structures of the monomeric E46K mutant-type α-synuclein protein as well as the impact of the E46K missense mutation on the conformations and free energy landscapes of the wild-type α-synuclein are required for gaining insights into the pathogenic mechanism of Parkinson’s disease. In this study, we use extensive parallel tempering molecular dynamics simulations along with thermodynamic calculations to assess the secondary and tertiary structural properties as well as the conformational preferences of the monomeric wild-type and E46K mutant-type α-synuclein proteins in an aqueous solution environment. We also present the residual secondary structure component conversion stabilities with dynamics using a theoretical strategy, which we most recently developed. To the best of our knowledge, this study presents the first detailed comparison of the structural and thermodynamic properties of the wild-type and E46K mutant-type α-synuclein proteins in an aqueous solution environment at the atomic level with dynamics. We find that the E46K mutation results not only in local but also in long-range changes in the structural properties of the wild-type α-synuclein protein. The mutation site shows a significant decrease in helical content as well as a large increase in β-sheet structure formation upon E46K mutation. In addition, the β-sheet content of the C-terminal region increases significantly in the E46K mutant-type αS in comparison to the wild-type αS. Our theoretical strategy developed to assess the thermodynamic preference of secondary structure transitions indicates that this shift in secondary structure is the result of a decrease in the thermodynamic preference of turn to helix conversions while the coil to β-sheet preference increases for these residues. Long

Community integration outcomes of people with spinal cord injury and multiple matched controls: A pilot study.

PubMed

Callaway, Libby; Enticott, Joanne; Farnworth, Louise; McDonald, Rachael; Migliorini, Christine; Willer, Barry

2017-06-01

Australia's National Disability Insurance Scheme (NDIS) is designed to influence home, social and economic participation for Scheme participants. Given the major disability reform underway, this pilot study aimed to: (i) examine community integration outcomes of people with spinal cord injury (SCI); (ii) compare findings with multiple matched controls and (iii) consider findings within the context of Australia's NDIS. Setting: Victoria, Australia. Matched analysis (people with and without SCI). Community Integration Questionnaire (CIQ). n = 40 adults with SCI (M age = 52.8 years; 61% male; 77% traumatic SCI). Matched analyses from each SCI subject aged <70 years (n = 31) with four CIQ normative data subjects (from n = 1927) was undertaken, with key demographic variables matched (age range, gender, living location and living situation). Risk of low CIQ score as a function of SCI was also examined using conditional Poisson regression. With key demographic variables held constant, small to medium effect sizes were found in favour of the normative sample, with statistically significant differences in home (ρ = 0.003) and productivity integration (ρ = 0.02). Relative risk of low home integration was significant in the SCI cohort (conditional RR (95% CI) = 3.1 (1.5-6.3), ρ = 0.001). Relative risk of low CIQ total, social integration and productivity scores did not reach significance. This cohort of SCI participants was less integrated into home and productive occupations than matched norms, holding implications for planning and allocation of supports to influence outcomes within an NDIS. Further research is necessary to understand community integration outcomes in larger matched samples. © 2016 Occupational Therapy Australia.

Interaction of Root Gravitropism and Phototropism in Arabidopsis Wild-Type and Starchless Mutants1

PubMed Central

Vitha, Stanislav; Zhao, Liming; Sack, Fred David

2000-01-01

Root gravitropism in wild-type Arabidopsis and in two starchless mutants, pgm1-1 and adg1-1, was evaluated as a function of light position to determine the relative strengths of negative phototropism and of gravitropism and how much phototropism affects gravitropic measurements. Gravitropism was stronger than phototropism in some but not all light positions in wild-type roots grown for an extended period, indicating that the relationship between the two tropisms is more complex than previously reported. Root phototropism significantly influenced the time course of gravitropic curvature and the two measures of sensitivity. Light from above during horizontal exposure overestimated all three parameters for all three genotypes except the wild-type perception time. At the irradiance used (80 μmol m−2 s−1), the shortest periods of illumination found to exaggerate gravitropism were 45 min of continuous illumination and 2-min doses of intermittent illumination. By growing roots in circumlateral light or by gravistimulating in the dark, corrected values were obtained for each gravitropic parameter. Roots of both starchless mutants were determined to be about three times less sensitive than prior estimates. This study demonstrates the importance of accounting for phototropism in the design of root gravitropism experiments in Arabidopsis. PMID:10677438

Comparison of body weight and gene expression in amelogenin null and wild-type mice.

PubMed

Li, Yong; Yuan, Zhi-An; Aragon, Melissa A; Kulkarni, Ashok B; Gibson, Carolyn W

2006-05-01

Amelogenin (AmelX) null mice develop hypomineralized enamel lacking normal prism structure, but are healthy and fertile. Because these mice are smaller than wild-type mice prior to weaning, we undertook a detailed analysis of the weight of mice and analyzed AmelX expression in non-dental tissues. Wild-type mice had a greater average weight each day within the 3-wk period. Using reverse transcription-polymerase chain reaction (RT-PCR), products of approximately 200 bp in size were generated from wild-type teeth, brain, eye, and calvariae. DNA sequence analysis of RT-PCR products from calvariae indicated that the small amelogenin leucine-rich amelogenin peptide (LRAP), both with and without exon 4, was expressed. No products were obtained from any of the samples from the AmelX null mice. We also isolated mRNAs that included AmelX exons 8 and 9, and identified a duplication within the murine AmelX gene with 91% homology. Our results add additional support to the hypothesis that amelogenins are multifunctional proteins, with potential roles in non-ameloblasts and in non-mineralizing tissues during development. The smaller size of AmelX null mice could potentially be explained by the lack of LRAP expression in some of these tissues, leading to a delay in development.

Advancing age increases sperm chromatin damage and impairs fertility in peroxiredoxin 6 null mice

PubMed Central

Ozkosem, Burak; Feinstein, Sheldon I.; Fisher, Aron B.; O’Flaherty, Cristian

2015-01-01

Due to socioeconomic factors, more couples are choosing to delay conception than ever. Increasing average maternal and paternal age in developed countries over the past 40 years has raised the question of how aging affects reproductive success of males and females. Since oxidative stress in the male reproductive tract increases with age, we investigated the impact of advanced paternal age on the integrity of sperm nucleus and reproductive success of males by using a Prdx6−/− mouse model. We compared sperm motility, cytoplasmic droplet retention sperm chromatin quality and reproductive outcomes of young (2-month-old), adult (8-month-old), and old (20-month-old) Prdx6−/− males with their age-matched wild type (WT) controls. Absence of PRDX6 caused age-dependent impairment of sperm motility and sperm maturation and increased sperm DNA fragmentation and oxidation as well as decreased sperm DNA compaction and protamination. Litter size, total number of litters and total number of pups per male were significantly lower in Prdx6−/− males compared to WT controls. These abnormal reproductive outcomes were severely affected by age in Prdx6−/− males. In conclusion, the advanced paternal age affects sperm chromatin integrity and fertility more severely in the absence of PRDX6, suggesting a protective role of PRDX6 in age-associated decline in the sperm quality and fertility in mice. PMID:25796034

Advancing age increases sperm chromatin damage and impairs fertility in peroxiredoxin 6 null mice.

PubMed

Ozkosem, Burak; Feinstein, Sheldon I; Fisher, Aron B; O'Flaherty, Cristian

2015-08-01

Due to socioeconomic factors, more couples are choosing to delay conception than ever. Increasing average maternal and paternal age in developed countries over the past 40 years has raised the question of how aging affects reproductive success of males and females. Since oxidative stress in the male reproductive tract increases with age, we investigated the impact of advanced paternal age on the integrity of sperm nucleus and reproductive success of males by using a Prdx6(-/-) mouse model. We compared sperm motility, cytoplasmic droplet retention sperm chromatin quality and reproductive outcomes of young (2-month-old), adult (8-month-old), and old (20-month-old) Prdx6(-/-) males with their age-matched wild type (WT) controls. Absence of PRDX6 caused age-dependent impairment of sperm motility and sperm maturation and increased sperm DNA fragmentation and oxidation as well as decreased sperm DNA compaction and protamination. Litter size, total number of litters and total number of pups per male were significantly lower in Prdx6(-/-) males compared to WT controls. These abnormal reproductive outcomes were severely affected by age in Prdx6(-/-) males. In conclusion, the advanced paternal age affects sperm chromatin integrity and fertility more severely in the absence of PRDX6, suggesting a protective role of PRDX6 in age-associated decline in the sperm quality and fertility in mice. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Individual and interpersonal emotion regulation among adults with substance use disorders and matched controls.

PubMed

Dingle, Genevieve A; Neves, Diana da Costa; Alhadad, Sakinah S J; Hides, Leanne

2018-06-01

Self-report studies show that negative emotional states and ineffective use of emotion regulation strategies are key maintaining factors of substance use disorders (SUD). However, experimental research into emotional processing in adults with SUD is in its infancy. Theoretical conceptualizations of emotion regulation have shifted from a focus on individual (internal) processes to one that encompasses social and interpersonal functions - including the regulation of facial expression of emotion. The purpose of this study was to examine the individual and interpersonal emotion regulation capacity of 35 adults in residential treatment diagnosed with a SUD compared to 35 demographically matched controls (both samples M age  = 25 years; 37% females). Participants completed a facial emotion expression flexibility task while viewing emotive images, as well as the Difficulties of Emotion Regulation Scale (DERS) and the Social (Emotion) Expectancy Scale (SES). Adults in SUD treatment experienced significantly more emotion regulation difficulties on all DERS subscales than controls. They also reported higher levels of negative self-evaluation and social expectancies not to feel negative emotions (anxiety and depression) compared to controls. Moreover, when viewing emotive images, the treatment sample showed significantly less flexibility of their emotional expression compared to the control sample. These findings demonstrate that the awareness, expression, and regulation of emotions are particularly difficult for people with SUD and this may maintain their substance use and provide an important target for treatment. Compared to matched controls, adults with substance use disorders self-report significantly more difficulties with emotional awareness and regulation. Compared to matched controls, adults with substance use disorders report significantly greater expectancies not to show depression and anxiety. When viewing positive and negative images, adults with substance use

43 CFR 9264.7 - Wild free-roaming horse and burro protection, management, and control.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) LAW ENFORCEMENT-CRIMINAL Range Management § 9264.7 Wild free-roaming horse and burro protection, management, and control. (a) Prohibited acts. In accordance with section 8 of the Wild Free-Roaming Horse and... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Wild free-roaming horse and burro...

43 CFR 9264.7 - Wild free-roaming horse and burro protection, management, and control.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) LAW ENFORCEMENT-CRIMINAL Range Management § 9264.7 Wild free-roaming horse and burro protection, management, and control. (a) Prohibited acts. In accordance with section 8 of the Wild Free-Roaming Horse and... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Wild free-roaming horse and burro...

43 CFR 9264.7 - Wild free-roaming horse and burro protection, management, and control.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) LAW ENFORCEMENT-CRIMINAL Range Management § 9264.7 Wild free-roaming horse and burro protection, management, and control. (a) Prohibited acts. In accordance with section 8 of the Wild Free-Roaming Horse and... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Wild free-roaming horse and burro...

43 CFR 9264.7 - Wild free-roaming horse and burro protection, management, and control.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) LAW ENFORCEMENT-CRIMINAL Range Management § 9264.7 Wild free-roaming horse and burro protection, management, and control. (a) Prohibited acts. In accordance with section 8 of the Wild Free-Roaming Horse and... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Wild free-roaming horse and burro...

A Comparison of the Metalinguistic Performance and Spelling Development of Children With Inconsistent Speech Sound Disorder and Their Age-Matched and Reading-Matched Peers.

PubMed

McNeill, Brigid C; Wolter, Julie; Gillon, Gail T

2017-05-17

This study explored the specific nature of a spelling impairment in children with speech sound disorder (SSD) in relation to metalinguistic predictors of spelling development. The metalinguistic (phoneme, morphological, and orthographic awareness) and spelling development of 28 children ages 6-8 years with a history of inconsistent SSD were compared to those of their age-matched (n = 28) and reading-matched (n = 28) peers. Analysis of the literacy outcomes of children within the cohort with persistent (n = 18) versus resolved (n = 10) SSD was also conducted. The age-matched peers outperformed the SSD group on all measures. Children with SSD performed comparably to their reading-matched peers on metalinguistic measures but exhibited lower spelling scores. Children with persistent SSD generally had less favorable outcomes than children with resolved SSD; however, even children with resolved SSD performed poorly on normative spelling measures. Children with SSD have a specific difficulty with spelling that is not commensurate with their metalinguistic and reading ability. Although low metalinguistic awareness appears to inhibit these children's spelling development, other factors should be considered, such as nonverbal rehearsal during spelling attempts and motoric ability. Integration of speech-production and spelling-intervention goals is important to enhance literacy outcomes for this group.

Taste detection and recognition thresholds in Japanese patients with Alzheimer-type dementia.

PubMed

Ogawa, Takao; Irikawa, Naoya; Yanagisawa, Daijiro; Shiino, Akihiko; Tooyama, Ikuo; Shimizu, Takeshi

2017-04-01

Alzheimer-type dementia (AD) is pathologically characterized by massive neuronal loss in the brain, and the taste cortex is thought to be affected. However, there are only a few reports regarding the gustatory function of AD patients, and the conclusions of this research are inconsistent. This prospective study enrolled 22 consecutive patients with mild to moderately severe Alzheimer-type dementia (AD) with mean age of 84.0 years, and 49 elderly volunteers without dementia with mean age of 71.0 years as control subjects. The control subjects were divided into two groups according to age: a younger group (N=28, mean age: 68.5) and an older group (N=21, mean age: 83.0). The gustatory function was investigated using the filter paper disc method (FPD) and electrogustometry (EGM). The gustatory function as measured by the FPD was significantly impaired in patients with AD as compared with age-matched control subjects; no such difference was found between the younger and the older control groups. On the other hand, as for the EGM thresholds, there were no differences between the AD patient group and the age-matched controls. The FPD method demonstrated decreased gustatory function in AD patients beyond that of aging. On the other hand, EGM thresholds did not differ between the AD patient group and the age-matched controls. These results suggest that failure of taste processing in the brain, but not taste transmission in the peripheral taste system, occurs in patients with AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Unique perceptuomotor control of stone hammers in wild monkeys.

PubMed

Mangalam, Madhur; Pacheco, Matheus Maia; Izar, Patrícia; Visalberghi, Elisabetta; Fragaszy, Dorothy Munkenbeck

2018-01-01

We analysed the patterns of coordination of striking movement and perceptuomotor control of stone hammers in wild bearded capuchin monkeys, Sapajus libidinosus as they cracked open palm nut using hammers of different mass, a habitual behaviour in our study population. We aimed to determine why these monkeys cannot produce conchoidally fractured flakes as do contemporary human knappers or as did prehistoric hominin knappers. We found that the monkeys altered their patterns of coordination of movement to accommodate changes in hammer mass. By altering their patterns of coordination, the monkeys kept the strike's amplitude and the hammer's velocity at impact constant with respect to hammer mass. In doing so, the hammer's kinetic energy at impact-which determines the propagation of a fracture/crack in a nut-varied across hammers of different mass. The monkeys did not control the hammer's kinetic energy at impact, the key parameter a perceiver-actor should control while knapping stones. These findings support the hypothesis that the perceptuomotor control of stone hammers in wild bearded capuchin monkeys is inadequate to produce conchoidally fractured flakes by knapping stones, as do humans. © 2018 The Author(s).

Senescence or selective disappearance? Age trajectories of body mass in wild and captive populations of a small-bodied primate.

PubMed

Hämäläinen, Anni; Dammhahn, Melanie; Aujard, Fabienne; Eberle, Manfred; Hardy, Isabelle; Kappeler, Peter M; Perret, Martine; Schliehe-Diecks, Susanne; Kraus, Cornelia

2014-09-22

Classic theories of ageing consider extrinsic mortality (EM) a major factor in shaping longevity and ageing, yet most studies of functional ageing focus on species with low EM. This bias may cause overestimation of the influence of senescent declines in performance over condition-dependent mortality on demographic processes across taxa. To simultaneously investigate the roles of functional senescence (FS) and intrinsic, extrinsic and condition-dependent mortality in a species with a high predation risk in nature, we compared age trajectories of body mass (BM) in wild and captive grey mouse lemurs (Microcebus murinus) using longitudinal data (853 individuals followed through adulthood). We found evidence of non-random mortality in both settings. In captivity, the oldest animals showed senescence in their ability to regain lost BM, whereas no evidence of FS was found in the wild. Overall, captive animals lived longer, but a reversed sex bias in lifespan was observed between wild and captive populations. We suggest that even moderately condition-dependent EM may lead to negligible FS in the wild. While high EM may act to reduce the average lifespan, this evolutionary process may be counteracted by the increased fitness of the long-lived, high-quality individuals. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Mechanical response of wild-type and Alport murine lens capsules during osmotic swelling.

PubMed

Gyoneva, Lazarina; Segal, Yoav; Dorfman, Kevin D; Barocas, Victor H

2013-08-01

The mechanical support of basement membranes, such as the lens capsule, is believed to arise from one of their main constituents - collagen IV. The basement membranes of the lens, kidney, and ear normally contain two different types of collagen IV networks, referred to as the major and minor chain networks. In Alport syndrome, a mutation in one of the minor chain COL4 genes leads to the absence of the minor chain network, causing life-threatening disturbances. We hypothesized that the absence of the minor chain network increases basement membrane distensibility, as measured in wild-type (n = 25) and Alport syndrome (n = 21) mice using the lens capsule as a model. Osmotic swelling experiments revealed direction-dependent changes. As a reflection of lens capsule properties, Alport lenses strained significantly more than wild-type lenses in the anterior-posterior direction, i.e. along their thickness, but not in the equatorial direction (p = 0.03 and p = 0.08, respectively). This is consistent with clinical data: Alport patients develop conical protrusions on the anterior and posterior lenticular poles. There was no evidence of significant change in total amount of collagen between Alport and wild-type lenses (p = 0.6). The observed differences in distensibility could indicate that the major chain network alone cannot fully compensate for the absence of the more highly cross-linked minor chain network, which is believed to be stronger, more stable, and resistant to deformation. The addition of mechanical information on Alport syndrome to the currently available biological data provides a fuller picture into the progression of the disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gravitropism in lateral roots of Arabidopsis pgm-1 mutants is indistinguishable from that of wild-type

PubMed Central

Bai, Hanwen

2011-01-01

The majority of understanding of root gravity responses comes from the study of primary roots, even though lateral roots make a far greater contribution to root system architecture. The focus of this report is the analysis of gravitropic responses in lateral roots of wild-type background and pgm-1 mutants. Despite the significant reduction in gravitropic response of primary roots of pgm-1 mutants, the lateral roots of this mutant demonstrate wild-type rates of gravitropism, suggesting a significant difference in gravity signal transduction between primary and lateral roots. PMID:21921698

Gravitropism in lateral roots of Arabidopsis pgm-1 mutants is indistinguishable from that of wild-type.

PubMed

Bai, Hanwen; Wolverton, Chris

2011-10-01

The majority of understanding of root gravity responses comes from the study of primary roots, even though lateral roots make a far greater contribution to root system architecture. The focus of this report is the analysis of gravitropic responses in lateral roots of wild-type background and pgm-1 mutants. Despite the significant reduction in gravitropic response of primary roots of pgm-1 mutants, the lateral roots of this mutant demonstrate wild-type rates of gravitropism, suggesting a significant difference in gravity signal transduction between primary and lateral roots.

Balance training reduces falls risk in older individuals with type 2 diabetes.

PubMed

Morrison, Steven; Colberg, Sheri R; Mariano, Mira; Parson, Henri K; Vinik, Arthur I

2010-04-01

This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes. Sixteen individuals with type 2 diabetes and 21 age-matched control subjects (aged 50-75 years) participated. Postural stability and falls risk was assessed before and after a 6-week exercise program. Diabetic individuals had significantly higher falls risk score compared with control subjects. The diabetic group also exhibited evidence of mild-to-moderate neuropathy, slower reaction times, and increased postural sway. Following exercise, the diabetic group showed significant improvements in leg strength, faster reaction times, decreased sway, and, consequently, reduced falls risk. Older individuals with diabetes had impaired balance, slower reactions, and consequently a higher falls risk than age-matched control subjects. However, all these variables improved after resistance/balance training. Together these results demonstrate that structured exercise has wide-spread positive effects on physiological function for older individuals with type 2 diabetes.

Balance Training Reduces Falls Risk in Older Individuals With Type 2 Diabetes

PubMed Central

Morrison, Steven; Colberg, Sheri R.; Mariano, Mira; Parson, Henri K.; Vinik, Arthur I.

