Mature aggressive B-cell lymphoma across age groups - molecular advances and therapeutic implications.

PubMed

Lange, Jonas; Lenz, Georg; Burkhardt, Birgit

2017-02-01

Mature B-cell lymphoma represents the most common type of Non-Hodgkin lymphoma, and different subtypes prevail at different patient ages. Areas covered: We review recent data on differences and commonalities in mature B-cell lymphoma occurring in adult and pediatric patients, with a special emphasis on molecular advances and therapeutic implications. To this end, we will discuss knowledge on diffuse large B-cell lymphoma and Burkitt lymphoma/leukemia, which are the most frequent subtypes in adult and pediatric patients, respectively, and on primary mediastinal B-cell lymphoma, which is a subtype of mature B-cell lymphoma occurring mainly in adolescents and young adults with a female predominance. Expert commentary: Molecular profiling has revealed molecular alterations that can be used to further classify the subtypes of mature B-cell lymphoma. These new subgroups frequently respond differentially to targeted therapeutic strategies. Future clinical trials utilizing new drugs will address this issue by combining clinical data and response assessment with a molecular workup of the corresponding lymphomas.

Stem cells and female reproduction.

PubMed

Du, Hongling; Taylor, Hugh S

2009-02-01

Several recent findings in stem cell biology have resulted in new opportunities for the treatment of reproductive disease. Endometrial regeneration can be driven by bone marrow derived stem cells. This finding has potential implications for the treatment of uterine disorders. It also supports a new theory for the etiology of endometriosis. The ovaries have been shown to contain stem cells that form oocytes in adults and can be cultured in vitro to develop mature oocytes. Stem cells from the fetus have been demonstrated to lead to microchimerism in the mother and implicated in several maternal diseases. Additionally the placenta may be another source of hematopoietic stem cell. Finally endometrial derived stem cells have been demonstrated to differentiate into non-reproductive tissues. While we are just beginning to understand stem cells and many key questions remain, the potential advantages of stem cells in reproductive biology and medicine are apparent.

Correlation between three-dimensional morphological changes of the hyoid bone with other skeletal maturation methods in adolescents.

PubMed

Shim, Jocelyne; Heo, Giseon; Lagravère, Manuel O

2013-10-01

The study compares growth changes of hyoid bone in cone-beam computed tomography (CBCT) with conventional skeletal maturation methods to examine their potential implications in the development of a three-dimensional method. Subjects (n = 62, 11-17 years of age) were exposed to CBCT at a six-month interval (T1/T2/T3). Ten-hyoid distances were compared with age, hand wrist skeletal maturation index (SMI), and cervical vertebral maturation stage (CS). The length of greater cornua (GC) was most frequently, moderate to highly correlated with age (right: 0.57/0.53/0.58; left: 0.45/0.50/0.48), SMI (right: 0.52/0.40/0.45; left: 0.42 at T3), and CS (right: 0.52 at T1), followed by the length of the hyoid bone with age (right: 0.50/0.49/0.47; left: 0.44/0.47 at T1/T2), SMI (right: 0.45/0.41 at T1/T2), and CS (right: 0.48 at T1). The width of body of the hyoid (HB) width was correlated with age (0.43/0.44/0.44). The GC-HB gap was correlated with age (right: -0.41 at T3) and SMI (right: -0.42 at T1). Peripubertal hyoid maturation did not yield sufficient diagnostic information for considerations in the development of a 3D-skeletal maturation method. Copyright © 2013 Elsevier Inc. All rights reserved.

GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A: Implications for Multiple Sclerosis.

PubMed

Qin, Jing; Sikkema, Arend H; van der Bij, Kristine; de Jonge, Jenny C; Klappe, Karin; Nies, Vera; Jonker, Johan W; Kok, Jan Willem; Hoekstra, Dick; Baron, Wia

2017-10-11

Remyelination failure by oligodendrocytes contributes to the functional impairment that characterizes the demyelinating disease multiple sclerosis (MS). Since incomplete remyelination will irreversibly damage axonal connections, treatments effectively promoting remyelination are pivotal in halting disease progression. Our previous findings suggest that fibronectin aggregates, as an environmental factor, contribute to remyelination failure by perturbing oligodendrocyte progenitor cell (OPC) maturation. Here, we aim at elucidating whether exogenously added gangliosides (i.e., cell surface lipids with a potential to modulate signaling pathways) could counteract fibronectin-mediated inhibition of OPC maturation. Exclusive exposure of rat oligodendrocytes to GD1a, but not other gangliosides, overcomes aggregated fibronectin-induced inhibition of myelin membrane formation, in vitro , and OPC differentiation in fibronectin aggregate containing cuprizone-induced demyelinated lesions in male mice. GD1a exerts its effect on OPCs by inducing their proliferation and, at a late stage, by modulating OPC maturation. Kinase activity profiling revealed that GD1a activated a protein kinase A (PKA)-dependent signaling pathway and increased phosphorylation of the transcription factor cAMP response element-binding protein. Consistently, the effect of GD1a in restoring myelin membrane formation in the presence of fibronectin aggregates was abolished by the PKA inhibitor H89, whereas the effect of GD1a was mimicked by the PKA activator dibutyryl-cAMP. Together, GD1a overcomes the inhibiting effect of aggregated fibronectin on OPC maturation by activating a PKA-dependent signaling pathway. Given the persistent presence of fibronectin aggregates in MS lesions, ganglioside GD1a might act as a potential novel therapeutic tool to selectively modulate the detrimental signaling environment that precludes remyelination. SIGNIFICANCE STATEMENT As an environmental factor, aggregates of the extracellular matrix protein fibronectin perturb the maturation of oligodendrocyte progenitor cells (OPCs), thereby impeding remyelination, in the demyelinating disease multiple sclerosis (MS). Here we demonstrate that exogenous addition of ganglioside GD1a overcomes the inhibiting effect of aggregated fibronectin on OPC maturation, both in vitro and in vivo , by activating a PKA-dependent signaling pathway. We propose that targeted delivery of GD1a to MS lesions may act as a potential novel molecular tool to boost maturation of resident OPCs to overcome remyelination failure and halt disease progression. Copyright © 2017 the authors 0270-6474/17/379925-14$15.00/0.

Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility.

PubMed

Ollero, M; Gil-Guzman, E; Lopez, M C; Sharma, R K; Agarwal, A; Larson, K; Evenson, D; Thomas, A J; Alvarez, J G

2001-09-01

Reactive oxygen species (ROS)-induced damage of membrane phospholipids and DNA in human spermatozoa has been implicated in the pathogenesis of male infertility. In this study, variations in ROS production, DNA structure (as measured by the sperm chromatin structure assay) and lipid composition, were studied in human spermatozoa at different stages of maturation. Sperm subsets were isolated by discontinuous density gradient centrifugation of semen samples obtained from healthy donors and from infertility patients. DNA damage and ROS production were highest in immature spermatozoa with cytoplasmic retention and abnormal head morphology, and lowest in mature spermatozoa. Docosahexaenoic acid and sterol content were highest in immature germ cells and immature spermatozoa, and lowest in mature spermatozoa. The relative proportion of ROS-producing immature spermatozoa in the sample was directly correlated with DNA damage in mature spermatozoa, and inversely correlated with the recovery of motile spermatozoa. There was no correlation between DNA damage and sperm morphology in mature spermatozoa. The high levels of ROS production and DNA damage observed in immature spermatozoa may be indicative of derangements in the regulation of spermiogenesis. DNA damage in mature spermatozoa may be the result of oxidative damage by ROS-producing immature spermatozoa during sperm migration from the seminiferous tubules to the epididymis.

TorsinA dysfunction causes persistent neuronal nuclear pore defects.

PubMed

Pappas, Samuel S; Liang, Chun-Chi; Kim, Sumin; Rivera, CheyAnne O; Dauer, William T

2018-02-01

A critical challenge to deciphering the pathophysiology of neurodevelopmental disease is identifying which of the myriad abnormalities that emerge during CNS maturation persist to contribute to long-term brain dysfunction. Childhood-onset dystonia caused by a loss-of-function mutation in the AAA+ protein torsinA exemplifies this challenge. Neurons lacking torsinA develop transient nuclear envelope (NE) malformations during CNS maturation, but no NE defects are described in mature torsinA null neurons. We find that during postnatal CNS maturation torsinA null neurons develop mislocalized and dysfunctional nuclear pore complexes (NPC) that lack NUP358, normally added late in NPC biogenesis. SUN1, a torsinA-related molecule implicated in interphase NPC biogenesis, also exhibits localization abnormalities. Whereas SUN1 and associated nuclear membrane abnormalities resolve in juvenile mice, NPC defects persist into adulthood. These findings support a role for torsinA function in NPC biogenesis during neuronal maturation and implicate altered NPC function in dystonia pathophysiology. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Antenatal environmental stress and maturation of the breathing control, experimental data.

PubMed

Cayetanot, F; Larnicol, N; Peyronnet, J

2009-08-31

The nervous respiratory system undergoes postnatal maturation and yet still must be functional at birth. Any antenatal suboptimal environment could upset either its building prenatally and/or its maturation after birth. Here, we would like to briefly summarize some of the major stresses leading to clinical postnatal respiratory dysfunction that can occur during pregnancy, we then relate them to experimental models that have been developed in order to better understand the underlying mechanisms implicated in the respiratory dysfunctions observed in neonatal care units. Four sections are aimed to review our current knowledge based on experimental data. The first will deal with the metabolic factors such as oxygen and glucose, the second with consumption of psychotropic substances (nicotine, cocaine, alcohol, morphine, cannabis and caffeine), the third with psychoactive molecules commonly consumed by pregnant women within a therapeutic context and/or delivered to premature neonates in critical care units (benzodiazepine, caffeine). In the fourth section, we take into account care protocols involving extended maternal-infant separation due to isolation in incubators. The effects of this stress potentially adds to those previously described.

CERES-Maize model-based simulation of climate change impacts on maize yields and potential adaptive measures in Heilongjiang Province, China.

PubMed

Lin, Yumei; Wu, Wenxiang; Ge, Quansheng

2015-11-01

Climate change would cause negative impacts on future agricultural production and food security. Adaptive measures should be taken to mitigate the adverse effects. The objectives of this study were to simulate the potential effects of climate change on maize yields in Heilongjiang Province and to evaluate two selected typical household-level autonomous adaptive measures (cultivar changes and planting time adjustments) for mitigating the risks of climate change based on the CERES-Maize model. The results showed that flowering duration and maturity duration of maize would be shortened in the future climate and thus maize yield would reduce by 11-46% during 2011-2099 relative to 1981-2010. Increased CO2 concentration would not benefit maize production significantly. However, substituting local cultivars with later-maturing ones and delaying the planting date could increase yields as the climate changes. The results provide insight regarding the likely impacts of climate change on maize yields and the efficacy of selected adaptive measures by presenting evidence-based implications and mitigation strategies for the potential negative impacts of future climate change. © 2014 Society of Chemical Industry.

Maturation of oral feeding skills in preterm infants

USDA-ARS?s Scientific Manuscript database

Safe and successful oral feeding requires proper maturation of sucking, swallowing and respiration. We hypothesized that oral feeding difficulties result from different temporal development of the musculatures implicated in these functions. Sixteen medically stable preterm infants (26 to 29 weeks ge...

Transportation Energy Futures Series. Projected Biomass Utilization for Fuels and Power in a Mature Market

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

Ruth, M.; Mai, T.; Newes, E.

2013-03-01

The viability of biomass as transportation fuel depends upon the allocation of limited resources for fuel, power, and products. By focusing on mature markets, this report identifies how biomass is projected to be most economically used in the long term and the implications for greenhouse gas (GHG) emissions and petroleum use. In order to better understand competition for biomass between these markets and the potential for biofuel as a market-scale alternative to petroleum-based fuels, this report presents results of a micro-economic analysis conducted using the Biomass Allocation and Supply Equilibrium (BASE) modeling tool. The findings indicate that biofuels can outcompetemore » biopower for feedstocks in mature markets if research and development targets are met. The BASE tool was developed for this project to analyze the impact of multiple biomass demand areas on mature energy markets. The model includes domestic supply curves for lignocellulosic biomass resources, corn for ethanol and butanol production, soybeans for biodiesel, and algae for diesel. This is one of a series of reports produced as a result of the Transportation Energy Futures (TEF) project, a Department of Energy-sponsored multi-agency project initiated to pinpoint underexplored strategies for abating GHGs and reducing petroleum dependence related to transportation.« less

Transportation Energy Futures Series: Projected Biomass Utilization for Fuels and Power in a Mature Market

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

Ruth, M.; Mai, T.; Newes, E.

2013-03-01

The viability of biomass as transportation fuel depends upon the allocation of limited resources for fuel, power, and products. By focusing on mature markets, this report identifies how biomass is projected to be most economically used in the long term and the implications for greenhouse gas (GHG) emissions and petroleum use. In order to better understand competition for biomass between these markets and the potential for biofuel as a market-scale alternative to petroleum-based fuels, this report presents results of a micro-economic analysis conducted using the Biomass Allocation and Supply Equilibrium (BASE) modeling tool. The findings indicate that biofuels can outcompetemore » biopower for feedstocks in mature markets if research and development targets are met. The BASE tool was developed for this project to analyze the impact of multiple biomass demand areas on mature energy markets. The model includes domestic supply curves for lignocellulosic biomass resources, corn for ethanol and butanol production, soybeans for biodiesel, and algae for diesel. This is one of a series of reports produced as a result of the Transportation Energy Futures (TEF) project, a Department of Energy-sponsored multi-agency project initiated to pinpoint underexplored strategies for abating GHGs and reducing petroleum dependence related to transportation.« less

Interannual and Spatial Variability in Maturity of Walleye Pollock Gadus chalcogrammus and Implications for Spawning Stock Biomass Estimates in the Gulf of Alaska

PubMed Central

Kruse, Gordon H.; Dorn, Martin W.

2016-01-01

Catch quotas for walleye pollock Gadus chalcogrammus, the dominant species in the groundfish fishery off Alaska, are set by applying harvest control rules to annual estimates of spawning stock biomass (SSB) from age-structured stock assessments. Adult walleye pollock abundance and maturity status have been monitored in early spring in Shelikof Strait in the Gulf of Alaska for almost three decades. The sampling strategy for maturity status is largely characterized as targeted, albeit opportunistic, sampling of trawl tows made during hydroacoustic surveys. Trawl sampling during pre-spawning biomass surveys, which do not adequately account for spatial patterns in the distribution of immature and mature fish, can bias estimated maturity ogives from which SSB is calculated. Utilizing these maturity data, we developed mixed-effects generalized additive models to examine spatial and temporal patterns in walleye pollock maturity and the influence of these patterns on estimates of SSB. Current stock assessment practice is to estimate SSB as the product of annual estimates of numbers at age, weight at age, and mean maturity at age for 1983-present. In practice, we found this strategy to be conservative for a time period from 2003–2013 as, on average, it underestimates SSB by a 4.7 to 11.9% difference when compared to our estimates of SSB that account for spatial structure or both temporal and spatial structure. Inclusion of spatially explicit information for walleye pollock maturity has implications for understanding stock reproductive biology and thus the setting of sustainable harvest rates used to manage this valuable fishery. PMID:27736982

Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

PubMed

Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

2006-09-15

Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.

Profound Effects of Population Density on Fitness-Related Traits in an Invasive Freshwater Snail

PubMed Central

Zachar, Nicholas; Neiman, Maurine

2013-01-01

Population density can profoundly influence fitness-related traits and population dynamics, and density dependence plays a key role in many prominent ecological and evolutionary hypotheses. Here, we evaluated how individual-level changes in population density affect growth rate and embryo production early in reproductive maturity in two different asexual lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail that is an important model system for ecotoxicology and the evolution of sexual reproduction as well as a potentially destructive worldwide invader. We showed that population density had a major influence on individual growth rate and early-maturity embryo production, effects that were often apparent even when comparing treatments that differed in population density by only one individual. While individual growth rate generally decreased as population density increased, we detected a hump-shaped relationship between embryo production and density, with females from intermediate-density treatments producing the most embryos and females from low- and high-density treatments producing the fewest embryos. The two lineages responded similarly to the treatments, indicating that these effects of population density might apply more broadly across P. antipodarum. These results indicate that there are profound and complex relationships between population density, growth rate, and early-maturity embryo production in at least two lineages of this important model system, with potential implications for the study of invasive populations, research on the maintenance of sex, and approaches used in ecotoxicology. PMID:24278240

Profound effects of population density on fitness-related traits in an invasive freshwater snail.

PubMed

Zachar, Nicholas; Neiman, Maurine

2013-01-01

Population density can profoundly influence fitness-related traits and population dynamics, and density dependence plays a key role in many prominent ecological and evolutionary hypotheses. Here, we evaluated how individual-level changes in population density affect growth rate and embryo production early in reproductive maturity in two different asexual lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail that is an important model system for ecotoxicology and the evolution of sexual reproduction as well as a potentially destructive worldwide invader. We showed that population density had a major influence on individual growth rate and early-maturity embryo production, effects that were often apparent even when comparing treatments that differed in population density by only one individual. While individual growth rate generally decreased as population density increased, we detected a hump-shaped relationship between embryo production and density, with females from intermediate-density treatments producing the most embryos and females from low- and high-density treatments producing the fewest embryos. The two lineages responded similarly to the treatments, indicating that these effects of population density might apply more broadly across P. antipodarum. These results indicate that there are profound and complex relationships between population density, growth rate, and early-maturity embryo production in at least two lineages of this important model system, with potential implications for the study of invasive populations, research on the maintenance of sex, and approaches used in ecotoxicology.

Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms.

PubMed

Figueroa-Romero, Claudia; Hur, Junguk; Lunn, J Simon; Paez-Colasante, Ximena; Bender, Diane E; Yung, Raymond; Sakowski, Stacey A; Feldman, Eva L

2016-03-01

Amyotrophic lateral sclerosis is a late-onset and terminal neurodegenerative disease. The majority of cases are sporadic with unknown causes and only a small number of cases are genetically linked. Recent evidence suggests that post-transcriptional regulation and epigenetic mechanisms, such as microRNAs, underlie the onset and progression of neurodegenerative disorders; therefore, altered microRNA expression may result in the dysregulation of key genes and biological pathways that contribute to the development of sporadic amyotrophic lateral sclerosis. Using systems biology analyses on postmortem human spinal cord tissue, we identified dysregulated mature microRNAs and their potential targets previously implicated in functional process and pathways associated with the pathogenesis of ALS. Furthermore, we report a global reduction of mature microRNAs, alterations in microRNA processing, and support for a role of the nucleotide binding protein, TAR DNA binding protein 43, in regulating sporadic amyotrophic lateral sclerosis-associated microRNAs, thereby offering a potential underlying mechanism for sporadic amyotrophic lateral sclerosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Organic geochemistry and petrology of oil source rocks, Carpathian Overthrust region, southeastern Poland - Implications for petroleum generation

USGS Publications Warehouse

Kruge, M.A.; Mastalerz, Maria; Solecki, A.; Stankiewicz, B.A.

1996-01-01

The organic mailer rich Oligocene Menilite black shales and mudstones are widely distributed in the Carpathian Overthrust region of southeastern Poland and have excellent hydrocarbon generation potential, according to TOC, Rock-Eval, and petrographic data. Extractable organic matter was characterized by an equable distribution of steranes by carbon number, by varying amounts of 28,30-dinor-hopane, 18??(H)-oleanane and by a distinctive group of C24 ring-A degraded triterpanes. The Menilite samples ranged in maturity from pre-generative to mid-oil window levels, with the most mature in the southeastern portion of the study area. Carpathian petroleum samples from Campanian Oligocene sandstone reservoirs were similar in biomarker composition to the Menilite rock extracts. Similarities in aliphatic and aromatic hydrocarbon distributions between petroleum asphaltene and source rock pyrolyzates provided further evidence genetically linking Menilite kerogens with Carpathian oils.

Pm-miR-133 hosting in one potential lncRNA regulates RhoA expression in pearl oyster Pinctada martensii.

PubMed

Zheng, Zhe; Huang, RongLian; Tian, RongRong; Jiao, Yu; Du, Xiaodong

2016-10-15

Long non-coding RNAs (LncRNAs) are abundant in the genome of higher forms of eukaryotes and implicated in regulating the diversity of biological processes partly because they host microRNAs (miRNAs), which are repressors of target gene expression. In vertebrates, miR-133 regulates the differentiation and proliferation of cardiac and skeletal muscles. Pinctada martensii miR-133 (pm-miR-133) was identified in our previous research through Solexa deep sequencing. In the present study, the precise sequence of mature pm-miR-133 was validated through miR-RACE. Stem loop qRT-PCR analysis demonstrated that mature pm-miR-133 was constitutively expressed in the adductor muscle, gonad, hepatopancreas, mantle, foot, and gill of P. martensii. Among these tissues, the adductor muscle exhibited the highest pm-miR-133 expression. Target analysis indicated that pm-RhoA was the potential regulatory target of pm-miR-133. Bioinformatics analyses revealed that a potential LncRNA (designated as Lnc133) with a mature pm-miR-133 could generate a hairpin structure that was highly homologous to that of Lottia gigantea. Lnc133 was also highly expressed in the adductor muscle, gill, hepatopancreas, and gonad. Phylogenetic analysis further showed that the miR-133s derived from chordate and achordate were separated into two classes. Therefore, Lnc133 hosting pm-miR-133 could be involved in regulating the cell proliferation of adductor muscles by targeting pm-RhoA. Copyright © 2016 Elsevier B.V. All rights reserved.

A maturational model for the study of airway smooth muscle adaptation to mechanical oscillation.

PubMed

Wang, Lu; Chitano, Pasquale; Murphy, Thomas M

2005-10-01

It has been shown that mechanical stretches imposed on airway smooth muscle (ASM) by deep inspiration reduce the subsequent contractile response of the ASM. This passive maneuver of lengthening and retraction of the muscle is beneficial in normal subjects to counteract bronchospasm. However, it is detrimental to hyperresponsive airways because it triggers further bronchoconstriction. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in ASM adaptability to mechanical oscillation. Healthy immature airways of both human and animal exhibit hyperresponsiveness, but whether the adaptative properties of hyperresponsive airway differ from normal is still unknown. In this article, we review the phenomenon of ASM adaptation to mechanical oscillation and its relevance and implication to airway hyperresponsiveness. We demonstrate that the age-specific expression of ASM adaptation is prominent using an established maturational animal model developed in our laboratory. Our data on immature ASM showed potentiated contractile force shortly after a length oscillation compared with the maximum force generated before oscillation. Several potential mechanisms such as myogenic response, changes in actin polymerization, or changes in the quantity of the cytoskeletal regulatory proteins plectin and vimentin, which may underlie this age-specific force potentiation, are discussed. We suggest a working model of the structure of smooth muscle associated with force transmission, which may help to elucidate the mechanisms responsible for the age-specific expression of smooth muscle adaptation. It is important to study the maturational profile of ASM adaptation as it could contribute to juvenile hyperresponsiveness.

Workshop summary: New silicon cells

NASA Technical Reports Server (NTRS)

Meulenberg, A.; Iles, P. A.

1993-01-01

The workshop on new silicon cells held during SPRAT12 is summarized. A smaller than average group attended this workshop reflecting the reduction in research dollars available to this portion of the photovoltaics community. Despite the maturity of the silicon technology, a core of the group maintained an excitement about new developments and potential opportunities. The group addressed both the implications and the applications of recent developments. Topics discussed include: light trapping and ultrathin silicon cells; different uses for silicon cells; new silicon cell developments; and radiation tolerant high efficiency cells.

Plasmacytoid pre-dendritic cells (pDC): from molecular pathways to function and disease association.

PubMed

Alculumbre, Solana; Raieli, Salvatore; Hoffmann, Caroline; Chelbi, Rabie; Danlos, François-Xavier; Soumelis, Vassili

2018-02-19

Plasmacytoid pre-dendritic cells (pDC) are a specialized DC population with a great potential to produce large amounts of type I interferon (IFN). pDC are involved in the initiation of antiviral immune responses through their interaction with innate and adaptive immune cell populations. In a context-dependent manner, pDC activation can induce their differentiation into mature DC able to induce both T cell activation or tolerance. In this review, we described pDC functions during immune responses and their implication in the clearance or pathogenicity of human diseases during infection, autoimmunity, allergy and cancer. We discuss recent advances in the field of pDC biology and their implication for future studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anti-osteopontin monoclonal antibody prevents ovariectomy-induced osteoporosis in mice by promotion of osteoclast apoptosis

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

Zhang, Bo; PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing; Dai, Jianxin

Highlight: • We first report that anti-osteopontin mAb could protect osteoporosis in mice. • Anti-osteopontin mAb could promote the osteoclast apoptosis. • Targeting osteopontin might have therapeutic potentials for osteoporosis. - Abstract: Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation. In vitro assay showed that 23C3 mAb reduced osteoclasts (OCs)-mediated bone resorptionmore » through promotion of mature OC apoptosis. Thus, the study has important implications for understanding the role of OPN in OC bone resorption and survival, and OPN antagonists may have therapeutic potential for osteoporosis and other osteopenic diseases.« less

Maturation experiments reveal bias in the fossil record of feathers

NASA Astrophysics Data System (ADS)

McNamara, Maria; Field, Daniel

2016-04-01

The evolutionary history of birds and feathers is a major focus in palaeobiology and evolutionary biology. Diverse exceptionally preserved birds and feathered dinosaurs from Jurassic and Cretaceous biotas in China have provided pivotal evidence of early feathers and feather-like integumentary features, but the true nature of many of these fossil soft tissues is still debated. Interpretations of feathers at intermediate developmental stages (i.e. Stages II, III and IV) and of simple quill-like (Stage I) feathers are particularly controversial. This reflects key uncertainties relating to the preservation potential of feathers at different evolutionary-developmental stages, and to the relative preservation potential of diagnostic features of Stage I feathers and hair. To resolve these issues, we used high pressure-high temperature autoclave experiments to simulate the effects of burial on modern feathers from the Black Coucal (Centropus grilii) and Common Starling (Sturnus vulgaris), and on human hair. Our results reveal profound differences in the recalcitrance of feathers of different types during maturation: Stage I and Stage V feathers retain diagnostic morphological and ultrastructural details following maturation, whereas other feather types do not. Further, the morphology and arrangement of certain ultrastructural features diagnostic of Stages III and IV, e.g. barbules, are preferentially lost during maturation. These results indicate a pervasive bias in the fossil record of feathers, whereby preservation of feathers at Stages I and V is favored. Critical stages in the evolution of feathers, i.e. Stages II, III and IV, are less likely to be preserved and more likely to be misinterpreted as feathers at earlier developmental stages. Our discovery has major implications for our understanding of the fidelity of the fossil record of feathers and provides a framework for testing the significance of putative examples of fossil feathers at different developmental stages.

Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for pathology resulting from EFEMP2 mutations

PubMed Central

Papke, Christina L.; Tsunezumi, Jun; Ringuette, Léa-Jeanne; Nagaoka, Hideaki; Terajima, Masahiko; Yamashiro, Yoshito; Urquhart, Greg; Yamauchi, Mitsuo; Davis, Elaine C.; Yanagisawa, Hiromi

2015-01-01

Homozygous recessive mutations in either EFEMP2 (encoding fibulin-4) or FBLN5 (encoding fibulin-5), critical genes for elastogenesis, lead to autosomal recessive cutis laxa types 1B and 1A, respectively. Previously, fibulin-4 was shown to bind lysyl oxidase (LOX), an elastin/collagen cross-linking enzyme, in vitro. Consistently, reported defects in humans with EFEMP2 mutations are more severe and broad in range than those due to FBLN5 mutations and encompass both elastin-rich and collagen-rich tissues. However, the underlying disease mechanism in EFEMP2 mutations has not been fully addressed. Here, we show that fibulin-4 is important for the integrity of aortic collagen in addition to elastin. Smooth muscle-specific Efemp2 loss in mouse (termed SMKO) resulted in altered fibrillar collagen localization with larger, poorly organized fibrils. LOX activity was decreased in Efemp2-null cells, and collagen cross-linking was diminished in SMKO aortas; however, elastin cross-linking was unaffected and the level of mature LOX was maintained to that of wild-type aortas. Proteomic screening identified multiple proteins involved in procollagen processing and maturation as potential fibulin-4-binding partners. We showed that fibulin-4 binds procollagen C-endopeptidase enhancer 1 (Pcolce), which enhances proteolytic cleavage of the procollagen C-terminal propeptide during procollagen processing. Interestingly, however, procollagen cleavage was not affected by the presence or absence of fibulin-4 in vitro. Thus, our data indicate that fibulin-4 serves as a potential scaffolding protein during collagen maturation in the extracellular space. Analysis of collagen in other tissues affected by fibulin-4 loss should further increase our understanding of underlying pathologic mechanisms in patients with EFEMP2 mutations. PMID:26220971

Increasing abscisic acid levels by immunomodulation in barley grains induces precocious maturation without changing grain composition.

PubMed

Staroske, Nicole; Conrad, Udo; Kumlehn, Jochen; Hensel, Götz; Radchuk, Ruslana; Erban, Alexander; Kopka, Joachim; Weschke, Winfriede; Weber, Hans

2016-04-01

Abscisic acid (ABA) accumulates in seeds during the transition to the seed filling phase. ABA triggers seed maturation, storage activity, and stress signalling and tolerance. Immunomodulation was used to alter the ABA status in barley grains, with the resulting transgenic caryopses responding to the anti-ABA antibody gene expression with increased accumulation of ABA. Calculation of free versus antibody-bound ABA reveals large excess of free ABA, increasing signficantly in caryopses from 10 days after fertilization. Metabolite and transcript profiling in anti-ABA grains expose triggered and enhanced ABA-functions such as transcriptional up-regulation of sucrose-to-starch metabolism, storage protein synthesis and ABA-related signal transduction. Thus, enhanced ABA during transition phases induces precocious maturation but negatively interferes with growth and development. Anti-ABA grains display broad constitutive gene induction related to biotic and abiotic stresses. Most of these genes are ABA- and/or stress-inducible, including alcohol and aldehyde dehydrogenases, peroxidases, chaperones, glutathione-S-transferase, drought- and salt-inducible proteins. Conclusively, ABA immunomodulation results in precocious ABA accumulation that generates an integrated response of stress and maturation. Repression of ABA signalling, occurring in anti-ABA grains, potentially antagonizes effects caused by overshooting production. Finally, mature grain weight and composition are unchanged in anti-ABA plants, although germination is somewhat delayed. This indicates that anti-ABA caryopses induce specific mechanisms to desensitize ABA signalling efficiently, which finally yields mature grains with nearly unchanged dry weight and composition. Such compensation implicates the enormous physiological and metabolic flexibilities of barley grains to adjust effects of unnaturally high ABA amounts in order to ensure and maintain proper grain development. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Increasing abscisic acid levels by immunomodulation in barley grains induces precocious maturation without changing grain composition

PubMed Central

Staroske, Nicole; Conrad, Udo; Kumlehn, Jochen; Hensel, Götz; Radchuk, Ruslana; Erban, Alexander; Kopka, Joachim; Weschke, Winfriede; Weber, Hans

2016-01-01

Abscisic acid (ABA) accumulates in seeds during the transition to the seed filling phase. ABA triggers seed maturation, storage activity, and stress signalling and tolerance. Immunomodulation was used to alter the ABA status in barley grains, with the resulting transgenic caryopses responding to the anti-ABA antibody gene expression with increased accumulation of ABA. Calculation of free versus antibody-bound ABA reveals large excess of free ABA, increasing signficantly in caryopses from 10 days after fertilization. Metabolite and transcript profiling in anti-ABA grains expose triggered and enhanced ABA-functions such as transcriptional up-regulation of sucrose-to-starch metabolism, storage protein synthesis and ABA-related signal transduction. Thus, enhanced ABA during transition phases induces precocious maturation but negatively interferes with growth and development. Anti-ABA grains display broad constitutive gene induction related to biotic and abiotic stresses. Most of these genes are ABA- and/or stress-inducible, including alcohol and aldehyde dehydrogenases, peroxidases, chaperones, glutathione-S-transferase, drought- and salt-inducible proteins. Conclusively, ABA immunomodulation results in precocious ABA accumulation that generates an integrated response of stress and maturation. Repression of ABA signalling, occurring in anti-ABA grains, potentially antagonizes effects caused by overshooting production. Finally, mature grain weight and composition are unchanged in anti-ABA plants, although germination is somewhat delayed. This indicates that anti-ABA caryopses induce specific mechanisms to desensitize ABA signalling efficiently, which finally yields mature grains with nearly unchanged dry weight and composition. Such compensation implicates the enormous physiological and metabolic flexibilities of barley grains to adjust effects of unnaturally high ABA amounts in order to ensure and maintain proper grain development. PMID:26951372

Placing Ion Channels into a Signaling Network of T Cells: From Maturing Thymocytes to Healthy T Lymphocytes or Leukemic T Lymphoblasts

PubMed Central

Delgado-Enciso, Iván; Best-Aguilera, Carlos; Rojas-Sotelo, Rocío Monserrat; Pottosin, Igor

2015-01-01

T leukemogenesis is a multistep process, where the genetic errors during T cell maturation cause the healthy progenitor to convert into the leukemic precursor that lost its ability to differentiate but possesses high potential for proliferation, self-renewal, and migration. A new misdirecting “leukemogenic” signaling network appears, composed by three types of participants which are encoded by (1) genes implicated in determined stages of T cell development but deregulated by translocations or mutations, (2) genes which normally do not participate in T cell development but are upregulated, and (3) nondifferentially expressed genes which become highly interconnected with genes expressed differentially. It appears that each of three groups may contain genes coding ion channels. In T cells, ion channels are implicated in regulation of cell cycle progression, differentiation, activation, migration, and cell death. In the present review we are going to reveal a relationship between different genetic defects, which drive the T cell neoplasias, with calcium signaling and ion channels. We suggest that changes in regulation of various ion channels in different types of the T leukemias may provide the intracellular ion microenvironment favorable to maintain self-renewal capacity, arrest differentiation, induce proliferation, and enhance motility. PMID:25866806

Tracking the elusive 5' exonuclease activity of Chlamydomonas reinhardtii RNase J.

PubMed

Liponska, Anna; Jamalli, Ailar; Kuras, Richard; Suay, Loreto; Garbe, Enrico; Wollman, Francis-André; Laalami, Soumaya; Putzer, Harald

2018-04-01

Chlamydomonas RNase J is the first member of this enzyme family that has endo- but no intrinsic 5' exoribonucleolytic activity. This questions its proposed role in chloroplast mRNA maturation. RNA maturation and stability in the chloroplast are controlled by nuclear-encoded ribonucleases and RNA binding proteins. Notably, mRNA 5' end maturation is thought to be achieved by the combined action of a 5' exoribonuclease and specific pentatricopeptide repeat proteins (PPR) that block the progression of the nuclease. In Arabidopsis the 5' exo- and endoribonuclease RNase J has been implicated in this process. Here, we verified the chloroplast localization of the orthologous Chlamydomonas (Cr) RNase J and studied its activity, both in vitro and in vivo in a heterologous B. subtilis system. Our data show that Cr RNase J has endo- but no significant intrinsic 5' exonuclease activity that would be compatible with its proposed role in mRNA maturation. This is the first example of an RNase J ortholog that does not possess a 5' exonuclease activity. A yeast two-hybrid screen revealed a number of potential interaction partners but three of the most promising candidates tested, failed to induce the latent exonuclease activity of Cr RNase J. We still favor the hypothesis that Cr RNase J plays an important role in RNA metabolism, but our findings suggest that it rather acts as an endoribonuclease in the chloroplast.

Prolonged myelination in human neocortical evolution.

PubMed

Miller, Daniel J; Duka, Tetyana; Stimpson, Cheryl D; Schapiro, Steven J; Baze, Wallace B; McArthur, Mark J; Fobbs, Archibald J; Sousa, André M M; Sestan, Nenad; Wildman, Derek E; Lipovich, Leonard; Kuzawa, Christopher W; Hof, Patrick R; Sherwood, Chet C

2012-10-09

Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.

Does implied volatility of currency futures option imply volatility of exchange rates?

NASA Astrophysics Data System (ADS)

Wang, Alan T.

2007-02-01

By investigating currency futures options, this paper provides an alternative economic implication for the result reported by Stein [Overreactions in the options market, Journal of Finance 44 (1989) 1011-1023] that long-maturity options tend to overreact to changes in the implied volatility of short-maturity options. When a GARCH process is assumed for exchange rates, a continuous-time relationship is developed. We provide evidence that implied volatilities may not be the simple average of future expected volatilities. By comparing the term-structure relationship of implied volatilities with the process of the underlying exchange rates, we find that long-maturity options are more consistent with the exchange rates process. In sum, short-maturity options overreact to the dynamics of underlying assets rather than long-maturity options overreacting to short-maturity options.

Promises of formal and informal musical activities in advancing neurocognitive development throughout childhood.

PubMed

Putkinen, Vesa; Tervaniemi, Mari; Saarikivi, Katri; Huotilainen, Minna

2015-03-01

Adult musicians show superior neural sound discrimination when compared to nonmusicians. However, it is unclear whether these group differences reflect the effects of experience or preexisting neural enhancement in individuals who seek out musical training. Tracking how brain function matures over time in musically trained and nontrained children can shed light on this issue. Here, we review our recent longitudinal event-related potential (ERP) studies that examine how formal musical training and less formal musical activities influence the maturation of brain responses related to sound discrimination and auditory attention. These studies found that musically trained school-aged children and preschool-aged children attending a musical playschool show more rapid maturation of neural sound discrimination than their control peers. Importantly, we found no evidence for pretraining group differences. In a related cross-sectional study, we found ERP and behavioral evidence for improved executive functions and control over auditory novelty processing in musically trained school-aged children and adolescents. Taken together, these studies provide evidence for the causal role of formal musical training and less formal musical activities in shaping the development of important neural auditory skills and suggest transfer effects with domain-general implications. © 2015 New York Academy of Sciences.

[Considerations for the Definition of a Interval of Vulnerability/Possibility in Adolescence].

PubMed

Orón Semper, José Víctor; Echarte Alonso, Luis Enrique

2017-01-01

This article explores the hypothesis that while maturation related cognitive abilities reaches maturity around the age of fifteen, maturation related social skills is delayed until well into the twenties. Our goal is to try to define what is the window of opportunity/vulnerability and what is the maturational status of the young in this interval. In this context, we argue how the maturational time of the closing of adolescence has an impact on the valuation of autonomy in decision-making of the person. Particularly, we figure out implications for the assessment of the autonomy of youth in health issues, and also criminal liability. In the conclusion, we offer some educational criteria that may provide guidance for implementing both social policy and educational programs.

Mechanisms affecting neuroendocrine and epigenetic regulation of body weight and onset of puberty: potential implications in the child born small for gestational age (SGA).

PubMed

Roth, Christian L; Sathyanarayana, Sheela

2012-06-01

Signaling peptides produced in peripheral tissues such as gut, adipose tissue, and pancreas communicate with brain centers, such as hypothalamus and hindbrain to manage energy homeostasis. These regulatory mechanisms of energy intake and storage have evolved during long periods of hunger in the evolution of man to protect the species from extinction. It is now clear that these circuitries are influenced by prenatal and postnatal environmental factors including endocrine disruptive chemicals. Hypothalamic appetite regulatory systems develop and mature in utero and early infancy, and involve signaling pathways that are important also for the regulation of puberty onset. Recent studies in humans and animals have shown that metabolic pathways involved in regulation of growth, body weight gain and sexual maturation are largely affected by epigenetic programming that can impact both current and future generations. In particular, intrauterine and early infantile developmental phases of high plasticity are susceptible to factors that affect metabolic programming that therefore, affect metabolic function throughout life. In children born small for gestational age, poor nutritional conditions during gestation can modify metabolic systems to adapt to expectations of chronic undernutrition. These children are potentially poorly equipped to cope with energy-dense diets and are possibly programmed to store as much energy as possible, leading to later obesity, metabolic syndrome, disturbed regulation of normal puberty and early onset of cardiovascular disease. Most cases of disturbed energy balance are likely a result of a combination of genetics, epigenetics and environment. This review will discuss potential mechanisms linking intrauterine growth retardation with changes in growth, energy homeostasis and sexual maturation.

Adjuvant properties of thermal component of hyperthermia enhanced transdermal immunization: effect on dendritic cells.

PubMed

Joshi, Neha; Duhan, Vikas; Lingwal, Neelam; Bhaskar, Sangeeta; Upadhyay, Pramod

2012-01-01

Hyperthermia enhanced transdermal (HET) immunization is a novel needle free immunization strategy employing application of antigen along with mild local hyperthermia (42°C) to intact skin resulting in detectable antigen specific Ig in serum. In the present study, we investigated the adjuvant effect of thermal component of HET immunization in terms of maturation of dendritic cells and its implication on the quality of the immune outcome in terms of antibody production upon HET immunization with tetanus toxoid (TT). We have shown that in vitro hyperthermia exposure at 42°C for 30 minutes up regulates the surface expression of maturation markers on bone marrow derived DCs. This observation correlated in vivo with an increased and accelerated expression of maturation markers on DCs in the draining lymph node upon HET immunization in mice. This effect was found to be independent of the antigen delivered and depends only on the thermal component of HET immunization. In vitro hyperthermia also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell response. HET immunization also induced a systemic T cell response to TT, as suggested by proliferation of splenocytes from immunized animal upon in vitro stimulation by TT. Exposure to heat during primary immunization led to generation of mainly IgG class of antibodies upon boosting, similar to the use of conventional alum adjuvant, thus highlighting the adjuvant potential of heat during HET immunization. Lastly, we have shown that mice immunized by tetanus toxoid using HET route exhibited protection against challenge with a lethal dose of tetanus toxin. Thus, in addition to being a painless, needle free delivery system it also has an immune modulatory potential.

Tectono-thermal Evolution of the Lower Paleozoic Petroleum Source Rocks in the Southern Lublin Trough: Implications for Shale Gas Exploration from Maturity Modelling

NASA Astrophysics Data System (ADS)

Botor, Dariusz

2018-03-01

The Lower Paleozoic basins of eastern Poland have recently been the focus of intensive exploration for shale gas. In the Lublin Basin potential unconventional play is related to Lower Silurian source rocks. In order to assess petroleum charge history of these shale gas reservoirs, 1-D maturity modeling has been performed. In the Łopiennik IG-1 well, which is the only well that penetrated Lower Paleozoic strata in the study area, the uniform vitrinite reflectance values within the Paleozoic section are interpreted as being mainly the result of higher heat flow in the Late Carboniferous to Early Permian times and 3500 m thick overburden eroded due to the Variscan inversion. Moreover, our model has been supported by zircon helium and apatite fission track dating. The Lower Paleozoic strata in the study area reached maximum temperature in the Late Carboniferous time. Accomplished tectono-thermal model allowed establishing that petroleum generation in the Lower Silurian source rocks developed mainly in the Devonian - Carboniferous period. Whereas, during Mesozoic burial, hydrocarbon generation processes did not develop again. This has negative influence on potential durability of shale gas reservoirs.

Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

PubMed

Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

2009-10-01

Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

Engineered BDNF producing cells as a potential treatment for neurologic disease

PubMed Central

Deng, Peter; Anderson, Johnathon D.; Yu, Abigail S.; Annett, Geralyn; Fink, Kyle D.; Nolta, Jan A.

2018-01-01

Introduction Brain-derived neurotrophic factor (BDNF) has been implicated in wide range of neurological diseases and injury. This neurotrophic factor is vital for neuronal health, survival, and synaptic connectivity. Many therapies focus on the restoration or enhancement of BDNF following injury or disease progression. Areas covered The present review will focus on the mechanisms in which BDNF exerts its beneficial functioning, current BDNF therapies, issues and potential solutions for delivery of neurotrophic factors to the central nervous system, and other disease indications that may benefit from overexpression or restoration of BDNF. Expert opinion Due to the role of BDNF in neuronal development, maturation, and health, BDNF is implicated in numerous neurological diseases making it a prime therapeutic agent. Numerous studies have shown the therapeutic potential of BDNF in a number of neurodegenerative disease models and in acute CNS injury, however clinical translation has fallen short due to issues in delivering this molecule. The use of MSC as a delivery platform for BDNF holds great promise for clinical advancement of neurotrophic factor restoration. The ease with which MSC can be engineered opens the door to the possibility of using this cell-based delivery system to advance a BDNF therapy to the clinic. PMID:27159050

Staying or Leaving the Course: Non-Completion and Retention of Mature Students in Further and Higher Education.

ERIC Educational Resources Information Center

McGivney, Veronica

This book combines findings of existing research with fresh evidence supplied from a sample of institutions regarding noncompletion rates of mature students in postcompulsory education. Chapter 1 considers the changes that have taken place in postcompulsory education and the implications of having an expanded and more diverse student population.…

Genetic subpopulation structuring and its implications in a mature eastern white pine stand

Treesearch

Samuel E. Nijensohn; Paul G. Schaberg; Gary J. Hawley; Donald H. DeHayes; Donald H. DeHayes

2005-01-01

We examined patterns of genetic structuring within a mature eastern white pine (Pinus strobus L.) forest, using geographic information system (GIS)-based data and maps that combined genetic (isozyme analysis of 46 loci) and other tree-specific information (e.g., size, growth, age, and location) for 220 trees in Jericho, Vermont. Interconnections between genotypic...

Water relations in culture media influence maturation of avocado somatic embryos.

PubMed

Márquez-Martín, Belén; Sesmero, Rafael; Quesada, Miguel A; Pliego-Alfaro, Fernando; Sánchez-Romero, Carolina

2011-11-15

Application of transformation and other biotechnological tools in avocado (Persea americana Mill.) is hampered by difficulties in obtaining mature somatic embryos capable of germination at an acceptable rate. In this work, we evaluated the effect of different compounds affecting medium water relations on maturation of avocado somatic embryos. Culture media were characterized with respect to gel strength, water potential and osmotic potential. Improved production of mature somatic embryos was achieved with gelling agent concentrations higher than those considered standard. The osmotic agents such as sorbitol and PEG did not have positive effects on embryo maturation. The number of w-o mature somatic embryos per culture was positively correlated with medium gel strength. Gel strength was significantly affected by gelling agent type as well as by gelling agent and PEG concentration. Medium water potential was influenced by sorbitol concentration; incorporation of PEG to a culture medium did not affect medium water potential. The highest maturation results were achieved on a medium gelled with 10 gl(-1) agar. Moreover, these somatic embryos had improved germination rates. These results corroborate the role of water restriction as a key factor controlling maturation of somatic embryos. Copyright © 2011 Elsevier GmbH. All rights reserved.

Misdiagnosis of attention deficit hyperactivity disorder: ‘Normal behaviour’ and relative maturity

PubMed Central

Ford-Jones, Polly Christine

2015-01-01

Attention deficit hyperactivity disorder (ADHD) is one of the most frequently diagnosed disorders in children, yet it remains poorly understood. Substantial controversy exists regarding correct diagnosis of ADHD, and areas of subjectivity in diagnosis have been identified. Concerns for appropriate diagnosis are critical in terms of children’s educational outcomes, as well as health concerns associated with the use and potential overuse of stimulant medications. There exists a relative-age effect in which children who are relatively younger than their peers and born closest to the school start age cut-off are more frequently diagnosed and treated for ADHD. Additionally, substantial variation exists in ADHD diagnosis between boys and girls, with boys often presenting with more stereotypical symptoms. Both the relative-age effect and variation in sex diagnosis, as well as the challenges of early preschool diagnosis, emphasize the importance of considering relative maturity in ADHD diagnosis of children. Implications and knowledge translation strategies for practitioners, parents and the education system are presented. PMID:26038639

The Role of Affect Spin in the Relationships between Proactive Personality, Career Indecision, and Career Maturity

PubMed Central

Park, In-Jo

2015-01-01

This study attempted to investigate the influence of proactive personality on career indecision and career maturity, and to examine the moderating effects of affect spin. The author administered proactive personality, career indecision, and career maturity scales to 70 college students. Affect spin was calculated using the day reconstruction method, wherein participants evaluated their affective experiences by using 20 affective terms at the same time each day for 21 consecutive days. Hierarchical regression analyses showed that proactive personality significantly predicted career indecision and career maturity, even after controlling for valence and activation variability, neuroticism, age, and gender. Furthermore, affect spin moderated the associations of proactive personality with career indecision and maturity. The theoretical and practical implications of the moderating effects of affect spin are discussed. PMID:26635665

Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process.

PubMed

Adamson, Catherine S

2012-01-01

Protease-mediated maturation of HIV-1 virus particles is essential for virus infectivity. Maturation occurs concomitant with immature virus particle release and is mediated by the viral protease (PR), which sequentially cleaves the Gag and Gag-Pol polyproteins into mature protein domains. Maturation triggers a second assembly event that generates a condensed conical capsid core. The capsid core organizes the viral RNA genome and viral proteins to facilitate viral replication in the next round of infection. The fundamental role of proteolytic maturation in the generation of mature infectious particles has made it an attractive target for therapeutic intervention. Development of small molecules that target the PR active site has been highly successful and nine protease inhibitors (PIs) have been approved for clinical use. This paper provides an overview of their development and clinical use together with a discussion of problems associated with drug resistance. The second-half of the paper discusses a novel class of antiretroviral drug termed maturation inhibitors, which target cleavage sites in Gag not PR itself. The paper focuses on bevirimat (BVM) the first-in-class maturation inhibitor: its mechanism of action and the implications of naturally occurring polymorphisms that confer reduced susceptibility to BVM in phase II clinical trials.

Stand compositional dynamics in a mature Illinois Ozarks forest: implications for management

Treesearch

John W. Groninger; Trevor B. Ozier; Charles M. Ruffner

2003-01-01

The Ozark Hills region of southern Illinois is characterized by the severe topography typical of the Ozark Plateau, but is overlain by loess deposits and therefore supports site conditions more typical of mesophytic forests. As is common in lightly disturbed and undisturbed mesic upland sites throughout this region, mature stands in Trail of Tears State Forest are...

Hop/Sti1 – A Two-Faced Cochaperone Involved in Pattern Recognition Receptor Maturation and Viral Infection

PubMed Central

Lamm, Christian E.; Kraner, Max. E.; Hofmann, Jörg; Börnke, Frederik; Mock, Hans-Peter; Sonnewald, Uwe

2017-01-01

Perception of pathogens by host pattern recognition receptors (PRRs) or R proteins is a prerequisite to promote successful immune responses. The Hsp70/Hsp90 organizing protein Hop/Sti1, a multifunctional cochaperone, has been implicated in the maturation of a receptor-like kinase (RLK) necessary for chitin sensing. However, it remains unknown whether Hop/Sti1 is generally participating in PRR genesis. Using RNA-interference (RNAi), we silenced Hop/Sti1 expression in Nicotiana tabacum to gain further insight into the role of the cochaperone in plant defense responses. As expected, transgenic plants do not respond to chitin treatment anymore. In contrast to this, trafficking and functionality of the flagellin PRR FLS2 were unaltered, suggesting a selective involvement of Hop/Sti1 during PRR maturation. Furthermore, Hop/Sti1 was identified as a cellular determinant of Potato virus Y (PVY) symptom development in tobacco, since PVY was able to accumulate to near wild-type level without provoking the usual veinal necrosis phenotype. In addition, typical antiviral host defense responses were suppressed in the transgenic plants. These data suggest that perception of PVY is dependent on Hop/Sti1-mediated receptor maturation, while viral symptoms represent a failing attempt to restrict PVY spread. In addition, Hop/Sti1 colocalized with virus-induced membrane aggregates in wild-type plants. The retention of Hop/Sti1 in potential viral replication complexes suggests a role during viral translation/replication, explaining why RNAi-lines do not exhibit increased susceptibility to PVY. This study provides evidence for a dual role of Hop/Sti1 in PRR maturation and pathogen perception as well as in promoting viral proliferation. PMID:29075278

Error and bias in size estimates of whale sharks: implications for understanding demography.

PubMed

Sequeira, Ana M M; Thums, Michele; Brooks, Kim; Meekan, Mark G

2016-03-01

Body size and age at maturity are indicative of the vulnerability of a species to extinction. However, they are both difficult to estimate for large animals that cannot be restrained for measurement. For very large species such as whale sharks, body size is commonly estimated visually, potentially resulting in the addition of errors and bias. Here, we investigate the errors and bias associated with total lengths of whale sharks estimated visually by comparing them with measurements collected using a stereo-video camera system at Ningaloo Reef, Western Australia. Using linear mixed-effects models, we found that visual lengths were biased towards underestimation with increasing size of the shark. When using the stereo-video camera, the number of larger individuals that were possibly mature (or close to maturity) that were detected increased by approximately 10%. Mean lengths calculated by each method were, however, comparable (5.002 ± 1.194 and 6.128 ± 1.609 m, s.d.), confirming that the population at Ningaloo is mostly composed of immature sharks based on published lengths at maturity. We then collated data sets of total lengths sampled from aggregations of whale sharks worldwide between 1995 and 2013. Except for locations in the East Pacific where large females have been reported, these aggregations also largely consisted of juveniles (mean lengths less than 7 m). Sightings of the largest individuals were limited and occurred mostly prior to 2006. This result highlights the urgent need to locate and quantify the numbers of mature male and female whale sharks in order to ascertain the conservation status and ensure persistence of the species.

The microRNA signature of mouse spermatozoa is substantially modified during epididymal maturation.

PubMed

Nixon, Brett; Stanger, Simone J; Mihalas, Bettina P; Reilly, Jackson N; Anderson, Amanda L; Tyagi, Sonika; Holt, Janet E; McLaughlin, Eileen A

2015-10-01

In recent years considerable effort has been devoted to understanding the epigenetic control of sperm development, leading to an increased appreciation of the importance of RNA interference pathways, and in particular miRNAs, as key regulators of spermatogenesis and epididymal maturation. It has also been shown that sperm are endowed with an impressive array of miRNA that have been implicated in various aspects of fertilization and embryo development. However, to date there have been no reports on whether the sperm miRNA signature is static or whether it is influenced by their prolonged maturation within the male reproductive tract. To investigate this phenomenon, we employed next-generation sequencing to systematically profile the miRNA signature of maturing mouse spermatozoa. In so doing we have provided the first evidence for the posttesticular modification of the sperm miRNA profile under normal physiological conditions. Such modifications include the apparent loss and acquisition of an impressive cohort of some 113 and 115 miRNAs, respectively, between the proximal and distal epididymal segments. Interestingly, the majority of these changes occur late in maturation and include the uptake of novel miRNA species in addition to a significant increase in many miRNAs natively expressed in immature sperm. Because sperm are not capable of de novo transcription, these findings identify the epididymis as an important site in establishing the sperm epigenome with the potential to influence the peri-conceptual environment of the female reproductive tract, contribute to the inheritance of acquired characteristics, and/or alter the developmental trajectory of the resulting offspring. © 2015 by the Society for the Study of Reproduction, Inc.

Changes in the sialylation and sulfation of secreted thyrotropin in congenital hypothyroidism

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

Gyves, P.W.; Gesundheit, N.; Thotakura, N.R.