2010-01-01

OBJECTIVE This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS Sixteen individuals with type 2 diabetes and 21 age-matched control subjects (aged 50–75 years) participated. Postural stability and falls risk was assessed before and after a 6-week exercise program. RESULTS Diabetic individuals had significantly higher falls risk score compared with control subjects. The diabetic group also exhibited evidence of mild-to-moderate neuropathy, slower reaction times, and increased postural sway. Following exercise, the diabetic group showed significant improvements in leg strength, faster reaction times, decreased sway, and, consequently, reduced falls risk. CONCLUSIONS Older individuals with diabetes had impaired balance, slower reactions, and consequently a higher falls risk than age-matched control subjects. However, all these variables improved after resistance/balance training. Together these results demonstrate that structured exercise has wide-spread positive effects on physiological function for older individuals with type 2 diabetes. PMID:20097781

Economic benefit of fertility control in wild horse populations

USGS Publications Warehouse

Bartholow, J.

2007-01-01

I projected costs for several contraceptive treatments that could be used by the Bureau of Land Management (BLM) to manage 4 wild horse (Equus caballus) populations. Potential management alternatives included existing roundup and selective removal methods combined with contraceptives of different duration and effectiveness. I projected costs for a 20-year economic life using the WinEquus?? wild horse population model and state-by-state cost estimates reflecting BLM's operational expenses. Findings revealed that 1) currently available 2-year contraceptives in most situations are capable of reducing variable operating costs by 15%, 2) experimental 3-year contraceptives may be capable of reducing costs by 18%, and 3) combining contraceptives with modest changes to herd sex ratio (e.g., 55-60% M) could trim costs by 30%. Predicted savings can increase when contraception is applied in conjunction with a removal policy that targets horses aged 0-4 years instead of 0-5 years. However, reductions in herd size result in greater variation in annual operating expenses. Because the horse program's variable operating costs make up about half of the total program costs (which include other fixed costs), contraceptive application and management can only reduce total costs by 14%, saving about $6.1 million per year. None of the contraceptive options I examined eliminated the need for long-term holding facilities over the 20-year period simulated, but the number of horses held may be reduced by about 17% with contraceptive treatment. Cost estimates were most sensitive to the oldest age adoptable and per-day holding costs. The BLM will experience significant cost savings as carefully designed contraceptive programs become widespread in the wild horse herds it manages.

Psychosocial factors in childhood pedestrian injury: a matched case-control study. Kid's'n'Cars Team.

PubMed

Christoffel, K K; Donovan, M; Schofer, J; Wills, K; Lavigne, J V

1996-01-01

Psychosocial factors--such as hyperactivity and low family cohesion--contribute to the risk for child pedestrian injury (PI), even after controlling for known demographic risk factors. Urban PI victims aged 5 to 12 years were recruited from one large, urban pediatric trauma center in a large city. One hundred twenty-eight cases were matched to uninjured children on age, sex, race, location of residence, and parental education. Among matched cases: 70% were male, 41% were black, 33% were Hispanic, and 66% of the mothers had a high school education or less. RESEARCH DESIGN AND MEASUREMENTS: Case-control comparisons on 19 psychosocial variables drawn from interviews and standardized tests, using one-tailed matched-pairs t tests and conditional logistic regression analyses. Cases had higher reported physical quotient [PQ] (P = .01), self-help quotient (P = .04), and family stress (P = .02), and lower family supportiveness (P = .03). Multivariate analyses confirmed that PQ was higher in cases (10-point increase: odds ratio (OR) = 1.32 [90% confidence interval (CI) 1.01-1.76], that stress was higher in cases (1 log increase: OR 2.13, [1.26-3.61]), and that cases had lower family supportiveness (25-point decrease: OR 1.43 [1.25-1.63]). It also identified household crowding as a factor for non-black cases (OR for increase of 0.25 people per room: 2.18, [1.31-3.62]). Even when controlling for demographic risk, several family factors and one child factor place children at risk for PI. Clinicians may choose to use these as indicators for injury prevention counseling. Research on family effects may help clarify means to protect children who are demographically at risk for PI.

Cost-Effectiveness of Immune Checkpoint Inhibition in BRAF Wild-Type Advanced Melanoma

PubMed Central

Zeichner, Simon B.; Chen, Qiushi; Montero, Alberto J.; Goldstein, Daniel A.; Flowers, Christopher R.

2017-01-01

Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration–approved immune checkpoint inhibitors—pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)—demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma. Materials and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US$) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of $90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $198,867/QALY. Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost

Excess atherosclerosis in systemic lupus erythematosus,—A matter of renal involvement: Case control study of 281 SLE patients and 281 individually matched population controls

PubMed Central

Gustafsson, Johanna T.; Herlitz Lindberg, Marie; Gunnarsson, Iva; Pettersson, Susanne; Elvin, Kerstin; Öhrvik, John; Larsson, Anders; Jensen-Urstad, Kerstin

2017-01-01

Background Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups. Methods 281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls. Results Median age was 49 (IQR 36–59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis

Match running performance and skill execution improves with age but not the number of disposals in young Australian footballers.

PubMed

Gastin, Paul B; Tangalos, Christie; Torres, Lorena; Robertson, Sam

2017-12-01

This study investigated age-related differences in maturity, physical and functional characteristics and playing performance in youth Australian Football (AF). Young male players (n = 156) were recruited from 12 teams across 6 age groups (U10-U15) of a recreational AF club. All players were tested for body size, maturity and fitness. Player performance was assessed during a match in which disposals (kicks and handballs) and their effectiveness were coded from a video recording and match running performance measured using Global Positioning System. Significant main effects (P < 0.01) for age group were observed for age, years to peak height velocity, body mass, height, 20 m sprint, maximal speed over 20 m, vertical jump, 20 m multistage shuttle run, match distance, high-speed running distance, peak speed, number of effective disposals and percentage of effective disposals. Age-related differences in fitness characteristics (speed, lower body power and endurance) appeared to transfer to match running performance. The frequency in which players disposed of the football did not differ between age groups, however the effectiveness of each disposal (i.e., % effective disposals) improved with age. Match statistics, particularly those that evaluate skill execution outcome (i.e., effectiveness), are useful to assess performance and to track player development over time. Differences between age groups, and probably variability within age groups, are strongly associated with chronological age and maturity.

COMPARISON OF IN VITRO-CULTURED AND WILD-TYPE PERKINSUS MARINUS I: PATHOGEN VIRULENCE

EPA Science Inventory

Perkinsus marinus is a highly contagious pathogen of the eastern oyster Crassostrea virginica. Until recently, transmission studies have employed wild-type parasites isolated directly from infected oysters. Newly developed methods to propagate P. marinus in vitro have led to usin...

Disappearance of GFP-Positive Hepatocytes Transplanted into the Liver of Syngeneic Wild-Type Rats Pretreated with Retrorsine

PubMed Central

Maeda, Hiromichi; Shigoka, Masatoshi; Wang, Yongchun; Fu, Yingxin; Wesson, Russell N.; Lin, Qing; Montgomery, Robert A.; Enzan, Hideaki; Sun, Zhaoli

2014-01-01

Background and Aim Green fluorescent protein (GFP) is a widely used molecular tag to trace transplanted cells in rodent liver injury models. The differing results from various previously reported studies using GFP could be attributed to the immunogenicity of GFP. Methods Hepatocytes were obtained from GFP-expressing transgenic (Tg) Lewis rats and were transplanted into the livers of wild-type Lewis rats after they had undergone a partial hepatectomy. The proliferation of endogenous hepatocytes in recipient rats was inhibited by pretreatment with retrorsine to enhance the proliferation of the transplanted hepatocytes. Transplantation of wild-type hepatocytes into GFP-Tg rat liver was also performed for comparison. Results All biopsy specimens taken seven days after transplantation showed engraftment of transplanted hepatocytes, with the numbers of transplanted hepatocytes increasing until day 14. GFP-positive hepatocytes in wild-type rat livers were decreased by day 28 and could not be detected on day 42, whereas the number of wild-type hepatocytes steadily increased in GFP-Tg rat liver. Histological examination showed degenerative change of GFP-positive hepatocytes and the accumulation of infiltrating cells on day 28. PCR analysis for the GFP transgene suggested that transplanted hepatocytes were eliminated rather than being retained along with the loss of GFP expression. Both modification of the immunological response using tacrolimus and bone marrow transplantation prolonged the survival of GFP-positive hepatocytes. In contrast, host immunization with GFP-positive hepatocytes led to complete loss of GFP-positive hepatocytes by day 14. Conclusion GFP-positive hepatocytes isolated from GFP-Tg Lewis rats did not survive long term in the livers of retrorsine-pretreated wild-type Lewis rats. The mechanism underlying this phenomenon most likely involves an immunological reaction against GFP. The influence of GFP immunogenicity on cell transplantation models should be

Glucose Starvation Alters Heat Shock Response, Leading to Death of Wild Type Cells and Survival of MAP Kinase Signaling Mutant

PubMed Central

Higgins, LeeAnn; Markowski, Todd; Brambl, Robert

2016-01-01

A moderate heat shock induces Neurospora crassa to synthesize large quantities of heat shock proteins that are protective against higher, otherwise lethal temperatures. However, wild type cells do not survive when carbohydrate deprivation is added to heat shock. In contrast, a mutant strain defective in a stress-activated protein kinase does survive the combined stresses. In order to understand the basis for this difference in survival, we have determined the relative levels of detected proteins in the mutant and wild type strain during dual stress, and we have identified gene transcripts in both strains whose quantities change in response to heat shock or dual stress. These data and supportive experimental evidence point to reasons for survival of the mutant strain. By using alternative respiratory mechanisms, these cells experience less of the oxidative stress that proves damaging to wild type cells. Of central importance, mutant cells recycle limited resources during dual stress by undergoing autophagy, a process that we find utilized by both wild type and mutant cells during heat shock. Evidence points to inappropriate activation of TORC1, the central metabolic regulator, in wild type cells during dual stress, based upon behavior of an additional signaling mutant and inhibitor studies. PMID:27870869

Resistance to age-dependent thymic atrophy in long-lived mice that are deficient in pregnancy-associated plasma protein A

PubMed Central

Vallejo, Abbe N.; Michel, Joshua J.; Bale, Laurie K.; Lemster, Bonnie H.; Borghesi, Lisa; Conover, Cheryl A.

2009-01-01

Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase that controls the tissue availability of insulin-like growth factor (IGF). Homozygous deletion of PAPPA in mice leads to lifespan extension. Since immune function is an important determinant of individual fitness, we examined the natural immune ecology of PAPPA−/− mice and their wild-type littermates reared under specific pathogen-free condition with aging. Whereas wild-type mice exhibit classic age-dependent thymic atrophy, 18-month-old PAPPA−/− mice maintain discrete thymic cortex and medulla densely populated by CD4+CD8+ thymocytes that are capable of differentiating into single-positive CD4 and CD8 T cells. Old PAPPA−/− mice have high levels of T cell receptor excision circles, and have bone marrows enriched for subsets of thymus-seeding progenitors. PAPPA−/− mice have an overall larger pool of naive T cells, and also exhibit an age-dependent accumulation of CD44+CD43+ memory T cells similar to wild-type mice. However, CD43+ T cell subsets of old PAPPA−/− mice have significantly lower prevalence of 1B11 and S7, glycosylation isoforms known to inhibit T cell activation with normal aging. In bioassays of cell activation, splenic T cells of old PAPPA−/− mice have high levels of activation antigens and cytokine production, and also elicit Ig production by autologous B cells at levels equivalent to young wild-type mice. These data suggest an IGF-immune axis of healthy longevity. Controlling the availability of IGF in the thymus by targeted manipulation of PAPPA could be a way to maintain immune homeostasis during postnatal development and aging. PMID:19549878

Sex- and age-dependent effects of celiac disease on growth and weight gain in children with type 1 diabetes: Analysis of the type 1 diabetes Exchange Clinic Registry.

PubMed

Simmons, Jill H; Foster, Nicole C; Riddlesworth, Tonya D; DuBose, Stephanie N; Redondo, Maria J; Liu, Edwin; Freemark, Michael

2018-06-01

Celiac disease (CD) is common in patients with type 1 diabetes (T1D) and effects of CD on growth in children with T1D remain unclear. We analyzed heights, weights, and body mass index (BMI) in 215 matched pediatric CD/control pairs in the T1D Exchange Clinic Registry. CD was defined by a clinic-reported diagnosis and positive celiac serology (n = 80) and/or positive small bowel biopsy (n = 135). Cases and controls were matched by age (mean: 14 years), diabetes duration (median: 7 years), sex (57% female), and clinic site. There were 5569 height/weight measurements. Gluten was restricted for varying periods of time in 61% of females and 51% of males with CD. Females with CD were shorter than female controls at all ages (P = 0.01). Weight z-scores were initially lower in preschool females with CD but similar to controls by middle childhood. Males with CD were initially shorter but adult heights were similar. Height in both sexes and weight in males were lower in CD participants diagnosed at younger age. Growth in T1D children with biopsy-proven CD, 76% of them were gluten-restricted, was comparable to that of T1D controls. Concurrent CD impairs linear growth in T1D females at all stages of development and in young T1D males. Young females with CD have lower weights, but both sexes have similar weights by middle childhood. Children younger at CD onset remain shorter throughout childhood; males younger at CD onset have persistently lower weights. Long-term gluten restriction may restore weight gain and linear growth in children with CD and T1D. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mutagenic frequencies of site-specifically located O6-methylguanine in wild-type Escherichia coli and in a strain deficient in ada-methyltransferase.

PubMed

Rossi, S C; Topal, M D

1991-02-01

The adaptive response of Escherichia coli involves protection of the cells against the toxic and mutagenic consequences of exposure to high doses of a methylating agent by prior exposure to low doses of the agent. Ada protein, a major repair activity for O6-methylguanine, is activated to positively control the adaptive response; O6-methylguanine is one of the major mutagenic lesions produced by methylating agents. We investigated the mutation frequency of wild-type Escherichia coli and strains containing the ada-5 mutation in response to site-specifically synthesized O6-methylguanine under conditions in which the adaptive response was not induced. Site-directed mutagenesis and oligonucleotide self-selection techniques were used to isolate the progeny of M13mp18 DNAs constructed to contain O6-methylguanine at any of eight different positions. The progeny were isolated from E. coli strains isogeneic except for deficiency in Ada-methyltransferase repair, UvrABC excision repair, or both. The resulting O6-methylguanine mutation levels at each position were determined by using differential oligonucleotide hybridization. We found that the wild type had up to a 2.6-fold higher mutation frequency than ada-5 mutants. In addition, the mutation frequency varied with the position of the O6-methylguanine in the DNA in the wild type but not in ada-5 mutants; O6-methylguanine lesions at the 5' ends of runs of consecutive guanines gave the highest mutation frequencies. Determination of the mutation frequency of O6-methylguanine in wild-type and mutS cells showed that mismatch repair can affect O6-methylguanine mutation levels.

Wild chimpanzees plan their breakfast time, type, and location

PubMed Central

Janmaat, Karline R. L.; Polansky, Leo; Ban, Simone Dagui; Boesch, Christophe

2014-01-01

Not all tropical fruits are equally desired by rainforest foragers and some fruit trees get depleted more quickly and carry fruit for shorter periods than others. We investigated whether a ripe-fruit specialist, the chimpanzee (Pan troglodytes verus), arrived earlier at breakfast sites with very ephemeral and highly sought-after fruit, like figs, than sites with less ephemeral fruit that can be more predictably obtained throughout the entire day. We recorded when and where five adult female chimpanzees spent the night and acquired food for a total of 275 full days during three fruit-scarce periods in a West African tropical rainforest. We found that chimpanzees left their sleeping nests earlier (often before sunrise when the forest is still dark) when breakfasting on very ephemeral fruits, especially when they were farther away. Moreover, the females positioned their sleeping nests more in the direction of the next day’s breakfast sites with ephemeral fruit compared with breakfast sites with other fruit. By analyzing departure times and nest positioning as a function of fruit type and location, while controlling for more parsimonious explanations, such as temperature, we found evidence that wild chimpanzees flexibly plan their breakfast time, type, and location after weighing multiple disparate pieces of information. Our study reveals a cognitive mechanism by which large-brained primates can buffer the effects of seasonal declines in food availability and increased interspecific competition to facilitate first access to nutritious food. We discuss the implications for theories on hominoid brain-size evolution. PMID:25349399

Life history context of reproductive aging in a wild primate model

PubMed Central

Altmann, Jeanne; Gesquiere, Laurence; Galbany, Jordi; Onyango, Patrick O.; Alberts, Susan C.

2012-01-01

The pace of reproductive aging has been of considerable interest, especially in regard to the long postreproductive period in modern women. Here we use data for both sexes from a 37-year longitudinal study of a wild baboon population to place reproductive aging within a life history context for this species, a primate relative of humans that evolved in the same savannah habitat as humans did. We examine the patterns and pace of reproductive aging, including birth rates and reproductive hormones for both sexes, and compare reproductive aging to age-related changes in several other traits. Reproductive senescence occurs later in baboon females than males. Delayed senescence in females relative to males is also found in several other traits, such as dominance status and body condition, but not in molar wear or glucocorticoid profiles. Survival, health, and well-being are the product of risk factors in morphological, physiological, and behavioral traits that differ in rate of senescence and in dependence on social or ecological conditions; some will be very sensitive to differences in circumstances and others less so. PMID:20738283

Brain size growth in wild and captive chimpanzees (Pan troglodytes).

PubMed

Cofran, Zachary

2018-05-24

Despite many studies of chimpanzee brain size growth, intraspecific variation is under-explored. Brain size data from chimpanzees of the Taï Forest and the Yerkes Primate Research Center enable a unique glimpse into brain growth variation as age at death is known for individuals, allowing cross-sectional growth curves to be estimated. Because Taï chimpanzees are from the wild but Yerkes apes are captive, potential environmental effects on neural development can also be explored. Previous research has revealed differences in growth and health between wild and captive primates, but such habitat effects have yet to be investigated for brain growth. Here, I use an iterative curve fitting procedure to estimate brain growth and regression parameters for each population, statistically comparing growth models using bootstrapped confidence intervals. Yerkes and Taï brain sizes overlap at all ages, although the sole Taï newborn is at the low end of captive neonatal variation. Growth rate and duration are statistically indistinguishable between the two populations. Resampling the Yerkes sample to match the Taï sample size and age group composition shows that ontogenetic variation in the two groups are remarkably similar despite the latter's limited size. Best fit growth curves for each sample indicate cessation of brain size growth at around 2 years, earlier than has previously been reported. The overall similarity between wild and captive chimpanzees points to the canalization of brain growth in this species. © 2018 Wiley Periodicals, Inc.

Dietary restriction ameliorates haematopoietic ageing independent of telomerase, whilst lack of telomerase and short telomeres exacerbates the ageing phenotype.

PubMed

Al-Ajmi, Nouf; Saretzki, Gabriele; Miles, Colin; Spyridopoulos, Ioakim

2014-10-01

Ageing is associated with an overall decline in the functional capacity of tissues and stem cells, including haematopoietic stem and progenitor cells (HSPCs), as well as telomere dysfunction. Dietary restriction (DR) is a recognised anti-ageing intervention that extends lifespan and improves health in several organisms. To investigate the role of telomeres and telomerase in haematopoietic ageing, we compared the HSPC profile and clonogenic capacity of bone marrow cells from wild type with telomerase-deficient mice and the effect of DR on these parameters. Compared with young mice, aged wild type mice demonstrated a significant accumulation of HSPCs (1.3% vs 0.2%, P=0.002) and elevated numbers of granulocyte/macrophage colony forming units (CFU-GM, 26.4 vs 17.3, P=0.0037) consistent with myeloid "skewing" of haematopoiesis. DR was able to restrict the increase in HSPC number as well as the myeloid "skewing" in aged wild type mice. In order to analyse the influence of short telomeres on the ageing phenotype we examined mice lacking the RNA template for telomerase, TERC(-/-). Telomere shortening resulted in a similar bone marrow phenotype to that seen in aged mice, with significantly increased HSPC numbers and an increased formation of all myeloid colony types but at a younger age than wild type mice. However, an additional increase in erythroid colonies (BFU-E) was also evident. Mice lacking telomerase reverse transcriptase without shortened telomeres, TERT(-/-), also presented with augmented haematopoietic ageing which was ameliorated by DR, demonstrating that the effect of DR was not dependent on the presence of telomerase in HSPCs. We conclude that whilst shortened telomeres mimic some aspects of haematopoietic ageing, both shortened telomeres and the lack of telomerase produce specific phenotypes, some of which can be prevented by dietary restriction. Copyright © 2014 Elsevier Inc. All rights reserved.

Wild-type NM23-H1, but not its S120 mutants, suppresses desensitization of muscarinic potassium current.

PubMed

Otero, A S; Doyle, M B; Hartsough, M T; Steeg, P S

1999-03-08

NM23 (NDP kinase) modulates the gating of muscarinic K+ channels by agonists through a mechanism distinct from GTP regeneration. To better define the function of NM23 in this pathway and to identify sites in NM23 that are important for its role in muscarinic K+ channel function, we utilized MDA-MB-435 human breast carcinoma cells that express low levels of NM23-H1. M2 muscarinic receptors and GIRK1/GIRK4 channel subunits were co-expressed in cells stably transfected with vector only (control), wild-type NM23-H1, or several NM23-H1 mutants. Lysates from all cell lines tested exhibit comparable nucleoside diphosphate (NDP) kinase activity. Whole cell patch clamp recordings revealed a substantial reduction of the acute desensitization of muscarinic K+ currents in cells overexpressing NM23-H1. The mutants NM23-H1P96S and NM23-H1S44A resembled wild-type NM23-H1 in their ability to reduce desensitization. In contrast, mutants NM23-H1S120G and NM23-H1S120A completely abolished the effect of NM23-H1 on desensitization of muscarinic K+ currents. Furthermore, NM23-H1S120G potentiated acute desensitization, indicating that this mutant retains the ability to interact with the muscarinic pathway, but has properties antithetical to those of the wild-type protein. We conclude that NM23 acts as a suppressor of the processes leading to the desensitization of muscarinic K+ currents, and that Ser-120 is essential for its actions.

Characterization of Circulating and Endothelial Progenitor Cells in Patients With Extreme-Duration Type 1 Diabetes

PubMed Central

Hernandez, Sonia L.; Gong, Jennifer H.; Chen, Liming; Wu, I-Hsien; Sun, Jennifer K.; Keenan, Hillary A.; King, George L.

2014-01-01

OBJECTIVE We characterized and correlated endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) with lack of vascular complications in the Joslin Medalist Study in patients with type 1 diabetes for 50 years or longer. RESEARCH DESIGN AND METHODS EPC and CPC levels were ascertained by flow cytometry and compared among Medalists (n = 172) with or without diabetic retinopathy (DR; n = 84 of 162), neuropathy (n = 94 of 165), diabetic nephropathy (DN; n = 18 of 172), cardiovascular disease (CVD; n = 63 of 168), age-matched controls (n = 83), type 2 diabetic patients (n = 36), and younger type 1 diabetic patients (n = 31). Mitogens, inflammatory cytokines, and oxidative markers were measured in blood or urine. Migration of cultured peripheral blood mononuclear cells (PBMCs) from Medalists and age-matched controls were compared. RESULTS Medalists’ EPC and CPC levels equaled those of their nondiabetic age-matched controls, were 10% higher than those in younger type 1 diabetic patients, and were 20% higher than those in age-matched type 2 diabetic patients. CPC levels were 15% higher in Medalists without CVD and nephropathy than in those affected, whereas EPC levels were significantly higher in those without peripheral vascular disease (PVD) than those with PVD. Stromal-derived factor 1 (SDF-1) levels were higher in Medalists with CVD, DN, and DR than in those not affected and their controls. IGF-I levels were lower in Medalists and correlated inversely with CPC levels. Additionally, cultured PBMCs from Medalists migrated more than those from nondiabetic controls. CONCLUSIONS Normal levels of EPC and CPC in the Medalists, unlike other groups with diabetes, especially those without CVD, support the idea that endogenous factors exist to neutralize the adverse effects of metabolic abnormalities of diabetes on vascular tissues. PMID:24780357

De novo establishment of wild-type song culture in the zebra finch

PubMed Central

Feher, Olga; Wang, Haibin; Saar, Sigal; Mitra, Partha P.; Tchernichovski, Ofer

2009-01-01

What sort of culture would evolve in an island colony of naive founders? This question cannot be studied experimentally in humans. We performed the analogous experiment using socially learned birdsong. Culture is typically viewed as consisting of traits inherited epigenetically, via social learning. However, cultural diversity has species-typical constraints1, presumably of genetic origin. A celebrated, if contentious, example is whether a universal grammar constrains syntactic diversity in human languages2. Oscine songbirds exhibit song learning and provide biologically tractable models of culture: members of a species show individual variation in song3 and geographically separated groups have local song dialects 4,5. Different species exhibit distinct song cultures6,7, suggestive of genetic constraints8,9. Absent such constraints, innovations and copying errors should cause unbounded variation over multiple generations or geographical distance, contrary to observations9. We asked if wild-type song culture might emerge over multiple generations in an isolated colony founded by isolates, and if so, how this might happen and what type of social environment is required10. Zebra finch isolates, unexposed to singing males during development, produce song with characteristics that differ from the wild-type song found in laboratory11 or natural colonies. In tutoring lineages starting from isolate founders, we quantified alterations in song across tutoring generations in two social environments: tutor-pupil pairs in sound-isolated chambers and an isolated semi-natural colony. In both settings, juveniles imitated the isolate tutors, but changed certain characteristics of the songs. These alterations accumulated over learning generations. Consequently, songs evolved toward the wild-type in 3–4 generations. Thus, species-typical song culture can appear de novo. Our study has parallels with language change and evolution12,13. In analogy to models in quantitative genetics14

A comparison of GluR-A-deficient and wild-type mice on a test battery assessing sensorimotor, affective, and cognitive behaviors.

PubMed

Bannerman, D M; Deacon, R M J; Brady, S; Bruce, A; Sprengel, R; Seeburg, P H; Rawlins, J N P

2004-06-01

Previous studies have demonstrated a spatial working memory deficit in glutamate receptor (GluR)-A (GluR1) AMPA receptor subunit knockout mice. The present study evaluated male and female wild-type and GluR-A-/- mice on a test battery that assessed sensorimotor, affective, and cognitive behaviors. Results revealed a behavioral phenotype more extensive than previously described. GluR-A-/- mice were hyperactive, displayed a subtle lack of motor coordination, and were generally more anxious than wild-type controls. In addition, they showed a deficit in spontaneous alternation, consistent with previous reports of a role for GluR-A-dependent plasticity in hippocampus-dependent, spatial working memory. Although changes in motor coordination or anxiety cannot explain the dissociations already reported within the spatial memory domain, it is clear that they could significantly affect interpretation of results obtained in other kinds of behavioral tasks. ((c) 2004 APA, all rights reserved)

Right ventricular sex differences in patients with idiopathic pulmonary arterial hypertension characterised by magnetic resonance imaging: pair-matched case controlled study.

PubMed

Swift, Andrew J; Capener, Dave; Hammerton, Charlotte; Thomas, Steven M; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2015-01-01

Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females.

Structural differences in the brain between wild and laboratory rats (Rattus norvegicus): potential contribution to wariness.

PubMed

Koizumi, Ryoko; Kiyokawa, Yasushi; Mikami, Kaori; Ishii, Akiko; Tanaka, Kazuyuki D; Tanikawa, Tsutomu; Takeuchi, Yukari

2018-05-11

Wild animals typically exhibit defensive behaviors in response to a wider range and/or a weaker intensity of stimuli compared with domestic animals. However, little is known about the neural mechanisms underlying "wariness" in wild animals. Wild rats are one of the most accessible wild animals for experimental research. Laboratory rats are a domesticated form of wild rat, belonging to the same species, and are therefore considered suitable control animals for wild rats. Based on these factors, we analyzed structural differences in the brain between wild and laboratory rats to elucidate the neural mechanisms underlying wariness. We examined wild rats trapped in Tokyo, and weight-matched laboratory rats. We then prepared brain sections and compared the basolateral complex of the amygdala (BLA), the bed nucleus of the stria terminalis (BNST), the main olfactory bulb, and the accessory olfactory bulb. The results revealed that wild rats exhibited larger BLA, BNST and caudal part of the accessory olfactory bulb compared with laboratory rats. These results suggest that the BLA, BNST, and vomeronasal system potentially contribute to wariness in wild rats.

Improving excellence in scoliosis rehabilitation: a controlled study of matched pairs.

PubMed

Weiss, H-R; Klein, R

2006-01-01

Physiotherapy programmes so far mainly address the lateral deformity of scoliosis, a few aim at the correction of rotation and only very few address the sagittal profile. Meanwhile, there is evidence that correction forces applied in the sagittal plane are also able to correct the scoliotic deformity in the coronal and frontal planes. So it should be possible to improve excellence in scoliosis rehabilitation by the implementation of exercises to correct the sagittal deformity in scoliosis patients. An exercise programme (physio-logic exercises) aiming at a physiologic sagittal profile was developed to add to the programme applied at the centre or to replace certain exercises or exercising positions. To test the hypothesis that physio-logic exercises improve the outcome of Scoliosis Intensive Rehabilitation (SIR), the following study design was chosen: Prospective controlled trial of pairs of patients with idiopathic scoliosis matched by sex, age, Cobb angle and curve pattern. There were 18 patients in the treatment group (SIR + physio-logic exercises) and 18 patients in the control group (SIR only), all in matched pairs. Average Cobb angle in the treatment group was 34.5 degrees (SD 7.8) Cobb angle in the control group was 31.6 degrees (SD 5.8). Age in the treatment group was at average 15.3 years (SD 1.1) and in the control group 14.7 years (SD 1.3). Thirteen of the 18 patients in either group had a brace. Outcome parameter: average lateral deviation (mm), average surface rotation ( degrees ) and maximum Kyphosis angle ( degrees ) as evaluated with the help of surface topography (Formetric-system). Lateral deviation (mm) decreased significantly after the performance of the physio-logic programme and highly significantly in the physio-logic ADL posture; however, it was not significant after completion of the whole rehabilitation programme (2.3 vs 0.3 mm in the controls). Surface rotation improved at average 1.2 degrees in the treatment group and 0.8 degrees in the

Real-time reverse transcription polymerase chain reaction method for detection of Canine distemper virus modified live vaccine shedding for differentiation from infection with wild-type strains.

PubMed

Wilkes, Rebecca P; Sanchez, Elena; Riley, Matthew C; Kennedy, Melissa A

2014-01-01

Canine distemper virus (CDV) remains a common cause of infectious disease in dogs, particularly in high-density housing situations such as shelters. Vaccination of all dogs against CDV is recommended at the time of admission to animal shelters and many use a modified live virus (MLV) vaccine. From a diagnostic standpoint for dogs with suspected CDV infection, this is problematic because highly sensitive diagnostic real-time reverse transcription polymerase chain reaction (RT-PCR) tests are able to detect MLV virus in clinical samples. Real-time PCR can be used to quantitate amount of virus shedding and can differentiate vaccine strains from wild-type strains when shedding is high. However, differentiation by quantitation is not possible in vaccinated animals during acute infection, when shedding is low and could be mistaken for low level vaccine virus shedding. While there are gel-based RT-PCR assays for differentiation of vaccine strains from field strains based on sequence differences, the sensitivity of these assays is unable to match that of the real-time RT-PCR assay currently used in the authors' laboratory. Therefore, a real-time RT-PCR assay was developed that detects CDV MLV vaccine strains and distinguishes them from wild-type strains based on nucleotide sequence differences, rather than the amount of viral RNA in the sample. The test is highly sensitive, with detection of as few as 5 virus genomic copies (corresponding to 10(-1) TCID(50)). Sequencing of the DNA real-time products also allows phylogenetic differentiation of the wild-type strains. This test will aid diagnosis during outbreaks of CDV in recently vaccinated animals.

Antibody titers against vaccine and contemporary wild poliovirus type 1 in children immunized with IPV+OPV and young adults immunized with OPV.

PubMed

Lukashev, Alexander N; Yarmolskaya, Maria S; Shumilina, Elena Yu; Sychev, Daniil A; Kozlovskaya, Liubov I

2016-02-02

In 2010, a type 1 poliovirus outbreak in Congo with 445 lethal cases was caused by a virus that was neutralized by sera of German adults vaccinated with inactivated polio vaccine with a reduced efficiency. This seroprevalence study was done in two cohorts immunized with other vaccination schedules. Russian children aged 3-6 years immunized with a combination of inactivated and live polio vaccines were reasonably well protected against any wild type poliovirus 1, including the Congolese isolate. Adults aged 20-29 years immunized only with live vaccine were apparently protected against the vaccine strain (92% seropositive), but only 50% had detectable antibodies against the Congo-2010 isolate. Both waning immunity and serological divergence of the Congolese virus could contribute to this result. Copyright © 2015 Elsevier B.V. All rights reserved.

[Prevalence, awareness, status of treatment and control on type 2 diabetes mellitus among Chinese premenopausal women aged 18-49 in 2013].

PubMed

Zhao, Y F; Wang, Z Q; Yang, J; Wang, L M; Zhao, Z P; Zeng, X Y; Wang, L H

2018-02-10

Objective: To analyze the rates on prevalence, awareness, status on treatment and control of type 2 diabetes mellitus among Chinese premenopausal women aged 18-49, in 2013. Methods: Data on China Chronic and Non-Communicable Disease Surveillance in year 2013 was used for analysis. Source of data covered 302 surveillance points which were selected by Multi-stage cluster random sampling method that including 176 534 adults over 18 years of age, with 46 674 premenopausal women aged 18-49. Plasma glucose and hemoglobin A1c levels were determined after a 10-hour overnight fast for all the participants, before a 2-hour oral glucose tolerance test was conducted among participants without a self-reported history of diagnosed diabetes. Diabetes was defined according to the 1999 WHO diagnostic criteria-fasting blood glucose level as ≥7.0 mmol/L and/or 2 hours oral glucose tolerance test (OGTT-2 h) level as ≥11.1 mmol/L. After being weighed, according to complex sampling scheme and post-stratification, the sample was used to estimate the rates of prevalence, awareness, treatment and control of type 2 diabetes mellitus by age, education, urban and rural areas, and geographic locations. Results: The overall prevalence of type 2 diabetes mellitus was 5.6% among the Chinese premenopausal women aged 18-49. No statistical difference on the prevalence rates (5.7% and 5.4%, respectively) was seen, between participants from the rural or the urban areas. Prevalence rates in the eastern, central or western geographic areas were 5.8%, 6.2% and 4.4% respectively. The rates of awareness, treatment and control of diabetes appeared as 29.3%, 27.9% and 29.4% in childbearing women aged 18-49. The rate of treatment was 95.4% among those who knew their diabetic situation in childbearing women aged 18-49 years. The control rate of diabetes was 38.9% among those who had taken measures to control glucose, in 18-49-year-old childbearing women. The rate of awareness on diabetes in childbearing

Long-Term Effects of Pregnancy on Renal Graft Function in Women After Kidney Transplantation Compared With Matched Controls.

PubMed

Svetitsky, S; Baruch, R; Schwartz, I F; Schwartz, D; Nakache, R; Goykhman, Y; Katz, P; Grupper, A

2018-06-01

An important benefit associated with kidney transplantation in women of child-bearing age is increased fertility. We retrospectively evaluated the maternal and fetal complications and evolution of graft function associated with 22 pregnancies post-kidney and kidney-pancreas transplantation, compared with controls without pregnancy post-transplantation, who were matched for gender, year of transplantation, type of donor, age at transplantation, number of transplants, type of transplant (kidney vs kidney-pancreas), and cause of native kidney failure, as well as for renal parameters including serum creatinine and urine protein excretion 1 year before delivery. The mean age at time of transplantation was 22.32 (range, 19.45-33.1) years. The mean interval between transplantation and delivery was 75.7 (range, 34-147.8) months. Main maternal complications were pre-eclampsia in 27.3%. The main fetal complications included delayed intrauterine growth (18.2%), preterm deliveries (89.4%), and one death at 3 days postdelivery. The mean serum creatinine level pre-pregnancy was 1.17 (range, 0.7-3.1) mg/dL. Graft failure was higher in the pregnancy group (6 vs 3) but did not differ statistically from the control group, and was associated with creatinine pre-pregnancy (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.15-3.45; P = .04), age at transplantation (1.13 [1.03-1.21]; P = .032), and time of follow-up (2.14 [1.27-2.98]; P = .026). Delta serum creatinine was not different in both groups: 1.05 ± 0.51 versus 0.99 ± 0.92 mg/dL, study versus control group, respectively (P = .17). Pregnancy after kidney transplantation is associated with serious maternal and fetal complications. We did not observe a significantly increased risk of graft loss or reduced graft function in comparison with recipients with similar clinical characteristics. Copyright © 2018 Elsevier Inc. All rights reserved.

Matched samples logistic regression in case-control studies with missing values: when to break the matches.

PubMed

Hansson, Lisbeth; Khamis, Harry J

2008-12-01

Simulated data sets are used to evaluate conditional and unconditional maximum likelihood estimation in an individual case-control design with continuous covariates when there are different rates of excluded cases and different levels of other design parameters. The effectiveness of the estimation procedures is measured by method bias, variance of the estimators, root mean square error (RMSE) for logistic regression and the percentage of explained variation. Conditional estimation leads to higher RMSE than unconditional estimation in the presence of missing observations, especially for 1:1 matching. The RMSE is higher for the smaller stratum size, especially for the 1:1 matching. The percentage of explained variation appears to be insensitive to missing data, but is generally higher for the conditional estimation than for the unconditional estimation. It is particularly good for the 1:2 matching design. For minimizing RMSE, a high matching ratio is recommended; in this case, conditional and unconditional logistic regression models yield comparable levels of effectiveness. For maximizing the percentage of explained variation, the 1:2 matching design with the conditional logistic regression model is recommended.

Perceiving control: a double-edged sword in old age.

PubMed

Kunzmann, Ute; Little, Todd; Smith, Jacqui

2002-11-01

Although control beliefs are thought to be pivotal contributors to emotional well-being in old age, questions remain about the specific and long-term emotional implications of different types of control beliefs. We examined three generalized beliefs about control (personal control over desirable outcomes, personal responsibility for undesirable outcomes, perceived others' control) and their associations with emotional well-being (positive and negative affect) using cross-sectional (N = 516) and longitudinal (N = 206) samples from the Berlin Aging Study (age range = 70-103 years). Relationships between control beliefs and emotional well-being were dependent on the type of control belief and the dimension of emotional well-being considered, the sample investigated, and on whether individual differences at a given point in time or individual differences in intraindividual changes over time were examined. Despite these complexities, findings suggest that perceived control over desirable outcomes is associated with high emotional well-being, whereas perceived others' control is an emotional risk factor in old age.

Effects of phorbol ester on mitogen-activated protein kinase kinase activity in wild-type and phorbol ester-resistant EL4 thymoma cells.

PubMed

Gause, K C; Homma, M K; Licciardi, K A; Seger, R; Ahn, N G; Peterson, M J; Krebs, E G; Meier, K E

1993-08-05

Phorbol ester-sensitive and -resistant EL4 thymoma cell lines differ in their ability to activate mitogen-activated protein kinase (MAPK) in response to phorbol ester. Treatment of wild-type EL4 cells with phorbol ester results in the rapid activations of MAPK and pp90rsk kinase, a substrate for MAPK, while neither kinase is activated in response to phorbol ester in variant EL4 cells. This study examines the activation of MAPK kinase (MAPKK), an activator of MAPK, in wild-type and variant EL4 cells. Phosphorylation of a 40-kDa substrate, identified as MAPK, was observed following in vitro phosphorylation reactions using cytosolic extracts or Mono Q column fractions prepared from phorbol ester-treated wild-type EL4 cells. MAPKK activity coeluted with a portion of the inactive MAPK upon Mono Q anion-exchange chromatography, permitting detection of the MAPKK activity in fractions containing both kinases. This MAPKK activity was present in phorbol ester-treated wild-type cells, but not in phorbol ester-treated variant cells or in untreated wild-type or variant cells. The MAPKK from wild-type cells was able to activate MAPK prepared from either wild-type or variant cells. MAPKK activity could be stimulated in both wildtype and variant EL4 cells in response to treatment of cells with okadaic acid. These results indicate that the failure of variant EL4 cells to activate MAP kinase in response to phorbol ester is due to a failure to activate MAPKK. Therefore, the step that confers phorbol ester resistance to variant EL4 cells lies between the activation of protein kinase C and the activation of MAPKK.

Differential composition of culture supernatants from wild-type Brucella abortus and its isogenic virB mutants.

PubMed

Delpino, M Victoria; Comerci, Diego J; Wagner, Mary Ann; Eschenbrenner, Michel; Mujer, Cesar V; Ugalde, Rodolfo A; Fossati, Carlos A; Baldi, Pablo C; Delvecchio, Vito G

2009-07-01

The virB genes coding type IV secretion system are necessary for the intracellular survival and replication of Brucella spp. In this study, extracellular proteins from B. abortus 2308 (wild type, WT) and its isogenic virB10 polar mutant were compared. Culture supernatants harvested in the early stationary phase were concentrated and subjected to 2D electrophoresis. Spots present in the WT strain but absent in the virB10 mutant (differential spots) were considered extracellular proteins released in a virB-related manner, and were identified by MALDI-TOF analysis and matching with Brucella genomes. Among the 11 differential proteins identified, DnaK chaperone (Hsp70), choloylglycine hydrolase (CGH) and a peptidyl-prolyl cis-trans isomerase (PPIase) were chosen for further investigation because of their homology with extracellular and/or virulence factors from other bacteria. The three proteins were obtained in recombinant form and specific monoclonal antibodies (mAbs) were prepared. By Western blot with these mAbs, the three proteins were detected in supernatants from the WT but not in those from the virB10 polar mutant or from strains carrying non-polar mutations in virB10 or virB11 genes. These results suggest that the expression of virB genes affects the extracellular release of DnaK, PPIase and CGH, and possibly other proteins from B. abortus.