1990-05-01

The authors have examined the oligosaccharide structure of secreted thyrotropin (TSH) in perinatal and mature rats with congenital primary hypothyroidism. Rat pituitaries from euthyroid control animals and those rendered hypothyroid by methimazole treatment were incubated with ({sup 3}H)glucosamine in vitro. Secreted TSH was purified, and oligosaccharides were enzymatically released and characterized by anion-exchange HPLC. In perinatal hypothyroid animals compared with control animals, oligosaccharides from TSH {alpha} and {beta} subunits contained more species with three or more negative charges. Moreover, perinatal hypothyroid animals demonstrated a dramatic increase in the ratio of sialylated to sulfated species within oligosaccharides of the same negativemore » charge. In mature hypothyroid 9-week-old animals compared with control animals, changes were less pronounced, suggesting that endocrine regulation of oligosaccharide structure is dependent upon the maturational state of the animal. Together, these data provide direct evidence and characterization of specific changes in the structure of a secreted pituitary glycoprotein hormone occurring as a result of in vivo endocrine alterations during early development. Moreover, they provide a potential structural basis to explain the delayed clearance of both TSH and the gonadotropins with end-organ deficiency, which may have important implications for the in vivo biological activities of these hormones.« less

Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway

NASA Technical Reports Server (NTRS)

Chakravarthy, M. V.; Abraha, T. W.; Schwartz, R. J.; Fiorotto, M. L.; Booth, F. W.

2000-01-01

Interest is growing in methods to extend replicative life span of non-immortalized stem cells. Using the insulin-like growth factor I (IGF-I) transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle development and maturation prior to isolation and during culture of satellite cells (the myogenic stem cells of mature skeletal muscle fibers) as a model system, we elucidated the underlying molecular mechanisms of IGF-I-mediated enhancement of proliferative potential of these cells. Satellite cells from IGF-I transgenic muscles achieved at least five additional population doublings above the maximum that was attained by wild type satellite cells. This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence. These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known.

Concepts and implications of altruism bias and pathological altruism

PubMed Central

Oakley, Barbara A.

2013-01-01

The profound benefits of altruism in modern society are self-evident. However, the potential hurtful aspects of altruism have gone largely unrecognized in scientific inquiry. This is despite the fact that virtually all forms of altruism are associated with tradeoffs—some of enormous importance and sensitivity—and notwithstanding that examples of pathologies of altruism abound. Presented here are the mechanistic bases and potential ramifications of pathological altruism, that is, altruism in which attempts to promote the welfare of others instead result in unanticipated harm. A basic conceptual approach toward the quantification of altruism bias is presented. Guardian systems and their over arching importance in the evolution of cooperation are also discussed. Concepts of pathological altruism, altruism bias, and guardian systems may help open many new, potentially useful lines of inquiry and provide a framework to begin moving toward a more mature, scientifically informed understanding of altruism and cooperative behavior. PMID:23754434

Injuries from non-retention in gillnet fisheries suppress reproductive maturation in escaped fish.

PubMed

Baker, Matthew R; Swanson, Penny; Young, Graham

2013-01-01

Exploitation of fisheries resources has unintended consequences, not only in the bycatch and discard of non-target organisms, but also in damage to targeted fish that are injured by gear but not landed (non-retention). Delayed mortality due to non-retention represents lost reproductive potential in exploited stocks, while not contributing to harvest. Our study examined the physiological mechanisms by which delayed mortality occurs and the extent to which injuries related to disentanglement from commercial gear compromise reproductive success in spawning stocks of Pacific salmon (Oncorhynchus spp.). We found evidence for elevated stress in fish injured via non-retention in gillnet fisheries. Plasma cortisol levels correlated with the severity of disentanglement injury and were elevated in fish that developed infections related to disentanglement injuries. We also analyzed sex steroid concentrations in females (estradiol-17β and 17,20β-dihydroxy-4-pregnen-3-one) to determine whether non-retention impairs reproductive potential in escaped individuals. We demonstrate evidence for delayed or inhibited maturation in fish with disentanglement injuries. These findings have important implications for effective conservation and management of exploited fish stocks and suggest means to improve spawning success in such stocks if retention in commercial fisheries is improved and incidental mortality reduced.

Injuries from Non-Retention in Gillnet Fisheries Suppress Reproductive Maturation in Escaped Fish

PubMed Central

Baker, Matthew R.; Swanson, Penny; Young, Graham

2013-01-01

Exploitation of fisheries resources has unintended consequences, not only in the bycatch and discard of non-target organisms, but also in damage to targeted fish that are injured by gear but not landed (non-retention). Delayed mortality due to non-retention represents lost reproductive potential in exploited stocks, while not contributing to harvest. Our study examined the physiological mechanisms by which delayed mortality occurs and the extent to which injuries related to disentanglement from commercial gear compromise reproductive success in spawning stocks of Pacific salmon (Oncorhynchus spp.). We found evidence for elevated stress in fish injured via non-retention in gillnet fisheries. Plasma cortisol levels correlated with the severity of disentanglement injury and were elevated in fish that developed infections related to disentanglement injuries. We also analyzed sex steroid concentrations in females (estradiol-17β and 17,20β-dihydroxy-4-pregnen-3-one) to determine whether non-retention impairs reproductive potential in escaped individuals. We demonstrate evidence for delayed or inhibited maturation in fish with disentanglement injuries. These findings have important implications for effective conservation and management of exploited fish stocks and suggest means to improve spawning success in such stocks if retention in commercial fisheries is improved and incidental mortality reduced. PMID:23894510

Relationships between thermal maturity indices calculated using Arrhenius equation and Lopatin method: implications for petroleum exploration

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

Wood, D.A.

1988-02-01

Thermal maturity can be calculated with time-temperature indices (TTI) based on the Arrhenius equation using kinetics applicable to a range of Types II and III kerogens. These TTIs are compared with TTI calculations based on the Lopatin method and are related theoretically (and empirically via vitrinite reflectance) to the petroleum-generation window. The TTIs for both methods are expressed mathematically as integrals of temperature combined with variable linear heating rates for selected temperature intervals. Heating rates control the thermal-maturation trends of buried sediments. Relative to Arrhenius TTIs, Lopatin TTIs tend to underestimate thermal maturity at high heating rates and overestimate itmore » as low heating rates. Complex burial histories applicable to a range of tectonic environments illustrate the different exploration decisions that might be made on the basis of independent results of these two thermal-maturation models. 15 figures, 8 tables.« less

Cervical (pre)neoplastic microenvironment promotes the emergence of tolerogenic dendritic cells via RANKL secretion

PubMed Central

Demoulin, Stéphanie A; Somja, Joan; Duray, Anaëlle; Guénin, Samuel; Roncarati, Patrick; Delvenne, Philippe O; Herfs, Michael F; Hubert, Pascale M

2015-01-01

The progression of genital human papillomavirus (HPV) infections into preneoplastic lesions suggests that infected/malignant cells are not adequately recognized by the immune system. In this study, we demonstrated that cervical/vulvar cancer cells secrete factor(s) that affect both the maturation and function of dendritic cells (DC) leading to a tolerogenic profile. Indeed, DC cocultured with cancer cell lines display both a partially mature phenotype after lipopolysaccharide (LPS) maturation and an altered secretory profile (IL-10high and IL-12p70low). In addition, tumor-converted DC acquire the ability to alter T-cell proliferation and to induce FoxP3+ suppressive T cells from naive CD4+ T cells. Among the immunosuppressive factors implicated in DC alterations in genital (pre)neoplastic microenvironment, we identified receptor activator of nuclear factor kappa-B ligand (RANKL), a TNF family member, as a potential candidate. For the first time, we showed that RANKL expression strongly increases during cervical progression. We also confirmed that RANKL is directly secreted by cancer cells and this expression is not related to HPV viral oncoprotein induction. Interestingly, the addition of osteoprotegerin (OPG) in coculture experiments reduces significantly the inhibition of DC maturation, the release of a tolerogenic cytokine profile (IL-12low IL-10high) and the induction of regulatory T (Treg) cells. Our findings suggest that the use of inhibitory molecules directed against RANKL in cervical/vulvar (pre)neoplastic lesions might prevent alterations of DC functionality and represent an attractive strategy to overcome immune tolerance in such cancers. PMID:26155412

Comparison of glucose metabolism in in vivo- and in vitro-matured tammar wallaby oocytes and its relationship to developmental potential following intracytoplasmic sperm injection.

PubMed

Magarey, Genevieve M; Mate, Karen E

2004-01-01

Although marsupial oocytes undergo nuclear maturation in vitro, there is, at present, no indication of their developmental potential, largely owing to the lack of in vitro fertilisation and related technologies for marsupials. Glucose metabolism has proven a useful indicator of oocyte cytoplasmic maturation and developmental potential in several eutherian species. Therefore, the aims of the present study were to compare: (1) the rates of glycolysis and glucose oxidation in immature, in vitro-matured and in vivo-matured tammar wallaby oocytes; and (2) the metabolic rate of individual oocytes with their ability to form pronuclei after intracytoplasmic sperm injection. The rates of glycolysis measured in immature (2.18 pmol oocyte(-1) h(-1)), in vitro- matured (0.93 pmol oocyte(-1) h(-1)) and in vivo-matured tammar wallaby oocytes (0.54 pmol oocyte(-1) h(-1)) were within a similar range to values obtained in eutherian species. However, unlike the trend observed in eutherian oocytes, the glycolytic rate was significantly higher in immature oocytes compared with either in vivo- or in vitro-matured oocytes (P < 0.001) and significantly higher in in vitro-matured oocytes compared with in vivo-matured oocytes (P < 0.001). No relationship was identified between glucose metabolism and the developmental capacity of oocytes after intracytoplasmic sperm injection when assessed after 17-19 h. Oocytes that became fertilised (two pronuclei) or activated (one or more pronucleus) were not distinguished from others by their metabolic rates. Longer culture after intracytoplasmic sperm injection (e.g. blastocyst stage) may show oocyte glucose metabolism to be predictive of developmental potential; however, culture to the single-cell stage did not reveal any significant differences in normally developing embryos.

Alternative reproductive tactics increase effective population size and decrease inbreeding in wild Atlantic salmon

PubMed Central

Perrier, Charles; Normandeau, Éric; Dionne, Mélanie; Richard, Antoine; Bernatchez, Louis

2014-01-01

While nonanadromous males (stream-resident and/or mature male parr) contribute to reproduction in anadromous salmonids, little is known about their impacts on key population genetic parameters. Here, we evaluated the contribution of Atlantic salmon mature male parr to the effective number of breeders (Nb) using both demographic (variance in reproductive success) and genetic (linkage disequilibrium) methods, the number of alleles, and the relatedness among breeders. We used a recently published pedigree reconstruction of a wild anadromous Atlantic salmon population in which 2548 fry born in 2010 were assigned parentage to 144 anadromous female and 101 anadromous females that returned to the river to spawn in 2009 and to 462 mature male parr. Demographic and genetic methods revealed that mature male parr increased population Nb by 1.79 and 1.85 times, respectively. Moreover, mature male parr boosted the number of alleles found among progenies. Finally, mature male parr were in average less related to anadromous females than were anadromous males, likely because of asynchronous sexual maturation between mature male parr and anadromous fish of a given cohort. By increasing Nb and allelic richness, and by decreasing inbreeding, the reproductive contribution of mature male parr has important evolutionary and conservation implications for declining Atlantic salmon populations. PMID:25553070

Elevated α-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson's patient-derived induced pluripotent stem cells

PubMed Central

Oliveira, L M A; Falomir-Lockhart, L J; Botelho, M G; Lin, K-H; Wales, P; Koch, J C; Gerhardt, E; Taschenberger, H; Outeiro, T F; Lingor, P; Schüle, B; Arndt-Jovin, D J; Jovin, T M

2015-01-01

We have assessed the impact of α-synuclein overexpression on the differentiation potential and phenotypic signatures of two neural-committed induced pluripotent stem cell lines derived from a Parkinson's disease patient with a triplication of the human SNCA genomic locus. In parallel, comparative studies were performed on two control lines derived from healthy individuals and lines generated from the patient iPS-derived neuroprogenitor lines infected with a lentivirus incorporating a small hairpin RNA to knock down the SNCA mRNA. The SNCA triplication lines exhibited a reduced capacity to differentiate into dopaminergic or GABAergic neurons and decreased neurite outgrowth and lower neuronal activity compared with control cultures. This delayed maturation phenotype was confirmed by gene expression profiling, which revealed a significant reduction in mRNA for genes implicated in neuronal differentiation such as delta-like homolog 1 (DLK1), gamma-aminobutyric acid type B receptor subunit 2 (GABABR2), nuclear receptor related 1 protein (NURR1), G-protein-regulated inward-rectifier potassium channel 2 (GIRK-2) and tyrosine hydroxylase (TH). The differentiated patient cells also demonstrated increased autophagic flux when stressed with chloroquine. We conclude that a two-fold overexpression of α-synuclein caused by a triplication of the SNCA gene is sufficient to impair the differentiation of neuronal progenitor cells, a finding with implications for adult neurogenesis and Parkinson's disease progression, particularly in the context of bioenergetic dysfunction. PMID:26610207

Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma

PubMed Central

Lee, Chen-Chen; Wang, Chien-Neng; Lai, Yu-Ting; Kang, Jaw-Jou; Liao, Jiunn-Wang; Chiang, Bor-Luen; Chen, Hui-Chen; Cheng, Yu-Wen

2010-01-01

BACKGROUND AND PURPOSE Shikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow-derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma. EXPERIMENTAL APPROACH Cultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and their stimulation of T-cell proliferation and cytokine production. The therapeutic potential of shikonin was evaluated in a model of allergic airway disease. KEY RESULTS Shikonin dose-dependently inhibited expression of major histocompatibility complex class II, CD80, CD86, CCR7 and OX40L on BM-DCs, induced by a mixture of ovalbumin (OVA; 100 µg·mL−1) and thymic stromal lymphopoietin (TSLP; 20 ng·mL−1). Shikonin-treated BM-DCs were poor stimulators of CD4+ T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor (TNF)-α release by responding T-cells. After intratracheal instillation of shikonin in OVA-immunized mice, OVA challenge induced lower IL-4, IL-5, IL-13, TNF-α and eotaxin release in bronchial alveolar lavage fluid, lower IL-4 and IL-5 production in lung cells and mediastinal lymph node cells and attenuated OVA-induced lung eosinophilia and airway hyperresponsiveness. CONCLUSION AND IMPLICATIONS Shikonin effectively suppressed OVA + TSLP-induced BM-DC maturation in vitro and inhibited allergic inflammation and airway hyperresponsiveness in a murine model of asthma, showing good potential as a treatment for allergic asthma. Also, our model provides a novel platform for screening drugs for allergic diseases. PMID:20735407

New foliage growth is a significant, unaccounted source for volatiles in boreal evergreen forests

NASA Astrophysics Data System (ADS)

Aalto, J.; Kolari, P.; Hari, P.; Kerminen, V.-M.; Schiestl-Aalto, P.; Aaltonen, H.; Levula, J.; Siivola, E.; Kulmala, M.; Bäck, J.

2013-11-01

Estimates of volatile organic compound (VOC) emissions from forests are based on the assumption that foliage has a steady emission potential over its lifetime, and that emissions are mainly modified by short term variations in light and temperature. However, in many field studies this has been challenged, and high emissions and atmospheric concentrations have been measured during periods of low biological activity such as in springtime. We conducted measurements during three years, using an online gas-exchange monitoring system to observe volatile organic emissions from a mature (1 yr old) and a growing Scots pine shoot. The emission rates of organic vapours (monoterpenes, methyl butenol (MBO), acetone and methanol) from vegetative buds of Scots pine during the dehardening and rapid shoot growth stages were one to two orders of magnitude higher than those from mature foliage. The normally assumed temperature dependency was not sufficient to explain the variations in emission rates during spring. The diurnal emission pattern of growing shoots differed from the diurnal cycle in temperature as well as from the diurnal emission pattern of mature shoots, which may be related to processes involved in shoot or needle elongation. Our findings imply that global estimations of monoterpene emission rates from forests are in need of revision, and that the physiological state of the plants should be taken into account when emissions of the reactive gases such as monoterpenes are estimated. The significant interannual variation in emission rates, related to changes in plant metabolic activity, has important implications to the aerosol precursor concentrations and chemical reactions in atmosphere, and potentially offers an explanation for the frequent aerosol formation events in spring.

The development of sex typing in middle childhood.

PubMed

Serbin, L A; Powlishta, K K; Gulko, J

1993-01-01

The present study examined the development of sex typing during middle childhood, using a sample of 558 children aged 5-12 years. The purpose of the study was to provide information about the developmental course and stability of various aspects of sex typing during this period and to examine the relative contributions of cognitive and environmental factors to sex-role development. Multiple measures of sex typing were obtained, including indices of personal preference, knowledge of stereotypes, and flexibility in the domains of activities, occupations, and traits. We also collected information about the child's cognitive maturity, exposure to sex-typed models at home, and socioeconomic status. Results supported the need for an integrative theory of sex-role development, incorporating factors emphasized by cognitive-developmental, schematic-processing, and social learning theories. Knowledge of stereotypes, flexibility, and sex-typed personal preferences all increased with age during middle childhood. There were also individual differences in sex typing that were stable over a 1-year period. Distinct "cognitive" and "affective" aspects of sex typing were identified using a principal components analysis. Cognitive elements (flexibility and knowledge of stereotypes) were largely a function of the child's cognitive maturity level, although social-environmental factors such as father's presence in the home also had some effect. Affective elements (sex-typed preferences for activities, occupations, and peers), on the other hand, were related more consistently to sex typing of the home environment. Children whose mothers frequently modeled "reversed" sex-role behaviors (i.e., traditionally "masculine" household and child-care tasks) were less sex typed in their own preferences. However, cognitive factors were also important, in that children who believed gender stereotypes to be flexible were less sex typed in their choices of activities, occupations, and peers. In sum, both cognitive maturation and socialization experiences contribute to the development of sex typing during middle childhood. Potential practical implications of these findings, as well as implications for stereotyping in other social domains such as race and ethnicity, are discussed.

Connective Tissue Mineralization in Abcc6−/− Mice, a Model for Pseudoxanthoma Elasticum

PubMed Central

Kavukcuoglu, N. Beril; Li, Qiaoli; Pleshko, Nancy; Uitto, Jouni

2012-01-01

Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by ectopic mineralization. However, the structure of the mineral deposits, their interactions with the connective tissue matrix, and the details of the progressive maturation of the mineral crystals are currently unknown. In this study, we examined the mineralization processes in Abcc6−/− mice, a model system for PXE, by energy dispersive X-ray, and Fourier transform infrared imaging spectroscopy (FT-IRIS). The results indicated that the principal components of the mineral deposits were calcium and phosphate which co-localized within the histologically demonstrable lesions determined by topographic mapping. The Ca/P ratio increased in samples with progressive mineralization reaching the value comparable to that in endochondral bone. A progressive increase in mineralization was also reflected by increased mineral-to-matrix ratio determined by FT-IRIS. Determination of the mineral phases by FT-IRIS suggested progressive maturation of the mineral deposits from amorphous calcium phosphate to hydroxyapatite. These results provide critical information of the mechanisms of mineralization in PXE, with potential pharmacologic implications. PMID:22421595

Mucin-Microbiota Interaction During Postnatal Maturation of the Intestinal Ecosystem: Clinical Implications.

PubMed

Rokhsefat, Sana; Lin, Aifeng; Comelli, Elena M

2016-06-01

The mucus layer and gut microbiota interplay contributes to host homeostasis. The mucus layer serves as a scaffold and a carbon source for gut microorganisms; conversely, gut microorganisms, including mucin degraders, influence mucin gene expression, glycosylation, and secretion. Conjointly they shield the epithelium from luminal pathogens, antigens, and toxins. Importantly, the mucus layer and gut microbiota are established in parallel during early postnatal life. During this period, the development of gut microbiota and mucus layer is coupled with that of the immune system. Developmental changes of different mucin types can impact the age-dependent patterns of intestinal infection in terms of incidence and severity. Altered mucus layer, dysbiotic microbiota, and abnormal mucus-gut microbiota interaction have the potential for inducing systemic effects, and accompany several intestinal diseases such as inflammatory bowel disease, colorectal cancer, and radiation-induced mucositis. Early life provides a pivotal window of opportunity to favorably modulate the mucus-microbiota interaction. The support of a health-compatible mucin-microbiota maturation in early life is paramount for long-term health and serves as an important opportunity for clinical intervention.

Adolescent athletes with learning disability display atypical maturational trajectories on concussion baseline testing: Implications based on a Finnish sample.

PubMed

Peltonen, Kati; Vartiainen, Matti; Laitala-Leinonen, Tiina; Koskinen, Sanna; Luoto, Teemu; Pertab, Jon; Hokkanen, Laura

2018-05-21

Previous research has reported lower cognitive test scores on baseline testing in athletes reporting multiple previous concussions or a history of learning disability (LD). Age also has an important influence on cognitive performance. While these factors have been considered individually in previous studies, the present study is the first to explore the interaction of age, self-reported LD, and history of concussion on baseline Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT®) in a nationwide study of adolescent athletes. ImPACT® was administered to 1823 Finnish male ice hockey players (aged 12-21 years old) prior to the 2015-2016 or 2016-2017 playing seasons. Linear regressions and simple slopes analyses were used for clarifying the impact of LD and previous concussion history on maturational trajectories. In comparison to typically developing athletes, athletes with LD had lower neurocognitive scores in all composites and differing maturational trajectory in verbal memory and visual motor speed. The number of previous concussions did not impair neurocognitive performance at baseline assessment. Application of standard age-based norms to adolescent athletes with a history of LD has the potential to negatively skew clinical decision-making. Separate reference values for LD athletes are warranted due to their unique developmental cognitive trajectories. The reference values for the Finnish participants in this study are presented.

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

Examining the Potential Impact of Full Tuition Fees on Mature Part-Time Students in English Higher Education

ERIC Educational Resources Information Center

Shaw, Angela

2014-01-01

This paper examines current part-time mature learners' views on the potential impact upon future students as full fees are introduced from 2012. It investigates the problems which part-time mature learners may face with the advent of student loans and subsequent debt, given that they are usually combining complex lives with their studies, with…

A Review of Physiological and Psychological Changes in Aging and Their Implications for Teachers of Adults.

ERIC Educational Resources Information Center

Hand, Samuel E.

This review of literature on the aging process points out primary physiological and psychological changes in maturing adults which have implications for teachers of adults. Visual acuity and hearing decline during adult years and there is a general slowing down process of most bodily activities. Teachers should be aware of the need for good…

EXPLORING PATERNAL MATURITY IN THE RELATIONSHIPS BETWEEN OLDER FATHERS AND ADULT CHILDREN

PubMed Central

STELLE, CHARLIE D.; SHEEHAN, NANCY W.

2013-01-01

While research on parent-adult child relationships has expanded over the last two decades, most research has ignored the experiences of older fathers and their relationships with adult children. The present study sought to explore how midlife and older men assess the costs and rewards associated with their fatherhood experiences and how fathers’ level of paternal maturity influences their perceptions of fatherhood. More specifically, the purpose of the present study was two-fold: to explore the costs and rewards of fatherhood and whether paternal maturity serves as a moderator of older men’s fatherhood experiences. A purposive sample of 96 fathers (age 50–80) completed measures assessing ego development, generativity, and costs and rewards of fatherhood. The construct of paternal maturity, hypothesized to influence assessment of fatherhood experiences, was operationally defined as combining both affective (generativity) and cognitive (ego development) levels of psychological maturity. Results indicate mixed support for the influence of paternal maturity on fathers’ perceptions of costs and rewards. Overall, findings note that the affective side of maturity (generativity) is more strongly associated with fathers’ accounts of the costs and rewards than the cognitive side of maturity (ego development). Discussion centers on the utility of these concepts and the implications for continued research into the ongoing relationships between fathers and adult children. PMID:21391406

Ca2+/Calmodulin-dependent kinase II signaling causes skeletal overgrowth and premature chondrocyte maturation.

PubMed

Taschner, Michael J; Rafigh, Mehran; Lampert, Fabienne; Schnaiter, Simon; Hartmann, Christine

2008-05-01

The long bones of vertebrate limbs originate from cartilage templates and are formed by the process of endochondral ossification. This process requires that chondrocytes undergo a progressive maturation from proliferating to postmitotic prehypertrophic to mature, hypertrophic chondrocytes. Coordinated control of proliferation and maturation regulates growth of the skeletal elements. Various signals and pathways have been implicated in orchestrating these processes, but the underlying intracellular molecular mechanisms are often not entirely known. Here we demonstrated in the chick using replication-competent retroviruses that constitutive activation of Calcium/Calmodulin-dependent kinase II (CaMKII) in the developing wing resulted in elongation of skeletal elements associated with premature differentiation of chondrocytes. The premature maturation of chondrocytes was a cell-autonomous effect of constitutive CaMKII signaling associated with down-regulation of cell-cycle regulators and up-regulation of chondrocyte maturation markers. In contrast, the elongation of the skeletal elements resulted from a non-cell autonomous up-regulation of the Indian hedgehog responsive gene encoding Parathyroid-hormone-related peptide. Reduction of endogenous CaMKII activity by overexpressing an inhibitory peptide resulted in shortening of the skeletal elements associated with a delay in chondrocyte maturation. Thus, CaMKII is an essential component of intracellular signaling pathways regulating chondrocyte maturation.

Extracellular Matrix-Mediated Maturation of Human Pluripotent Stem Cell-Derived Cardiac Monolayer Structure and Electrophysiological Function.

PubMed

Herron, Todd J; Rocha, Andre Monteiro Da; Campbell, Katherine F; Ponce-Balbuena, Daniela; Willis, B Cicero; Guerrero-Serna, Guadalupe; Liu, Qinghua; Klos, Matt; Musa, Hassan; Zarzoso, Manuel; Bizy, Alexandra; Furness, Jamie; Anumonwo, Justus; Mironov, Sergey; Jalife, José

2016-04-01

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) monolayers generated to date display an immature embryonic-like functional and structural phenotype that limits their utility for research and cardiac regeneration. In particular, the electrophysiological function of hPSC-CM monolayers and bioengineered constructs used to date are characterized by slow electric impulse propagation velocity and immature action potential profiles. Here, we have identified an optimal extracellular matrix for significant electrophysiological and structural maturation of hPSC-CM monolayers. hPSC-CM plated in the optimal extracellular matrix combination have impulse propagation velocities ≈2× faster than previously reported (43.6±7.0 cm/s; n=9) and have mature cardiomyocyte action potential profiles, including hyperpolarized diastolic potential and rapid action potential upstroke velocity (146.5±17.7 V/s; n=5 monolayers). In addition, the optimal extracellular matrix promoted hypertrophic growth of cardiomyocytes and the expression of key mature sarcolemmal (SCN5A, Kir2.1, and connexin43) and myofilament markers (cardiac troponin I). The maturation process reported here relies on activation of integrin signaling pathways: neutralization of β1 integrin receptors via blocking antibodies and pharmacological blockade of focal adhesion kinase activation prevented structural maturation. Maturation of human stem cell-derived cardiomyocyte monolayers is achieved in a 1-week period by plating cardiomyocytes on PDMS (polydimethylsiloxane) coverslips rather than on conventional 2-dimensional cell culture formats, such as glass coverslips or plastic dishes. Activation of integrin signaling and focal adhesion kinase is essential for significant maturation of human cardiac monolayers. © 2016 American Heart Association, Inc.

Education for Adulthood.

ERIC Educational Resources Information Center

Ogilvie, Doug

1984-01-01

Indicates that human beings do not develop to the maturity of genuine adulthood. Adult educators must address the implications and consequences of assuming consensual collaboration to be the appropriate relationship for human beings. (JOW)

[Maturity fears and weight phobia in eating disorders: research of a relationship].

PubMed

Grasso, Maria; Nazzaro, Francesca; Vona, Laura; Capacchione, Giulietta; Loriedo, Camillo

2012-01-01

This study investigate presence, the psychopathological and treatment implications of weight phobia and maturity fears in patient with eating disorders. The study group comprised 43 patients, with diagnosis DSM-IV-TR for anorexia, bulimia and eating disorders not otherwise specified. Subjects completed the following self-administered questionnaires: Eating Disorder Inventory 2 (EDI -2), Body Uneasiness Test (BUT), MMPI-2. Associations emerged between MF and: K-correction, Antisocial behaviour, Cynicism, Negative Treatment Indicators (MMPI-II) and with Ineffectiveness (EDI-II). No association emerged between maturity fears and BUT subscales, neither with the biological variables. Maturity fears is a dimension without differences both in the AN that in BN, associated with personality traits, which denotes insecurity, relationship incompetence, ineffectiveness, incapability in to ask and to get help from the others with distrust. It doesn't associate with weight phobia.

From archaic narcissism to empathy for the self: the evolution of new capacities in psychoanalysis.

PubMed

Gehrie, Mark J

2011-04-01

The concept of the selfobject was central to Heinz Kohut's psychology of the self. With an eye to studying the development of narcissism and its implications for the growth of new psychic structure, this concept is reviewed and reassessed. Post-Kohutian complexities regarding its definition and use extend our consideration of the development of narcissism beyond archaic configurations toward further evolution of the self and the nature of mature narcissism. The hypothesis is offered that developing narcissism and the growth of self-regulation impact the acquisition of new structure and new capacities through the emergence of newly potentiated aspects of the self. The implications of these emergent qualities of the self are examined in the context of our understanding of self-esteem regulation, the state of the self, and the goals of psychoanalysis. A clinical example illustrates how technique and process in an analysis may be organized around the development of such new capacities.

Urocortin 3 Marks Mature Human Primary and Embryonic Stem Cell-Derived Pancreatic Alpha and Beta Cells

PubMed Central

van der Meulen, Talitha; Xie, Ruiyu; Kelly, Olivia G.; Vale, Wylie W.; Sander, Maike; Huising, Mark O.

2012-01-01

The peptide hormone Urocortin 3 (Ucn 3) is abundantly and exclusively expressed in mouse pancreatic beta cells where it regulates insulin secretion. Here we demonstrate that Ucn 3 first appears at embryonic day (E) 17.5 and, from approximately postnatal day (p) 7 and onwards throughout adult life, becomes a unifying and exclusive feature of mouse beta cells. These observations identify Ucn 3 as a potential beta cell maturation marker. To determine whether Ucn 3 is similarly restricted to beta cells in humans, we conducted comprehensive immunohistochemistry and gene expression experiments on macaque and human pancreas and sorted primary human islet cells. This revealed that Ucn 3 is not restricted to the beta cell lineage in primates, but is also expressed in alpha cells. To substantiate these findings, we analyzed human embryonic stem cell (hESC)-derived pancreatic endoderm that differentiates into mature endocrine cells upon engraftment in mice. Ucn 3 expression in hESC-derived grafts increased robustly upon differentiation into mature endocrine cells and localized to both alpha and beta cells. Collectively, these observations confirm that Ucn 3 is expressed in adult beta cells in both mouse and human and appears late in beta cell differentiation. Expression of Pdx1, Nkx6.1 and PC1/3 in hESC-derived Ucn 3+ beta cells supports this. However, the expression of Ucn 3 in primary and hESC-derived alpha cells demonstrates that human Ucn 3 is not exclusive to the beta cell lineage but is a general marker for both the alpha and beta cell lineages. Ucn 3+ hESC-derived alpha cells do not express Nkx6.1, Pdx1 or PC1/3 in agreement with the presence of a separate population of Ucn 3+ alpha cells. Our study highlights important species differences in Ucn 3 expression, which have implications for its utility as a marker to identify mature beta cells in (re)programming strategies. PMID:23251699

Absence of Intracellular Ion Channels TPC1 and TPC2 Leads to Mature-Onset Obesity in Male Mice, Due to Impaired Lipid Availability for Thermogenesis in Brown Adipose Tissue

PubMed Central

Lear, Pamela V.; González-Touceda, David; Porteiro Couto, Begoña; Viaño, Patricia; Guymer, Vanessa; Remzova, Elena; Tunn, Ruth; Chalasani, Annapurna; García-Caballero, Tomás; Hargreaves, Iain P.; Tynan, Patricia W.; Christian, Helen C.; Nogueiras, Rubén

2015-01-01

Intracellular calcium-permeable channels have been implicated in thermogenic function of murine brown and brite/beige adipocytes, respectively transient receptor potential melastin-8 and transient receptor potential vanilloid-4. Because the endo-lysosomal two-pore channels (TPCs) have also been ascribed with metabolic functionality, we studied the effect of simultaneously knocking out TPC1 and TPC2 on body composition and energy balance in male mice fed a chow diet. Compared with wild-type mice, TPC1 and TPC2 double knockout (Tpcn1/2−/−) animals had a higher respiratory quotient and became obese between 6 and 9 months of age. Although food intake was unaltered, interscapular brown adipose tissue (BAT) maximal temperature and lean-mass adjusted oxygen consumption were lower in Tpcn1/2−/− than in wild type mice. Phosphorylated hormone-sensitive lipase expression, lipid density and expression of β-adrenergic receptors were also lower in Tpcn1/2−/− BAT, whereas mitochondrial respiratory chain function and uncoupling protein-1 expression remained intact. We conclude that Tpcn1/2−/− mice show mature-onset obesity due to reduced lipid availability and use, and a defect in β-adrenergic receptor signaling, leading to impaired thermogenic activity, in BAT. PMID:25545384

Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils.

PubMed

Gounni, A S; Gregory, B; Nutku, E; Aris, F; Latifa, K; Minshall, E; North, J; Tavernier, J; Levit, R; Nicolaides, N; Robinson, D; Hamid, Q

2000-09-15

Interleukin-9 (IL-9) has been implicated in the pathogenesis of allergic disorders. To examine the interaction between IL-9 and eosinophils, we evaluated mature peripheral blood eosinophils for their expression of the specific alpha-subunit of the IL-9 receptor (IL-9R-alpha). The expression of IL-9R-alpha by human eosinophils was detected at the messenger RNA (mRNA) and protein levels by reverse transcriptase-polymerase chain reaction (RT-PCR), flow cytometry, and immunocytochemical analysis, respectively. Functional analyses demonstrated that recombinant human (rh)IL-9 inhibited in vitro peripheral blood human eosinophil apoptosis in a concentration-dependent manner. We then examined the role of IL-9 in eosinophil differentiation using the human cord blood CD34(+) cells and human promyelocytic leukemia cells (HL-60). The addition of IL-9 to CD34(+) cells cultured in IL-3 and IL-5 enhanced eosinophil development, and IL-9 alone induced the expression of IL-5R-alpha. IL-9 also up-regulated the IL-5R-alpha chain cell surface expression during terminal eosinophil differentiation of the HL-60 cell line. Our findings suggest that IL-9 may potentiate in vivo eosinophil function by increasing their survival and IL-5-mediated differentiation and maturation. Taken together, these results suggest a mechanism by which IL-9 potentiates airway and tissue eosinophilia.

Decoding the Long Noncoding RNA During Cardiac Maturation: A Roadmap for Functional Discovery.

PubMed

Touma, Marlin; Kang, Xuedong; Zhao, Yan; Cass, Ashley A; Gao, Fuying; Biniwale, Reshma; Coppola, Giovanni; Xiao, Xinshu; Reemtsen, Brian; Wang, Yibin

2016-10-01

Cardiac maturation during perinatal transition of heart is critical for functional adaptation to hemodynamic load and nutrient environment. Perturbation in this process has major implications in congenital heart defects. Transcriptome programming during perinatal stages is an important information but incomplete in current literature, particularly, the expression profiles of the long noncoding RNAs (lncRNAs) are not fully elucidated. From comprehensive analysis of transcriptomes derived from neonatal mouse heart left and right ventricles, a total of 45 167 unique transcripts were identified, including 21 916 known and 2033 novel lncRNAs. Among these lncRNAs, 196 exhibited significant dynamic regulation along maturation process. By implementing parallel weighted gene co-expression network analysis of mRNA and lncRNA data sets, several lncRNA modules coordinately expressed in a developmental manner similar to protein coding genes, while few lncRNAs revealed chamber-specific patterns. Out of 2262 lncRNAs located within 50 kb of protein coding genes, 5% significantly correlate with the expression of their neighboring genes. The impact of Ppp1r1b-lncRNA on the corresponding partner gene Tcap was validated in cultured myoblasts. This concordant regulation was also conserved in human infantile hearts. Furthermore, the Ppp1r1b-lncRNA/Tcap expression ratio was identified as a molecular signature that differentiated congenital heart defect phenotypes. The study provides the first high-resolution landscape on neonatal cardiac lncRNAs and reveals their potential interaction with mRNA transcriptome during cardiac maturation. Ppp1r1b-lncRNA was identified as a regulator of Tcap expression, with dynamic interaction in postnatal cardiac development and congenital heart defects. © 2016 American Heart Association, Inc.

The Role of Capsid Maturation on Adenovirus Priming for Sequential Uncoating*

PubMed Central

Pérez-Berná, Ana J.; Ortega-Esteban, Alvaro; Menéndez-Conejero, Rosa; Winkler, Dennis C.; Menéndez, Margarita; Steven, Alasdair C.; Flint, S. Jane; de Pablo, Pedro J.; San Martín, Carmen

2012-01-01

Adenovirus assembly concludes with proteolytic processing of several capsid and core proteins. Immature virions containing precursor proteins lack infectivity because they cannot properly uncoat, becoming trapped in early endosomes. Structural studies have shown that precursors increase the network of interactions maintaining virion integrity. Using different biophysical techniques to analyze capsid disruption in vitro, we show that immature virions are more stable than the mature ones under a variety of stress conditions and that maturation primes adenovirus for highly cooperative DNA release. Cryoelectron tomography reveals that under mildly acidic conditions mimicking the early endosome, mature virions release pentons and peripheral core contents. At higher stress levels, both mature and immature capsids crack open. The virus core is completely released from cracked capsids in mature virions, but it remains connected to shell fragments in the immature particle. The extra stability of immature adenovirus does not equate with greater rigidity, because in nanoindentation assays immature virions exhibit greater elasticity than the mature particles. Our results have implications for the role of proteolytic maturation in adenovirus assembly and uncoating. Precursor proteins favor assembly by establishing stable interactions with the appropriate curvature and preventing premature ejection of contents by tightly sealing the capsid vertices. Upon maturation, core organization is looser, particularly at the periphery, and interactions preserving capsid curvature are weakened. The capsid becomes brittle, and pentons are more easily released. Based on these results, we hypothesize that changes in core compaction during maturation may increase capsid internal pressure to trigger proper uncoating of adenovirus. PMID:22791715

Direct and rapid determination of cotton maturity by FT-Mid-IR technique

USDA-ARS?s Scientific Manuscript database

FT-mid-IR (FT-MIR) spectra of seed and lint cottons were collected to explore the potential for the discrimination of immature cottons from mature ones and also for the determination of actual cotton maturity. Spectral features of immature and mature cottons revealed large differences in the 1200-90...

Control of the rate of cell enlargement: Excision, wall relaxation, and growth-induced water potentials.

PubMed

Boyer, J S; Cavalieri, A J; Schulze, E D

1985-04-01

A new guillotine thermocouple psychrometer was used to make continuous measurements of water potential before and after the excision of elongating and mature regions of darkgrown soybean (Glycine max L. Merr.) stems. Transpiration could not occur, but growth took place during the measurement if the tissue was intact. Tests showed that the instrument measured the average water potential of the sampled tissue and responded rapidly to changes in water potential. By measuring tissue osmotic potential (Ψ s ), turgor pressure (Ψ p ) could be calculated. In the intact plant, Ψ s and Ψ p were essentially constant for the entire 22 h measurement, but Ψ s was lower and Ψ p higher in the elongating region than in the mature region. This caused the water potential in the elongating region to be lower than in the mature region. The mature tissue equilibrated with the water potential of the xylem. Therefore, the difference in water potential between mature and elongating tissue represented a difference between the xylem and the elongating region, reflecting a water potential gradient from the xylem to the epidermis that was involved in supplying water for elongation. When mature tissue was excised with the guillotine, Ψ s and Ψ p did not change. However, when elongating tissue was excised, water was absorbed from the xylem, whose water potential decreased. This collapsed the gradient and prevented further water uptake. Tissue Ψ p then decreased rapidly (5 min) by about 0.1 MPa in the elongating tissue. The Ψ p decreased because the cell walls relaxed as extension, caused by Ψ p , continued briefly without water uptake. The Ψ p decreased until the minimum for wall extension (Y) was reached, whereupon elongation ceased. This was followed by a slow further decrease in Y but no additional elongation. In elongating tissue excised with mature tissue attached, there was almost no effect on water potential or Ψ p for several hours. Nevertheless, growth was reduced immediately and continued at a decreasing rate. In this case, the mature tissue supplied water to the elongating tissue and the cell walls did not relax. Based on these measurements, a theory is presented for simultaneously evaluating the effects of water supply and water demand associated with growth. Because wall relaxation measured with the psychrometer provided a new method for determining Y and wall extensibility, all the factors required by the theory could be evaluated for the first time in a single sample. The analysis showed that water uptake and wall extension co-limited elongation in soybean stems under our conditions. This co-limitation explains why elongation responded immediately to a decrease in the water potential of the xylem and why excision with attached mature tissue caused an immediate decrease in growth rate without an immediate change in Ψ p.

Natural migration rates of trees: Global terrestrial carbon cycle implications. Book chapter

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

Solomon, A.M.

The paper discusses the forest-ecological processes which constrain the rate of response by forests to rapid future environmental change. It establishes a minimum response time by natural tree populations which invade alien landscapes and reach the status of a mature, closed canopy forest when maximum carbon storage is realized. It considers rare long-distance and frequent short-distance seed transport, seedling and tree establishment, sequential tree and stand maturation, and spread between newly established colonies.

Tanner-Whitehouse Skeletal Ages in Male Youth Soccer Players: TW2 or TW3?

PubMed

Malina, Robert M; Coelho-E-Silva, Manuel J; Figueiredo, António J; Philippaerts, Renaat M; Hirose, Norikazu; Peña Reyes, Maria Eugenia; Gilli, Giulio; Benso, Andrea; Vaeyens, Roel; Deprez, Dieter; Guglielmo, Luiz F; Buranarugsa, Rojapon

2018-04-01

The Tanner-Whitehouse radius-ulna-short bone protocol (TW2 RUS) for the assessment of skeletal age (SA) is widely used to estimate the biological (skeletal) maturity status of children and adolescents. The scale for converting TW RUS ratings to an SA has been revised (TW3 RUS) and has implications for studies of youth athletes in age-group sports. The aim of this study was to compare TW2 and TW3 RUS SAs in an international sample of male youth soccer players and to compare distributions of players by maturity status defined by each SA protocol. SA assessments with the TW RUS method were collated for 1831 male soccer players aged 11-17 years from eight countries. RUS scores were converted to TW2 and TW3 SAs using the appropriate tables. SAs were related to chronological age (CA) in individual athletes and compared by CA groups. The difference of SA minus CA with TW2 SA and with TW3 SA was used to classify players as late, average, or early maturing with each method. Concordance of maturity classifications was evaluated with Cohen's Kappa coefficients. For the same RUS score, TW3 SAs were systematically and substantially reduced compared with TW2 SAs; mean differences by CA group ranged from - 0.97 to - 1.16 years. Kappa coefficients indicated at best fair concordance of TW2 and TW3 maturity classifications. Across the age range, 42% of players classified as average with TW2 SA were classified as late with TW3 SA, and 64% of players classified as early with TW2 SA were classified as average with TW3 SA. TW3 SAs were systematically lower than corresponding TW2 SAs in male youth soccer players. The differences between scales have major implications for the classification of players by maturity status, which is central to some talent development programs.

Service quality and maturity of health care organizations through the lens of Complexity Leadership Theory.

PubMed

Horvat, Ana; Filipovic, Jovan

2018-02-01

This research focuses on Complexity Leadership Theory and the relationship between leadership-examined through the lens of Complexity Leadership Theory-and organizational maturity as an indicator of the performance of health organizations. The research adopts a perspective that conceptualizes organizations as complex adaptive systems and draws upon a survey of opinion of 189 managers working in Serbian health organizations. As the results indicate a dependency between functions of leadership and levels of the maturity of health organizations, we propose a model that connects the two. The study broadens our understanding of the implications of complexity thinking and its reflection on leadership functions and overall organizational performance. The correlations between leadership functions and maturity could have practical applications in policy processing, thus improving the quality of outcomes and the overall level of service quality. © 2017 John Wiley & Sons, Ltd.

An investigation into mature adults' attitudinal reluctance to register as organ donors.

PubMed

Quick, Brian L; Reynolds-Tylus, Tobias; Fico, Ashley E; Feeley, Thomas Hugh

2016-10-01

Mature adults (age 50-64) make up a large proportion of organ transplant recipients, and waiting list candidates yet are underrepresented in terms of actual donors. Understanding the reasons why mature adults fail to register as deceased organ donors is critical in achieving the goal of increasing the actionable supply of organs available for transplant. Conceptual models propose certain factors such as bodily integrity, ick (i.e., disgust), jinx (i.e., superstition), medical mistrust, salience, self-efficacy, and stake are associated with organ donation registration attitudes. Moreover, the age myth, or the belief that one's age prevents them from becoming an organ donor, was examined among mature adults between the ages of 50-64. An online survey was disseminated to mature adults (N=709). Results indicated jinx, salience, self-efficacy, and stake each predicted organ donation attitudes among mature adults. Moreover, results indicated that age myth accounted for attitudes toward registering as an organ donor among non-registered mature adults after controlling for non-cognitive and vested interest constructs. This study demonstrates the age myth is negatively associated with attitudes toward registering as organ donors. The results are discussed with an emphasis on both the theoretical and practical implications of study findings. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of biological and technical factors on brain and muscle cholinesterases in Nile tilapia, Oreochromis niloticus: implications for biomonitoring neurotoxic contaminations.

PubMed

Pathiratne, A; Chandrasekera, L W H U; De Seram, P K C

2008-02-01

Influence of body length, body weight, gender, sexual maturity, and tissue storage on brain and muscle cholinesterases (ChE) in Nile tilapia was evaluated considering its potential use in biomonitoring neurotoxic contaminations in tropical environments. Results show that ChE activities in both tissues decreased significantly with increased total length (4-24.5 cm) or body weight (1-186 g) of the fish and the relationships were curvilinear. Comparisons of the slopes and elevations of the regression lines of the logarithmic ChE and body size relationships of males with those of females indicated that gender had no significant effect on the body size-specific ChE activities. Response of the ChE of sexually mature males to chlorpyrifos exposure was similar to that of females. Gonadal maturity stage of this fish does not seem to influence ChE activities. Storage of tissues at -80 degrees C for 28 days had no significant effect on ChE activities in the control fish and the fish exposed to carbofuran. However, a partial reactivation of brain ChE activities was observed in the fish exposed to carbosulfan after 28 days of storage. The results emphasize the importance of consideration of body size of the fish and storage time of the tissues in order to formulate accurate conclusions about the neurotoxic chemical exposure when ChE of the fish is used in biomonitoring programs.

MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies

PubMed Central

Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L.; Hacia, Joseph G.; Paine, Michael L.

2017-01-01

Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3′-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI. PMID:28287144

MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways-Novel Insight into the Origins of Enamel Pathologies.

PubMed

Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L; Hacia, Joseph G; Paine, Michael L

2017-03-13

Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3'-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI.

The Roles of Family B and D DNA Polymerases in Thermococcus Species 9°N Okazaki Fragment Maturation*

PubMed Central

Greenough, Lucia; Kelman, Zvi; Gardner, Andrew F.

2015-01-01

During replication, Okazaki fragment maturation is a fundamental process that joins discontinuously synthesized DNA fragments into a contiguous lagging strand. Efficient maturation prevents repeat sequence expansions, small duplications, and generation of double-stranded DNA breaks. To address the components required for the process in Thermococcus, Okazaki fragment maturation was reconstituted in vitro using purified proteins from Thermococcus species 9°N or cell extracts. A dual color fluorescence assay was developed to monitor reaction substrates, intermediates, and products. DNA polymerase D (polD) was proposed to function as the replicative polymerase in Thermococcus replicating both the leading and the lagging strands. It is shown here, however, that it stops before the previous Okazaki fragments, failing to rapidly process them. Instead, Family B DNA polymerase (polB) was observed to rapidly fill the gaps left by polD and displaces the downstream Okazaki fragment to create a flap structure. This flap structure was cleaved by flap endonuclease 1 (Fen1) and the resultant nick was ligated by DNA ligase to form a mature lagging strand. The similarities to both bacterial and eukaryotic systems and evolutionary implications of archaeal Okazaki fragment maturation are discussed. PMID:25814667

The current challenges to efficient immature oocyte cryopreservation.

PubMed

Brambillasca, Fausta; Guglielmo, Maria Cristina; Coticchio, Giovanni; Mignini Renzini, Mario; Dal Canto, Mariabeatrice; Fadini, Rubens

2013-12-01

Oocyte cryopreservation represents an important tool for assisted reproductive technology. It offers the opportunity to preserve fertility in women at risk of loss of the ovarian function for various pathologies. It also represents a treatment alternative for couples that cannot benefit from embryo cryopreservation because of moral, religious, or legal constrains. On the other hand, in vitro oocyte maturation has a range of applications. It can be applied in patients with a contraindication to ovarian stimulation to prevent ovarian hyperstimulation syndrome or to eliminate the risk of stimulation of hormone-sensitive tumours in cancer patients. However, while mature oocyte cryopreservation has found wide-spread application and oocyte in vitro maturation has a place for the treatment of specific clinical conditions, data on the efficiency of freezing of immature or in vitro matured oocytes are poorer. In this review we will focus on the combination of oocyte in vitro maturation with oocyte cryopreservation with particular emphasis on the biological implications of the cryopreservation of immature or in vitro matured oocytes. The two cryopreservation approaches, slow freezing and vitrification, will be discussed in relation to possible cryodamage occurring to subcellular structures of the oocyte and the functional interaction between oocyte and cumulus cells.

The postcranial skeletal maturation of Australopithecus sediba.

PubMed

Cameron, Noel; Bogin, Barry; Bolter, Debra; Berger, Lee R

2017-07-01

In 2008, an immature hominin defined as the holotype of the new species Australopithecus sediba was discovered at the 1.9 million year old Malapa site in South Africa. The specimen (MH1) includes substantial post-cranial skeletal material, and provides a unique opportunity to assess its skeletal maturation. Skeletal maturity indicators observed on the proximal and distal humerus, proximal ulna, distal radius, third metacarpal, ilium and ischium, proximal femur and calcaneus were used to assess the maturity of each bone in comparison to references for modern humans and for wild chimpanzees (Pan troglodytes). In comparison to humans the skeletal maturational ages for Au. sediba correspond to between 12.0 years and 15.0 years with a mean (SD) age of 13.1 (1.1) years. In comparison to the maturational pattern of chimpanzees the Au. sediba indicators suggest a skeletal maturational age of 9-11 years. Based on either of these skeletal maturity estimates and the body length at death of MH1, an adult height of 150-156 cm is predicted. We conclude that the skeletal remains of MH1 are consistent with an ape-like pattern of maturity when dental age estimates are also taken into consideration. This maturity schedule in australopiths is consistent with ape-like estimates of age at death for the Nariokotome Homo erectus remains (KMN-WT 15000), which are of similar postcranial immaturity to MH1. The findings suggest that humans may have distinctive and delayed post-cranial schedules from australopiths and H. erectus, implicating a recent evolution of somatic and possibly life history strategies in human evolution. © 2017 Wiley Periodicals, Inc.

The psycholegal factors for juvenile transfer and reverse transfer evaluations.

PubMed

King, Christopher M

2018-01-01

It remains unclear whether forensic mental health assessments for juvenile reverse transfer (to juvenile court) are distinct from those for juvenile transfer (to adult court). This survey consisted of an updated review of transfer and reverse transfer laws (in jurisdictions that have both mechanisms) in light of the generally accepted three-factor model of functional legal capacities involved in transfer evaluations (i.e., risk, sophistication-maturity, and treatment amenability). Results indicated that a majority of states' reverse transfer statutes refer explicitly or implicitly to the same three psycholegal constructs identified as central for transfer. Given the legal similarity between transfer and reverse transfer, potential practice implications and directions for future research are discussed. Copyright © 2017 John Wiley & Sons, Ltd.

Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: Mechanisms and implications for psychopathology

PubMed Central

McNamara, Robert K; Vannest, Jennifer J; Valentine, Christina J

2015-01-01

Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In non-human primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with long-standing deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder (ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies. PMID:25815252

Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

PubMed

Obata, Yuuki; Kimura, Shunsuke; Nakato, Gaku; Iizuka, Keito; Miyagawa, Yurika; Nakamura, Yutaka; Furusawa, Yukihiro; Sugiyama, Machiko; Suzuki, Keiichiro; Ebisawa, Masashi; Fujimura, Yumiko; Yoshida, Hisahiro; Iwanaga, Toshihiko; Hase, Koji; Ohno, Hiroshi

2014-12-01

Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation. This defect can be attributed to the expansion of goblet cells, which leads to the down-regulation of CCL20 in FAE. These data demonstrate that epithelial Notch signaling maintained by stromal cells contributes to the full maturation of GALT by restricting secretory cell differentiation in FAE. © 2014 The Authors.

Cell culture purity issues and DFAT cells

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

Wei, Shengjuan; Department of Animal Sciences, Washington State University, Pullman, WA 99164; Bergen, Werner G.

2013-04-12

Highlights: •DFAT cells are progeny cells derived from dedifferentiated mature adipocytes. •Common problems in this research is potential cell contamination of initial cultures. •The initial cell culture purity is crucial in DFAT cell research field. -- Abstract: Dedifferentiation of mature adipocytes, in vitro, has been pursued/documented for over forty years. The subsequent progeny cells are named dedifferentiated adipocyte-derived progeny cells (DFAT cells). DFAT cells are proliferative and likely to possess mutilineage potential. As a consequence, DFAT cells and their progeny/daughter cells may be useful as a potential tool for various aspects of tissue engineering and as potential vectors for themore » alleviation of several disease states. Publications in this area have been increasing annually, but the purity of the initial culture of mature adipocytes has seldom been documented. Consequently, it is not always clear whether DFAT cells are derived from dedifferentiated mature (lipid filled) adipocytes or from contaminating cells that reside in an impure culture.« less

Plasmodium falciparum-Derived Uric Acid Precipitates Induce Maturation of Dendritic Cells

PubMed Central

van de Hoef, Diana L.; Coppens, Isabelle; Holowka, Thomas; Ben Mamoun, Choukri; Branch, OraLee; Rodriguez, Ana

2013-01-01

Malaria is characterized by cyclical fevers and high levels of inflammation, and while an early inflammatory response contributes to parasite clearance, excessive and persistent inflammation can lead to severe forms of the disease. Here, we show that Plasmodium falciparum-infected erythrocytes contain uric acid precipitates in the cytoplasm of the parasitophorous vacuole, which are released when erythrocytes rupture. Uric acid precipitates are highly inflammatory molecules that are considered a danger signal for innate immunity and are the causative agent in gout. We determined that P. falciparum-derived uric acid precipitates induce maturation of human dendritic cells, increasing the expression of cell surface co-stimulatory molecules such as CD80 and CD86, while decreasing human leukocyte antigen-DR expression. In accordance with this, uric acid accounts for a significant proportion of the total stimulatory activity induced by parasite-infected erythrocytes. Moreover, the identification of uric acid precipitates in P. falciparum- and P. vivax-infected erythrocytes obtained directly from malaria patients underscores the in vivo and clinical relevance of our findings. Altogether, our data implicate uric acid precipitates as a potentially important contributor to the innate immune response to Plasmodium infection and may provide a novel target for adjunct therapies. PMID:23405174

A mucin-like peptide from Fasciola hepatica instructs dendritic cells with parasite specific Th1-polarizing activity.