Major childhood infectious diseases and other determinants associated with type 1 diabetes: a case-control study.

PubMed

Tenconi, M T; Devoti, G; Comelli, M; Pinon, M; Capocchiano, A; Calcaterra, V; Pretti, G

2007-03-01

The objective of the study was to evaluate the association between infectious diseases and other events pertaining to childhood medical history and type 1 diabetes. A case-control study was carried out, taking as cases 159 type 1 diabetic patients (0-29 years) recorded from 1988 to 2000 within the population registry of the Pavia province (North Italy). As controls 318 non-diabetic subjects were matched by age and sex. A questionnaire was administered by standardised interviewers. Data were analysed by conditional logistic regression. Viral childhood diseases (OR 4.29; 95%CI 1.57-11.74) and bottle feeding (OR 1.83; 95%CI 1.08-3.09) were directly correlated to type 1 diabetes; an inverse correlation was found for vitamin D administration during lactation (0-14 years) (OR 0.31; 95%CI 0.11-0.86) and for history of scarlet fever in both sexes and age groups (OR 0.19; 95%CI 0.08-0.46). Most associations of the studied variables confirm already known findings. The significant inverse correlation of type 1 diabetes with scarlet fever history is a peculiar finding, the meaning of which is still obscure, although it has been recently described that streptococcal A infections are regulated by HLA class II alleles.

Genetic characterization of the hemagglutinin genes of wild-type measles virus circulating in china, 1993-2009.

PubMed

Xu, Songtao; Zhang, Yan; Zhu, Zhen; Liu, Chunyu; Mao, Naiying; Ji, Yixin; Wang, Huiling; Jiang, Xiaohong; Li, Chongshan; Tang, Wei; Feng, Daxing; Wang, Changyin; Zheng, Lei; Lei, Yue; Ling, Hua; Zhao, Chunfang; Ma, Yan; He, Jilan; Wang, Yan; Li, Ping; Guan, Ronghui; Zhou, Shujie; Zhou, Jianhui; Wang, Shuang; Zhang, Hong; Zheng, Huanying; Liu, Leng; Ma, Hemuti; Guan, Jing; Lu, Peishan; Feng, Yan; Zhang, Yanjun; Zhou, Shunde; Xiong, Ying; Ba, Zhuoma; Chen, Hui; Yang, Xiuhui; Bo, Fang; Ma, Yujie; Liang, Yong; Lei, Yake; Gu, Suyi; Liu, Wei; Chen, Meng; Featherstone, David; Jee, Youngmee; Bellini, William J; Rota, Paul A; Xu, Wenbo

2013-01-01

China experienced several large measles outbreaks in the past two decades, and a series of enhanced control measures were implemented to achieve the goal of measles elimination. Molecular epidemiologic surveillance of wild-type measles viruses (MeV) provides valuable information about the viral transmission patterns. Since 1993, virologic surveillnace has confirmed that a single endemic genotype H1 viruses have been predominantly circulating in China. A component of molecular surveillance is to monitor the genetic characteristics of the hemagglutinin (H) gene of MeV, the major target for virus neutralizing antibodies. Analysis of the sequences of the complete H gene from 56 representative wild-type MeV strains circulating in China during 1993-2009 showed that the H gene sequences were clustered into 2 groups, cluster 1 and cluster 2. Cluster1 strains were the most frequently detected cluster and had a widespread distribution in China after 2000. The predicted amino acid sequences of the H protein were relatively conserved at most of the functionally significant amino acid positions. However, most of the genotype H1 cluster1 viruses had an amino acid substitution (Ser240Asn), which removed a predicted N-linked glycosylation site. In addition, the substitution of Pro397Leu in the hemagglutinin noose epitope (HNE) was identified in 23 of 56 strains. The evolutionary rate of the H gene of the genotype H1 viruses was estimated to be approximately 0.76×10(-3) substitutions per site per year, and the ratio of dN to dS (dN/dS) was <1 indicating the absence of selective pressure. Although H genes of the genotype H1 strains were conserved and not subjected to selective pressure, several amino acid substitutions were observed in functionally important positions. Therefore the antigenic and genetic properties of H genes of wild-type MeVs should be monitored as part of routine molecular surveillance for measles in China.

Energy demands during a judo match and recovery.

PubMed

Degoutte, F; Jouanel, P; Filaire, E

2003-06-01

To assess energy demand during a judo match and the kinetics of recovery by measuring the metabolites of the oxypurine cascade, lipolytic activity, and glycolytic pathway. Venous blood samples were taken from 16 national judoists (mean (SEM) age 18.4 (1.6) years), before (T(1)) and three minutes (T(2)), one hour (T(3)), and 24 hours (T(4)) after a match. A seven day diet record was used to evaluate nutrient intake. Nutrient analysis indicated that these athletes followed a low carbohydrate diet. Plasma lactate concentration had increased to 12.3 (1.8) mmol/l at the end of the match. An increase in the levels of extracellular markers of muscle adenine nucleotide catabolism, urea, and creatinine was observed at T(2), while uric acid levels remained unchanged. High concentrations of urea persisted for 24 hours during the recovery period. Ammonia, hypoxanthine, xanthine, and creatinine returned to control levels within the 24 hour recovery period. Uric acid concentrations rose from T(3) and had not returned to baseline 24 hours after the match. The levels of triglycerides, glycerol, and free fatty acids had increased significantly (p<0.05) after the match (T(2)) but returned to baseline values within 24 hours. Concentrations of high density lipoprotein cholesterol and total cholesterol were significantly increased after the match. These results show that a judo match induces both protein and lipid metabolism. Carbohydrate availability, training adaptation, and metabolic stress may explain the requirement for these types of metabolism.

Wild-type and mutated IDH1/2 enzymes and therapy responses.

PubMed

Molenaar, Remco J; Maciejewski, Jaroslaw P; Wilmink, Johanna W; van Noorden, Cornelis J F

2018-04-01

Isocitrate dehydrogenase 1 and 2 (IDH1/2) are key enzymes in cellular metabolism, epigenetic regulation, redox states, and DNA repair. IDH1/2 mutations are causal in the development and/or progression of various types of cancer due to supraphysiological production of D-2-hydroxyglutarate. In various tumor types, IDH1/2-mutated cancers predict for improved responses to treatment with irradiation or chemotherapy. The present review discusses the molecular basis of the sensitivity of IDH1/2-mutated cancers with respect to the function of mutated IDH1/2 in cellular processes and their interactions with novel IDH1/2-mutant inhibitors. Finally, lessons learned from IDH1/2 mutations for future clinical applications in IDH1/2 wild-type cancers are discussed.

Combined Non-alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Sleeve Gastrectomy or Gastric Bypass?-a Controlled Matched Pair Study of 34 Patients.

PubMed

Billeter, Adrian T; Senft, Jonas; Gotthardt, Daniel; Knefeli, Philipp; Nickel, Felix; Schulte, Thilo; Fischer, Lars; Nawroth, Peter P; Büchler, Markus W; Müller-Stich, Beat P

2016-08-01

Although all bariatric procedures improve non-alcoholic fatty liver disease (NAFLD) in metabolically sick obese patients, it remains unclear whether different procedures achieve similar effects. Sleeve gastrectomy (SG) and Roux-Y-gastric bypass (RYGB) were compared for their effects on liver function tests (LFT) and glycemic control in a highly selected group of metabolically sick obese patients with both elevated alanine aminotransferase (ALT), a common marker for NAFLD and type 2 diabetes mellitus (T2DM). Thirty-four obese patients with a body mass index (BMI) >35 kg/m(2), ALT > 35 U/L, and T2DM were well-matched from a prospective database and retrospectively analyzed. Seventeen patients each underwent RYGB and SG, respectively. The effects on LFT and glycemic control were evaluated over 12 months. Both procedures significantly lowered ALT and aspartate aminotransferase (AST) after 12 months, but SG improved both LFT significantly better than RYGB (ALT 17.8 ± 8.8 vs. 31.1 ± 11.2 U/L, p = 0.003; AST 17.0 ± 8.8 vs. 24.3 ± 7.5 U/L, p = 0.004). In contrast to RYGB, SG normalized elevated ALT levels completely (41 vs. 0 %, p = 0.007). Both SG and RYGB improved insulin resistance, glycemic control, and reduced the need of insulin significantly without any difference between the procedures. SG appears to improve LFT better than RYGB in well-matched obese patients with both elevated ALT and T2DM. This suggests that SG may have a better effect on NAFLD than RYGB with similar effects on glycemic control. The present findings should be verified in randomized controlled trials to obtain further evidence for the decision-making on the most appropriate bariatric procedure for metabolically sick patients.

The effect of wild card designations and rare alleles in forensic DNA database searches.

PubMed

Tvedebrink, Torben; Bright, Jo-Anne; Buckleton, John S; Curran, James M; Morling, Niels

2015-05-01

Forensic DNA databases are powerful tools used for the identification of persons of interest in criminal investigations. Typically, they consist of two parts: (1) a database containing DNA profiles of known individuals and (2) a database of DNA profiles associated with crime scenes. The risk of adventitious or chance matches between crimes and innocent people increases as the number of profiles within a database grows and more data is shared between various forensic DNA databases, e.g. from different jurisdictions. The DNA profiles obtained from crime scenes are often partial because crime samples may be compromised in quantity or quality. When an individual's profile cannot be resolved from a DNA mixture, ambiguity is introduced. A wild card, F, may be used in place of an allele that has dropped out or when an ambiguous profile is resolved from a DNA mixture. Variant alleles that do not correspond to any marker in the allelic ladder or appear above or below the extent of the allelic ladder range are assigned the allele designation R for rare allele. R alleles are position specific with respect to the observed/unambiguous allele. The F and R designations are made when the exact genotype has not been determined. The F and R designation are treated as wild cards for searching, which results in increased chance of adventitious matches. We investigated the probability of adventitious matches given these two types of wild cards. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A Herpes Simplex Virus Type 1 Mutant Expressing a Baculovirus Inhibitor of Apoptosis Gene in Place of Latency-Associated Transcript Has a Wild-Type Reactivation Phenotype in the Mouse

PubMed Central

Jin, Ling; Perng, Guey-Chuen; Mott, Kevin R.; Osorio, Nelson; Naito, Julia; Brick, David J.; Carpenter, Dale; Jones, Clinton; Wechsler, Steven L.

2005-01-01

The latency-associated transcript (LAT) is essential for the wild-type herpes simplex virus type 1 (HSV-1) high-reactivation phenotype since LAT− mutants have a low-reactivation phenotype. We previously reported that LAT can decrease apoptosis and proposed that this activity is involved in LAT's ability to enhance the HSV-1 reactivation phenotype. The first 20% of the primary 8.3-kb LAT transcript is sufficient for enhancing the reactivation phenotype and for decreasing apoptosis, supporting this proposal. For this study, we constructed an HSV-1 LAT− mutant that expresses the baculovirus antiapoptosis gene product cpIAP under control of the LAT promoter and in place of the LAT region mentioned above. Mice were ocularly infected with this mutant, designated dLAT-cpIAP, and the reactivation phenotype was determined using the trigeminal ganglion explant model. dLAT-cpIAP had a reactivation phenotype similar to that of wild-type virus and significantly higher than that of (i) the LAT− mutant dLAT2903; (ii) dLAT1.5, a control virus containing the same LAT deletion as dLAT-cpIAP, but with no insertion of foreign DNA, thereby controlling for potential readthrough transcription past the cpIAP insert; and (iii) dLAT-EGFP, a control virus identical to dLAT-cpIAP except that it contained the enhanced green fluorescent protein open reading frame (ORF) in place of the cpIAP ORF, thereby controlling for expression of a random foreign gene instead of the cpIAP gene. These results show that an antiapoptosis gene with no sequence similarity to LAT can efficiently substitute for the LAT function involved in enhancing the in vitro-induced HSV-1 reactivation phenotype in the mouse. PMID:16160155

A concordance index for matched case-control studies with applications in cancer risk.

PubMed

Brentnall, Adam R; Cuzick, Jack; Field, John; Duffy, Stephen W

2015-02-10

In unmatched case-control studies, the area under the receiver operating characteristic (ROC) curve (AUC) may be used to measure how well a variable discriminates between cases and controls. The AUC is sometimes used in matched case-control studies by ignoring matching, but it lacks interpretation because it is not based on an estimate of the ROC for the population of interest. We introduce an alternative measure of discrimination that is the concordance of risk factors conditional on the matching factors. Parametric and non-parametric estimators are given for different matching scenarios, and applied to real data from breast and lung cancer case-control studies. Diagnostic plots to verify the constancy of discrimination over matching factors are demonstrated. The proposed simple measure is easy to use, interpret, more efficient than unmatched AUC statistics and may be applied to compare the conditional discrimination performance of risk factors. Copyright © 2014 John Wiley & Sons, Ltd.

Use of context in emotion perception: The role of top-down control, cue type, and perceiver's age.

PubMed

Ngo, Nhi; Isaacowitz, Derek M

2015-06-01

Although context is crucial to emotion perception, there are various factors that can modulate contextual influence. The current research investigated how cue type, top-down control, and the perceiver's age influence attention to context in facial emotion perception. In 2 experiments, younger and older adults identified facial expressions contextualized by other faces, isolated objects, and scenes. In the first experiment, participants were instructed to ignore face, object, and scene contexts. Face context was found to influence perception the least, whereas scene context produced the most contextual effect. Older adults were more influenced by context than younger adults, but both age groups were similarly influenced by different types of contextual cues, even when they were instructed to ignore the context. In the second experiment, when explicitly instructed that the context had no meaningful relationship to the target, younger and older adults both were less influenced by context than when they were instructed that the context was relevant to the target. Results from both studies indicate that contextual influence on emotion perception is not constant, but can vary based on the type of contextual cue, cue relevance, and the perceiver's age. (c) 2015 APA, all rights reserved).

Age-Related Normogram for Ovarian Antral Follicle Count in Women with Polycystic Ovary Syndrome and Comparison with Age Matched Controls Using Magnetic Resonance Imaging.

PubMed

Aiyappan, Senthil Kumar; Karpagam, Bulabai; Vadanika, V; Chidambaram, Prem Kumar; Vinayagam, S; Saravanan, K C

2016-01-01

Antral Follicle count (AFC) is a reliable marker for ovarian reserve. Previous studies have used transvaginal ultrasound for estimation of AFC, however we used magnetic resonance imaging (MRI) for estimation of AFC and for creating an age-related normogram in patients with polycystic ovary syndrome (PCOS) and compared it with normal patients. The aim of this study is to create an age related normogram for AFC in women with PCOS and to compare that with women without polycystic ovarian syndrome using MRI. A total of 1500 women were examined, out of which 400 fitted the criteria for PCOS. They all underwent MRI study and similar age matched women without PCOS also underwent MRI examination. Normogram for AFC were obtained using LMS software and a percentile chart was obtained. Normogram for AFC in PCOS women showed decline in number of AFC as the age progresses and the decline was linear. The normogram for AFC was compared with equal number of patients without PCOS and they also showed decline in AFC as the age progresses, however the decline was exponential and faster. Age related normogram for AFC is widely used and considered as best clinical predictor for ovarian response in assisted reproductive technology. Knowledge of ovarian reserve is important in PCOS and non-PCOS females as PCOS patients are at risk for ovarian hyperstimulation syndrome during gonadotrophin theraphy. MRI is an equally effective and in some times better alternative to transvaginal ultrasound as it has got its own advantages.

Incorporation of excess wild-type and mutant tRNA(3Lys) into human immunodeficiency virus type 1.

PubMed Central

Huang, Y; Mak, J; Cao, Q; Li, Z; Wainberg, M A; Kleiman, L

1994-01-01

Human immunodeficiency virus (HIV) particles produced in COS-7 cells transfected with HIV type 1 (HIV-1) proviral DNA contain 8 molecules of tRNA(3Lys) per 2 molecules of genomic RNA and 12 molecules of tRNA1,2Lys per 2 molecules of genomic RNA. When COS-7 cells are transfected with a plasmid containing both HIV-1 proviral DNA and a human tRNA3Lys gene, there is a large increase in the amount of cytoplasmic tRNA3Lys per microgram of total cellular RNA, and the tRNA3Lys content in the virus increases from 8 to 17 molecules per 2 molecules of genomic RNA. However, the total number of tRNALys molecules per 2 molecules of genomic RNA remains constant at 20; i.e., the viral tRNA1,2Lys content decreases from 12 to 3 molecules per 2 molecules of genomic RNA. All detectable tRNA3Lys is aminoacylated in the cytoplasm of infected cells and deacylated in the virus. When COS-7 cells are transfected with a plasmid containing both HIV-1 proviral DNA and a mutant amber suppressor tRNA3Lys gene (in which the anticodon is changed from TTT to CTA), there is also a large increase in the relative concentration of cytoplasmic tRNA3Lys, and the tRNA3Lys content in the virus increases from 8 to 15 molecules per 2 molecules of genomic RNA, with a decrease in viral tRNA1,2Lys from 12 to 5 molecules per 2 molecules of genomic RNA. Thus, the total number of molecules of tRNALys in the virion remains at 20. The alteration of the anticodon has little effect on the viral packaging of this mutant tRNA in spite of the fact that it no longer contains the modified base mcm 5s2U at position 34, and its ability to be aminoacylated is significantly impaired compared with that of wild-type tRNA3Lys. Viral particles which have incorporated either excess wild-type tRNA3Lys or mutant suppressor tRNA3Lys show no differences in viral infectivity compared with wild-type HIV-1. Images PMID:7966556

A ten-week biochemistry lab project studying wild-type and mutant bacterial alkaline phosphatase.

PubMed

Witherow, D Scott

2016-11-12

This work describes a 10-week laboratory project studying wild-type and mutant bacterial alkaline phosphatase, in which students purify, quantitate, and perform kinetic assays on wild-type and selected mutants of the enzyme. Students also perform plasmid DNA purification, digestion, and gel analysis. In addition to simply learning important techniques, students acquire novel biochemical data in their kinetic analysis of mutant enzymes. The experiments are designed to build on students' work from week to week in a way that requires them to apply quantitative analysis and reasoning skills, reinforcing traditional textbook biochemical concepts. Students are assessed through lab reports focused on journal style writing, quantitative and conceptual question sheets, and traditional exams. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):555-564, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts

PubMed Central

Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

2017-01-01

Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and recorded, and at the end of experiments, tumor xenografts were removed for Western blot and immunohistochemical analyses. Compared to control groups (negative control, regular-dose icotinib [IcoR], high-dose icotinib [IcoH], and docetaxel [DTX]) and regular icotinib dose (60 mg/kg) with docetaxel, treatment of mice with a high-dose (1200 mg/kg) of icotinib plus sequential docetaxel for 3 weeks (IcoH-DTX) had an additive effect on suppression of tumor xenograft size and volume (P < 0.05). Icotinib-containing treatments markedly reduced phosphorylation of EGFR, mitogen activated protein kinase (MAPK), and protein kinase B (Akt), but only the high-dose icotinib-containing treatments showed an additive effect on CD34 inhibition (P < 0.05), an indication of reduced microvessel density in tumor xenografts. Moreover, high-dose icotinib plus docetaxel had a similar effect on mouse weight loss (a common way to measure adverse reactions in mice), compared to the other treatment combinations. The study indicate that the high dose of icotinib plus sequential docetaxel (IcoH-DTX) have an additive effect on suppressing the growth of wild-type EGFR NSCLC cell nude mouse xenografts, possibly through microvessel density reduction. Future clinical trials are needed to confirm the findings of this study. PMID:27852073

The effect of mild traumatic brain injury on peripheral nervous system pathology in wild-type mice and the G93A mutant mouse model of motor neuron disease.

PubMed

Evans, T M; Jaramillo, C A; Sataranatarajan, K; Watts, L; Sabia, M; Qi, W; Van Remmen, H

2015-07-09

Traumatic brain injury (TBI) is associated with a risk of neurodegenerative disease. Some suggest a link between TBI and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). To investigate the potential mechanisms linking TBI to MND, we measured motor function and neuropathology following mild-TBI in wild-type and a transgenic model of ALS, G93A mutant mice. Mild-TBI did not alter the lifespan of G93A mice or age of onset; however, rotarod performance was impaired in G93A verses wild-type mice. Grip strength was reduced only in G93A mice after mild-TBI. Increased electromyography (EMG) abnormalities and markers of denervation (AchR, Runx1) indicate that mild-TBI may result in peripheral effects that are exaggerated in G93A mice. Markers of inflammation (cell edema, astrogliosis and microgliosis) were detected at 24 and 72h in the brain and spinal cord in wild-type and G93A mice. Levels of F2-isoprostanes, a marker of oxidative stress, were increased in the spinal cord 24h post mild-TBI in wild-type mice but were not affected by TBI in G93A mice. In summary, our data demonstrate that mild-TBI induces inflammation and oxidative stress and negatively impacts muscle denervation and motor performance, suggesting mild-TBI can potentiate motor neuron pathology and influence the development of MND in mice. Published by Elsevier Ltd.