PubMed

Noya, Verónica; Brossard, Natalie; Rodríguez, Ernesto; Dergan-Dylon, L Sebastián; Carmona, Carlos; Rabinovich, Gabriel A; Freire, Teresa

2017-01-12

Fasciolosis is a trematode zoonosis of interest in public health and cattle production. We report here the immunostimulatory effect of a 66 mer mucin-like peptide from Fasciola hepatica (Fhmuc), which synergizes with lipopolysaccharide (LPS) to promote dendritic cell (DC) maturation, endowing these cells with Th1-polarizing capacity. Exposure of DCs to Fhmuc in presence of LPS induced enhanced secretion of pro-inflammatory cytokines and expression of co-stimulatory molecules by DCs, promoting their T cell stimulatory capacity and selectively augmenting IFN-γ secretion by allogeneic T cells. Furthermore, exposure of DCs to Fhmuc augmented LPS-induced Toll-like receptor (TLR) 4 expression on the cell surface. Finally, Fhmuc-conditioned DCs induced parasite specific-adaptive immunity with increased levels of IFN-γ secreted by splenocytes from vaccinated animals, and higher parasite-specific IgG antibodies. However, Fhmuc-treated DC conferred modest protection against F. hepatica infection highlighting the potent immuno-regulatory capacity of the parasite. In summary, this work highlights the capacity of a mucin-derived peptide from F. hepatica to enhance LPS-maturation of DCs and induce parasite-specific immune responses with potential implications in vaccination and therapeutic strategies.

A mucin-like peptide from Fasciola hepatica instructs dendritic cells with parasite specific Th1-polarizing activity

PubMed Central

Noya, Verónica; Brossard, Natalie; Rodríguez, Ernesto; Dergan-Dylon, L. Sebastián; Carmona, Carlos; Rabinovich, Gabriel A.; Freire, Teresa

2017-01-01

Fasciolosis is a trematode zoonosis of interest in public health and cattle production. We report here the immunostimulatory effect of a 66 mer mucin-like peptide from Fasciola hepatica (Fhmuc), which synergizes with lipopolysaccharide (LPS) to promote dendritic cell (DC) maturation, endowing these cells with Th1-polarizing capacity. Exposure of DCs to Fhmuc in presence of LPS induced enhanced secretion of pro-inflammatory cytokines and expression of co-stimulatory molecules by DCs, promoting their T cell stimulatory capacity and selectively augmenting IFN-γ secretion by allogeneic T cells. Furthermore, exposure of DCs to Fhmuc augmented LPS-induced Toll-like receptor (TLR) 4 expression on the cell surface. Finally, Fhmuc-conditioned DCs induced parasite specific-adaptive immunity with increased levels of IFN-γ secreted by splenocytes from vaccinated animals, and higher parasite-specific IgG antibodies. However, Fhmuc-treated DC conferred modest protection against F. hepatica infection highlighting the potent immuno-regulatory capacity of the parasite. In summary, this work highlights the capacity of a mucin-derived peptide from F. hepatica to enhance LPS-maturation of DCs and induce parasite-specific immune responses with potential implications in vaccination and therapeutic strategies. PMID:28079156

Effect of Thermal Maturation on n-alkanes and Kerogen in Preserved Organic Matter: Implications for Paleoenvironment Biomarkers

NASA Astrophysics Data System (ADS)

Craven, O. D.; Longbottom, T. L.; Hockaday, W. C.; Blackaby, E.

2017-12-01

Understanding the effects of maturity on biomarkers is vital in assessing biomarker reliability in mature sediments. It is well known for n-alkanes that increased maturity shortens chain lengths and decreases the odd over even preference however, the amount of change in these variables has not been determined for different maturities and types of preserved organic matter. For this reason, it is difficult to judge the trustworthiness of even lightly matured samples for paleoenvironment reconstruction. Another complication is the difficulty of accurately determining maturity as many maturity indicators are error-prone or not appropriate at low maturities. Using hydrous pyrolysis, we artificially matured black shale samples with type I (lacustrine) and type II (marine) kerogen to measure changes in n-alkane length and odd over even preference. Whole rock samples underwent hydrous pyrolysis for 72 hours, at 250 °C, 300 °C, 325 °C, 350 °C, and 375 °C to cover a wide maturity range. From the immature and artificially matured samples, the bitumen was extracted and the saturate fraction was separated using column chromatography. The saturate fraction was analyzed for n-alkanes using gas chromatography-mass spectroscopy. Kerogen structural changes were also measured using solid-state 13C NMR to relate changes in n-alkane biomarkers to changes in kerogen structure. Results show that for type I bitumen the n-alkanes did not change at low maturities considered premature in terms of oil generation (<325 °C). The NMR spectra of the type I kerogen support the lack of change, at low maturities no changes in the aliphatic portion (Fal) were observed, however, after 325 °C Fal decreased with increasing maturity. The loss of Fal indicates kerogen contributing hydrocarbons to bitumen that cause changes in n-alkane measurements. The type II kerogen's Fal also decreased with increasing maturity, but unlike the type I kerogen Fal loss started at low maturities. The differences between the matured type I and II organic matter indicate that organic matter type affects when n-alkane measurements change due to maturity. Additionally, the kerogen carbonyl functional group (FaC) decreases greatly from immature to low maturities, leveling off between 300 °C and 325 °C, allowing FaC to be a tool for determining low maturities.

MET receptor tyrosine kinase controls dendritic complexity, spine morphogenesis, and glutamatergic synapse maturation in the hippocampus.

PubMed

Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

2014-12-03

The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. Copyright © 2014 the authors 0270-6474/14/3416166-14$15.00/0.

MET Receptor Tyrosine Kinase Controls Dendritic Complexity, Spine Morphogenesis, and Glutamatergic Synapse Maturation in the Hippocampus

PubMed Central

Lu, Zhongming; Levitt, Pat

2014-01-01

The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. PMID:25471559

Heterogeneity of Clonal Expansion and Maturation-Linked Mutation Acquisition in Hematopoietic Progenitors in Human Acute Myeloid Leukemia

PubMed Central

Walter, Roland B.; Laszlo, George S.; Lionberger, Jack M.; Pollard, Jessica A.; Harrington, Kimberly H.; Gudgeon, Chelsea J.; Othus, Megan; Rafii, Shahin; Meshinchi, Soheil; Appelbaum, Frederick R.; Bernstein, Irwin D.

2014-01-01

Recent technological advances led to an appreciation of the genetic complexity of human acute myeloid leukemia (AML) but underlying progenitor cells remain poorly understood because their rarity precludes direct study. We developed a co-culture method integrating hypoxia, aryl hydrocarbon receptor inhibition, and micro-environmental support via human endothelial cells to isolate these cells. X-chromosome inactivation studies of the least mature precursors derived following prolonged culture of CD34+/CD33− cells revealed polyclonal growth in highly curable AMLs, suggesting mutations necessary for clonal expansion were acquired in more mature progenitors. Consistently, in core-binding factor (CBF) leukemias with known complementing mutations, immature precursors derived following prolonged culture of CD34+/CD33− cells harbored neither mutation or the CBF mutation alone, whereas more mature precursors often carried both mutations. These results were in contrast to those with leukemias with poor prognosis that showed clonal dominance in the least mature precursors. These data indicate heterogeneity among progenitors in human AML that may have prognostic and therapeutic implications. PMID:24721792

Bird densities and diversity in clearcut and mature oak-hickory forest.

Treesearch

Frank R. III Thompson; Erik K. Fritzell

1990-01-01

Describes nongame bird densities and diversity in a central Missouri oak-hickory forest 1 year before and 3 years after portions were clearcut. Discusses changes in species density and diversity and their management implications.

Soil stabilization by a prokaryotic desert crust - Implications for Precambrian land biota

NASA Technical Reports Server (NTRS)

Campbell, S. E.

1979-01-01

The ecology of the cyanophyte-dominated stromatolitic mat forming the ground cover over desert areas of Utah and Colorado is investigated and implications for the formation of mature Precambrian soils are discussed. The activation of the growth of the two species of filamentous cyanophyte identified and the mobility of their multiple trichromes upon wetting are observed, accompanied by the production and deposition of a sheath capable of accreting and stabilizing sand and clay particles. The formation of calcium carbonate precipitates upon the repeated wetting and drying of desert crust is noted, and it is suggested that the desert crust community may appear in fossil calcrete deposits as lithified microscopic tubes and cellular remains of algal trichromes. The invasion of dry land by both marine and freshwater algae on the model of the desert crust is proposed to be responsible for the accumulation, stabilization and biogenic modification of mature Precambrian soils.

Properties of the [NiFe]-hydrogenase maturation protein HypD.

PubMed

Blokesch, Melanie; Böck, August

2006-07-24

A mutational screen of amino acid residues of hydrogenase maturation protein HypD from Escherichia coli disclosed that seven conserved cysteine residues located in three different motifs in HypD are essential. Evidence is presented for potential functions of these motifs in the maturation process.

Maternally Recruited DCP1A and DCP2 Contribute to Messenger RNA Degradation During Oocyte Maturation and Genome Activation in Mouse1

PubMed Central

Ma, Jun; Flemr, Matyas; Strnad, Hynek; Svoboda, Petr; Schultz, Richard M.

2012-01-01

ABSTRACT The oocyte-to-zygote transition entails transforming a highly differentiated oocyte into totipotent blastomeres and represents one of the earliest obstacles that must be successfully hurdled for continued development. Degradation of maternal mRNAs, which likely lies at the heart of this transition, is characterized by a transition from mRNA stability to instability during oocyte maturation. Although phosphorylation of the oocyte-specific RNA-binding protein MSY2 during maturation is implicated in making maternal mRNAs more susceptible to degradation, mechanisms underlying mRNA degradation during oocyte maturation remain poorly understood. We report that DCP1A and DCP2, proteins responsible for decapping mRNA, are encoded by maternal mRNAs recruited for translation during maturation via cytoplasmic polyadenylation elements located in their 3′ untranslated regions. Both DCP1A and DCP2 are phosphorylated during maturation, with CDC2A being the kinase likely responsible for both, although MAPK may be involved in DCP1A phosphorylation. Inhibiting accumulation of DCP1A and DCP2 by RNA interference or morpholinos decreases not only degradation of mRNAs during meiotic maturation but also transcription of the zygotic genome. The results indicate that maternally recruited DCP1A and DCP2 are critical players in the transition from mRNA stability to instability during meiotic maturation and that proper maternal mRNA degradation must be successful to execute the oocyte-to-zygote transition. PMID:23136299

The Between-Population Genetic Architecture of Growth, Maturation, and Plasticity in Atlantic Salmon

PubMed Central

Debes, Paul Vincent; Fraser, Dylan John; Yates, Matthew; Hutchings, Jeffrey A.

2014-01-01

The between-population genetic architecture for growth and maturation has not been examined in detail for many animal species despite its central importance in understanding hybrid fitness. We studied the genetic architecture of population divergence in: (i) maturation probabilities at the same age; (ii) size at age and growth, while accounting for maturity status and sex; and (iii) growth plasticity in response to environmental factors, using divergent wild and domesticated Atlantic salmon (Salmo salar). Our work examined two populations and their multigenerational hybrids in a common experimental arrangement in which salinity and quantity of suspended sediments were manipulated to mimic naturally occurring environmental variation. Average specific growth rates across environments differed among crosses, maturity groups, and cross-by-maturity groups, but a growth-rate reduction in the presence of suspended sediments was equal for all groups. Our results revealed both additive and nonadditive outbreeding effects for size at age and for growth rates that differed with life stage, as well as the presence of different sex- and size-specific maturation probabilities between populations. The major implication of our work is that estimates of the genetic architecture of growth and maturation can be biased if one does not simultaneously account for temporal changes in growth and for different maturation probabilities between populations. Namely, these correlated traits interact differently within each population and between sexes and among generations, due to nonadditive effects and a level of independence in the genetic control for traits. Our results emphasize the challenges to investigating and predicting phenotypic changes resulting from between-population outbreeding. PMID:24473933

Digestion products of the PH20 hyaluronidase inhibit remyelination.

PubMed

Preston, Marnie; Gong, Xi; Su, Weiping; Matsumoto, Steven G; Banine, Fatima; Winkler, Clayton; Foster, Scott; Xing, Rubing; Struve, Jaime; Dean, Justin; Baggenstoss, Bruce; Weigel, Paul H; Montine, Thomas J; Back, Stephen A; Sherman, Larry S

2013-02-01

Oligodendrocyte progenitor cells (OPCs) recruited to demyelinating lesions often fail to mature into oligodendrocytes (OLs) that remyelinate spared axons. The glycosaminoglycan hyaluronan (HA) accumulates in demyelinating lesions and has been implicated in the failure of OPC maturation and remyelination. We tested the hypothesis that OPCs in demyelinating lesions express a specific hyaluronidase, and that digestion products of this enzyme inhibit OPC maturation. Mouse OPCs grown in vitro were analyzed for hyaluronidase expression and activity. Gain of function studies were used to define the hyaluronidases that blocked OPC maturation. Mouse and human demyelinating lesions were assessed for hyaluronidase expression. Digestion products from different hyaluronidases and a hyaluronidase inhibitor were tested for their effects on OPC maturation and functional remyelination in vivo. OPCs demonstrated hyaluronidase activity in vitro and expressed multiple hyaluronidases, including HYAL1, HYAL2, and PH20. HA digestion by PH20 but not other hyaluronidases inhibited OPC maturation into OLs. In contrast, inhibiting HA synthesis did not influence OPC maturation. PH20 expression was elevated in OPCs and reactive astrocytes in both rodent and human demyelinating lesions. HA digestion products generated by the PH20 hyaluronidase but not another hyaluronidase inhibited remyelination following lysolecithin-induced demyelination. Inhibition of hyaluronidase activity lead to increased OPC maturation and promoted increased conduction velocities through lesions. We determined that PH20 is elevated in demyelinating lesions and that increased PH20 expression is sufficient to inhibit OPC maturation and remyelination. Pharmacological inhibition of PH20 may therefore be an effective way to promote remyelination in multiple sclerosis and related conditions. Copyright © 2012 American Neurological Association.

The between-population genetic architecture of growth, maturation, and plasticity in Atlantic salmon.

PubMed

Debes, Paul Vincent; Fraser, Dylan John; Yates, Matthew; Hutchings, Jeffrey A

2014-04-01

The between-population genetic architecture for growth and maturation has not been examined in detail for many animal species despite its central importance in understanding hybrid fitness. We studied the genetic architecture of population divergence in: (i) maturation probabilities at the same age; (ii) size at age and growth, while accounting for maturity status and sex; and (iii) growth plasticity in response to environmental factors, using divergent wild and domesticated Atlantic salmon (Salmo salar). Our work examined two populations and their multigenerational hybrids in a common experimental arrangement in which salinity and quantity of suspended sediments were manipulated to mimic naturally occurring environmental variation. Average specific growth rates across environments differed among crosses, maturity groups, and cross-by-maturity groups, but a growth-rate reduction in the presence of suspended sediments was equal for all groups. Our results revealed both additive and nonadditive outbreeding effects for size at age and for growth rates that differed with life stage, as well as the presence of different sex- and size-specific maturation probabilities between populations. The major implication of our work is that estimates of the genetic architecture of growth and maturation can be biased if one does not simultaneously account for temporal changes in growth and for different maturation probabilities between populations. Namely, these correlated traits interact differently within each population and between sexes and among generations, due to nonadditive effects and a level of independence in the genetic control for traits. Our results emphasize the challenges to investigating and predicting phenotypic changes resulting from between-population outbreeding.

The sperm epigenome and potential implications for the developing embryo.

PubMed

Jenkins, Timothy G; Carrell, Douglas T

2012-06-01

Recent work in the field of male fertility has yielded significant increases in our understanding of the sperm epigenome and its potential role in embryonic development. These new findings have enabled a broad classification of a normal epigenetic state in the male gamete and have provided insight into the possible etiologies of some idiopathic male infertility cases. Histone retention and modification, protamine incorporation into the chromatin, DNA methylation, and spermatozoal RNA transcripts appear to play important roles in the epigenetic state of mature sperm. These epigenetic factors may reveal a historical record of spermatogenesis, portend future functions in embryogenesis, and help to elucidate mechanism of pluripotency. In contrast to the once held dogma regarding the importance of the paternal epigenome, the unique epigenetic landscape in sperm appears to serve more than the gamete itself and is likely influential in the developing embryo. In fact, growing evidence suggests that mature sperm provide appropriate epigenetic marks that drive specific genes toward activation and contribute to the pluripotent state of the embryonic cells. Although not definitive, the current literature provides evidence for the role of the sperm epigenome in the embryo. Future work must be focused on the characterization of epigenetic abnormalities commonly found in individuals with compromised fertility to further establish this role. Additionally, studies should target the effects of environment and aging on the sperm epigenetic program and subsequent fertility loss to determine the etiology of aberrant epigenetic profiles.

The development and use of a molecular model for soybean maturity groups

USDA-ARS?s Scientific Manuscript database

Achieving appropriate maturity in a target environment is essential to maximizing crop yield potential. In soybean [Glycine max (L.) Merr.], the time to maturity is largely dependent on developmental response to dark periods. Once the critical photoperiod is reached, flowering is initiated and rep...

Delayed plumage maturation and delayed reproductive investment in birds.

PubMed

Hawkins, Gerard L; Hill, Geoffrey E; Mercadante, Austin

2012-05-01

Delayed plumage maturation is the delayed acquisition of a definitive colour and pattern of plumage until after the first potential breeding period in birds. Here we provide a comprehensive overview of the numerous studies of delayed plumage maturation and a revised theoretical framework for understanding the function of delayed plumage maturation in all birds. We first distinguish between hypotheses that delayed plumage maturation is attributable to a moult constraint with no adaptive function and hypotheses that propose that delayed plumage maturation is a component of an adaptive life-history strategy associated with delayed reproductive investment. We then recognize three potential benefits of delayed plumage maturation: crypsis, mimicry and status signaling. Evidence suggests that delayed plumage maturation is not a consequence of developmental constraints and instead represents a strategy to maximize reproductive success in circumstances where young adults cannot effectively compete with older adults for limited resources, particularly breeding opportunities. A multi-factorial explanation that takes into account lifespan and the degree of competition for limited breeding resources and that combines the benefits of an inconspicuous appearance with the benefits of honest signaling of reduced competitiveness provides a general explanation for the function of delayed plumage maturation in most bird species. Delayed plumage maturation should be viewed as a component of alternative reproductive strategies that can include delay in both plumage and sexual development. Such strategies are frequently facultative, with individuals breeding prior to the acquisition of definitive plumages when conditions are favourable. Presumably, the benefits of delayed plumage maturation ultimately enhance lifetime reproductive success, and studying delayed plumage maturation within the context of lifetime reproductive success should be a goal of future studies. © 2011 The Authors. Biological Reviews © 2011 Cambridge Philosophical Society.

The effect of protective nutrients on mucosal defense in the immature intestine.

PubMed

Forchielli, Maria L; Walker, W Allan

2005-10-01

Oral nutrition plays a dual role in the gut, providing nutrition to the body while affecting the function of the gastrointestinal tract. The exposure of the gut to food antigens, in the form of either beneficial or harmful nutritional substances, contributes to a vast array of physiological and pathologic gastrointestinal responses with secondary systemic implications. The immune system of the gastrointestinal tract is always involved in the first line of defense, and its actions are particularly important in the early period of life as maturation takes place. From maturation, a balance ensues in the regulatory mechanism of host defense, ultimately leading to either tolerance or immune reaction. This paper emphasizes how some nutrients may beneficially affect the gastrointestinal immune system's maturation in both term and especially premature neonates.

TAM Receptors in Leukemia: Expression, Signaling, and Therapeutic Implications

PubMed Central

Brandão, Luis; Migdall-Wilson, Justine; Eisenman, Kristen; Graham, Douglas K.

2016-01-01

In the past 30 years there has been remarkable progress in the treatment of leukemia and lymphoma. However, current treatments are largely ineffective against relapsed leukemia and, in the case of pediatric patients, are often associated with severe long-term toxicities. Thus, there continues to be a critical need for the development of effective biologically targeted therapies. The TAM family of receptor tyrosine kinases—Tyro3, Axl, and Mer—plays an important role in normal hematopoiesis, including natural killer cell maturation, macrophage function, and platelet activation and signaling. Furthermore, TAM receptor activation leads to upregulation of pro-survival and proliferation signaling pathways, and aberrant TAM receptor expression contributes to cancer development, including myeloid and lymphoid leukemia. This review summarizes the role of TAM receptors in leukemia. We outline TAM receptor expression patterns in different forms of leukemia, describe potential mechanisms leading to their overexpression, and delineate the signaling pathways downstream of receptor activation that have been implicated in leukemogenesis. Finally, we discuss the current research focused on inhibitors against these receptors in an effort to develop new therapeutic strategies for leukemia. PMID:22150307

The influence of maturity and variety of potato plants on oviposition and probing of Bactericera cockerelli (Hemiptera: Triozidae).

PubMed

Prager, Sean M; Lewis, O Milo; Michels, Jerry; Nansen, Christian

2014-04-01

The ecological theory on host plant choice by herbivores suggests that mothers should choose plants that will maximize their offspring's success. In annual host plants, physiology (and therefore host suitability) is sometimes influenced by maturity and growth stage, which may influence female choice. Potato plants were grown under greenhouse conditions and used in choice and no-choice bioassays to determine the effect of plant maturity and variety on oviposition and number of stylet sheaths (which approximate stylet insertions) by tomato/potato psyllids. No-choice bioassays suggested that maturity (time since planting) did not influence oviposition behavior, but oviposition varied significantly among potato plant varieties. There was a significant effect of both maturity and variety on the number of stylet sheaths, which peak toward the middle of the growing season. We also examined tomato/potato psyllid responses to plants grown in a commercial field and again found no effect on oviposition but differences in stylet sheaths. The results suggest that differential susceptibility to zebra chip disease may be associated with unequal feeding rates. Future studies should examine whether the maturity of plants influences larval fitness. Finally, potato variety has an influence on both oviposition and "probing," and has implications for management strategies and the development of resistant potato varieties.

The roles of family B and D DNA polymerases in Thermococcus species 9°N Okazaki fragment maturation.

PubMed

Greenough, Lucia; Kelman, Zvi; Gardner, Andrew F

2015-05-15

During replication, Okazaki fragment maturation is a fundamental process that joins discontinuously synthesized DNA fragments into a contiguous lagging strand. Efficient maturation prevents repeat sequence expansions, small duplications, and generation of double-stranded DNA breaks. To address the components required for the process in Thermococcus, Okazaki fragment maturation was reconstituted in vitro using purified proteins from Thermococcus species 9°N or cell extracts. A dual color fluorescence assay was developed to monitor reaction substrates, intermediates, and products. DNA polymerase D (polD) was proposed to function as the replicative polymerase in Thermococcus replicating both the leading and the lagging strands. It is shown here, however, that it stops before the previous Okazaki fragments, failing to rapidly process them. Instead, Family B DNA polymerase (polB) was observed to rapidly fill the gaps left by polD and displaces the downstream Okazaki fragment to create a flap structure. This flap structure was cleaved by flap endonuclease 1 (Fen1) and the resultant nick was ligated by DNA ligase to form a mature lagging strand. The similarities to both bacterial and eukaryotic systems and evolutionary implications of archaeal Okazaki fragment maturation are discussed. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Empirical relation between carbonate porosity and thermal maturity: an approach to regional porosity prediction

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

Schmoker, J.W.

1984-11-01

Data indicate that porosity loss in subsurface carbonate rocks can be empirically represented by the power function, theta = a (TTI) /SUP b/ , where theta is regional porosity, TTI is Lopatin's time-temperature index of thermal maturity, the exponent, b, equals approximately -0.372, and the multiplier, a, is constant for a given data population but varies by an order of magnitude overall. Implications include the following. 1. The decrease of carbonate porosity by burial diagenesis is a maturation process depending exponentially on temperature and linearly on time. 2. The exponent, b, is essentially independent of the rock matrix, and maymore » reflect rate-limiting processes of diffusive transport. 3. The multiplying coefficient, a, incorporates the net effect on porosity of all depositional and diagenetic parameters. Within constraints, carbonate-porosity prediction appears possible on a regional measurement scale as a function of thermal maturity. Estimation of carbonate porosity at the time of hydrocarbon generation, migration, or trapping also appears possible.« less

The revised APTA code of ethics for the physical therapist and standards of ethical conduct for the physical therapist assistant: theory, purpose, process, and significance.

PubMed

Swisher, Laura Lee; Hiller, Peggy

2010-05-01

In June 2009, the House of Delegates (HOD) of the American Physical Therapy Association (APTA) passed a major revision of the APTA Code of Ethics for physical therapists and the Standards of Ethical Conduct for the Physical Therapist Assistant. The revised documents will be effective July 1, 2010. The purposes of this article are: (1) to provide a historical, professional, and theoretical context for this important revision; (2) to describe the 4-year revision process; (3) to examine major features of the documents; and (4) to discuss the significance of the revisions from the perspective of the maturation of physical therapy as a doctoring profession. PROCESS OF REVISION: The process for revision is delineated within the context of history and the Bylaws of APTA. FORMAT, STRUCTURE, AND CONTENT OF REVISED CORE ETHICS DOCUMENTS: The revised documents represent a significant change in format, level of detail, and scope of application. Previous APTA Codes of Ethics and Standards of Ethical Conduct for the Physical Therapist Assistant have delineated very broad general principles, with specific obligations spelled out in the Ethics and Judicial Committee's Guide for Professional Conduct and Guide for Conduct of the Physical Therapist Assistant. In contrast to the current documents, the revised documents address all 5 roles of the physical therapist, delineate ethical obligations in organizational and business contexts, and align with the tenets of Vision 2020. The significance of this revision is discussed within historical parameters, the implications for physical therapists and physical therapist assistants, the maturation of the profession, societal accountability and moral community, potential regulatory implications, and the inclusive and deliberative process of moral dialogue by which changes were developed, revised, and approved.

Alterations in dendritic cell function in aged mice: potential implications for immunotherapy design.

PubMed

Paula, Carine; Motta, Adriana; Schmitz, Carla; Nunes, Claudia P; Souza, Ana Paula; Bonorino, Cristina

2009-02-01

It is known that immune system functions decrease with age, and that adaptive immune responses, especially CD4+ T cell function, seem to be the main affected point in immunity with aging. Dendritic cells (DC) are the major antigen presenting cell (APC), and at least part of the defects observed in adaptive immunity of aged individuals could be due to diminished potential of bone marrow to generate new DC, or defects in DC function. In this study, we investigated if the ability of aged bone marrow (BM) to generate new DC in vitro, as well as aged BM-derived DC responses to lypopolysaccharide (LPS). Because DC are important tools in newly developing anti-tumor therapies, we also studied the ability of aged DC to phagocytose and present antigen from necrotic tumor cells. We found that aged BM generated fewer DC in vitro compared to young BM. While LPS-induced DC maturation is reduced in DC of aged mice, a high TNF-alpha production is observed in aged DC even without LPS stimulation. While phagocytosis of tumor cells is not affected by age, and DC derived from aged BM show a higher TNF-alpha production in response to phagocytosis, presentation of tumor antigens was decreased in aged DC. Because class II upregulation in response to phagocytosis was similar between aged and young DC, this could indicate an age associated processing defect in the exogenous pathway. These findings suggest that age of BM used to generate DC does not impair their phagocytic ability or TNF-alpha production, however leads to a decreased yield in mature DC, reduced response to LPS, and diminished antigen processing/presentation potential. Our results are relevant to optimization DC-based vaccine design for aged populations.

Commentary.

ERIC Educational Resources Information Center

Helwig, C. C.

1993-01-01

Comments on Moshman's article in this issue concerning questions about adolescent reasoning, maturity, and rights to intellectual and other freedoms. Discusses the implications for public schools, government, and parents. Suggests that the evidence needed for a full rebuttal of the adolescent-as-child view involves demonstrated adultlike…

Coping and Adaptation in Adolescence.

ERIC Educational Resources Information Center

Newman, Barbara N.

1979-01-01

Describes the results of four longitudinal studies of adolescent development that focus on coping styles, maturity of defenses, adaptation to school environments, and predictors of educational and occupational attainment. Implications are discussed in terms of linking adolescence with other phases of development. (Author/SS)

Critical overview of applications of genetic testing in sport talent identification.

PubMed

Roth, Stephen M

2012-12-01

Talent identification for future sport performance is of paramount interest for many groups given the challenges of finding and costs of training potential elite athletes. Because genetic factors have been implicated in many performance- related traits (strength, endurance, etc.), a natural inclination is to consider the addition of genetic testing to talent identification programs. While the importance of genetic factors to sport performance is generally not disputed, whether genetic testing can positively inform talent identification is less certain. The present paper addresses the science behind the genetic tests that are now commercially available (some under patent protection) and aimed at predicting future sport performance potential. Also discussed are the challenging ethical issues that emerge from the availability of these tests. The potential negative consequences associated with genetic testing of young athletes will very likely outweigh any positive benefit for sport performance prediction at least for the next several years. The paper ends by exploring the future possibilities for genetic testing as the science of genomics in sport matures over the coming decade(s).

Lifespan oxytocin signaling: Maturation, flexibility, and stability in newborn, adolescent, and aged brain.

PubMed

Sannino, Sara; Chini, Bice; Grinevich, Valery

2017-02-01

The hypothalamic neuropeptide oxytocin (OT) is a forefront molecule among neuropeptides due to its pronounced prosocial effects and its potential use in socioemotional deficits that characterize the most prevalent neurodevelopmental and psychiatric disorders (autism spectrum disorders and schizophrenia). The effects of OT have been studied in young and adult subjects (either animals or humans), while the complete lifespan trajectories of OT system development and activity have been far less investigated. In this (mini) review, we will primarily focus on three temporal distinct periods of life-early postnatal period, puberty/adolescence, and elderly. We selected the neonatal period to discuss the role of OT in the switch of GABA action from excitation to inhibition in the first days after birth (in rodents), with potential implications in neurodevelopmental disorders. In the puberty/adolescence period, we consider of particular relevance the OT impact on drug consumption, stress and aggression. Finally, OT could potentially contribute to maintain social capacities of aged people and to ameliorate socially emotional deficits and symptoms of neurodegenerative diseases. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 158-168, 2017. © 2016 Wiley Periodicals, Inc.

Bitumen II from the Paleoproterozoic Here’s Your Chance Pb/Zn/Ag deposit: Implications for the analysis of depositional environment and thermal maturity of hydrothermally-altered sediments

NASA Astrophysics Data System (ADS)

Holman, Alex I.; Grice, Kliti; Jaraula, Caroline M. B.; Schimmelmann, Arndt

2014-08-01

The formation of sedimentary exhalative (SEDEX) Pb/Zn deposits is linked to ocean euxinia, but recent evidence suggests that ferruginous conditions may have dominated the deep ocean during the Middle Proterozoic, a maximum period for SEDEX distribution. Biomarkers of sulfate-reducing and sulfide-oxidising bacteria are valuable indicators of euxinic conditions in such settings. Organic matter (OM) from SEDEX deposits is often affected by alteration and/or migration, but OM entrapped within the kerogen/mineral matrix (Bitumen II) may be less affected than the freely-extractable OM (Bitumen I). We analysed Bitumen II from the Paleoproterozoic Here’s Your Chance (HYC) Pb/Zn/Ag deposit to find evidence of euxinic conditions in the depositional environment. n-Alkane distributions in Bitumen II are markedly distinct from previously-reported Bitumen I. Bitumen II contains long-chain n-alkanes (up to C36 or C38) and a strong even-over-odd distribution in a number of samples, which are 4‰ to 7‰ depleted in 13C compared to n-alkanes in Bitumen I and verified as indigenous by comparison with δ13C of isolated kerogen. These features are interpreted as evidence of sulfate-reducing and sulfide-oxidising bacteria, confirming that HYC was deposited under euxinic conditions. Bitumen II has the potential to reveal information from OM that is degraded and/or overprinted in Bitumen I. Commonly-used methylphenanthrene maturity ratios give conflicting information as to the relative maturity of Bitumens I and II. Bitumen I contains a far higher proportion of methylated phenanthrenes than Bitumen II. As Bitumen II is sequestered within the kerogen/mineral matrix it may have restricted access to the ‘methyl pool’ of organic compounds that can donate methyl groups to aromatic hydrocarbons. Parameters that include both phenanthrene and methylphenanthrenes do not appear suitable to compare the maturity of Bitumens I and II; hence there is no clear evidence that Bitumen II is of lower thermal maturity than Bitumen I.

Importance of β-defensins in sperm function.

PubMed

Dorin, Julia R; Barratt, Christopher L R

2014-09-01

Recent work in humans and mouse has confirmed the involvement of the host defence β-defensin peptides in male fertility. We discuss here the work that has implicated β-defensins in sperm function including the identification of the epididymis as the predominant site of expression of the peptides and the in vivo consequences of mutation and deletion. The potential dual role of these peptides in the regulation of infection and control of sperm maturation is compelling and may combine their antimicrobial activity with the ability of these molecules to interact with cell membrane receptors and modulate ion transport. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

FKBP51 and FKBP52 in Signaling and Disease

PubMed Central

Storer, Cheryl L.; Dickey, Chad A.; Galigniana, Mario D.; Rein, Theo; Cox, Marc B.

2011-01-01

FKBP51 and FKBP52 are diverse regulators of steroid hormone receptor signaling including regulation of receptor maturation, hormone binding, and nuclear translocation. Although structurally similar, they are functionally divergent, which is largely attributed to differences in the FK1 domain and the proline-rich loop. FKBP51 and FKBP52 have emerged as likely contributors to a variety of hormone-dependent diseases including stress-related diseases, immune function, reproductive functions and a variety of cancers. In addition, recent studies have implicated FKBP51 and FKBP52 in Alzheimer’s disease and other protein aggregation disorders. This review summarizes our current understanding of FKBP51 and FKBP52 interactions within the receptor-chaperone complex, their contributions to health and disease, and their potential as therapeutic targets for the treatment of these diseases. PMID:21889356

Garcinia xanthochymus Benzophenones Promote Hyphal Apoptosis and Potentiate Activity of Fluconazole against Candida albicans Biofilms

PubMed Central

Jackson, Desmond N.; Yang, Lin; Wu, ShiBiao; Kennelly, Edward J.

2015-01-01

Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia xanthochymus fruits, showed multiple activities against Candida albicans biofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic, with MICs of 1 to 3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatidyl serine and DNA fragmentation, as evidenced by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms, xanthochymol and garcinol caused the death of biofilm hyphae, with 50% effective concentrations (EC50s) of 30 to 50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50 from >1,024 μg/ml to 13 μg/ml. Therefore, xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis. PMID:26195512

Variation in carbon isotope discrimination in Cleistogenes squarrosa (Trin.) Keng: patterns and drivers at tiller, local, catchment, and regional scales

PubMed Central

Yang, Hao; Auerswald, Karl; Bai, Yongfei; Wittmer, Maximilian H. O. M.; Schnyder, Hans

2011-01-01

Understanding the patterns and drivers of carbon isotope discrimination in C4 species is critical for predicting the effects of global change on C3/C4 ratio of plant community and consequently on ecosystem functioning and services. Cleistogenes squarrosa (Trin.) Keng is a dominant C4 perennial bunchgrass of arid and semi-arid ecosystems across the Mongolian plateau of the Eurasian steppe. Its carbon isotope discrimination (13Δ) during photosynthesis is relatively large among C4 species and it is variable. Here the 13Δ of C. squarrosa and its potential drivers at a nested set of scales were examined. Within cohorts of tillers, 13Δ of leaves increased from 5.1‰ to 8.1‰ from old to young leaves. At the local scale, 13Δ of mature leaves varied from 5.8‰ to 8.4‰, increasing with decreasing grazing intensity. At the catchment scale, 13Δ of mature leaves varied from 6.2‰ to 8.5‰ and increased with topsoil silt content. At the regional scale, 13Δ of mature leaves varied from 5.5‰ to 8.9‰, increasing with growing-season precipitation. At all scales, 13Δ decreased with increasing leaf nitrogen content (Nleaf). Nleaf was positively correlated with grazing intensity and leaf position along tillers, but negatively correlated with precipitation. The presence of the correlations across a range of different environmental contexts strongly implicates Nleaf as a major driver of 13Δ in C. squarrosa and, possibly, other C4 species. PMID:21527626

Brain responses to audiovisual speech mismatch in infants are associated with individual differences in looking behaviour.

PubMed

Kushnerenko, Elena; Tomalski, Przemyslaw; Ballieux, Haiko; Ribeiro, Helena; Potton, Anita; Axelsson, Emma L; Murphy, Elizabeth; Moore, Derek G

2013-11-01

Research on audiovisual speech integration has reported high levels of individual variability, especially among young infants. In the present study we tested the hypothesis that this variability results from individual differences in the maturation of audiovisual speech processing during infancy. A developmental shift in selective attention to audiovisual speech has been demonstrated between 6 and 9 months with an increase in the time spent looking to articulating mouths as compared to eyes (Lewkowicz & Hansen-Tift. (2012) Proc. Natl Acad. Sci. USA, 109, 1431-1436; Tomalski et al. (2012) Eur. J. Dev. Psychol., 1-14). In the present study we tested whether these changes in behavioural maturational level are associated with differences in brain responses to audiovisual speech across this age range. We measured high-density event-related potentials (ERPs) in response to videos of audiovisually matching and mismatched syllables /ba/ and /ga/, and subsequently examined visual scanning of the same stimuli with eye-tracking. There were no clear age-specific changes in ERPs, but the amplitude of audiovisual mismatch response (AVMMR) to the combination of visual /ba/ and auditory /ga/ was strongly negatively associated with looking time to the mouth in the same condition. These results have significant implications for our understanding of individual differences in neural signatures of audiovisual speech processing in infants, suggesting that they are not strictly related to chronological age but instead associated with the maturation of looking behaviour, and develop at individual rates in the second half of the first year of life. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Serial profiles of electrostatic potential in five New Mexico thunderstorms

NASA Astrophysics Data System (ADS)

Stolzenburg, Maribeth; Marshall, Thomas C.

2008-07-01

Profiles of electric potential (V) integrated from balloon-borne electric field (E) measurements are used to investigate the electrical evolution of thunderstorms over the mountains in central New Mexico. With sequential soundings through multiple storms, the time skew associated with obtaining V from a noninstantaneous sounding is also studied. The data show that a basic V profile, with a maximum above a minimum, forms in the early stage of the storm and is maintained throughout its mature stage. Series of soundings from individual storms show only a gradual evolution in the V profile from the early through the mature stage, as the extrema descend in altitude and become shallower and vertically closer together. More evolution occurs in the late stage, when the shape of the V profile reverses to have a minimum above a maximum. The 17 V(z) profiles from the mature stage of five different storms are also very similar in overall shape, suggesting that the basic shape is not significantly affected by differences in lightning flash rate among these storms. The findings indicate that the potential profile during a typical sounding in the mature stage is relatively stable, and the overall shape of the mature stage V profile does not change markedly on the time scale of a particular balloon sounding (10-30 min) through New Mexico mountain storms. Thus time-skew problems in the V profiles are minor during a storm's mature stage.

Medical student burnout: interdisciplinary exploration and analysis.

PubMed

Jennings, M L

2009-12-01

Burnout--a stress-related syndrome characterized by exhaustion, depersonalization, and a diminished sense of accomplishment--is a common phenomenon among medical students with significant potential consequences for student health, professionalism, and patient care. This essay proposes that the epidemic of medical student burnout can be attributed to a technocratic paradigm that fails to value medical students as persons with human needs and limitations. After briefly reviewing the literature on medical student burnout, the author uses two theories to elucidate potential causes: unsatisfactory aspects of the learning environment and a feeling one's efforts are meaningless or irrelevant. Cultural factors also facilitate burnout in medical students immersed in a clinical environment that cultivates excessive detachment from patient and self, impairing self-care, damaging a sense of self, and impeding the development of a mature, well-integrated professional identity. The ethical implications of medical student burnout are also addressed. Finally, this paper suggests possible preventive and remediative strategies such as optimizing the learning environment as well as narrative approaches that promise enhancement of both individual and institutional well-being.

Small body size in an insect shifts development, prior to adult eclosion, towards early reproduction

PubMed Central

Thorne, Ashley D; Pexton, John J; Dytham, Calvin; Mayhew, Peter J

2006-01-01

Life-history theory has suggested that individual body size can strongly affect the allocation of resources to reproduction and away from other traits such as survival. In many insects, adults eclose with a proportion of their potential lifetime egg production that is already mature (the ovigeny index). We establish for the solitary parasitoid wasp Aphaereta genevensis that the ovigeny index decreases with adult body size, despite both initial egg load and potential lifetime fecundity increasing with body size. This outcome is predicted by adaptive models and is the first unequivocal intraspecific demonstration. Evidence suggests that a high ovigeny index carries a cost of reduced longevity in insects. Our results therefore contribute to the emerging evidence that small body size can favour a developmental shift in juveniles that favours early reproduction, but which has adverse late-life consequences. These findings are likely to have important implications for developmental biologists and population biologists. PMID:16600887

Helminth Genomics: The Implications for Human Health

PubMed Central

Brindley, Paul J.; Mitreva, Makedonka; Ghedin, Elodie; Lustigman, Sara

2009-01-01

More than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings. PMID:19855829

Heat stress and antioxidant enzyme activity in bubaline ( Bubalus bubalis) oocytes during in vitro maturation

NASA Astrophysics Data System (ADS)

Waiz, Syma Ashraf; Raies-ul-Haq, Mohammad; Dhanda, Suman; Kumar, Anil; Goud, T. Sridhar; Chauhan, M. S.; Upadhyay, R. C.

2016-09-01

In vitro environments like heat stress usually increase the production of reactive oxygen species in bubaline oocytes which have been implicated as one of the major causes for reduced developmental competence. Oocytes during meiotic maturation are sensitive to oxidative stress, and heat stress accelerates cellular metabolism, resulting in the higher production of free radicals. Therefore, the aim of present work was to assess the impact of heat stress during meiotic maturation on bubaline cumulus-oocyte complexes (COC), denuded oocytes (DO), and cumulus cell mass in terms of their oxidative status. Accordingly, for control group, COC were matured at 38.5 °C for complete 24 h of meiotic maturation and heat stress of 40.5 and 41.5 °C was applied to COC during the first 12 h of maturation and then moved to 38.5 °C for rest of the 12 h. In another group, COC after maturation were denuded from the surrounding cumulus cells by manual pipetting. Results indicated that the production of reactive oxygen species (ROS), lipid peroxides, and nitric oxide (NO) was significantly ( P < 0.05) higher in the oocytes subjected to heat stress (40.5 and 41.5 °C) during meiotic maturation compared to the oocytes matured under standard in vitro culture conditions (38.5 °C). Also, the antioxidant enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were significantly ( P < 0.05) increased in all the treatment groups compared to the control group. Therefore, the present study clearly establishes that heat stress ensues oxidative stress in bubaline oocytes which triggers the induction of antioxidant enzymatic defense system for scavenging the ROS.

Naturally designed strong, tough and renewable biocomposites

USDA-ARS?s Scientific Manuscript database

The discovery that natural fiber filled materials have increased sound absorbency has led to their use in various automotive applications. However, the impact on structural implications of these natural fibers has not yet been investigated. Plant maturity may influence cell stiffness, which may in...

45 CFR Appendix A to Part 1211 - Standards for Examiners

Code of Federal Regulations, 2011 CFR

2011-10-01

..., professional, investigative, or technical work which has demonstrated the possession of: (i) The personal... problems and apply mature judgment in assessing the practical implications of alternative solutions to those problems; Interpret and apply regulations and other complex written material; Communicate...

45 CFR Appendix A to Part 1211 - Standards for Examiners

Code of Federal Regulations, 2010 CFR

2010-10-01

..., professional, investigative, or technical work which has demonstrated the possession of: (i) The personal... problems and apply mature judgment in assessing the practical implications of alternative solutions to those problems; Interpret and apply regulations and other complex written material; Communicate...

Forced cell cycle exit and modulation of GABAA, CREB, and GSK3β signaling promote functional maturation of induced pluripotent stem cell-derived neurons.

PubMed

Telezhkin, Vsevolod; Schnell, Christian; Yarova, Polina; Yung, Sun; Cope, Emma; Hughes, Alis; Thompson, Belinda A; Sanders, Philip; Geater, Charlene; Hancock, Jane M; Joy, Shona; Badder, Luned; Connor-Robson, Natalie; Comella, Andrea; Straccia, Marco; Bombau, Georgina; Brown, Jon T; Canals, Josep M; Randall, Andrew D; Allen, Nicholas D; Kemp, Paul J

2016-04-01

Although numerous protocols have been developed for differentiation of neurons from a variety of pluripotent stem cells, most have concentrated on being able to specify effectively appropriate neuronal subtypes and few have been designed to enhance or accelerate functional maturity. Of those that have, most employ time courses of functional maturation that are rather protracted, and none have fully characterized all aspects of neuronal function, from spontaneous action potential generation through to postsynaptic receptor maturation. Here, we describe a simple protocol that employs the sequential addition of just two supplemented media that have been formulated to separate the two key phases of neural differentiation, the neurogenesis and synaptogenesis, each characterized by different signaling requirements. Employing these media, this new protocol synchronized neurogenesis and enhanced the rate of maturation of pluripotent stem cell-derived neural precursors. Neurons differentiated using this protocol exhibited large cell capacitance with relatively hyperpolarized resting membrane potentials; moreover, they exhibited augmented: 1) spontaneous electrical activity; 2) regenerative induced action potential train activity; 3) Na(+) current availability, and 4) synaptic currents. This was accomplished by rapid and uniform development of a mature, inhibitory GABAAreceptor phenotype that was demonstrated by Ca(2+) imaging and the ability of GABAAreceptor blockers to evoke seizurogenic network activity in multielectrode array recordings. Furthermore, since this protocol can exploit expanded and frozen prepatterned neural progenitors to deliver mature neurons within 21 days, it is both scalable and transferable to high-throughput platforms for the use in functional screens. Copyright © 2016 the American Physiological Society.

Expression, Localization of SUMO-1, and Analyses of Potential SUMOylated Proteins in Bubalus bubalis Spermatozoa

PubMed Central

Brohi, Rahim Dad; Wang, Li; Hassine, Najla Ben; Cao, Jing; Talpur, Hira Sajjad; Wu, Di; Huang, Chun-Jie; Rehman, Zia-Ur; Bhattarai, Dinesh; Huo, Li-Jun

2017-01-01

Mature spermatozoa have highly condensed DNA that is essentially silent both transcriptionally and translationally. Therefore, post translational modifications are very important for regulating sperm motility, morphology, and for male fertility in general. Protein sumoylation was recently demonstrated in human and rodent spermatozoa, with potential consequences for sperm motility and DNA integrity. We examined the expression and localization of small ubiquitin-related modifier-1 (SUMO-1) in the sperm of water buffalo (Bubalus bubalis) using immunofluorescence analysis. We confirmed the expression of SUMO-1 in the acrosome. We further found that SUMO-1 was lost if the acrosome reaction was induced by calcium ionophore A23187. Proteins modified or conjugated by SUMO-1 in water buffalo sperm were pulled down and analyzed by mass spectrometry. Sixty proteins were identified, including proteins important for sperm morphology and motility, such as relaxin receptors and cytoskeletal proteins, including tubulin chains, actins, and dyneins. Forty-six proteins were predicted as potential sumoylation targets. The expression of SUMO-1 in the acrosome region of water buffalo sperm and the identification of potentially SUMOylated proteins important for sperm function implicates sumoylation as a crucial PTM related to sperm function. PMID:28659810

Deciphering the interplay among genotype, maturity stage and low-temperature storage on phytochemical composition and transcript levels of enzymatic antioxidants in Prunus persica fruit.

PubMed

Manganaris, George A; Drogoudi, Pavlina; Goulas, Vlasios; Tanou, Georgia; Georgiadou, Egli C; Pantelidis, George E; Paschalidis, Konstantinos A; Fotopoulos, Vasileios; Manganaris, Athanasios

2017-10-01

The aim of this study was to understand the antioxidant metabolic changes of peach (cvs. 'Royal Glory', 'Red Haven' and 'Sun Cloud') and nectarine fruits (cv. 'Big Top') exposed to different combinations of low-temperature storage (0, 2, 4 weeks storage at 0 °C, 90% R.H.) and additional ripening at room temperature (1, 3 and 5 d, shelf life, 20 °C) with an array of analytical, biochemical and molecular approaches. Initially, harvested fruit of the examined cultivars were segregated non-destructively at advanced and less pronounced maturity stages and qualitative traits, physiological parameters, phytochemical composition and antioxidant capacity were determined. 'Big Top' and 'Royal Glory' fruits were characterized by slower softening rate and less pronounced ripening-related alterations. The coupling of HPLC fingerprints, consisted of 7 phenolic compounds (chlorogenic, neochlorogenic acid, catechin, epicatechin, rutin, quecetin-3-O-glucoside, procyanidin B1) and spectrophotometric methods disclosed a great impact of genotype on peach bioactive composition, with 'Sun Cloud' generally displaying the highest contents. Maturity stage at harvest did not seem to affect fruit phenolic composition and no general guidelines for the impact of cold storage and shelf-life on individual phenolic compounds can be extrapolated. Subsequently, fruit of less pronounced maturity at harvest were used for further molecular analysis. 'Sun Cloud' was proven efficient in protecting plasmid pBR322 DNA against ROO attack throughout the experimental period and against HO attack after 2 and 4 weeks of cold storage. Interestingly, a general down-regulation of key genes implicated in the antioxidant apparatus with the prolongation of storage period was recorded; this was more evident for CAT, cAPX, Cu/ZnSOD2, perAPX3 and GPX8 genes. Higher antioxidant capacity of 'Sun Cloud' fruit could potentially be linked with compounds other than enzymatic antioxidants that further regulate peach fruit ripening. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Possible secondary population-level effects of selective harvest of adult male muskoxen.

PubMed

Schmidt, Joshua H; Gorn, Tony S

2013-01-01

Selective harvest regimes are often focused on males resulting in skewed sex-ratios, and for many ungulate species this strategy is sustainable. However, muskoxen (Ovibos moschatus) are very social and mature bulls (≥4 years old), particularly prime-age bulls (6-10 years old), play important roles in predator defense and recruitment. A year-round social structure incorporating large males into mixed-sex groups could make this species more susceptible to the effects of selective harvest if population composition and sex-ratios influence overall survival and reproductive success. Using detailed data collected on the muskox population occupying the Seward Peninsula, Alaska during 2002-2012, we formulated the hypothesis that the selective harvest of mature bulls may be related to documented changes in population composition and growth rates in this species. In addition, we reviewed existing published information from two other populations in Alaska, the Cape Thompson and Northeastern populations, to compare population growth rates among the three areas under differential harvest rates relative to our hypothesis. We found that on the Seward Peninsula, mature bull:adult cow ratios declined 4-12%/year and short-yearling:adult cow ratios (i.e., recruitment) declined 8-9%/year in the most heavily harvested areas. Growth rates in all 3 populations decreased disproportionately after increases in the number of bulls harvested, and calf:cow ratios declined in the Northeastern population as harvest increased. While lack of appropriate data prevented us from excluding other potential causes such as density dependent effects and changes in predator densities, our results did align with our hypothesis, suggesting that in the interest of conservation, harvest of mature males should be restricted until causal factors can be more definitively identified. If confirmed by additional research, our findings would have important implications for harvest management and conservation of muskoxen and other ungulate species with similar life-histories.

PA6 Stromal Cell Co-Culture Enhances SH-SY5Y and VSC4.1 Neuroblastoma Differentiation to Mature Phenotypes

PubMed Central

Ferguson, Ross; Subramanian, Vasanta

2016-01-01

Neuroblastoma cell lines such as SH-SY5Y have been used for modelling neurodegenerative diseases and for studying basic mechanisms in neuroscience. Since neuroblastoma cells proliferate and generally do not express markers of mature or functional neurons, we exploited a co-culture system with the stromal cell line PA6 to better induce differentiation to a more physiologically relevant status. We found that co-culture of the neuroblastoma cell lines in the presence of neural inducers such retinoic acid was able to generate a high proportion of quiescent neurons with very long neurites expressing differentiation markers. The co-culture system additionally cuts short the time taken to produce a more mature phenotype. We also show the application of this system to study proteins implicated in motor neuron disease. PMID:27391595

PA6 Stromal Cell Co-Culture Enhances SH-SY5Y and VSC4.1 Neuroblastoma Differentiation to Mature Phenotypes.

PubMed

Ferguson, Ross; Subramanian, Vasanta

2016-01-01

Neuroblastoma cell lines such as SH-SY5Y have been used for modelling neurodegenerative diseases and for studying basic mechanisms in neuroscience. Since neuroblastoma cells proliferate and generally do not express markers of mature or functional neurons, we exploited a co-culture system with the stromal cell line PA6 to better induce differentiation to a more physiologically relevant status. We found that co-culture of the neuroblastoma cell lines in the presence of neural inducers such retinoic acid was able to generate a high proportion of quiescent neurons with very long neurites expressing differentiation markers. The co-culture system additionally cuts short the time taken to produce a more mature phenotype. We also show the application of this system to study proteins implicated in motor neuron disease.

Spacecraft Complexity Subfactors and Implications on Future Cost Growth

NASA Technical Reports Server (NTRS)

Leising, Charles J.; Wessen, Randii; Ellyin, Ray; Rosenberg, Leigh; Leising, Adam

2013-01-01

During the last ten years the Jet Propulsion Laboratory has used a set of cost-risk subfactors to independently estimate the magnitude of development risks that may not be covered in the high level cost models employed during early concept development. Within the last several years the Laboratory has also developed a scale of Concept Maturity Levels with associated criteria to quantitatively assess a concept's maturity. This latter effort has been helpful in determining whether a concept is mature enough for accurate costing but it does not provide any quantitative estimate of cost risk. Unfortunately today's missions are significantly more complex than when the original cost-risk subfactors were first formulated. Risks associated with complex missions are not being adequately evaluated and future cost growth is being underestimated. The risk subfactor process needed to be updated.

CX3CR1-dependent recruitment of mature NK cells into the central nervous system contributes to control autoimmune neuroinflammation.

PubMed

Hertwig, Laura; Hamann, Isabell; Romero-Suarez, Silvina; Millward, Jason M; Pietrek, Rebekka; Chanvillard, Coralie; Stuis, Hanna; Pollok, Karolin; Ransohoff, Richard M; Cardona, Astrid E; Infante-Duarte, Carmen

2016-08-01

Fractalkine receptor (CX3CR1)-deficient mice develop very severe experimental autoimmune encephalomyelitis (EAE), associated with impaired NK cell recruitment into the CNS. Yet, the precise implications of NK cells in autoimmune neuroinflammation remain elusive. Here, we investigated the pattern of NK cell mobilization and the contribution of CX3CR1 to NK cell dynamics in the EAE. We show that in both wild-type and CX3CR1-deficient EAE mice, NK cells are mobilized from the periphery and accumulate in the inflamed CNS. However, in CX3CR1-deficient mice, the infiltrated NK cells displayed an immature phenotype contrasting with the mature infiltrates in WT mice. This shift in the immature/mature CNS ratio contributes to EAE exacerbation in CX3CR1-deficient mice, since transfer of mature WT NK cells prior to immunization exerted a protective effect and normalized the CNS NK cell ratio. Moreover, mature CD11b(+) NK cells show higher degranulation in the presence of autoreactive 2D2 transgenic CD4(+) T cells and kill these autoreactive cells more efficiently than the immature CD11b(-) fraction. Together, these data suggest a protective role of mature NK cells in EAE, possibly through direct modulation of T cells inside the CNS, and demonstrate that mature and immature NK cells are recruited into the CNS by distinct chemotactic signals. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Processing of the Synaptic Cell Adhesion Molecule Neurexin-3β by Alzheimer Disease α- and γ-Secretases*

PubMed Central

Bot, Nathalie; Schweizer, Claude; Ben Halima, Saoussen; Fraering, Patrick C.