Matched comparison of primary versus salvage laparoscopic pyeloplasty.

PubMed

Ambani, Sapan N; Yang, David Y; Wolf, J Stuart

2017-06-01

To compare our experience with salvage laparoscopic pyeloplasty, using a matched control set of primary laparoscopic pyeloplasty patients. We retrospectively reviewed patients who underwent laparoscopic pyeloplasty from 1996 to 2014 by a single surgeon. At least 12 months of follow-up was required. Salvage patients were matched 1:3 with primary patients. Matching was based on age ±5 years, body mass index (BMI) ±5, and type of pyeloplasty (dismembered vs. non-dismembered). Primary outcome was failure as defined as re-intervention following laparoscopic pyeloplasty (does not include temporary stenting without definitive retreatment). Of 128 laparoscopic pyeloplasty procedures, ten were salvage. These patients were matched to 26 patients who underwent a primary laparoscopic pyeloplasty in a 1:3 manner. One salvage pyeloplasty failed to match due to BMI, and the closest matches were made. Four salvage patients had one overlapping match, reducing the primary group to 26 patients. There were no differences in pre-, intra-, and postoperative variables between groups, except for operative time (salvage 247 min, primary 175 min, p = 0.03). With similar duration of radiologic and symptomatic follow-up, there was no significant difference in the rate of freedom from intervention. When matching for factors that could affect success, salvage laparoscopic pyeloplasty performed as well as primary pyeloplasty except for a longer operative time. In experienced hands, salvage laparoscopic pyeloplasty for ureteropelvic junction obstruction recurrence after prior pyeloplasty is a safe and effective procedure, and should be considered an excellent alternative to the more commonly recommended endopyelotomy.

Aging and Haptic-Visual Solid Shape Matching.

PubMed

Norman, J Farley; Adkins, Olivia C; Dowell, Catherine J; Hoyng, Stevie C; Gilliam, Ashley N; Pedersen, Lauren E

2017-08-01

A total of 36 younger (mean age = 21.3 years) and older adults (mean age = 73.8 years) haptically explored plastic copies of naturally shaped objects (bell peppers, Capsicum annuum) one at a time for 7 s each. The participants' task was to then choose which of 12 concurrently visible objects had the same solid shape as the one they felt. The younger and older participants explored the object shapes using either one, three, or five fingers (there were six participants for each combination of number of fingers and age group). The outcome was different from that of previous research conducted with manmade objects. Unlike Jansson and Monaci (2006) , we found that for most objects, our participants' performance was unaffected by variations in the number of fingers used for haptic exploration. While there was no significant overall effect of the number of fingers, there was a significant main effect of age. The younger adults' shape matching performance was 48.6% higher than that of the older adults. When perceiving naturally shaped objects such as bell peppers, it appears that the usage of a single finger can be as effective as haptic exploration with a whole complement of five fingers.

A multiplex reverse transcription-nested polymerase chain reaction for detection and differentiation of wild-type and vaccine strains of canine distemper virus

PubMed Central

2010-01-01

A multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) method was developed for the detection and differentiation of wild-type and vaccine strains of canine distemper virus (CDV). A pair of primers (P1 and P4) specific for CDV corresponding to the highly conserved region of the CDV genome were used as a common primer pair in the first-round PCR of the nested PCR. Primers P2 specific for CDV wild-type strains, were used as the forward primer together with the common reverse primer P4 in the second round of nested PCR. Primers P3, P5 specific for CDV wild-type strain or vaccine strain, were used as the forward primer together with the common reverse primer P4+P6 in the second round of nested PCR. A fragment of 177 bp was amplified from vaccine strain genomic RNA, and a fragment of 247 bp from wild-type strain genomic RNA in the RT-nPCR, and two fragments of 247 bp and 177 bp were amplified from the mixed samples of vaccine and wild-type strains. No amplification was achieved for uninfected cells, or cells infected with Newcastle disease virus (NDV), canine parvovirus (CPV), canine coronavirus (CCV), rabies virus (RV), or canine adenovirus (CAV). The RT-nPCR method was used to detect 30 field samples suspected of canine distemper from Heilongjiang and Jilin Provinces, and 51 samples in Shandong province. As a result of 30 samples, were found to be wild-type-like, and 5 to be vaccine-strain-like. The RT-nPCR method can be used to effectively detect and differentiate wild-type CDV-infected dogs from dogs vaccinated with CDV vaccine, and thus can be used in clinical detection and epidemiological surveillance. PMID:20433759

The role of molecular typing and perfect match transfusion in sickle cell disease and thalassaemia: An innovative transfusion strategy.

PubMed

Putzulu, Rossana; Piccirillo, Nicola; Orlando, Nicoletta; Massini, Giuseppina; Maresca, Maddalena; Scavone, Fernando; Ricerca, Bianca Maria; Zini, Gina

2017-04-01

Chronic red blood cell transfusions remain an essential part of supportive treatment in patients with thalassaemia and sickle cell disease (SCD). Red blood cell (RBC) transfusions expose patients to the risk of developing antibodies: RBC alloimmunization occurs when the immune system meets foreign antigens. We created a register of extensively genotyped donors to achieve a better matched transfusion in order to reduce transfusion alloimmunization. Extended RBC antigen typing was determined and confirmed by molecular biology techniques using Human Erythrocyte Antigen (HEA) BeadChip (BioArray Solutions Ltd., Warren, NJ) in periodic blood donors and in patients with thalassaemia and SCD. During 3 years, we typed extensively 1220 periodic blood donors, 898 male and 322 female. We also studied 10 hematologic patients affected by thalassaemia and sickle cell disease referred to our institution as candidate to periodic transfusions. Our patients (8 females and 2 males with a median age of 48 years, range 24-76 years), extensively typed using molecular techniques and screened for RBC alloantibodies, were transfused with a median of 33.5 RBC units. After three years of molecular typing, the "perfect match" transfusion strategy avoided new alloantibodies development in all studied patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Excretion of Wild-Type and Vaccine-Derived Poliovirus in the Feces of Poliovirus Receptor-Transgenic Mice

PubMed Central

Boot, Hein J.; Kasteel, Daniella T. J.; Buisman, Anne-Marie; Kimman, Tjeerd G.

2003-01-01

The emergence of circulating vaccine-derived poliovirus (cVDPV) strains in suboptimally vaccinated populations is a serious threat to the global poliovirus eradication. The genetic determinants for the transmissibility phenotype of polioviruses, and in particularly of cVDPV strains, are currently unknown. Here we describe the fecal excretion of wild-type poliovirus, oral polio vaccine, and cVDPV (Hispaniola) strains after intraperitoneal injection in poliovirus receptor-transgenic mice. Both the pattern and the level of fecal excretion of the cVDPV strains resemble those of wild-type poliovirus type 1. In contrast, very little poliovirus was present in the feces after oral polio vaccine administration. This mouse model will be helpful in elucidating the genetic determinants for the high fecal-oral transmission phenotype of cVDPV strains. PMID:12743311

Right Ventricular Sex Differences in Patients with Idiopathic Pulmonary Arterial Hypertension Characterised by Magnetic Resonance Imaging: Pair-Matched Case Controlled Study

PubMed Central

Swift, Andrew J.; Capener, Dave; Hammerton, Charlotte; Thomas, Steven M.; Elliot, Charlie; Condliffe, Robin; Wild, Jim M.; Kiely, David G.

2015-01-01

Purpose Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). Methods A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. Results 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Conclusion Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females. PMID:25996939

Rapid authentication of different ages of tissue-cultured and wild Dendrobium huoshanense as well as wild Dendrobium henanense using FTIR and 2D-COS IR

NASA Astrophysics Data System (ADS)

Chen, Nai-Dong; Chen, Nai-Fu; Li, Jun; Cao, Cai-Yun; Wang, Jin-Mei

2015-12-01

The accumulating of pharmaceutical chemicals in medicinal plants would greatly be affected by their ages and establishing a fast quality-identification method to evaluate the similarity of medicinal herbs at different cultivated ages is a critical step for assurance of quality and safety in the TCM industry. In this work, tri-step IR macro-fingerprinting and 2D-COS IR spectrum techniques combined with statistical pattern recognition were applied for discrimination and similarity evaluation of different ages of tissue-cultured and wild Dendrobium huoshanense C. Z. Tang et S. J. Cheng as well as Dendrobium henanense J.L.Lu et L.X Gao. Both tissue-cultured and wild D. huoshanense were easily differentiated from D. henanense by FTIR and SD-IR spectra, while it's quite difficult to discriminate different cultivated years of the three investigated Dendrobiums. In 2D-COS IR spectra, 1-5 auto-peaks with different indensity and positions were located in the region 1160-1030 cm-1 of the twelve Dendrobium samples and thus could be used to identify Dendrobium samples at different ages. Principle component analysis (PCA) of synchronous 2D-COS data showed that the twelve samples were effectively identified and evaluated. The results indicated that the tri-step infrared macro-fingerprinting combined with PCA method was suitable to differentiate the cultivated ages of Dendrobiums with species and orgins rapidly and nondestructively.

Insights into wild-type and mutant p53 functions provided by genetically engineered mice.

PubMed

Donehower, Lawrence A

2014-06-01

Recent whole-exome sequencing studies of numerous human cancers have now conclusively shown that the TP53 tumor-suppressor gene is the most frequently mutated gene in human cancers. Despite extensive studies of the TP53 gene and its encoded protein (p53), our understanding of how TP53 mutations contribute to cancer initiation and progression remain incomplete. Genetically engineered mice with germline or inducible Trp53 somatic mutations have provided important insights into the mechanisms by which different types of p53 mutation influence cancer development. Trp53 germline mutations that alter specific p53 structural domains or posttranslation modification sites have benefitted our understanding of wild-type p53 functions in a whole organism context. Moreover, genetic approaches to reestablish functional wild-type p53 to p53-deficient tissues and tumors have increased our understanding of the therapeutic potential of restoring functional p53 signaling to cancers. This review outlines many of the key insights provided by the various categories of Trp53 mutant mice that have been generated by multiple genetic engineering approaches. © 2014 WILEY PERIODICALS, INC.

Eye pigments in wild-type and eye-color mutant strains of the African malaria vector Anopheles gambiae.

PubMed

Beard, C B; Benedict, M Q; Primus, J P; Finnerty, V; Collins, F H

1995-01-01

Chromatographic analysis of pigments extracted from wild-type eyes of the mosquito Anopheles gambiae reveals the presence of the ommatin precursor 3-hydroxykynurenine, its transamination derivative xanthurenic acid, and a dark, red-brown pigment spot that probably is composed of two or more low mobility xanthommatins. No colored or fluorescent pteridines are evident. Mosquitoes homozygous for an autosomal recessive mutation at the red-eye (r) locus have a brick-red eye color in larvae, pupae, and young adults, in contrast to the almost black color of the wild eye. Mosquitoes homozygous for this mutant allele have levels of ommochrome precursors that are indistinguishable from the wild-type, but the low-mobility xanthommatin spot is ochre-brown in color rather than red-brown as in the wild-type. Mosquitoes with two different mutant alleles at the X-linked pink-eye locus (p, which confers a pink eye color, and pw, which confers a white eye phenotype in homozygotes or hemizygous males) have normal levels of ommochrome precursors but no detectable xanthommatins. Mosquitoes homozygous for both the r and p mutant alleles have apricot-colored eyes and show no detectable xanthommatins. Both the pink-eye and red-eye mutations appear to involve defects in the transport into or assembly of pigments in the membrane-bound pigment granules rather then defects in ommochrome synthesis.

Do body mass index trajectories affect the risk of type 2 diabetes? A case-control study.

PubMed

Mano, Yoshihiko; Yokomichi, Hiroshi; Suzuki, Kohta; Takahashi, Atsunori; Yoda, Yoshioki; Tsuji, Masahiro; Sato, Miri; Shinohara, Ryoji; Mizorogi, Sonoko; Mochizuki, Mie; Yamagata, Zentaro

2015-07-28

Although obesity is a well-studied risk factor for diabetes, there remains an interest in whether "increasing body mass index (BMI)," "high BMI per se," or both are the actual risk factors for diabetes. The present study aimed to retrospectively compare BMI trajectories of individuals with and without diabetes in a case-control design and to assess whether increasing BMI alone would be a risk factor. Using comprehensive health check-up data measured over ten years, we conducted a case-control study and graphically drew the trajectories of BMIs among diabetic patients and healthy subjects, based on coefficients in fitted linear mixed-effects models. Patient group was matched with healthy control group at the onset of diabetes with an optimal matching method in a 1:10 ratio. Simple fixed-effects models assessed the differences in increasing BMIs over 10 years between patient and control groups. At the time of matching, the mean ages in male patients and controls were 59.3 years [standard deviation (SD) = 9.2] and 57.7 years (SD = 11.2), whereas the mean BMIs were 25.0 kg/m(2) (SD = 3.1) and 25.2 kg/m(2) (SD = 2.9), respectively. In female patients and controls, the mean ages were 61.4 years (SD = 7.9) and 60.1 years (SD = 9.6), whereas the mean BMIs were 24.8 kg/m(2) (SD = 3.5) and 24.9 kg/m(2) (SD = 3.4), respectively. The simple fixed-effects models detected no statistical significance for the differences of increasing BMIs between patient and control groups in males (P = 0.19) and females (P = 0.67). Sudden increases in BMI were observed in both male and female patients when compared with BMIs 1 year prior to diabetes onset. The present study suggested that the pace of increasing BMIs is similar between Japanese diabetic patients and healthy individuals. The increasing BMI was not detected to independently affect the onset of type 2 diabetes.

The impact of type 2 diabetes on health related quality of life in Bangladesh: results from a matched study comparing treated cases with non-diabetic controls.

PubMed

Safita, Novie; Islam, Sheikh Mohammed Shariful; Chow, Clara K; Niessen, Louis; Lechner, Andreas; Holle, Rolf; Laxy, Michael

2016-09-13

Little is known about the association between diabetes and health related quality of life (HRQL) in lower-middle income countries. This study aimed to investigate HRQL among individuals with and without diabetes in Bangladesh. The analysis is based on data of a case-control study, including 591 patients with type 2 diabetes (cases) who attended an outpatient unit of a hospital in Dhaka and 591 age -and sex-matched individuals without diabetes (controls). Information about socio-demographic characteristics, health conditions, and HRQL were assessed in a structured interview. HRQL was measured with the EuroQol (EQ) visual analogue scale (VAS) and the EQ five-dimensional (5D) descriptive system. The association between diabetes status and quality of life was examined using multiple linear and logistic regression models. Mean EQ-VAS score of patients with diabetes was 11.5 points lower (95 %-CI: -13.5, -9.6) compared to controls without diabetes. Patients with diabetes were more likely to report problems in all EQ-5D dimensions than controls, with the largest effect observed in the dimensions 'self-care' (OR = 5.9; 95 %-CI: 2.9, 11.8) and 'mobility' (OR = 4.5; 95 %-CI: 3.0, -6.6). In patients with diabetes, male gender, high education, and high-income were associated with higher VAS score and diabetes duration and foot ulcer associated with lower VAS scores. Other diabetes-related complications were not significantly associated with HRQL. Our findings suggest that the impact of diabetes on HRQL in the Bangladeshi population is much higher than what is known from western populations and that unlike in western populations comorbidities/complications are not the driving factor for this effect.

[Classical Swine Fever in wild boar in Rhineland-Palatinate: evaluation of the official control measures from 2005-2011].

PubMed

Romelt, Maria; Klingelhefer, Irene; Konig, Astrid; Braun, Bettina; Reiner, Gerald

2015-01-01

The present study describes the control strategy for fighting Classical Swine Fever in wild boar in Rhineland-Palatinate from 2005 to 2011 and evaluates its effectiveness. The official control measures were based on the following three main pillars:--Serological and virological monitoring: By means of serological monitoring Classical Swine Fever outbreaks could be detected very early. Increasing antibody prevalences indicated an imminent Classical Swine Fever outbreak. This could be confirmed by the virological investigations. The geographical evaluations of the virological investigations showed that the outbreaks occurred only in localized areas and a spreading of the virus had not taken place yet or could be prevented.--Oral immunization: After virological detection of Classical Swine Fever Virus oral immunization was started immediately. This oral immunization achieved antibody prevalence rates of 57% on an average. The analysis of the distribution of the antibodies in the vaccination areas concerning the different age groups in the vaccination areas showed that 41% of the young animals, 66% of animals from one to two years and 77% of the adult animals were immunized.--Hunting measures: For the reduction of the wild boar population an all-year, intensive hunt with special attention to the young animals and the female animals was carried out. The hunting bag increased on more than 80 000 wild boar per hunting season. Out of the total 108,772 hunted wild boar were 47% of young animals, 40% of animals from one to two years and 13% of adult animals. Concerning the gender distribution on an average 53% female and 47% male animals were shot. in summary, the current control strategy was effective because there had been no further proof of Classical Swine Fever in wild boar in Rhineland-Palatinate since 2009. Nevertheless, the fight strategy can be optimized even further. For an optimum monitoring the development of a marker vaccine which allows a differentiation of

Entamoeba histolytica Infection in Female Sex Workers: A Matched Case-Control Study in Durango, Mexico.

PubMed

Alvarado-Esquivel, Cosme; Sanchez-Anguiano, Luis Francisco; Hernandez-Tinoco, Jesus; Estrada-Martinez, Sergio; Perez-Alamos, Alma Rosa; Ramos-Nevarez, Agar; Cerrillo-Soto, Sandra Margarita; Guido-Arreola, Carlos Alberto

2017-07-01

Infection with Entamoeba histolytica ( E. histolytica ) can be potentially transmitted by sexual contact. The seroepidemiology of E. histolytica in female sex workers has not been studied. The aim of the study was to determine whether E. histolytica is associated with the occupation of female sex work. In addition, the correlates of E. histolytica seroprevalence in female sex workers were also investigated. We performed an age- and gender-matched case-control study of 187 female sex workers and 374 women without sex work. Cases and controls were tested for the presence of E. histolytica IgG antibodies using a commercially available enzyme-linked immunoassay. Seroprevalence association with the characteristics of female sex workers was determined by bivariate analysis. Anti- E. histolytica IgG antibodies were found in five (2.7%) of 187 female sex workers and in 16 (4.3%) of 374 controls (odds ratios (OR) = 0.61; 95% confidence intervals (CI): 0.22 - 1.70; P = 0.34). Mean optical density of the immunoassay in seropositive cases and controls was 1.35 ± 0.93 and 0.73 ± 0.45, respectively (P = 0.05). Seroprevalence of E. histolytica infection did not vary significantly with age, education, socioeconomic level, or health status of sex workers. Seropositivity to E. histolytica did not correlate with work characteristics such as duration in the occupation, condom use, type of sex, or a history of sexually transmitted diseases, or with behavioral variables such as washing hands before eating, or consumption of untreated water. Results indicate that female sex workers do not have an increased risk for E. histolytica infection in Durango City, Mexico. Further studies to determine the risk of infection with E. histolytica by sexual contact should be conducted.

Entamoeba histolytica Infection in Female Sex Workers: A Matched Case-Control Study in Durango, Mexico

PubMed Central

Alvarado-Esquivel, Cosme; Sanchez-Anguiano, Luis Francisco; Hernandez-Tinoco, Jesus; Estrada-Martinez, Sergio; Perez-Alamos, Alma Rosa; Ramos-Nevarez, Agar; Cerrillo-Soto, Sandra Margarita; Guido-Arreola, Carlos Alberto

2017-01-01

Background Infection with Entamoeba histolytica (E. histolytica) can be potentially transmitted by sexual contact. The seroepidemiology of E. histolytica in female sex workers has not been studied. The aim of the study was to determine whether E. histolytica is associated with the occupation of female sex work. In addition, the correlates of E. histolytica seroprevalence in female sex workers were also investigated. Methods We performed an age- and gender-matched case-control study of 187 female sex workers and 374 women without sex work. Cases and controls were tested for the presence of E. histolytica IgG antibodies using a commercially available enzyme-linked immunoassay. Seroprevalence association with the characteristics of female sex workers was determined by bivariate analysis. Results Anti-E. histolytica IgG antibodies were found in five (2.7%) of 187 female sex workers and in 16 (4.3%) of 374 controls (odds ratios (OR) = 0.61; 95% confidence intervals (CI): 0.22 - 1.70; P = 0.34). Mean optical density of the immunoassay in seropositive cases and controls was 1.35 ± 0.93 and 0.73 ± 0.45, respectively (P = 0.05). Seroprevalence of E. histolytica infection did not vary significantly with age, education, socioeconomic level, or health status of sex workers. Seropositivity to E. histolytica did not correlate with work characteristics such as duration in the occupation, condom use, type of sex, or a history of sexually transmitted diseases, or with behavioral variables such as washing hands before eating, or consumption of untreated water. Conclusions Results indicate that female sex workers do not have an increased risk for E. histolytica infection in Durango City, Mexico. Further studies to determine the risk of infection with E. histolytica by sexual contact should be conducted. PMID:28611864

CD4+ T-cell engagement by both wild-type and variant HCV peptides modulates the conversion of viral clearing helper T cells to Tregs

PubMed Central

Cusick, Matthew F; Libbey, Jane E; Cox Gill, Joan; Fujinami, Robert S; Eckels, David D

2013-01-01

Aim To determine whether modulation of T-cell responses by naturally occurring viral variants caused an increase in numbers of Tregs in HCV-infected patients. Patients, materials & methods Human peripheral blood mononuclear cells, having proliferative responses to a wild-type HCV-specific CD4+ T-cell epitope, were used to quantify, via proliferative assays, flow cytometry and class II tetramers, the effects of naturally occurring viral variants arising in the immunodominant epitope. Results In combination, the wild-type and variant peptides led to enhanced suppression of an anti-HCV T-cell response. The variant had a lower avidity for the wild-type-specific CD4+ T cell. Variant-stimulated CD4+ T cells had increased Foxp3, compared with wild-type-stimulated cells. Conclusion A stable viral variant from a chronic HCV subject was able to induce Tregs in multiple individuals that responded to the wild-type HCV-specific CD4+ T-cell epitope. PMID:24421862

Substance P and central respiratory activity: a comparative in vitro study in NK1 receptor knockout and wild-type mice.