2011-01-01

Neurexins (NRXNs) are synaptic cell adhesion molecules having essential roles in the assembly and maturation of synapses into fully functional units. Immunocytochemical and electrophysiological studies have shown that specific binding across the synaptic cleft of the ectodomains of presynaptic NRXNs and postsynaptic neuroligins have the potential to bidirectionally coordinate and trigger synapse formation. Moreover, in vivo studies as well as genome-wide association studies pointed out implication of NRXNs in the pathogenesis of cognitive disorders including autism spectrum disorders and different types of addictions including opioid and alcohol dependences, suggesting an important role in synaptic function. Despite extensive investigations, the mechanisms by which NRXNs modulate the properties of synapses remain largely unknown. We report here that α- and γ-secretases can sequentially process NRXN3β, leading to the formation of two final products, an ∼80-kDa N-terminal extracellular domain of Neurexin-3β (sNRXN3β) and an ∼12-kDa C-terminal intracellular NRXN3β domain (NRXN3β-ICD), both of them being potentially implicated in the regulation of NRXNs and neuroligins functions at the synapses or in yet unidentified signal transduction pathways. We further report that this processing is altered by several PS1 mutations in the catalytic subunit of the γ-secretase that cause early-onset familial Alzheimer disease. PMID:21084300

Inhaled Vitamin D: A Novel Strategy to Enhance Neonatal Lung Maturation.

PubMed

Taylor, Sneha K; Sakurai, Reiko; Sakurai, Tokusho; Rehan, Virender K

2016-12-01

The physiologic vitamin D (VD), 1α,25(OH) 2 D 3 (1,25D) is a local paracrine/autocrine effecter of fetal lung maturation. By stimulating alveolar type II cell and lipofibroblast proliferation and differentiation, parenterally administered 1,25D has been shown to enhance neonatal lung maturation; but due to the potential systemic side effects of the parenteral route, the translational value of these findings might be limited. To minimize the possibility of systemic toxicity, we examined the effects of VD on neonatal lung maturation, when delivered directly to lungs via nebulization. One-day-old rat pups were administered three different doses of 1,25D and its physiologic precursor 25(OH)D (25D), or the diluent, via nebulization daily for 14 days. Pups were sacrificed for lung, kidneys, and blood collection to determine markers of lung maturation, and serum 25D and calcium levels. Compared to controls, nebulized 25D and 1,25D enhanced lung maturation as evidenced by the increased expression of markers of alveolar epithelial (SP-B, leptin receptor), mesenchymal (PPARγ, C/EBPα), and endothelial (VEGF, FLK-1) differentiation, surfactant phospholipid synthesis, and lung morphology without any significant increases in serum 25D and calcium levels. Inhaled VD is a potentially safe and effective novel strategy to enhance neonatal lung maturation.

Top 10 research questions related to growth and maturation of relevance to physical activity, performance, and fitness.

PubMed

Malina, Robert M

2014-06-01

Growth, maturation, and development dominate the daily lives of children and adolescents for approximately the first 2 decades of life. Growth and maturation are biological processes, while development is largely a behavioral process. The 3 processes occur simultaneously and interact. They can be influenced by physical activity and also can influence activity, performance, and fitness. Allowing for these potential interactions, 10 questions on growth and maturation that have relevance to physical activity, performance, and fitness are presented. The questions are not mutually exclusive and address several broadly defined topical areas: exercise and growth, body weight status (body mass index, adiposity rebound, "unhealthy weight gain"), movement proficiency (hypothesized barrier, role in obesity), individual differences, tracking, maturity-associated variation in performance, and corresponding variation in physical activity. Central to the discussion of each is the need for a biocultural approach recognizing the interactions of biology and behavior as potential influences on the variables of interest.

Social induction of maturation and sex determination in a coral reef fish.

PubMed Central

Hobbs, Jean-Paul A.; Munday, Philip L.; Jones, Geoffrey P.

2004-01-01

Labile maturation and sex determination should be advantageous where the probability of finding a mating partner is unpredictable. Here we tested the hypothesis that the presence of a potential mating partner induces maturation and sex determination in a coral-dwelling fish, Gobiodon erythrospilus. In natural populations at Lizard Island (Great Barrier Reef), single individuals were less likely to be mature than paired individuals and they matured at a larger size, indicating plasticity in the timing of maturation. By manipulating group structure we demonstrated that both the timing of maturation and the sex of maturing individuals are socially controlled. Single juveniles did not mature, but maturation was rapidly induced by the presence of an adult partner. In addition, sex determination was found to be labile, with juveniles maturing into the opposite sex of the partner encountered. To our knowledge, this is the first experimental demonstration of social induction of maturation in conjunction with labile sex determination at maturation in vertebrates. This flexibility enables individuals to maximize their reproductive success in an environment where the timing of mate acquisition and the sex of their future partner are unpredictable. PMID:15475329

Education for Critical Moral Consciousness

ERIC Educational Resources Information Center

Mustakova-Possardt, Elena

2004-01-01

This paper proposes a lifespan developmental model of critical moral consciousness and examines its implications for education in childhood, adolescence and adulthood. Mature moral consciousness, central to negotiating the challenges of the 21st century, is characterized by a deepening lifelong integration of moral motivation, agency and critical…

The impact of perinatal stress on the functional maturation of prefronto-cortical synaptic circuits: implications for the pathophysiology of ADHD?

PubMed

Bock, Jörg; Braun, Katharina

2011-01-01

Enriched as well as impoverished or adverse perinatal environment plays an essential role in the development and refinement of neuronal pathways, which are the neural substrate of intellectual capacity and socioemotional competence. Perinatal experience and learning events continuously interact with the adaptive shaping of excitatory, inhibitory, and neuromodulatory synaptic as well as the endocrine stress systems, including the neuronal corticotropin-releasing factor (CRF) pathways. Adverse environments, such as stress and emotional deprivation can not only delay experience-dependent maturation of these pathways, but also induce permanent changes in prefronto-cortical wiring patterns. We assume that such dysfunctional connections are the neuronal basis for the development of psychosocially induced mental disorders during later life. The aim of this review is to focus on the impact of perinatal stress on the neuronal and synaptic reorganization during brain development and possible implications for the etiology and therapy of mental disorders such as ADHD. Copyright © 2011 Elsevier B.V. All rights reserved.

Metabolic Maturation of the Human Brain From Birth Through Adolescence: Insights From In Vivo Magnetic Resonance Spectroscopy

PubMed Central

Blüml, Stefan; Wisnowski, Jessica L.; Nelson, Marvin D.; Paquette, Lisa; Gilles, Floyd H.; Kinney, Hannah C.; Panigrahy, Ashok

2013-01-01

Between birth and late adolescence, the human brain undergoes exponential maturational changes. Using in vivo magnetic resonance spectroscopy, we determined the developmental profile for 6 metabolites in 5 distinct brain regions based on spectra from 309 children from 0 to 18 years of age. The concentrations of N-acetyl-aspartate (an indicator for adult-type neurons and axons), creatine (energy metabolite), and glutamate (excitatory neurotransmitter) increased rapidly between birth and 3 months, a period of rapid axonal growth and synapse formation. Myo-inositol, implicated in cell signaling and a precursor of membrane phospholipid, as well as an osmolyte and astrocyte marker, declined rapidly during this period. Choline, a membrane metabolite and indicator for de novo myelin and cell membrane synthesis, peaked from birth until approximately 3 months, and then declined gradually, reaching a plateau at early childhood. Similarly, taurine, involved in neuronal excitability, synaptic potentiation, and osmoregulation, was high until approximately 3 months and thereafter declined. These data indicate that the first 3 months of postnatal life are a critical period of rapid metabolic changes in the development of the human brain. This study of the developmental profiles of the major brain metabolites provides essential baseline information for future analyses of the pediatric health and disease. PMID:22952278

The bacterial pigment pyocyanin inhibits the NLRP3 inflammasome through intracellular reactive oxygen and nitrogen species

PubMed Central

Virreira Winter, Sebastian; Zychlinsky, Arturo

2018-01-01

Inflammasomes are cytosolic complexes that mature and secrete the inflammatory cytokines interleukin 1β (IL-1β) and IL-18 and induce pyroptosis. The NLRP3 (NACHT, LRR, and PYD domains–containing protein 3) inflammasome detects many pathogen- and danger-associated molecular patterns, and reactive oxygen species (ROS)/reactive nitrogen species (RNS) have been implicated in its activation. The phenazine pyocyanin (PCN) is a virulence factor of Pseudomonas aeruginosa and generates superoxide in cells. Here we report that PCN inhibits IL-1β and IL-18 release and pyroptosis upon NLRP3 inflammasome activation in macrophages by preventing speck formation and Caspase-1 maturation. Of note, PCN did not regulate the AIM2 (absent in melanoma 2) or NLRC4 inflammasomes or tumor necrosis factor (TNF) secretion. Imaging of the fluorescent glutathione redox potential sensor Grx1-roGFP2 indicated that PCN provokes cytosolic and nuclear but not mitochondrial redox changes. PCN-induced intracellular ROS/RNS inhibited the NLRP3 inflammasome posttranslationally, and hydrogen peroxide or peroxynitrite alone were sufficient to block its activation. We propose that cytosolic ROS/RNS inhibit the NLRP3 inflammasome and that PCN's anti-inflammatory activity may help P. aeruginosa evade immune recognition. PMID:29414783

Tree proximity, soil pathways and common mycorrhizal networks: their influence on the utilization of redistributed water by understory seedlings.

PubMed

Schoonmaker, Amanda L; Teste, François P; Simard, Suzanne W; Guy, Robert D

2007-12-01

Hydraulic redistribution (HR) is a process by which water moves through plant roots from moist to dry soils. An experiment was conducted to quantify the influence of common mycorrhizal networks (CMNs) and proximity to mature HR-source trees on the water relations of surrounding seedlings. Douglas-fir (Pseudotsuga menziesii var glauca (Mirb.) Franco) seedlings were planted at four distances (0.5, 1, 2.5, and 5 m) from six mature Douglas-fir trees, either directly into soil (soil plus CMN pathway) or inside 0.5 microm mesh bags (soil-only pathway). Deuterated water was used to irrigate soil beside mature trees in order to identify different HR water pathways to surrounding seedlings. This was followed by measurements of seedling deuterium enrichment, seedling water potential, soil water potential, gravimetric soil water content, and tree root density surrounding the seedlings. There was no significantly detectable difference in the quantity of HR water transferred to seedlings having access to soil and CMN pathways or soil-only pathways of water movement. Water from the irrigation plot contributed up to 1.4% of the water of Douglas-fir seedlings. Based on the assumption that the only pathway through which seedlings could access irrigation water was through the mature trees, we estimate that as much as 21.6% of the seedling water was supplied by the nearby tree. Seedling water potential was not significantly affected either by proximity to mature trees or pathway, suggesting HR may have compensated for increasing tree competitive effects with proximity. It is also possible that the lack of difference was due to a relatively moist summer. Our results suggest that residual mature trees are potentially important for hydraulic redistribution to regenerating seedlings in harvested dry interior Douglas-fir forests.

Organic petrology of selected oil shale samples from lower Carboniferous Albert Formation, New Brunswick, Canada

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

Kalkreuth, W.; Macauley, G.

1984-04-01

Incident light microscopy was used to describe maturation and composition of organic material in oil shale samples from the Lower Carboniferous Albert Formation of New Brunswick. The maturation level was determined in normal (white) light by measuring vitrinite reflectance and in fluorescent light by measuring fluorescence spectral of alginite B. Results indicate low to intermediate maturation for all of the samples. Composition was determined by maceral analysis. Alginite B is the major organic component in all samples having significant oil potential. Oil yields obtained from the Fischer Assay process, and oil and gas potentials from Rock-Eval analyses correlate to themore » amounts of alginite B and bituminite determined in the samples. In some of the samples characterized by similar high concentrations of alginite B, decrease in Fischer Assay yields and oil and gas potentials is related to an increase in maturation, as expected by increase in the fluorescence parameter lambda/sub max/ and red/green quotient of alginite B. Incident light microscopy, particularly with fluorescent light, offers a valuable tool for the identification of the organic matter in oil shales and for the evaluation of their oil and gas potentials.« less

Ignoring the data and endangering children: why the mature minor standard for medical decision making must be abandoned.

PubMed

Cherry, Mark J

2013-06-01

In Roper v. Simmons (2005) the United States Supreme Court announced a paradigm shift in jurisprudence. Drawing specifically on mounting scientific evidence that adolescents are qualitatively different from adults in their decision-making capacities, the Supreme Court recognized that adolescents are not adults in all but age. The Court concluded that the overwhelming weight of the psychological and neurophysiological data regarding brain maturation supports the conclusion that adolescents are qualitatively different types of agents than adult persons. The Supreme Court further solidified its position regarding adolescents as less than fully mature and responsible decisionmakers in Graham v. Florida (2010) and Miller v. Alabama (2012). In each case, the Court concluded that the scientific evidence does not support the conclusion that children under 18 years of age possess adult capacities for personal agency, rationality, and mature choice. This study explores the implications of the Supreme Court decisions in Roper v. Simmons, Graham v. Florida, and Miller v. Alabama for the "mature minor" standard for medical decision making. It argues that the Supreme Court's holdings in Roper, Graham, and Miller require no less than a radical reassessment of how healthcare institutions, courts of law, and public policy are obliged to regard minors as medical decisionmakers. The "mature minor" standard for medical decision making must be abandoned.

Novel in silico multivariate mapping of intrinsic and anticorrelated connectivity to neurocognitive functional maps supports the maturational hypothesis of ADHD.

PubMed

de Lacy, Nina; Kodish, Ian; Rachakonda, Srinivas; Calhoun, Vince D

2018-04-22

From childhood to adolescence, strengthened coupling in frontal, striatal and parieto-temporal regions associated with cognitive control, and increased anticorrelation between task-positive and task-negative circuits, subserve the reshaping of behavior. ADHD is a common condition peaking in adolescence and regressing in adulthood, with a wide variety of cognitive control deficits. Alternate hypotheses of ADHD emphasize lagging circuitry refinement versus categorical differences in network function. However, quantifying the individual circuit contributions to behavioral findings, and relative roles of maturational versus categorical effects, is challenging in vivo or in meta-analyses using task-based paradigms within the same pipeline, given the multiplicity of neurobehavioral functions implicated. To address this, we analyzed 46 positively-correlated and anticorrelated circuits in a multivariate model in resting-state data from 504 age- and gender-matched youth, and created a novel in silico method to map individual quantified effects to reverse inference maps of 8 neurocognitive functions consistently implicated in ADHD, as well as dopamine and hyperactivity. We identified only age- and gender-related effects in intrinsic connectivity, and found that maturational refinement of circuits in youth with ADHD occupied 3-10x more brain locations than in typical development, with the footprint, effect size and contribution of individual circuits varying substantially. Our analysis supports the maturational hypothesis of ADHD, suggesting lagging connectivity reorganization within specific subnetworks of fronto-parietal control, ventral attention, cingulo-opercular, temporo-limbic and cerebellar sub-networks contribute across neurocognitive findings present in this complex condition. We present the first analysis of anti-correlated connectivity in ADHD and suggest new directions for exploring residual and non-responsive symptoms. © 2018 Wiley Periodicals, Inc.

Development of immature stomata: evidence for epigenetic selection of a spacing pattern.

PubMed

Kagan, M L; Sachs, T

1991-07-01

In Sansevieria trifasciata as many as half the potential stomata remain immature. The development of all stomatal structures started at the same time and the early stages of the development of immature stomata had no special characteristics. Statistical analysis showed that the mature stomata were more evenly spaced than all potential stomata, both mature and immature. Furthermore, the distribution of mature stomata per unit area was more predictable or orderly than comparable structures of a random model that developed in the same way. These facts indicate that a nonrandom loss of many stomata by "immaturity" is a major determinant, acting during rather than preceding development, of the distribution of the mature, functional stomata. Thus in Sansevieria there is a selection of an epidermal pattern from an excess of cells that undergo the early stages of stomatal development.

Maturation of Peripheral and Brainstem Auditory Function in the First Year Following Perinatal Asphyxia: A Longitudinal Study.

ERIC Educational Resources Information Center

Jiang, Ze D.

1998-01-01

A study of 44 infants who suffered asphyxia during the perinatal period examined the influence of perinatal asphyxia on the maturation of auditory pathways by serial recordings of the brainstem auditory evoked potentials (BAEP). The general maturational course of the BAEP following asphyxia was similar to a control group. (Author/CR)

Effect of a Spaced Thinning in Mature Lodgepole Pine on Within-Stand Microclimate and Fine Fuel Moisture Content

Treesearch

R. J. Whitehead; G. L. Russo; B. C. Hawkes; S. W. Taylor; B. N. Brown; H. J. Barclay; R. A. Benton

2006-01-01

Thinning mature forest stands to wide spacing is prescribed to reduce crown bulk density and likelihood of severe crown fire behaviour. However, it may adversely affect surface fuel load, moisture content and within-stand wind, which influence surface fire behaviour and crowning potential. Comparison of a mature lodgepole pine (Pinus contorta Dougl....

Debt-maturity structures should match risk preferences.

PubMed

Gapenski, L C

1999-12-01

Key to any debt-maturity matching strategy is financing assets with the appropriate debt structure. Financial managers need to establish an optimal capital structure and then choose the best maturity-matching structure for their debt. Two maturity-matching strategies that are available to healthcare financial managers are the accounting approach and the finance approach. The accounting approach, which defines asset maturities as current or fixed, is a riskier financing strategy than the finance approach, which defines asset maturities as permanent or temporary. The added risk occurs because of the accounting approach's heavy reliance on short-term debt. The accounting approach offers the potential for lower costs at the expense of higher risk. Healthcare financial managers who believe the financing function should support the organization's operations without adding undue risk should use the finance approach to maturity matching. Asset maturities in those organizations then should be considered permanent or temporary rather than current or fixed, and the debt-maturity structure should reflect this.

Moral Education and the Perils of Developmentalism.

ERIC Educational Resources Information Center

Carr, David

2002-01-01

Discusses conception of moral formation. Traces progress to moral maturity through well defined stages of cognitive, conative, and/or affective growth. Explains that logical status of developmental theories are not clear. Argues that the accounts are more evaluative than descriptive. Explores the problematic moral educational implications of this…

45 CFR Appendix A to Part 1210 - Standard for Examiners

Code of Federal Regulations, 2011 CFR

2011-10-01

... of: (i) The personal attributes essential to the effective performance of the duties of an Examiner... causes of complex problems and apply mature judgment in assessing the practical implications of alternative solutions to those problems; —Interpret and apply regulations and other complex written material...

45 CFR Appendix A to Part 1210 - Standard for Examiners

Code of Federal Regulations, 2010 CFR

2010-10-01

... of: (i) The personal attributes essential to the effective performance of the duties of an Examiner... causes of complex problems and apply mature judgment in assessing the practical implications of alternative solutions to those problems; —Interpret and apply regulations and other complex written material...

Factors affecting aggressive behaviour of spawning migratory males towards mature male parr in masu salmon Oncorhynchus masou.

PubMed

Watanabe, M; Maekawa, K

2010-07-01

This study examined whether dominant migratory males (adopting fighter tactics) of the masu salmon Oncorhynchus masou would more aggressively attack large mature male parr (adopting sneaker tactics) as large mature male parr are expected to have the potential to cause a greater decrease in fertilization success. The frequency of aggressive behaviour was not related to the body size of males, and it increased with the frequency of interactions with mature male parr. The fertilization success of mature male parr was much lower than migratory males, and no relationship was observed between fertilization success and aggressive behaviour. The low fertilization success of mature male parr, despite infrequent aggressive behaviour by migratory males, indicates that there might be little benefit for migratory males to attack mature male parr more aggressively according to their body size.

CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration.

PubMed

Schaffer, Ashleigh E; Eggens, Veerle R C; Caglayan, Ahmet Okay; Reuter, Miriam S; Scott, Eric; Coufal, Nicole G; Silhavy, Jennifer L; Xue, Yuanchao; Kayserili, Hulya; Yasuno, Katsuhito; Rosti, Rasim Ozgur; Abdellateef, Mostafa; Caglar, Caner; Kasher, Paul R; Cazemier, J Leonie; Weterman, Marian A; Cantagrel, Vincent; Cai, Na; Zweier, Christiane; Altunoglu, Umut; Satkin, N Bilge; Aktar, Fesih; Tuysuz, Beyhan; Yalcinkaya, Cengiz; Caksen, Huseyin; Bilguvar, Kaya; Fu, Xiang-Dong; Trotta, Christopher R; Gabriel, Stacey; Reis, André; Gunel, Murat; Baas, Frank; Gleeson, Joseph G

2014-04-24

Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Affect and sexual behavior in the transition to university.

PubMed

Dalton, Andrea L; Galambos, Nancy L

2009-10-01

This research applied a lifespan developmental framework to the study of sexual behavior among late adolescents by examining monthly covariations of penetrative and oral sex with positive and negative affect across the first year of university. Participants were 177 Canadian students who completed baseline questionnaires, followed by six monthly, web-based questionnaires assessing sexual behaviors and affect. Multilevel analyses revealed an average positive relation between oral sex and positive affect. Of six variables, five predicted individual differences in covariation between sex and affect: psychosocial maturity (immature and semi-mature status), attitudes toward sex, prior sexual experience, and living situation. During months when participants reported sexual behavior, psychosocially mature students reported more positive affect than did less mature students; students with more permissive attitudes reported more positive affect than did students with less permissive attitudes; students with no penetrative sexual experience reported more positive affect than students who had penetrative sexual experience; and living away from parents was associated with less negative affect. Implications for further study of sexual behavior from a developmental perspective are discussed.

The developmental dynamics of gait maturation with a focus on spatiotemporal measures.

PubMed

Kraan, C M; Tan, A H J; Cornish, K M

2017-01-01

Gait analysis is recognised as a powerful clinical tool for studying relationships between motor control and brain function. By drawing on the literature investigating gait in individuals with neurological disorders, this review provides insight into the neural processes that contribute to and regulate specific spatiotemporal sub-components of gait and how they may mature across early to late childhood. This review also discusses the roles of changing anthropomorphic characteristics, and maturing sensory and higher-order cognitive processes in differentiating the developmental trajectories of the sub-components of gait. Importantly, although studies have shown that cognitive-gait interference is larger in children compared to adults, the contributing neurocognitive mechanisms may vary across age groups who have different types of attentional or cognitive vulnerabilities. These findings have implications for current models of gait maturation by highlighting the need for a dynamic model that focuses on the integration of various factors that contribute to gait though experience and practice. This is essential to elucidating why gait and other motor deficits are often contiguous with cognitive neurodevelopmental disorders. Copyright © 2016. Published by Elsevier B.V.

Pubertal testosterone influences threat-related amygdala–orbitofrontal cortex coupling

PubMed Central

Forbes, Erika E.; Ladouceur, Cecile D.; Worthman, Carol M.; Olino, Thomas M.; Ryan, Neal D.; Dahl, Ronald E.

2015-01-01

Growing evidence indicates that normative pubertal maturation is associated with increased threat reactivity, and this developmental shift has been implicated in the increased rates of adolescent affective disorders. However, the neural mechanisms involved in this pubertal increase in threat reactivity remain unknown. Research in adults indicates that testosterone transiently decreases amygdala–orbitofrontal cortex (OFC) coupling. Consequently, we hypothesized that increased pubertal testosterone disrupts amygdala–OFC coupling, which may contribute to developmental increases in threat reactivity in some adolescents. Hypotheses were tested in a longitudinal study by examining the impact of testosterone on functional connectivity. Findings were consistent with hypotheses and advance our understanding of normative pubertal changes in neural systems instantiating affect/motivation. Finally, potential novel insights into the neurodevelopmental pathways that may contribute to adolescent vulnerability to behavioral and emotional problems are discussed. PMID:24795438

Life Cycle Reversal in Aurelia sp.1 (Cnidaria, Scyphozoa)

PubMed Central

He, Jinru; Zheng, Lianming; Zhang, Wenjing; Lin, Yuanshao

2015-01-01

The genus Aurelia is one of the major contributors to jellyfish blooms in coastal waters, possibly due in part to hydroclimatic and anthropogenic causes, as well as their highly adaptive reproductive traits. Despite the wide plasticity of cnidarian life cycles, especially those recognized in certain Hydroza species, the known modifications of Aurelia life history were mostly restricted to its polyp stage. In this study, we document the formation of polyps directly from the ectoderm of degenerating juvenile medusae, cell masses from medusa tissue fragments, and subumbrella of living medusae. This is the first evidence for back-transformation of sexually mature medusae into polyps in Aurelia sp.1. The resulting reconstruction of the schematic life cycle of Aurelia reveals the underestimated potential of life cycle reversal in scyphozoan medusae, with possible implications for biological and ecological studies. PMID:26690755

A comparative study of the course-related family and financial problems of mature nursing students in Scotland and Australia.

PubMed

Cuthbertson, Philip; Lauder, William; Steele, Rebekah; Cleary, Sonja; Bradshaw, Julie

2004-07-01

This study reports a comparative survey of mature students undertaking pre-registration undergraduate nursing education in Australia and Scotland. The study aimed to explore comparisons between the course-related and course-related financial difficulties faced by mature students in two very different educational and funding systems. Financial stress is a predictor of both physical and mental health problems. A similar pattern of course-related problems were reported by both Australian and Scottish students with the exception that Scottish students experienced more problems with childcare and caring for elderly relatives. Course-related problems may be inherent in the nature of undergraduate nursing education although the relatively time-intensive nature of Scottish curricula may explain the childcare and elderly relatives difference. Scottish students reported higher overall financial-related problems but Australian students reported more problems with funding placements. These findings have implications for both curriculum designers and policy makers.

Finding myself: a theory on the maturation of spirituality and its influence on behavior during late adolescence.

PubMed

Mason, Deanna M

2014-01-01

This study employed a grounded theory research design to develop a theoretical model focused on the maturation of spirituality and its influence on behavior during late adolescence. Quantitative research studies have linked spirituality with decreased health-risk behaviors and increased health-promotion behaviors during late adolescence. Qualitative, theoretical data is proposed to discover the underlying reasons this relationship exists and increase the ability to apply this knowledge to practice. Twenty-one adolescents, age 16-21 years, were e-mail interviewed and transcripts analyzed using a conceptual lens of Blumer's symbolic interactionism. From this analysis, a theoretical model emerged with the core concept, finding myself that represents 5 core process concepts. Implications of this study illustrate that late adolescents are aware of their personal spiritual maturation as well as its influence on behavior. In addition, a distinction between the generic concept of spirituality, personal spirituality, and religion emerged.

CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells.

PubMed

Kido, Taketomo; Koui, Yuta; Suzuki, Kaori; Kobayashi, Ayaka; Miura, Yasushi; Chern, Edward Y; Tanaka, Minoru; Miyajima, Atsushi

2015-10-13

To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs) with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM) is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs). CPM(+) cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM(+) cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM(+) cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells

PubMed Central

Kido, Taketomo; Koui, Yuta; Suzuki, Kaori; Kobayashi, Ayaka; Miura, Yasushi; Chern, Edward Y.; Tanaka, Minoru; Miyajima, Atsushi

2015-01-01

Summary To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs) with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM) is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs). CPM+ cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM+ cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM+ cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes. PMID:26365514

Maize aflatoxin accumulation segregates with early maturing selections from an S2 breeding cross population.