PubMed

Ptak, K; Hunt, S P; Monteau, R

2000-07-01

Neurokinin-1 receptors (NK1) are present within the respiratory medullary network and in the phrenic nucleus, which controls the diaphragm. We compared the efficacy of substance P (SP) at inducing changes in respiratory frequency or the amplitude of the respiratory motor output between NK1 knockout (NK1-/-) and wild-type mice, using the in vitro brainstem-spinal cord preparation. The in vitro respiratory frequency, as well as the variability of the rhythm and the amplitude of the motor output were similar in both lines. In wild-type mice, application of exogenous SP induced either an increase in respiratory frequency (superfusion of the medulla) or an increase of the inspiratory motor output, as defined by the integral of C4 cervical ventral root activity (superfusion of the spinal cord). These two effects were not apparent in NK1-/- mice. In conclusion, NK1 receptors mediate the respiratory responses to SP but the lack of NK1 receptors in newborn NK1-/- mice does not change the respiratory activity.

One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples.

PubMed

Gautam, Rashi; Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael D

2016-01-01

Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8-100% sensitivity, 99.7-100% specificity, 85-95% efficiency and a limit of detection of 4-60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81-92% efficiency and limit of detection of 150-600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98

One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples

PubMed Central

Mijatovic-Rustempasic, Slavica; Esona, Mathew D.; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael D.

2016-01-01

Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8–100% sensitivity, 99.7–100% specificity, 85–95% efficiency and a limit of detection of 4–60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81–92% efficiency and limit of detection of 150–600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8�

Toxoplasma gondii Infection and Headache: A Matched Case-Control Study in a Public Hospital in Durango City, Mexico

PubMed Central

Alvarado-Esquivel, Cosme; Rico-Almochantaf, Yazmin del Rosario; Sanchez-Anguiano, Luis Francisco; Quinones-Canales, Gerardo; Hernandez-Tinoco, Jesus; Torres-Gonzalez, Jorge; Gonzalez-Silva, Maria Felix; Ramirez-Valles, Eda Guadalupe

2018-01-01

Background Toxoplasma gondii (T. gondii) can disseminate to brain in infected hosts. Little is known about the magnitude of the association between this infection and headache. Therefore, we sought to determine the association of T. gondii seropositivity and headache in patients attending neurological consultations in a public hospital in Durango City, Mexico. Methods Through an age- and gender-matched case-control study, 105 patients suffering from headache and 105 subjects without headache were examined for anti-T. gondii IgG and IgM antibodies using commercially available enzyme-linked immunoassays. Seropositive cases were analyzed for detection of T. gondii DNA by polymerase chain reaction. Results Anti-T. gondii IgG antibodies were found in five (4.8%) of the 105 cases and in seven (6.7%) of the 105 controls (odds ratio (OR) = 0.70; 95% confidence interval (CI): 0.21 - 2.28; P = 0.76). The frequency of high (> 150 IU/mL) levels of anti-T. gondii IgG antibodies among anti-T. gondii IgG positive individuals was significantly (P = 0.01) higher in cases (5/5) than in controls (1/7). Anti-T. gondii IgM antibodies were found in one (20.0%) of the five IgG seropositive cases, and in three (42.9%) of the seven IgG seropositive controls (P = 0.60). T. gondii DNA was not detected in any of the five anti-T. gondii IgG positive cases. No association between T. gondii infection and specific headache types was found. Conclusions This is the first matched case-control study on the association between T. gondii infection and headache. Results suggest that high anti-T. gondii IgG antibody levels, but not T. gondii seropositivity, were associated with headache in the population studied. PMID:29238431

Toxoplasma gondii Infection and Headache: A Matched Case-Control Study in a Public Hospital in Durango City, Mexico.

PubMed

Alvarado-Esquivel, Cosme; Rico-Almochantaf, Yazmin Del Rosario; Sanchez-Anguiano, Luis Francisco; Quinones-Canales, Gerardo; Hernandez-Tinoco, Jesus; Torres-Gonzalez, Jorge; Gonzalez-Silva, Maria Felix; Ramirez-Valles, Eda Guadalupe

2018-01-01

Toxoplasma gondii ( T. gondii ) can disseminate to brain in infected hosts. Little is known about the magnitude of the association between this infection and headache. Therefore, we sought to determine the association of T. gondii seropositivity and headache in patients attending neurological consultations in a public hospital in Durango City, Mexico. Through an age- and gender-matched case-control study, 105 patients suffering from headache and 105 subjects without headache were examined for anti- T. gondii IgG and IgM antibodies using commercially available enzyme-linked immunoassays. Seropositive cases were analyzed for detection of T. gondii DNA by polymerase chain reaction. Anti- T. gondii IgG antibodies were found in five (4.8%) of the 105 cases and in seven (6.7%) of the 105 controls (odds ratio (OR) = 0.70; 95% confidence interval (CI): 0.21 - 2.28; P = 0.76). The frequency of high (> 150 IU/mL) levels of anti- T. gondii IgG antibodies among anti- T. gondii IgG positive individuals was significantly (P = 0.01) higher in cases (5/5) than in controls (1/7). Anti- T. gondii IgM antibodies were found in one (20.0%) of the five IgG seropositive cases, and in three (42.9%) of the seven IgG seropositive controls (P = 0.60). T. gondii DNA was not detected in any of the five anti- T. gondii IgG positive cases. No association between T. gondii infection and specific headache types was found. This is the first matched case-control study on the association between T. gondii infection and headache. Results suggest that high anti- T. gondii IgG antibody levels, but not T. gondii seropositivity, were associated with headache in the population studied.

Preschool Gender-Typed Play Behavior at Age 3.5 Years Predicts Physical Aggression at Age 13 Years.

PubMed

Kung, Karson T F; Li, Gu; Golding, Jean; Hines, Melissa

2018-05-01

Gender differences in play behavior and physical aggression have been consistently reported. Theoretical perspectives concerning evolutionary, social, and social-cognitive mechanisms suggest that male-typical play behavior during childhood increases subsequent physical aggression. The evidence supporting these connections is limited, however. The present study investigated the association between gender-typed play behavior in early childhood and physical aggression in early adolescence using a sample drawn from a longitudinal, population study, the Avon Longitudinal Study of Parents and Children. Based on gender-typed play behavior as measured by the Pre-School Activities Inventory at age 3.5 years, samples of masculine (64 boys, 60 girls), feminine (80 boys, 66 girls), and randomly selected control children (55 boys, 67 girls) were recruited at age 13 years and administered the Reinisch Aggression Inventory. After controlling for a range of sociodemographic variables, maternal characteristics, and behavioral problems, including hyperactivity and conduct problems at age 3.5, significant group differences in physical aggression at age 13 were found among children classified as masculine, control, and feminine at age 3.5. Masculine children exhibited significantly more physical aggression than control children or feminine children, and control children exhibited significantly more physical aggression than feminine children. The association between gender-typed play behavior and physical aggression was not moderated by sex. These results suggest that the degree of childhood gender-typed play behavior independently predicts the degree of physical aggression at adolescence in boys and in girls.

43 CFR 4710.7 - Maintenance of wild horses and burros on privately controlled lands.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RANGE MANAGEMENT (4000) PROTECTION, MANAGEMENT, AND CONTROL OF WILD FREE-ROAMING HORSES AND BURROS Management Considerations § 4710.7... who maintain wild free-roaming horses and burros on their land shall notify the authorized officer and...

43 CFR 4710.7 - Maintenance of wild horses and burros on privately controlled lands.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RANGE MANAGEMENT (4000) PROTECTION, MANAGEMENT, AND CONTROL OF WILD FREE-ROAMING HORSES AND BURROS Management Considerations § 4710.7... who maintain wild free-roaming horses and burros on their land shall notify the authorized officer and...

43 CFR 4710.7 - Maintenance of wild horses and burros on privately controlled lands.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RANGE MANAGEMENT (4000) PROTECTION, MANAGEMENT, AND CONTROL OF WILD FREE-ROAMING HORSES AND BURROS Management Considerations § 4710.7... who maintain wild free-roaming horses and burros on their land shall notify the authorized officer and...

43 CFR 4710.7 - Maintenance of wild horses and burros on privately controlled lands.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RANGE MANAGEMENT (4000) PROTECTION, MANAGEMENT, AND CONTROL OF WILD FREE-ROAMING HORSES AND BURROS Management Considerations § 4710.7... who maintain wild free-roaming horses and burros on their land shall notify the authorized officer and...

Hormonal control of aging in rodents: The somatotropic axis

PubMed Central

Brown-Borg, Holly M.

2015-01-01

There is a growing body of literature focusing on the somatotropic axis and regulation of aging and longevity. Many of these reports derive data from multiple endocrine mutants, those that exhibit both elevated growth hormone (GH) and insulin-like growth factor I (IGF-1) or deficiencies in one or both of these hormones. In general, both spontaneous and genetically engineered GH and IGF-1 deficiencies have lead to small body size, delayed development of sexual maturation and age-related pathology, and life span extension. In contrast, characteristics of high circulating GH included larger body sizes, early puberty and reproductive senescence, increased cancer incidence and reduced life span when compared to wild-type animals with normal plasma hormone concentrations. This information, along with that found in multiple other species, implicates this anabolic pathway as the major regulator of longevity in animals. PMID:18674587

Simultaneous co-detection of wild-type and vaccine strain measles virus using the BD MAX system.

PubMed

Thapa, Kiran; Ellem, Justin A; Basile, Kerri; Carter, Ian; Olma, Tom; Chen, Sharon C-A; Dwyer, Dominic E; Kok, Jen

2018-06-01

Despite the reported elimination of measles virus in Australia, importation of cases from endemic countries continues to lead to secondary local transmission and outbreaks. Rapid laboratory confirmation of measles is paramount for individual patient management and outbreak responses. Further, it is important to rapidly distinguish infection from wild-type virus or vaccine strains to guide public health responses. We developed a high throughput, TaqMan-based multiplex reverse-transcription-polymerase chain reaction (PCR) assay using the BD MAX platform (Becton Dickinson) that simultaneously detects measles virus and differentiates between wild-type and vaccine strains without the need for sequencing. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Tenofovir alafenamide demonstrates broad cross-genotype activity against wild-type HBV clinical isolates and maintains susceptibility to drug-resistant HBV isolates in vitro.

PubMed

Liu, Yang; Miller, Michael D; Kitrinos, Kathryn M

2017-03-01

Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir (TFV). This study evaluated the antiviral activity of TAF against wild-type genotype A-H HBV clinical isolates as well as adefovir-resistant, lamivudine-resistant, and entecavir-resistant HBV isolates. Full length HBV genomes or the polymerase/reverse transcriptase (pol/RT) region from treatment-naïve patients infected with HBV genotypes A-H were amplified and cloned into an expression vector under the control of a CMV promoter. In addition, 11 drug resistant HBV constructs were created by site-directed mutagenesis of a full length genotype D construct. Activity of TAF was measured by transfection of each construct into HepG2 cells and assessment of HBV DNA levels following treatment across a range of TAF concentrations. TAF activity in vitro was similar against wild-type genotype A-H HBV clinical isolates. All lamivudine- and entecavir-resistant isolates and 4/5 adefovir-resistant isolates were found to be sensitive to inhibition by TAF in vitro as compared to the wild-type isolate. The adefovir-resistant isolate rtA181V + rtN236T exhibited low-level reduced susceptibility to TAF. TAF is similarly active in vitro against wild-type genotype A-H HBV clinical isolates. The TAF sensitivity results for all drug-resistant isolates are consistent with what has been observed with the parent drug TFV. The in vitro cell-based HBV phenotyping assay results support the use of TAF in treatment of HBV infected subjects with diverse HBV genotypes, in both treatment-naive and treatment-experienced HBV infected patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic Characterization of the Hemagglutinin Genes of Wild-Type Measles Virus Circulating in China, 1993–2009

PubMed Central

Zhu, Zhen; Liu, Chunyu; Mao, Naiying; Ji, Yixin; Wang, Huiling; Jiang, Xiaohong; Li, Chongshan; Tang, Wei; Feng, Daxing; Wang, Changyin; Zheng, Lei; Lei, Yue; Ling, Hua; Zhao, Chunfang; Ma, Yan; He, Jilan; Wang, Yan; Li, Ping; Guan, Ronghui; Zhou, Shujie; Zhou, Jianhui; Wang, Shuang; Zhang, Hong; Zheng, Huanying; Liu, Leng; Ma, Hemuti; Guan, Jing; Lu, Peishan; Feng, Yan; Zhang, Yanjun; Zhou, Shunde; Xiong, Ying; Ba, Zhuoma; Chen, Hui; Yang, Xiuhui; Bo, Fang; Ma, Yujie; Liang, Yong; Lei, Yake; Gu, Suyi; Liu, Wei; Chen, Meng; Featherstone, David; Jee, Youngmee; Bellini, William J.; Rota, Paul A.; Xu, Wenbo

2013-01-01

Background China experienced several large measles outbreaks in the past two decades, and a series of enhanced control measures were implemented to achieve the goal of measles elimination. Molecular epidemiologic surveillance of wild-type measles viruses (MeV) provides valuable information about the viral transmission patterns. Since 1993, virologic surveillnace has confirmed that a single endemic genotype H1 viruses have been predominantly circulating in China. A component of molecular surveillance is to monitor the genetic characteristics of the hemagglutinin (H) gene of MeV, the major target for virus neutralizing antibodies. Principal Findings Analysis of the sequences of the complete H gene from 56 representative wild-type MeV strains circulating in China during 1993–2009 showed that the H gene sequences were clustered into 2 groups, cluster 1 and cluster 2. Cluster1 strains were the most frequently detected cluster and had a widespread distribution in China after 2000. The predicted amino acid sequences of the H protein were relatively conserved at most of the functionally significant amino acid positions. However, most of the genotype H1 cluster1 viruses had an amino acid substitution (Ser240Asn), which removed a predicted N-linked glycosylation site. In addition, the substitution of Pro397Leu in the hemagglutinin noose epitope (HNE) was identified in 23 of 56 strains. The evolutionary rate of the H gene of the genotype H1 viruses was estimated to be approximately 0.76×10−3 substitutions per site per year, and the ratio of dN to dS (dN/dS) was <1 indicating the absence of selective pressure. Conclusions Although H genes of the genotype H1 strains were conserved and not subjected to selective pressure, several amino acid substitutions were observed in functionally important positions. Therefore the antigenic and genetic properties of H genes of wild-type MeVs should be monitored as part of routine molecular surveillance for measles in China. PMID

Children and Wild Foods in the Context of Deforestation in Rural Malawi.

PubMed

Maseko, H; Shackleton, Charlie M; Nagoli, J; Pullanikkatil, D

2017-01-01

There is growing recognition of the contribution of wild foods to local diets, nutrition, and culture. Yet disaggregation of understanding of wild food use by gender and age is limited. We used a mixed methods approach to determine the types, frequencies, and perceptions of wild foods used and sold by children in four villages in southern Malawi that have different levels of deforestation. Household and individual dietary diversity scores are low at all sites. All households consume one or more wild foods. Across the four sites, children listed 119 wild foods, with a wider variety at the least deforested sites than the most deforested ones. Older children can name more wild foods than younger ones. More children from poor households sell wild foods than from well-off households. Several reasons were provided for the consumption or avoidance of wild foods (most commonly taste, contribution to health, limited alternatives, hunger, availability, local taboos).

Bcl-2 protein expression associated with resistance to apoptosis in clear cell adenocarcinomas of the vagina and cervix expressing wild-type p53.

PubMed

Waggoner, S E; Baunoch, D A; Anderson, S A; Leigh, F; Zagaja, V G

1998-09-01

Clear cell adenocarcinomas (CCAs) of the vagina and cervix are rare tumors that often overexpress wild-type p53. In vitro, expression of protooncogene bcl-2 can block p53-mediated apoptosis. The objective of this study was to determine if bcl-2 is expressed in CCAs and whether this expression is associated with inhibition of apoptosis. Twenty-one paraffin-embedded clear cell adenocarcinomas were immunohistochemically stained for bcl-2 (antibody M 887, Dako, Carpinteria, CA) and DNA fragmentation (ApopTag, Oncor, Gaithersburg, MD), a marker for apoptosis. Fifteen tumors were associated with in utero exposure to diethylstilbestrol (DES). Prior p53 gene analysis had indicated the presence of wild-type p53 in each tumor. Human lymphoid tissue containing bcl-2-expressing lymphocytes and DNase I-exposed CCA tissue sections were used as positive controls for the bcl-2 and apoptosis assays, respectively. Expression of bcl-2 and DNA fragmentation was classified (0 to 3+) according to percentage of positive cells and intensity of staining. Expression of bcl-2 was identified in each CCA examined, and was strongly positive (2+ to 3+) in 18 of 21 samples. Despite the presence of wild-type p53, only 4 of 21 tumors showed evidence of apoptosis as assessed through DNA fragmentation. DNA damage leads to increased intracellular p53 levels. Overexpression of p53 induces apoptosis as a means of protecting organisms from the development of malignancy. CCAs of the vagina and cervix, which contain wild-type p53 genes and often overexpress p53 protein, presumably have evolved mechanisms to avoid p53-induced apoptosis. Our observations are consistent with the hypothesis that overexpression of bcl-2 can inhibit p53-mediated apoptosis and suggest a mechanism by which these rare tumors can arise without mutation of the p53 gene.

Congenital lumbar spinal stenosis: a prospective, control-matched, cohort radiographic analysis.

PubMed

Singh, Kern; Samartzis, Dino; Vaccaro, Alexander R; Nassr, Ahmad; Andersson, Gunnar B; Yoon, S Tim; Phillips, Frank M; Goldberg, Edward J; An, Howard S

2005-01-01

Degenerative lumbar spinal stenosis manifests primarily after the sixth decade of life as a result of facet hypertrophy and degenerative disc disease. Congenital stenosis, on the other hand, presents earlier in age with similar clinical findings but with multilevel involvement and fewer degenerative changes. These patients may have subtle anatomic variations of the lumbar spine that may increase the likelihood of thecal sac compression. However, to the authors' knowledge, no quantitative studies have addressed various radiographic parameters of symptomatic, congenitally stenotic individuals to normal subjects. To radiographically quantify and compare the anatomy of the lumbar spine in symptomatic, congenitally stenotic individuals to age- and sex-matched, asymptomatic, nonstenotic controlled individuals. A prospective, control-matched, cohort radiographic analysis. Axial and sagittal magnetic resonance imaging (MRI) and lateral, lumbar, plain radiographs of 20 surgically treated patients who were given a clinical diagnosis of congenital lumbar stenosis by the senior author were randomized with images of 20, asymptomatic age- and sex-matched subjects. MRIs and lateral, lumbar, plain radiographs were independently quantitatively assessed by two individuals. Measurements obtained from the axial MRIs included: midline anterior-posterior (AP) vertebral body diameter, vertebral body width, midline AP canal diameter, canal width, spinal canal cross-sectional area, pedicle length, and pedicle width. From the sagittal MRIs, the following measurements were calculated: AP vertebral body diameter, vertebral body height, and AP canal diameter at the mid-vertebral level. On the lateral, lumbar, plain radiograph (L3 level), the AP diameters of the vertebral body spinal canal were measured. The images of these 40 individuals were then randomized and distributed in a blinded fashion to five separate spine surgeons who graded the presence and severity of congenital stenosis

Efficacy of intraoperative epidural triamcinolone application in lumbar microdiscectomy: a matched-control study.

PubMed

Stienen, Martin N; Joswig, Holger; Chau, Ivan; Neidert, Marian C; Bellut, David; Wälchli, Thomas; Schaller, Karl; Gautschi, Oliver P

2018-03-01

OBJECTIVE The purpose of this study was to investigate whether the intraoperative application of an epidural steroid (ES) on the decompressed nerve root improves short- and midterm subjective and objective clinical outcomes after lumbar microdiscectomy. METHODS This study was a retrospective analysis of a 2-center database including consecutive cases in which patients underwent lumbar microdiscectomy. All patients who received ES application (40 mg triamcinolone, ES group) were matched by age and sex to patients who had not received ES application (control group). Objective functional impairment (OFI) was determined using age- and sex-adjusted T-scores of the Timed Up and Go (TUG) test. Back and leg pain (visual analog scale), functional impairment (Oswestry Disability Index [ODI], Roland-Morris Disability Index [RMDI], and health-related quality of life (hrQoL; 12-Item Short Form Health Survey [SF-12] physical component summary [PSC] score and EuroQol [EQ-5D index]) were measured at baseline, on postoperative day 3, and at postoperative week 6. RESULTS Fifty-three patients who received ES application were matched with 101 controls. There were no baseline demographic or disease-specific differences between the study groups, and preoperative pain, functional impairment, and hrQoL were similar. On postoperative day 3, the ES group had less disability on the RMDI (mean 7.4 vs 10.3, p = 0.003) and higher hrQoL as determined by the SF-12 PCS (36.5 vs 32.7, p = 0.004). At week 6, the ES group had less disability on the RMDI (3.6 vs 5.7, p = 0.050) and on the ODI by trend (17.0 vs 24.4, p = 0.056); better hrQoL, determined by the SF-12 PCS (44.3 vs 39.9, p = 0.018); and lower OFI (TUG test T-score 100.5 vs 110.2, p = 0.005). The week 6 responder status based on the minimum clinically important difference (MCID) was similar in the ES and control groups for each metric. The rates and severity of complications were similar, with a 3.8% and 4.0% reoperation rate in the ES

Differential proteomic responses of selectively bred and wild-type Sydney rock oyster populations exposed to elevated CO2.

PubMed

Thompson, E L; O'Connor, W; Parker, L; Ross, P; Raftos, D A

2015-03-01

Previous work suggests that larvae from Sydney rock oysters that have been selectively bred for fast growth and disease resistance are more resilient to the impacts of ocean acidification than nonselected, wild-type oysters. In this study, we used proteomics to investigate the molecular differences between oyster populations in adult Sydney rock oysters and to identify whether these form the basis for observations seen in larvae. Adult oysters from a selective breeding line (B2) and nonselected wild types (WT) were exposed for 4 weeks to elevated pCO2 (856 μatm) before their proteomes were compared to those of oysters held under ambient conditions (375 μatm pCO2 ). Exposure to elevated pCO2 resulted in substantial changes in the proteomes of oysters from both the selectively bred and wild-type populations. When biological functions were assigned, these differential proteins fell into five broad, potentially interrelated categories of subcellular functions, in both oyster populations. These functional categories were energy production, cellular stress responses, the cytoskeleton, protein synthesis and cell signalling. In the wild-type population, proteins were predominantly upregulated. However, unexpectedly, these cellular systems were downregulated in the selectively bred oyster population, indicating cellular dysfunction. We argue that this reflects a trade-off, whereby an adaptive capacity for enhanced mitochondrial energy production in the selectively bred population may help to protect larvae from the effects of elevated CO2 , whilst being deleterious to adult oysters. © 2015 John Wiley & Sons Ltd.

Iron dysregulation combined with aging prevents sepsis-induced apoptosis.

PubMed

Javadi, Pardis; Buchman, Timothy G; Stromberg, Paul E; Turnbull, Isaiah R; Vyas, Dinesh; Hotchkiss, Richard S; Karl, Irene E; Coopersmith, Craig M

2005-09-01

Sepsis, iron loading, and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels. Hfe-/- mice (a murine homologue of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24-26 months) or mature (16-18 months) Hfe-/- mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 h later and assessed for apoptosis and cytokine levels. Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe-/- mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe-/- mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe-/- mice than septic mature Hfe-/- animals. Interleukin-6 was elevated in septic aged Hfe-/- mice compared to sham mice. Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe-/- mice are able to mount an inflammatory response following CLP and mature Hfe-/- mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation.

Nationwide Case-Control Study Examining the Association between Tamoxifen Use and Alzheimer's Disease in Aged Women with Breast Cancer in Taiwan.

PubMed

Liao, Kuan-Fu; Lin, Cheng-Li; Lai, Shih-Wei

2017-01-01

Background and Objectives: Little is known about the association between tamoxifen use and Alzheimer's disease in women with breast cancer. The study aimed to explore the association between tamoxifen use and Alzheimer's disease in aged women with breast cancer in Taiwan. Methods : We conducted a retrospective nationwide case-control study using the database of the Taiwan National Health Insurance Program. Totally, 173 female subjects with breast cancer aged ≥ 65 years with newly diagnosed Alzheimer's disease from 2000 to 2011 were identified as the cases. Additionally, 684 female subjects with breast cancer aged ≥ 65 years without any type of dementia were selected as the matched controls. The cases and the matched controls were matched with age and comorbidities. Ever use of tamoxifen was defined as subjects who had at least a prescription for tamoxifen before the index date. Never use of tamoxifen was defined as subjects who never had a prescription for tamoxifen before the index date. We used the logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of Alzheimer's disease associated with tamoxifen use. Results : The OR of Alzheimer's disease was 3.09 for subjects with ever use of tamoxifen (95% CI 2.10, 4.55), compared with never use. The OR of Alzheimer's disease was 1.23 for subjects with increasing cumulative duration of tamoxifen use for every 1 year (95% CI 1.13, 1.34), compared with never use. Conclusion: The increased odds of Alzheimer's disease associated with tamoxifen use may be due to the survival effect, not the toxic effect. That is, the longer the tamoxifen use, the longer the patients survive, and the greater the likelihood that she may have a chance to develop Alzheimer's disease.

Professional football (soccer) players have a markedly greater skeletal mineral content, density and size than age- and BMI-matched controls.

PubMed

Wittich, A; Mautalen, C A; Oliveri, M B; Bagur, A; Somoza, F; Rotemberg, E

1998-08-01

The total skeletal bone mineral content (BMC), bone mineral density (BMD), bone size, and body composition were measured by dual-energy x-ray absorptiometry (DXA) in all professional male football players of a 1st division team (n = 24) and age- and BMI-matched (n = 22) controls (less than 3 hours of recreational sport activities per week). Average (+/- 1 SD) age of the athletes was 22.6 +/- 2.5 years. Intensive training is conducted during 48 weeks a year for 20-22 hours/week. The length of the registered playing career before the study was 8.2 +/- 2.7 years. Total skeleton BMC was 18.0% (P < 0.001) greater in the football players. The difference resulted from the sum of 5.2% (P < 0.02) increment of bone size and 12.3% (P < 0.001) increment of BMD. The analysis of skeletal subareas revealed that the difference of the BMC and BMD was greater at the level of the pelvis and legs compared with the arms or trunk. The BMC and BMD of the head was equal for both groups. Also, the bone size of the legs and pelvis was significantly greater for the players compared with controls; there was no difference at the level of the arms or head. Within the group of football players the increment of total skeleton BMD was similar in the young players, with less than 7 years of practice (age 20.6 +/- 0.9 years) compared with relative older players (age 24.6 +/- 1.9) with more than 7 years of practice. Lean body mass was significantly greater in the players (63.3 +/- 4.0 kg) compared with the controls (56.7 +/- 3.6, P < 0.001) whereas fat mass was markedly lower (9.4 +/- 2.9 kg versus 14.9 +/- 6.3 kg), P < 0.002). The BMD of the controls was significantly correlated to total weight, height, and lean mass whereas the BMD of the players was only correlated to muscle mass. The calcium intake from dairy products was similar in both groups. The range of calcium intake was wide among the players (184-2519 mg/day) but it was not significantly correlated to BMD (r = 0.03). In conclusion, male

Wilde's worlds: Sir William Wilde in Victorian Ireland.

PubMed

McGeachie, J

2016-05-01

Other contributors to this collection have evoked the disparate worlds inhabited by Sir William Wilde. To provide an overall assessment of his career. Looking at the historical conditions that made possible such a career spanning such disparate worlds. Deploying methodologies developed by historians of medicine and sociologists of science, the article brings together Wilde the nineteenth century clinician and Dublin man of science, the Wilde of the Census and of the west of Ireland, William Wilde Victorian medical man and Wilde the Irish medical man-the historian of Irish medical traditions and the biographer of Irish medical men, and William Wilde as an Irish Victorian. A variety of close British Isles parallels can be drawn between Wilde and his cohort in the medical elite of Dublin and their clinical peers in Edinburgh and London both in terms of clinical practice and self-presentation and in terms of the social and political challenges facing their respective ancient regime hegemonies in an age of democratic radicalisation. The shared ideological interests of Wilde and his cohort, however, were also challenged by the socio-political particularities and complexities of Ireland during the first half of the nineteenth century culminating in the catastrophe of the Great Famine. William Wilde saw the practice of scientific medicine as offering a means of deliverance from historical catastrophe for Irish society and invoked a specifically Irish scientific and medical tradition going back to the engagement with the condition of Ireland by enlightened medical men in the seventeenth and eighteenth centuries.

Diabetes Camp as Continuing Education for Diabetes Self-Management in Middle-Aged and Elderly People with Type 2 Diabetes Mellitus

PubMed Central

Park, So Young; Kim, Sun Young; Lee, Hye Mi; Hur, Kyu Yeon; Kim, Jae Hyeon; Lee, Moon-Kyu

2017-01-01

Background Despite the established benefits of diabetes camps for the continuing education of children with type 1 diabetes mellitus, little is known about the long-term metabolic benefits of diabetes camps for middle-aged and elderly people with type 2 diabetes mellitus (T2DM), especially in terms of glycosylated hemoglobin (HbA1c) variability. Methods The 1-year mean and variability of HbA1c before and after the diabetes camp was compared between the participants of the diabetes camp (n=57; median age 65 years [range, 50 to 86 years]; median diabetes duration 14 years [range, 1 to 48 years]). Additional case-control analysis compared the metabolic outcomes of the participants of the diabetes camp and their propensity score-matched controls who underwent conventional diabetes education (n=93). Results The levels of HbA1c during the first year after the diabetes camp were comparable to those of the matched controls (P=0.341). In an analysis of all participants of the diabetes camp, the 1-year mean±standard deviation (SD) of HbA1c decreased (P=0.010 and P=0.041) after the diabetes camp, whereas the adjusted SD and coefficient of variance (CV) of HbA1c did not decrease. The adjusted SD and CV significantly decreased after the diabetes camp in participants whose 1-year mean HbA1c was ≥6.5% before the diabetes camp (n=40) and those with a duration of diabetes less than 15 years (n=32). Conclusion The 1-year mean and SD of HbA1c decreased after the diabetes camp, with significant reduction in the adjusted SD and CV in those with higher baseline HbA1c and a shorter duration of diabetes. PMID:28447438

Body Size Changes Among National Collegiate Athletic Association New England Division III Football Players, 1956-2014: Comparison With Age-Matched Population Controls.

PubMed

Elliott, Kayla R; Harmatz, Jerold S; Zhao, Yanli; Greenblatt, David J

2016-05-01

Collegiate football programs encourage athletes to pursue high body weights. To examine position-dependent trends over time in body size characteristics among football players in the National Collegiate Athletic Association Division III New England Small College Athletic Conference (NESCAC) from 1956 to 2014 and to compare the observed absolute and relative changes with those in age-matched male population controls. Descriptive laboratory study. Medical school affiliated with a NESCAC institution. Football team rosters from the 10-member NESCAC schools, available as public documents, were analyzed along with body size data from general population males aged 20 to 29 years from the National Health and Nutrition Examination Survey (NHANES). Body weight, height, and calculated body mass index were evaluated using analysis of variance, linear regression, and nonlinear regression to determine the distribution features of size variables and changes associated with time (year), school, and position. Among NESCAC linemen, absolute and relative changes over time in body weight and body mass index exceeded corresponding changes in the NHANES population controls. New England Small College Athletic Conference offensive linemen body weights increased by 37.5% from 1956 to 2014 (192 to 264 lb [86.4 to 118.8 kg]), compared with a 12% increase (164 to 184 lb [73.8 to 82.8 kg]) since 1961 in the NHANES population controls. Body mass index changed in parallel with body weight and exceeded 35 kg/m(2) in more than 30% of contemporary NESCAC offensive linemen. Among skill players in the NESCAC group, time-related changes in body size characteristics generally paralleled those in the NHANES controls. High body weight and body mass indices were evident in offensive linemen, even among those in Division III football programs with no athletic scholarships. These characteristics may be associated with adverse cardiovascular and metabolic outcomes. We need approaches to encourage risk

The effect of nitric oxide synthase inhibitors nitro-L-arginine and 7-nitroindazole on spatial learning and motor functions in Lurcher mutant and wild type mice.

PubMed

Markvartová, V; Vozeh, F

2008-01-01

Nitric oxide (NO) is an intercellular messenger that, among other things, plays an important role in the nervous system as a gaseous neurotransmitter, modulating long-term potentiation (LTP) induction of synaptic transmission. LTP has been suggested to be the basis of memory formation. On the other hand NO also participates in excitotoxic processes which play an important role in many neuropathological states. The aim of this work was to observe the effect of two NO synthase (NOS) inhibitors (N omega-Nitro-L-arginine, NA; 7-nitroindazole, NI) on spontaneous behaviour, spatial learning and motor functions in Lurcher (+/Lc) and wild type (+/+) mice, derived from the B6CBA strain. Heterozygous Lurcher mutant mice represent a natural model of the olivocerebellar degeneration. They suffer from postnatal, practically total, extinction of cerebellar Purkinje cells (due to the excitotoxic apoptosis) and a partial decrease of granule cells and inferior olive neurons (ION) because of the lost target of their axons. +/+ animals are healthy littermates of +/Lc. NA is a nonselective NOS inhibitor which influences, except neuronal (n), also endothelial (e) NOS with an impact on blood pressure, NI is a selective nNOS inhibitor without any circulatory effect. The adult animals of both types (+/Lc; +/+) were influenced by acute administration of both inhibitors (25 mg/kg i.p. 30 min. before experiments) and newborns only by both acute and long-term administration of NI (1 month, starting from postnatal day 2, P2). Control solutions - saline or solvents of both NA and NI inhibitors--diluted 1M HCl and dimethyl sulfoxide (DMSO) respectively, were given at a relevant volume in the same way. The effect of both inhibitors and control solutions on motor functions was tested using four standard procedures (horizontal wire, slanting ladder, rotating cylinder, foot-bridge); in newborns at the age of 14 days. Spatial learning ability was examined in five-day long procedure in the Morris

Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

PubMed Central

Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

2016-01-01

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

The maul of the wild. Animal attacks can produce significant trauma.

PubMed

Conrad, L

1994-03-01

Wild-animal attacks are almost an anachronism in our day and age. They remind us that humans can still be food or prey. Cougar attacks, though rare, produce significant trauma. Characteristic patterns of injury and wound infection should be appropriately identified and treated. As we protect wild-animal species and acknowledge their right to share territory, interactions--and possibly attacks--are likely to increase. Awareness, education, knowledge and prevention, rather than the elimination of animal populations, may be the best way to control wild-animal attacks on humans in the future.

A demographic and social profile of age- and sex-matched vegetarians and nonvegetarians.

PubMed

Freeland-Graves, J H; Greninger, S A; Young, R K

1986-07-01

A demographic and social profile was compiled for 150 vegetarians and 150 nonvegetarians who were matched for age and sex. A 328-item questionnaire containing both closed- and open-ended questions was administered. Information collected included personal and demographic data, personal habits, social activities, and possible influences of vegetarianism. No differences were observed in the cultural, ethnic, or familial background of the groups. Vegetarians were less influenced by parents and traditional religions, were slightly less well educated, and were employed in less-skilled occupations. However, vegetarians socialized more than nonvegetarians, as evidenced by their greater frequency of entertaining, going out with friends, and joining organizations. The commitment to vegetarianism was strong and appeared to be reinforced by an extensive network of family and friends who were also vegetarians. This strong support network was particularly evident for those who practiced the more restrictive forms of vegetarianism, the only major difference observed within the types of vegetarians studied.

Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging.

PubMed

Ghosh, Amiya K; O'Brien, Martin; Mau, Theresa; Yung, Raymond

2017-09-07

Adipose tissue (AT) inflammation is a central mechanism for metabolic dysfunction in both diet-induced obesity and age-associated obesity. Studies in diet-induced obesity have characterized the role of Fetuin A (Fet A) in Free Fatty Acids (FFA)-mediated TLR4 activation and adipose tissue inflammation. However, the role of Fet A & TLR4 in aging-related adipose tissue inflammation is unknown. In the current study, analysis of epidymymal fat pads of C57/Bl6 male mice, we found that, in contrast to data from diet-induced obesity models, adipose tissue from aged mice have normal Fet A and TLR4 expression. Interestingly, aged TLR4-deficient mice have diminished adipose tissue inflammation compared to normal controls. We further demonstrated that reduced AT inflammation in old TLR4-deficient mice is linked to impaired ER stress, augmented autophagy activity, and diminished senescence phenomenon. Importantly, old TLR4-deficient mice have improved glucose tolerance compared to age-matched wild type mice, suggesting that the observed reduced AT inflammation in aged TLR4-deficient mice has important physiological consequences. Taken together, our present study establishes novel aspect of aging-associated AT inflammation that is distinct from diet-induced AT inflammation. Our results also provide strong evidence that TLR4 plays a significant role in promoting aging adipose tissue inflammation.

Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging

PubMed Central

Ghosh, Amiya K.; O'Brien, Martin; Mau, Theresa; Yung, Raymond

2017-01-01

Adipose tissue (AT) inflammation is a central mechanism for metabolic dysfunction in both diet-induced obesity and age-associated obesity. Studies in diet-induced obesity have characterized the role of Fetuin A (Fet A) in Free Fatty Acids (FFA)-mediated TLR4 activation and adipose tissue inflammation. However, the role of Fet A & TLR4 in aging-related adipose tissue inflammation is unknown. In the current study, analysis of epidymymal fat pads of C57/Bl6 male mice, we found that, in contrast to data from diet-induced obesity models, adipose tissue from aged mice have normal Fet A and TLR4 expression. Interestingly, aged TLR4-deficient mice have diminished adipose tissue inflammation compared to normal controls. We further demonstrated that reduced AT inflammation in old TLR4-deficient mice is linked to impaired ER stress, augmented autophagy activity, and diminished senescence phenomenon. Importantly, old TLR4-deficient mice have improved glucose tolerance compared to age-matched wild type mice, suggesting that the observed reduced AT inflammation in aged TLR4-deficient mice has important physiological consequences. Taken together, our present study establishes novel aspect of aging-associated AT inflammation that is distinct from diet-induced AT inflammation. Our results also provide strong evidence that TLR4 plays a significant role in promoting aging adipose tissue inflammation. PMID:28898202

Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein.

PubMed

Fleming, Sheila M; Salcedo, Jonathan; Fernagut, Pierre-Olivier; Rockenstein, Edward; Masliah, Eliezer; Levine, Michael S; Chesselet, Marie-Françoise

2004-10-20

Accumulation of alpha-synuclein in brain is a hallmark of synucleinopathies, neurodegenerative diseases that include Parkinson's disease. Mice overexpressing alpha-synuclein under the Thy-1 promoter (ASO) show abnormal accumulation of alpha-synuclein in cortical and subcortical regions of the brain, including the substantia nigra. We examined the motor deficits in ASO mice with a battery of sensorimotor tests that are sensitive to alterations in the nigrostriatal dopaminergic system. Male wild-type and ASO mice were tested every 2 months for 8 months for motor performance and coordination on a challenging beam, inverted grid, and pole, sensorimotor deficits in an adhesive removal test, spontaneous activity in a cylinder, and gait. Fine motor skills were assessed by the ability to grasp cotton from a bin. ASO mice displayed significant impairments in motor performance and coordination and a reduction in spontaneous activity as early as 2 months of age. Motor performance and coordination impairments became progressively worse with age and sensorimotor deficits appeared at 6 months. Fine motor skills were altered at 4 months and worsened at 8 months. These data indicate that overexpression of alpha-synuclein induced an early and progressive behavioral phenotype that can be detected in multiple tests of sensorimotor function. These behavioral deficits provide a useful way to assess novel drug therapy in genetic models of synucleinopathies.

Loss of butt-end leg bands on male wild turkeys

USGS Publications Warehouse

Diefenbach, Duane R.; Casalena, Mary Jo; Schiavone, Michael V.; Swanson, David A.; Reynolds, Michael; Boyd, Robert C.; Eriksen, Robert; Swift, Bryan L.

2009-01-01

We estimated loss of butt-end leg bands on male wild turkeys (Meleagris gallapavo) captured in New York, Ohio, and Pennsylvania (USA) during December–March, 2006–2008. We used aluminum rivet leg bands as permanent marks to estimate loss of regular aluminum, enameled aluminum, anodized aluminum, and stainless steel butt-end leg bands placed below the spur. We used band loss information from 887 turkeys recovered between 31 days and 570 days after release (x¯  =  202 days). Band loss was greater for turkeys banded as adults (>1 yr old) than juveniles and was greater for aluminum than stainless steel bands. We estimated band retention was 79–96%, depending on age at banding and type of band, for turkeys recovered 3 months after release. Band retention was <50% for all age classes and band types 15 months after banding. We concluded that use of butt-end leg bands on male wild turkeys is inappropriate for use in mark–recapture studies.

Glycemic Control and Mortality in Diabetic Patients Undergoing Dialysis Focusing on the Effects of Age and Dialysis Type: A Prospective Cohort Study in Korea.

PubMed

Park, Ji In; Bae, Eunjin; Kim, Yong-Lim; Kang, Shin-Wook; Yang, Chul Woo; Kim, Nam-Ho; Lee, Jung Pyo; Kim, Dong Ki; Joo, Kwon Wook; Kim, Yon Su; Lee, Hajeong

2015-01-01

Active glycemic control has been proven to delay the onset and slow the progression of diabetic retinopathy, nephropathy, and neuropathy in diabetic patients, but the optimal level is obscure in end-stage renal disease. In this study, we evaluated the effect of hemoglobin A1c (HbA1c) on mortality of diabetic patients on dialysis, focusing on age and dialysis type. Of 3,302 patients enrolled in the prospective cohort for end-stage renal disease in Korea between August 2008 and October 2013, 1,239 diabetic patients who had been diagnosed with diabetes or having HbA1c≥6.5% at the time of enrollment were analyzed. Age was categorized as <55, 55-64 and ≥65 years old. Age, sex, modified Charlson comorbidity index, hemoglobin, primary renal disease, body mass index, and dialysis duration were adjusted. A total of 873 patients received hemodialysis (HD) and 366 underwent peritoneal dialysis (PD). During the mean follow-up of 19.1 months, 141 patients died. Patients with poor glucose control (HbA1c≥8%) showed worse survival than patients with HbA1c<8% (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.48-3.29; P<0.001). Subgroup analysis divided by age revealed that HbA1c≥8% was a predictor of mortality in age <55 (HR, 4.3; 95% CI, 1.78-10.41; P = 0.001) and age 55-64 groups (HR, 3.3; 95% CI, 1.56-7.05; P = 0.002), but not in age ≥65 group. Combining dialysis type and age, poor glucose control negatively affected survival only in age < 55 group among HD patients, but it was significant in age < 55 and age 55-64 groups in PD patients. Deaths from infection were more prevalent in the PD group, and poor glucose control tended to correlate with more deaths from infection in PD patients (P = 0.050). In this study, the effect of glycemic control differed according to age and dialysis type in diabetic patients. Thus, the target of glycemic control should be customized; further observational studies may strengthen the clinical relevance.

Characterization and structural analysis of wild type and a non-abscission mutant at the development funiculus (Def) locus in Pisum sativum L.

PubMed

Ayeh, Kwadwo Owusu; Lee, YeonKyeong; Ambrose, Mike J; Hvoslef-Eide, Anne Kathrine

2009-06-23

In pea seeds (Pisum sativum L.), the Def locus defines an abscission event where the seed separates from the funicle through the intervening hilum region at maturity. A spontaneous mutation at this locus results in the seed failing to abscise from the funicle as occurs in wild type peas. In this work, structural differences between wild type peas that developed a distinct abscission zone (AZ) between the funicle and the seed coat and non-abscission def mutant were characterized. A clear abscission event was observed in wild type pea seeds that were associated with a distinct double palisade layers at the junction between the seed coat and funicle. Generally, mature seeds fully developed an AZ, which was not present in young wild type seeds. The AZ was formed exactly below the counter palisade layer. In contrast, the palisade layers at the junction of the seed coat and funicle were completely absent in the def mutant pea seeds and the cells in this region were seen to be extensions of surrounding parenchymatous cells. The Def wild type developed a distinct AZ associated with palisade layer and counterpalisade layer at the junction of the seed coat and funicle while the def mutant pea seed showed non-abscission and an absence of the double palisade layers in the same region. We conclude that the presence of the double palisade layer in the hilum of the wild type pea seeds plays an important structural role in AZ formation by delimiting the specific region between the seed coat and the funicle and may play a structural role in the AZ formation and subsequent detachment of the seed from the funicle.

Uncontrolled Hemorrhage Differs From Volume- or Pressure-Matched Controlled Hemorrhage in Swine

DTIC Science & Technology

2007-10-01

differences between these models, we evaluated the relationship between blood volume loss and blood pressure in controlled versus uncontrolled hemorrhage...aortotomy; (2) group P, controlled hemorrhage matched to the blood pressure profile of group U; or (3) group V, controlled hemorrhage matched to the...hemorrhage and received no fluid resuscitation. Group U resulted in a blood loss of 17.6 T 0.7 mL kgj1 and a reduction in blood pressure to 28 T 3 mmHg at

The retinal nerve fibre layer thickness in glaucomatous hydrophthalmic eyes assessed by scanning laser polarimetry with variable corneal compensation in comparison with age-matched healthy children.

PubMed

Hložánek, Martin; Ošmera, Jakub; Ležatková, Pavlína; Sedláčková, Petra; Filouš, Aleš

2012-12-01

To compare the thickness of the retinal nerve fibre layer (RNFL) in hydrophthalmic glaucomatous eyes in children with age-matched healthy controls using scanning laser polarimetry with variable corneal compensation (GDxVCC). Twenty hydrophthalmic eyes of 20 patients with the mean age of 10.64 ± 3.02 years being treated for congenital or infantile glaucoma were included in the analysis. Evaluation of RNFL thickness measured by GDxVCC in standard Temporal-Superior-Nasal-Inferior-Temporal (TSNIT) parameters was performed. The results were compared to TSNIT values of an age-matched control group of 120 healthy children published recently as referential values. The correlation between horizontal corneal diameter and RNFL thickness in hydrophthalmic eyes was also investigated. The mean ± SD values in TSNIT Average, Superior Average, Inferior Average and TSNIT SD in hydrophthalmic eyes were 52.3 ± 11.4, 59.7 ± 17.1, 62.0 ± 15.6 and 20.0 ± 7.8 μm, respectively. All these values were significantly lower compared to referential TSNIT parameters of age-matched healthy eyes (p = 0.021, p = 0.001, p = 0.003 and p = 0.018, respectively). A substantial number of hydrophthalmic eyes laid below the level of 5% probability of normality in respective TSNIT parameters: 30% of the eyes in TSNIT average, 50% of the eyes in superior average, 30% of the eyes in inferior average and 45% of the eyes in TSNIT SD. No significant correlation between enlarged corneal diameter and RNFL thickness was found. The mean values of all standard TSNIT parameters assessed using GDxVCC in hydrophthalmic glaucomatous eyes in children were significantly lower in comparison with referential values of healthy age-matched children. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Impact of a soccer match on the cardiac autonomic control of referees.

PubMed

Boullosa, Daniel Alexandre; Abreu, Laurinda; Tuimil, José Luis; Leicht, Anthony Scott

2012-06-01

The purpose of this study was to assess the effect of a soccer match on the cardiac autonomic control of heart rate (HR) in soccer referees. Sixteen Spanish regional and third division referees (11 males: 26 ± 7 years, 74.4 ± 4.1 kg, 178 ± 3 cm, Yo-Yo IR1 ~600-1,560 m; 5 females: 22 ± 3 years, 59.3 ± 4.8 kg, 158 ± 8 cm, Yo-Yo IR1 ~200-520 m) participated with 24-h HR recordings measured with a Polar RS800 during a rest and a match day. Autonomic control of HR was assessed from HR variability (HRV) analysis. Inclusion of a soccer match (92.5% spent at >75% maximum HR) reduced pre-match (12:00-17:00 hours; small to moderate), post-match (19:00-00:00 hours; moderate to almost perfect), and night-time (00:00-05:00 hours; small to moderate) HRV. Various moderate-to-large correlations were detected between resting HRV and the rest-to-match day difference in HRV. The rest-to-match day differences of low and high-frequency bands ratio (LF/HF) and HR in the post-match period were moderately correlated with time spent at different exercise intensities. Yo-Yo IR1 performance was highly correlated with jump capacity and peak lactate, but not with any HRV parameter. These results suggest that a greater resting HRV may allow referees to tolerate stresses during a match day with referees who spent more time at higher intensities during matches exhibiting a greater LF/HF increment in the post-match period. The relationship between match activities, [Formula: see text] and HR recovery kinetics in referees and team sport athletes of different competitive levels remains to be clarified.

Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival

PubMed Central

Fei, Dennis Liang; Motowski, Hayley; Chatrikhi, Rakesh; Gao, Shaojian; Kielkopf, Clara L.; Varmus, Harold

2016-01-01

We have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so that U2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analyzing published data on human lung adenocarcinomas, we show that S34F-associated changes in alternative splicing are proportional to the ratio of S34F:wild-type gene products and not to absolute levels of either the mutant or wild-type factor. Preferential recognition of specific 3′ splice sites in S34F-expressing cells is largely explained by differential in vitro RNA-binding affinities of mutant versus wild-type U2AF1 for those same 3′ splice sites. Finally, we show that lung adenocarcinoma cell lines bearing U2AF1 mutations do not require the mutant protein for growth in vitro or in vivo. In contrast, wild-type U2AF1 is required for survival, regardless of whether cells carry the U2AF1S34F allele. Our results provide mechanistic explanations of the magnitude of splicing changes observed in U2AF1-mutant cells and why tumors harboring U2AF1 mutations always retain an expressed copy of the wild-type allele. PMID:27776121

Fitness of Crop-Wild Hybrid Sunflower under Competitive Conditions: Implications for Crop-to-Wild Introgression

PubMed Central

Mercer, Kristin L.; Emry, D. Jason; Snow, Allison A.; Kost, Matthew A.; Pace, Brian A.; Alexander, Helen M.

2014-01-01

Understanding the likelihood and extent of introgression of novel alleles in hybrid zones requires comparison of lifetime fitness of parents and hybrid progeny. However, fitness differences among cross types can vary depending on biotic conditions, thereby influencing introgression patterns. Based on past work, we predicted that increased competition would enhance introgression between cultivated and wild sunflower (Helianthus annuus) by reducing fitness advantages of wild plants. To test this prediction, we established a factorial field experiment in Kansas, USA where we monitored the fitness of four cross types (Wild, F1, F2, and BCw hybrids) under different levels of interspecific and intraspecific competition. Intraspecific manipulations consisted both of density of competitors and of frequency of crop-wild hybrids. We recorded emergence of overwintered seeds, survival to reproduction, and numbers of seeds produced per reproductive plant. We also calculated two compound fitness measures: seeds produced per emerged seedling and seeds produced per planted seed. Cross type and intraspecific competition affected emergence and survival to reproduction, respectively. Further, cross type interacted with competitive treatments to influence all other fitness traits. More intense competition treatments, especially related to density of intraspecific competitors, repeatedly reduced the fitness advantage of wild plants when considering seeds produced per reproductive plant and per emerged seedling, and F2 plants often became indistinguishable from the wilds. Wild fitness remained superior when seedling emergence was also considered as part of fitness, but the fitness of F2 hybrids relative to wild plants more than quadrupled with the addition of interspecific competitors and high densities of intraspecific competitors. Meanwhile, contrary to prediction, lower hybrid frequency reduced wild fitness advantage. These results emphasize the importance of taking a full life cycle

Fitness of crop-wild hybrid sunflower under competitive conditions: implications for crop-to-wild introgression.

PubMed

Mercer, Kristin L; Emry, D Jason; Snow, Allison A; Kost, Matthew A; Pace, Brian A; Alexander, Helen M

2014-01-01

Understanding the likelihood and extent of introgression of novel alleles in hybrid zones requires comparison of lifetime fitness of parents and hybrid progeny. However, fitness differences among cross types can vary depending on biotic conditions, thereby influencing introgression patterns. Based on past work, we predicted that increased competition would enhance introgression between cultivated and wild sunflower (Helianthus annuus) by reducing fitness advantages of wild plants. To test this prediction, we established a factorial field experiment in Kansas, USA where we monitored the fitness of four cross types (Wild, F1, F2, and BCw hybrids) under different levels of interspecific and intraspecific competition. Intraspecific manipulations consisted both of density of competitors and of frequency of crop-wild hybrids. We recorded emergence of overwintered seeds, survival to reproduction, and numbers of seeds produced per reproductive plant. We also calculated two compound fitness measures: seeds produced per emerged seedling and seeds produced per planted seed. Cross type and intraspecific competition affected emergence and survival to reproduction, respectively. Further, cross type interacted with competitive treatments to influence all other fitness traits. More intense competition treatments, especially related to density of intraspecific competitors, repeatedly reduced the fitness advantage of wild plants when considering seeds produced per reproductive plant and per emerged seedling, and F2 plants often became indistinguishable from the wilds. Wild fitness remained superior when seedling emergence was also considered as part of fitness, but the fitness of F2 hybrids relative to wild plants more than quadrupled with the addition of interspecific competitors and high densities of intraspecific competitors. Meanwhile, contrary to prediction, lower hybrid frequency reduced wild fitness advantage. These results emphasize the importance of taking a full life cycle

Transanal pullthrough for Hirschsprung disease: matched case-control comparison of Soave and Swenson techniques.

PubMed

Nasr, Ahmed; Haricharan, Ramanath N; Gamarnik, Julie; Langer, Jacob C

2014-05-01

Both the Swenson and the Soave procedures have been adapted to a transanal approach. The purpose of this study was to compare outcomes following the transanal Swenson and Soave procedures using a matched case control analysis. A retrospective chart review was performed to identify all transanal Soave and Swenson pullthroughs done at 2 tertiary care children's hospitals between 2000 and 2010. Patients were matched for gestational age, mean weight at time of the operation, level of aganglionosis, and presence of co-morbidities. Student's t-test and chi-squared analysis were performed. Fifty-four patients (Soave 27, Swenson 27) had adequate data for matching and analysis. Mean follow-up was 4±1.6 years and 3.2 ±2.7 years for the Soave and Swenson groups, respectively. No significant differences in mean operating time (Soave:191±55, Swenson:167±61 min, p=0.6), overall hospital stay (6±4 vs 7.8±5 days, p=0.7), and number with intra-operative complications (3 vs 4, p=1.0), post-operative obstructive symptoms (6 vs 9, p=0.5), enterocolitis episodes (4 vs 4, p=1.0), or fecal incontinence (0 vs 2, p=0.4) were noted. After controlling for potential confounders, there were no significant differences in the short and intermediate term outcome between transanal Soave and transanal Swenson pullthrough procedures. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of biomechanical gait parameters of young children with haemophilia and those of age-matched peers.

PubMed

Stephensen, D; Drechsler, W; Winter, M; Scott, O

2009-03-01

Quality of life for children with haemophilia has improved since the introduction of prophylaxis. The frequency of joint haemorrhages has reduced, but the consequences of reduced bleeding on the biomechanical parameters of walking are not well understood. This study explored the differences in sagittal plane biomechanics of walking between a control group (Group 1) of normal age-matched children and children with haemophilia (Group 2) with a target ankle joint. A motion capture system and two force platforms were used to collect sagittal plane kinematic, kinetic and temporal-spatial data during walking of 14 age-matched normal children and 14 children with haemophilia aged 7-13 years. Group differences in maximum and minimum flexion/extension angles and moments of the hip, knee and ankle joints, ground reaction forces and temporal-spatial gait cycle parameters were analysed using one-way anova. Significant changes (P < 0.05) in kinematic and kinetic parameters but not temporal-spatial parameters were found in children with haemophilia; greater flexion angles and external moments of force at the knee, greater ankle plantarflexion external moments and lower hip flexion external moments. These results suggest that early biomechanical changes are present in young haemophilic children with a history of a target ankle joint and imply that lower limb joint function is more impaired than current clinical evaluations indicate. Protocols and quantitative data on the biomechanical gait pattern of children with haemophilia reported in this study provide a baseline to evaluate lower limb joint function and clinical progression.

Kinetic properties of wild-type and altered recombinant amidases by the use of ion-selective electrode assay method.

PubMed

Martins, S; Karmali, A; Serralheiro, M L

2006-08-15

A novel assay method was investigated for wild-type and recombinant mutant amidases (EC 3.5.1.4) from Pseudomonas aeruginosa by ammonium ion-selective electrode (ISE). The initial velocity is proportional to the enzyme concentration by using the wild-type enzyme. The specific activities of the purified amidase were found to be 88.2 and 104.2 U mg protein(-1) for the linked assay and ISE methods, respectively. The kinetic constants--Vmax, Km, and Kcat--determined by Michaelis-Menten plot were 101.13 U mg protein(-1), 1.12x10(-2) M, and 64.04 s(-1), respectively, for acrylamide as the substrate. On the other hand, the lower limit of detection and range of linearity of enzyme concentration were found to be 10.8 and 10.8 to 500 ng, respectively, for the linked assay method and 15.0 and 15.0 to 15,000 ng, respectively, for the ISE method. Hydroxylamine was found to act as an uncompetitive activator of hydrolysis reaction catalyzed by amidase given that there is an increase in Vmax and Km when acetamide was used as the substrate. However, the effect of hydroxylamine on the hydrolysis reaction was dependent on the type of amidase and substrate involved in the reaction mixture. The degrees of activation (epsilon(a)) of the wild-type and mutant (T103I and C91A) enzymes were found to be 2.54, 12.63, and 4.33, respectively, for acetamide as the substrate. However, hydroxylamine did not activate the reaction catalyzed by wild-type and altered (C91A and W138G) amidases by using acrylamide and acetamide, respectively, as the substrate. The activating effect of hydroxylamine on the hydrolysis of acetamide, acrylamide, and p-nitrophenylacetamide can be explained by the fact that additional formation of ammonium ions occurred due to the transferase activity of amidases. However, the activating effect of hydroxylamine on the hydrolysis of p-nitroacetanilide may be due to a change in conformation of enzyme molecule. Therefore, the use of ISE permitted the study of the kinetic

Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.

PubMed

Sehgel, Nancy L; Sun, Zhe; Hong, Zhongkui; Hunter, William C; Hill, Michael A; Vatner, Dorothy E; Vatner, Stephen F; Meininger, Gerald A

2015-02-01

Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging. © 2014 American Heart Association, Inc.

Structural and functional analyses of Saccharomyces cerevisiae wild-type and mutant RNA1 genes.

PubMed Central

Traglia, H M; Atkinson, N S; Hopper, A K

1989-01-01

The yeast gene RNA1 has been defined by the thermosensitive rna1-1 lesion. This lesion interferes with the processing and production of all major classes of RNA. Each class of RNA is affected at a distinct and presumably unrelated step. Furthermore, RNA does not appear to exit the nucleus. To investigate how the RNA1 gene product can pleiotropically affect disparate processes, we undertook a structural analysis of wild-type and mutant RNA1 genes. The wild-type gene was found to contain a 407-amino-acid open reading frame that encodes a hydrophilic protein. No clue regarding the function of the RNA1 protein was obtained by searching banks for similarity to other known gene products. Surprisingly, the rna1-1 lesion was found to code for two amino acid differences from wild type. We found that neither single-amino-acid change alone resulted in temperature sensitivity. The carboxy-terminal region of the RNA1 open reading frame contains a highly acidic domain extending from amino acids 334 to 400. We generated genomic deletions that removed C-terminal regions of this protein. Deletion of amino acids 397 to 407 did not appear to affect cell growth. Removal of amino acids 359 to 397, a region containing 24 acidic residues, caused temperature-sensitive growth. This allele, rna1-delta 359-397, defines a second conditional lesion of the RNA1 locus. We found that strains possessing the rna1-delta 359-397 allele did not show thermosensitive defects in pre-rRNA or pre-tRNA processing. Removal of amino acids 330 to 407 resulted in loss of viability. Images PMID:2674676

Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer

PubMed Central

Roper, Jatin; Sinnamon, Mark J.; Coffee, Erin M.; Belmont, Peter; Keung, Lily; Georgeon-Richard, Larissa; Wang, Wei Vivian; Faber, Anthony C.; Yun, Jihye; Yilmaz, Omer H.; Bronson, Roderick T.; Martin, Eric S.; Tsichlis, Philip N.; Hung, Kenneth E.

2014-01-01

PI3K inhibition in combination with other agents has not been studied in the context of PIK3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced tumor regression in a mouse model of PIK3CA wild-type, KRAS mutant colorectal cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and activation of BIM. These findings implicate mitochondrial-dependent apoptotic mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the treatment of PIK3CA wild-type, KRAS mutant cancer. PMID:24576621

Cervical Spinal Cord Dimensions and Clinical Outcomes in Adults with Klippel-Feil Syndrome: A Comparison with Matched Controls