PubMed

Henry, W Brien

2013-01-15

Maize breeders continue to seek new sources of aflatoxin resistance, but most lines identified as resistance sources are late maturing. The vast difference in flowering time makes it hard to cross these lines with proprietary commercial lines that mature much earlier and often subjects the reproductive phase of these resistant lines to the hottest and driest portion of the summer, making silking, pollination and grain fill challenging. Two hundred crosses from the GEM Project were screened for aflatoxin accumulation at Mississippi State in 2008, and a subset of these lines were screened again in 2009. The breeding cross UR13085:S99g99u was identified as a potential source of aflatoxin resistance, and maturity-based selections were made from an S2 breeding population from this same germplasm source: UR13085:S99g99u-B-B. The earliest maturing selections performed poorly for aflatoxin accumulation, but later maturing selections were identified with favorable levels of aflatoxin accumulation. These selections, while designated as "late" within this study, matured earlier than most aflatoxin resistant lines presently available to breeders. Two selections from this study, designated S5_L7 and S5_L8, are potential sources of aflatoxin resistance and will be advanced for line development and additional aflatoxin screening over more site years and environments.

Treatment of refractory undifferentiated acute myelogenous leukemia with all-trans-retinoic acid.

PubMed

Griggs, J J; Henley, S E; Rowe, J M

1994-02-01

A patient is described with undifferentiated acute myeloblastic leukemia refractory to two courses of daunorubicin and cytosine arabinoside. Because some the myeloblasts developed morphologic features of promyelocytes, the patient was treated with all-trans-retinoic acid (ATRA) in an attempt to promote maturation. Cytogenetic studies and sensitive molecular analysis did not reveal any abnormality classically associated with acute promyelocytic leukemia. Serial bone marrow biopsies demonstrated myeloid maturation, and the patient uneventfully went into a sustained complete remission. A review of the literature confirms this to be an apparently hitherto undescribed response to ATRA that may have therapeutic implications in similar patients.

Genetic architecture of threshold reaction norms for male alternative reproductive tactics in Atlantic salmon (Salmo salar L.)

PubMed Central

Lepais, Olivier; Manicki, Aurélie; Glise, Stéphane; Buoro, Mathieu; Bardonnet, Agnès

2017-01-01

Alternative mating tactics have important ecological and evolutionary implications and are determined by complex interactions between environmental and genetic factors. Here, we study the genetic effect and architecture of the variability in reproductive tactics among Atlantic salmon males which can either mature sexually early in life in freshwater or more commonly only after completing a migration at sea. We applied the latent environmental threshold model (LETM), which provides a conceptual framework linking individual status to a threshold controlling the decision to develop alternative traits, in an innovative experimental design using a semi-natural river which allowed for ecologically relevant phenotypic expression. Early male parr maturation rates varied greatly across families (10 to 93%) which translated into 90% [64–100%] of the phenotypic variation explained by genetic variation. Three significant QTLs were found for the maturation status, however only one collocated with a highly significant QTL explaining 20.6% of the variability of the maturation threshold located on chromosome 25 and encompassing a locus previously shown to be linked to sea age at maturity in anadromous Atlantic salmon. These results provide new empirical illustration of the relevance of the LETM for a better understanding of alternative mating tactics evolution in natural populations. PMID:28281522

Correlation between plasma levels of arginine and citrulline in preterm and full-term neonates: Therapeutical implications.

PubMed

Contreras, Mike T; Gallardo, Maria J; Betancourt, Luis R; Rada, Pedro V; Ceballos, Gerardo A; Hernandez, Luis E; Hernandez, Luis F

2017-11-01

Preterm neonates exhibit several deficiencies that endanger their lives. Understanding those disturbances will provide tools for the management of preterm neonates. The present work focuses on arginine and citrulline which has been flagged among the biochemical landmarks of prematurity. We examined blood samples of preterm newborns as compared with mature neonates to determine the levels of arginine and citrulline by capillary zone electrophoresis with laser induced fluorescence detection (CZE-LIFD). Significantly lower levels of arginine and citrulline were found in preterm neonates than in mature neonates (P<.01). Interestingly there was a highly significant correlation between the two amino acids in mature neonates (P<.0001). Such correlation was present in preterm neonates too (P<.01). Pearson coefficient showed that 60% of the citrulline concentration depends on arginine concentration in mature neonates. Only 20% of the citrulline concentration depends on arginine concentration in preterm neonates. Although the ratio arginine/citrulline was lower in preterm neonates than in mature neonates the difference was not statistically significant. These results suggest that less arginine is converted to citrulline to form nitric oxide in preterm than in full-term neonates. The result is discussed in terms of the immature enzymatic systems in the preterm neonate. © 2017 Wiley Periodicals, Inc.

Junctophilin-2 is necessary for T-tubule maturation during mouse heart development

PubMed Central

Reynolds, Julia O.; Chiang, David Y.; Wang, Wei; Beavers, David L.; Dixit, Sayali S.; Skapura, Darlene G.; Landstrom, Andrew P.; Song, Long-Sheng; Ackerman, Michael J.; Wehrens, Xander H.T.

2013-01-01

Aims Transverse tubules (TTs) provide the basic subcellular structures that facilitate excitation–contraction (EC) coupling, the essential process that underlies normal cardiac contractility. Previous studies have shown that TTs develop within the first few weeks of life in mammals but the molecular determinants of this development have remained elusive. This study aims to elucidate the role of junctophilin-2 (JPH2), a junctional membrane complex protein, in the maturation of TTs in cardiomyocytes. Methods and results Using a novel cardiac-specific short-hairpin-RNA-mediated JPH2 knockdown mouse model (Mus musculus; αMHC-shJPH2), we assessed the effects of the loss of JPH2 on the maturation of the ventricular TT structure. Between embryonic day (E) 10.5 and postnatal day (P) 10, JPH2 mRNA and protein levels were reduced by >70% in αMHC-shJPH2 mice. At P8 and P10, knockdown of JPH2 significantly inhibited the maturation of TTs, while expression levels of other genes implicated in TT development remained mostly unchanged. At the same time, intracellular Ca2+ handling was disrupted in ventricular myocytes from αMHC- shJPH2 mice, which developed heart failure by P10 marked by reduced ejection fraction, ventricular dilation, and premature death. In contrast, JPH2 transgenic mice exhibited accelerated TT maturation by P8. Conclusion Our findings suggest that JPH2 is necessary for TT maturation during postnatal cardiac development in mice. In particular, JPH2 may be critical in anchoring the invaginating sarcolemma to the sarcoplasmic reticulum, thereby enabling the maturation of the TT network. PMID:23715556

The impact of stress on the structure of the adolescent brain: Implications for adolescent mental health.

PubMed

Romeo, Russell D

2017-01-01

Adolescent development is associated with major changes in emotional and cognitive functions, as well as a rise in stress-related psychological disorders such as anxiety and depression. It is also a time of significant maturation of the brain, marked by structural alterations in many limbic and cortical regions. Though many elegant human neuroimaging studies have described the adolescent-related changes in these regions, relatively little is known about these changes in non-human animals. Moreover, both human and non-human data are lacking on how exposure to chronic stress may disrupt this structural maturation. Given the fundamental structure-function relationship in the nervous system, it will be important to understand how these normative and stress-induced structural alterations during adolescence influence psychological function, which in turn can modify future neural development. The purpose of this brief review is to describe the impact of stress on the structure of brain regions that continue to show structural maturation during adolescence and are highly sensitive to the effects of chronic stress exposure. Specifically, this review will focus on the amygdala, hippocampal formation, and prefrontal cortex, particularly from a morphological perspective. As many unanswered questions remain in this area of investigation, potential future lines of research are also discussed. A deeper appreciation of how stress affects adolescent brain development will be needed if we are to gain a better understanding of the mechanisms that mediate the increase in stress-related psychological dysfunctions often observed during this stage of development. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibiting HER3-mediated tumor cell growth with affibody molecules engineered to low picomolar affinity by position-directed error-prone PCR-like diversification.

PubMed

Malm, Magdalena; Kronqvist, Nina; Lindberg, Hanna; Gudmundsdotter, Lindvi; Bass, Tarek; Frejd, Fredrik Y; Höidén-Guthenberg, Ingmarie; Varasteh, Zohreh; Orlova, Anna; Tolmachev, Vladimir; Ståhl, Stefan; Löfblom, John

2013-01-01

The HER3 receptor is implicated in the progression of various cancers as well as in resistance to several currently used drugs, and is hence a potential target for development of new therapies. We have previously generated Affibody molecules that inhibit heregulin-induced signaling of the HER3 pathways. The aim of this study was to improve the affinity of the binders to hopefully increase receptor inhibition efficacy and enable a high receptor-mediated uptake in tumors. We explored a novel strategy for affinity maturation of Affibody molecules that is based on alanine scanning followed by design of library diversification to mimic the result from an error-prone PCR reaction, but with full control over mutated positions and thus less biases. Using bacterial surface display and flow-cytometric sorting of the maturation library, the affinity for HER3 was improved more than 30-fold down to 21 pM. The affinity is among the higher that has been reported for Affibody molecules and we believe that the maturation strategy should be generally applicable for improvement of affinity proteins. The new binders also demonstrated an improved thermal stability as well as complete refolding after denaturation. Moreover, inhibition of ligand-induced proliferation of HER3-positive breast cancer cells was improved more than two orders of magnitude compared to the previously best-performing clone. Radiolabeled Affibody molecules showed specific targeting of a number of HER3-positive cell lines in vitro as well as targeting of HER3 in in vivo mouse models and represent promising candidates for future development of targeted therapies and diagnostics.

Context-Specific Effects on Reciprocity in Mentoring Relationships: Ethical Implications

ERIC Educational Resources Information Center

Shore, Wendelyn J.; Toyokawa, Teru; Anderson, Dana D.

2008-01-01

Reciprocity is fundamental to effective mentoring relationships. However, we argue that it is inappropriate, and perhaps unethical, to expect comparable levels of reciprocity in all mentoring relationships. Instead, contextual factors influence optimal levels of reciprocity. Foremost is the developmental stage of the protege, with less mature,…

Improving Student Writing through Sentence Combining: A Literature Review. Technical Note.

ERIC Educational Resources Information Center

Lawlor, Joseph

The theoretical roots of sentence combining as a pedagogical strategy are discussed in this paper, along with recent studies of the development of written syntactic maturity. The paper examines several major sentence combining studies in detail and briefly summarizes additional relevant literature. The instructional implications of sentence…

Implications of ultra-low gossypol cottonseed

USDA-ARS?s Scientific Manuscript database

Historically, cottonseed has not been a viable source of protein for any animals other than those with mature rumens due to gossypol. Consequently, approximately 70% of the cottonseed produced in the U.S. is fed to the dairy industry, with the other 30% sent to cottonseed oil mills for processing in...

How Research in Behavioral Pharmacology Informs Behavioral Science

ERIC Educational Resources Information Center

Branch, Marc N.

2006-01-01

Behavioral pharmacology is a maturing science that has made significant contributions to the study of drug effects on behavior, especially in the domain of drug-behavior interactions. Less appreciated is that research in behavioral pharmacology can have, and has had, implications for the experimental analysis of behavior, especially its…

Implications of gender differences for human health risk assessment and toxicology

EPA Science Inventory

This paper from The Human Health working group of SGOMSEC 16 examines a broad range of issues on gender effects in toxicology. Gender differences in toxicology begin at the gamete and embryo stage, continuing through development and maturation and into old age. Sex influences exp...

The effects of zinc status on early growth in infants with sickle cell disease

USDA-ARS?s Scientific Manuscript database

Growth failure, maturational delay, and alterations in body composition occur in older children and adults with Sickle Cell Disease (SCD). Poor nutritional status, specifically zinc deficiency, has been widely implicated, although infants with SCD have not been studied. We determined zinc status in ...

Dual function of TGFβ in lens epithelial cell fate: implications for secondary cataract

PubMed Central

Boswell, Bruce A.; Korol, Anna; West-Mays, Judith A.; Musil, Linda S.

2017-01-01

The most common vision-disrupting complication of cataract surgery is posterior capsule opacification (PCO; secondary cataract). PCO is caused by residual lens cells undergoing one of two very different cell fates: either transdifferentiating into myofibroblasts or maturing into lens fiber cells. Although TGFβ has been strongly implicated in lens cell fibrosis, the factors responsible for the latter process have not been identified. We show here for the first time that TGFβ can induce purified primary lens epithelial cells within the same culture to undergo differentiation into either lens fiber cells or myofibroblasts. Marker analysis confirmed that the two cell phenotypes were mutually exclusive. Blocking the p38 kinase pathway, either with direct inhibitors of the p38 MAP kinase or a small-molecule therapeutic that also inhibits the activation of p38, prevented TGFβ from inducing epithelial–myofibroblast transition and cell migration but did not prevent fiber cell differentiation. Rapamycin had the converse effect, linking MTOR signaling to induction of fiber cell differentiation by TGFβ. In addition to providing novel potential therapeutic strategies for PCO, our findings extend the so-called TGFβ paradox, in which TGFβ can induce two disparate cell fates, to a new epithelial disease state. PMID:28209733

Sternohyoid and diaphragm muscle form and function during postnatal development in the rat.

PubMed

O'Connell, R A; Carberry, J; O'Halloran, K D

2013-09-01

What is the central question of this study? Co-ordinated activity of the thoracic pump and pharyngeal dilator muscles is critical for maintaining airway calibre and respiratory homeostasis. Whilst postnatal maturation of the diaphragm has been well characterized, surprisingly little is known about the developmental programme in the airway dilator muscles. What is the main finding and its importance? Developmental increases in force-generating capacity and fatigue in the sternohyoid and diaphragm muscles are attributed to a maturational shift in muscle myosin heavy chain phenotype. This maturation is accelerated in the sternohyoid muscle relative to the diaphragm and may have implications for the control of airway calibre in vivo. The striated muscles of breathing, including the thoracic pump and pharyngeal dilator muscles, play a critical role in maintaining respiratory homeostasis. Whilst postnatal maturation of the diaphragm has been well characterized, surprisingly little is known about the developmental programme in airway dilator muscles given that co-ordinated activity of both sets of muscles is needed for the maintenance of airway calibre and effective pulmonary ventilation. The form and function of sternohyoid and diaphragm muscles from Wistar rat pups [postnatal day (PD) 10, 20 and 30] was determined. Isometric contractile and endurance properties were examined in tissue baths containing Krebs solution at 35°C. Myosin heavy chain (MHC) isoform composition was determined using immunofluorescence. Muscle oxidative and glycolytic capacity was assessed by measuring the activities of succinate dehydrogenase and glycerol-3-phosphate dehydrogenase using semi-quantitative histochemistry. Sternohyoid and diaphragm peak isometric force and fatigue increased significantly with postnatal maturation. Developmental myosin disappeared by PD20, whereas MHC2B areal density increased significantly from PD10 to PD30, emerging earlier and to a much greater extent in the sternohyoid muscle. The numerical density of fibres expressing MHC2X and MHC2B increased significantly during development in the sternohyoid. Diaphragm succinate dehydrogenase activity and sternohyoid glycerol-3-phosphate dehydrogenase activity increased significantly with age. Developmental increases in force-generating capacity and fatigue in the sternohyoid and diaphragm muscles are attributed to a postnatal shift in muscle MHC phenotype. The accelerated maturation of the sternohyoid muscle relative to the diaphragm may have implications for the control of airway calibre in vivo.

Large Blooms of Bacillales (Firmicutes) Underlie the Response to Wetting of Cyanobacterial Biocrusts at Various Stages of Maturity.

PubMed

Karaoz, Ulas; Couradeau, Estelle; da Rocha, Ulisses Nunes; Lim, Hsiao-Chien; Northen, Trent; Garcia-Pichel, Ferran; Brodie, Eoin L

2018-03-06

Biological soil crusts (biocrusts) account for a substantial portion of primary production in dryland ecosystems. They successionally mature to deliver a suite of ecosystem services, such as carbon sequestration, water retention and nutrient cycling, and climate regulation. Biocrust assemblages are extremely well adapted to survive desiccation and to rapidly take advantage of the periodic precipitation events typical of arid ecosystems. Here we focus on the wetting response of incipient cyanobacterial crusts as they mature from "light" to "dark." We sampled a cyanobacterial biocrust chronosequence before (dry) and temporally following a controlled wetting event and used high-throughput 16S rRNA and rRNA gene sequencing to monitor the dynamics of microbial response. Overall, shorter-term changes in phylogenetic beta diversity attributable to periodic wetting were as large as those attributable to biocrust successional stage. Notably, more mature crusts showed significantly higher resistance to precipitation disturbance. A large bloom of a few taxa within the Firmicutes , primarily in the order Bacillales , emerged 18 h after wetting, while filamentous crust-forming cyanobacteria showed variable responses to wet-up across the successional gradient, with populations collapsing in less-developed light crusts but increasing in later-successional-stage dark crusts. Overall, the consistent Bacillales bloom accompanied by the variable collapse of pioneer cyanobacteria of the Oscillatoriales order across the successional gradient suggests that the strong response of few organisms to a hydration pulse with the mortality of the autotroph might have important implications for carbon (C) balance in semiarid ecosystems. IMPORTANCE Desert biological soil crusts are terrestrial topsoil microbial communities common to arid regions that comprise 40% of Earth's terrestrial surface. They successionally develop over years to decades to deliver a suite of ecosystem services of local and global significance. Ecosystem succession toward maturity has been associated with both resistance and resilience to disturbance. Recent work has shown that the impacts of both climate change and physical disturbance on biocrusts increase the potential for successional resetting. A larger proportion of biocrusts are expected to be at an early developmental stage, hence increasing susceptibility to changes in precipitation frequencies. Therefore, it is essential to characterize how biocrusts respond to wetting across early developmental stages. In this study, we document the wetting response of microbial communities from a biocrust chronosequence. Overall, our results suggest that the cumulative effects of altered precipitation frequencies on the stability of biocrusts will depend on biocrust maturity. Copyright © 2018 Karaoz et al.

Drug evaluation: bevirimat--HIV Gag protein and viral maturation inhibitor.

PubMed

Temesgen, Zelalem; Feinberg, Judith E

2006-08-01

Panacos Pharmaceuticals Inc is developing the HIV Gag protein and viral maturation inhibitor bevirimat for the potential oral treatment of HIV infection. Phase II clinical trials are underway and phase III trials expected to commence in 2007.

Stem cells and reproduction.

PubMed

Du, Hongling; Taylor, Hugh S

2010-06-01

To review the latest developments in reproductive tract stem cell biology. In 2004, two studies indicated that ovaries contain stem cells which form oocytes in adults and that can be cultured in vitro into mature oocytes. A live birth after orthotopic transplantation of cryopreserved ovarian tissue in a woman whose ovaries were damaged by chemotherapy demonstrates the clinical potential of these cells. In the same year, another study provided novel evidence of endometrial regeneration by stem cells in women who received bone marrow transplants. This finding has potential for the use in treatment of uterine disorders. It also supports a new theory for the cause of endometriosis, which may have its origin in ectopic transdifferentiation of stem cells. Several recent studies have demonstrated that fetal cells enter the maternal circulation and generate microchimerism in the mother. The uterus is a dynamic organ permeable to fetal stem cells, capable of transdifferentiation and an end organ in which bone marrow stem cells may differentiate. Finally stem cell transformation can be an underlying cause of ovarian cancer. Whereas we are just beginning to understand stem cells, the potential implications of stem cells to reproductive biology and medicine are apparent.

Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest

PubMed Central

Mills, Richard J.; Titmarsh, Drew M.; Koenig, Xaver; Parker, Benjamin L.; Ryall, James G.; Quaife-Ryan, Gregory A.; Voges, Holly K.; Hodson, Mark P.; Ferguson, Charles; Drowley, Lauren; Plowright, Alleyn T.; Needham, Elise J.; Wang, Qing-Dong; Gregorevic, Paul; Xin, Mei; Thomas, Walter G.; Parton, Robert G.; Nielsen, Lars K.; Elliott, David A.; Porrello, Enzo R.

2017-01-01

The mammalian heart undergoes maturation during postnatal life to meet the increased functional requirements of an adult. However, the key drivers of this process remain poorly defined. We are currently unable to recapitulate postnatal maturation in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), limiting their potential as a model system to discover regenerative therapeutics. Here, we provide a summary of our studies, where we developed a 96-well device for functional screening in human pluripotent stem cell-derived cardiac organoids (hCOs). Through interrogation of >10,000 organoids, we systematically optimize parameters, including extracellular matrix (ECM), metabolic substrate, and growth factor conditions, that enhance cardiac tissue viability, function, and maturation. Under optimized maturation conditions, functional and molecular characterization revealed that a switch to fatty acid metabolism was a central driver of cardiac maturation. Under these conditions, hPSC-CMs were refractory to mitogenic stimuli, and we found that key proliferation pathways including β-catenin and Yes-associated protein 1 (YAP1) were repressed. This proliferative barrier imposed by fatty acid metabolism in hCOs could be rescued by simultaneous activation of both β-catenin and YAP1 using genetic approaches or a small molecule activating both pathways. These studies highlight that human organoids coupled with higher-throughput screening platforms have the potential to rapidly expand our knowledge of human biology and potentially unlock therapeutic strategies. PMID:28916735

Inhibition of Progenitor Dendritic Cell Maturation by Plasma from Patients with Peripartum Cardiomyopathy: Role in Pregnancy-associated Heart Disease

PubMed Central

Ellis, Jane E.; Ansari, Aftab A.; Fett, James D.; Carraway, Robert D.; Randall, Hugh W.; Mosunjac, Mario I.; Sundstrom, J. Bruce

2005-01-01

Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12) of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF- were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs) was significantly reduced (p < 0.001) in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM. PMID:16584112

Addressing gaps in the maturity of judgment literature: age differences and delinquency.

PubMed

Modecki, Kathryn Lynn

2008-02-01

Over the past decade, a majority of states have legislated to expand their capacity to try adolescents as adults [Griffin (2003). Trying and sentencing juveniles as adults: An analysis of state transfer and blended sentencing laws. Pittsburgh, PA: National Center for Juvenile Justice]. In response, researchers have investigated factors that may affect adolescent culpability [Steinberg and Scott (Am Psychol 58(12):1009-1018, 2003)]. Research on immature judgment posits that psychosocial influences on adolescent decision processes results in reduced criminal responsibility [Cauffman and Steinberg (Behav Sci Law 18(6):741-760, 2000); Scott, Reppucci, and Woolard (Law Hum Behav 19(3):221-244, 1995); Steinberg and Cauffman (Law Hum Behav 20(3):249-272, 1996)]. The current study utilizes hypothetical vignettes and standardized measures of maturity of judgment (responsibility, temperance, and perspective) to examine gaps in previous maturity of judgment findings (Cauffman and Steinberg 2000). This work suggests that adolescents (ages 14-17) display less responsibility and perspective relative to college students (ages 18-21), young-adults (ages 22-27), and adults (ages 28-40). Further, this research finds no maturity of judgment differences between delinquent and non-delinquent youth, but does find significant maturity of judgment differences between high and low delinquency male youth. Finally, results show that maturity of judgment predicts self-reported delinquency beyond the contributions of age, gender, race, education level, SES, and antisocial decision making. Implications for the juvenile justice system are discussed.

Cannabinoids induce incomplete maturation of cultured human leukemia cells

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

Murison, G.; Chubb, C.B.H.; Maeda, S.

Monocyte maturation markers were induced in cultured human myeloblastic ML-2 leukemia cells after treatment for 1-6 days with 0.03-30 ..mu..M ..delta../sup 9/-tetrahydrocannabinol (THC), the major psychoactive component of marijuana. After a 2-day or longer treatment, 2- to 5-fold increases were found in the percentages of cells exhibiting reactivity with either the murine OKM1 monoclonal antibody of the Leu-M5 monoclonal antibody, staining positively for nonspecific esterase activity, and displaying a promonocyte morphology. The increases in these differentiation markers after treatment with 0.03-1 ..mu..M THC were dose dependent. At this dose range, THC did not cause an inhibition of cell growth. Themore » THC-induced cell maturation was also characterized by specific changes in the patterns of newly synthesized proteins. The THC-induced differentiation did not, however, result in cells with a highly developed mature monocyte phenotype. However, treatment of these incompletely matured cells with either phorbol 12-myristate 13-acetate of 1..cap alpha..,25-dihydroxycholecalciferol, which are inducers of differentiation in myeloid leukemia cells (including ML-2 cells), produced cells with a mature monocyte morphology. The ML-2 cell system described here may be a useful tool for deciphering critical biochemical events that lead to the cannabinoid-induced incomplete cell differentiation of ML-2 cells and other related cell types. Findings obtained from this system may have important implications for studies of cannabinoid effects on normal human bone-marrow progenitor cells.« less

Accelerating bioelectric functional development of neural stem cells by graphene coupling: Implications for neural interfacing with conductive materials.

PubMed

Guo, Rongrong; Zhang, Shasha; Xiao, Miao; Qian, Fuping; He, Zuhong; Li, Dan; Zhang, Xiaoli; Li, Huawei; Yang, Xiaowei; Wang, Ming; Chai, Renjie; Tang, Mingliang

2016-11-01

In order to govern cell-specific behaviors in tissue engineering for neural repair and regeneration, a better understanding of material-cell interactions, especially the bioelectric functions, is extremely important. Graphene has been reported to be a potential candidate for use as a scaffold and neural interfacing material. However, the bioelectric evolvement of cell membranes on these conductive graphene substrates remains largely uninvestigated. In this study, we used a neural stem cell (NSC) model to explore the possible changes in membrane bioelectric properties - including resting membrane potentials and action potentials - and cell behaviors on graphene films under both proliferation and differentiation conditions. We used a combination of single-cell electrophysiological recordings and traditional cell biology techniques. Graphene did not affect the basic membrane electrical parameters (capacitance and input resistance), but resting membrane potentials of cells on graphene substrates were more strongly negative under both proliferation and differentiation conditions. Also, NSCs and their progeny on graphene substrates exhibited increased firing of action potentials during development compared to controls. However, graphene only slightly affected the electric characterizations of mature NSC progeny. The modulation of passive and active bioelectric properties on the graphene substrate was accompanied by enhanced NSC differentiation. Furthermore, spine density, synapse proteins expressions and synaptic activity were all increased in graphene group. Modeling of the electric field on conductive graphene substrates suggests that the electric field produced by the electronegative cell membrane is much higher on graphene substrates than that on control, and this might explain the observed changes of bioelectric development by graphene coupling. Our results indicate that graphene is able to accelerate NSC maturation during development, especially with regard to bioelectric evolvement. Our findings provide a fundamental understanding of the role of conductive materials in tuning the membrane bioelectric properties in a graphene model and pave the way for future studies on the development of methods and materials for manipulating membrane properties in a controllable way for NSC-based therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Carbon carry capacity and carbon sequestration potential in China based on an integrated analysis of mature forest biomass.

PubMed

Liu, YingChun; Yu, GuiRui; Wang, QiuFeng; Zhang, YangJian; Xu, ZeHong

2014-12-01

Forests play an important role in acting as a carbon sink of terrestrial ecosystem. Although global forests have huge carbon carrying capacity (CCC) and carbon sequestration potential (CSP), there were few quantification reports on Chinese forests. We collected and compiled a forest biomass dataset of China, a total of 5841 sites, based on forest inventory and literature search results. From the dataset we extracted 338 sites with forests aged over 80 years, a threshold for defining mature forest, to establish the mature forest biomass dataset. After analyzing the spatial pattern of the carbon density of Chinese mature forests and its controlling factors, we used carbon density of mature forests as the reference level, and conservatively estimated the CCC of the forests in China by interpolation methods of Regression Kriging, Inverse Distance Weighted and Partial Thin Plate Smoothing Spline. Combining with the sixth National Forest Resources Inventory, we also estimated the forest CSP. The results revealed positive relationships between carbon density of mature forests and temperature, precipitation and stand age, and the horizontal and elevational patterns of carbon density of mature forests can be well predicted by temperature and precipitation. The total CCC and CSP of the existing forests are 19.87 and 13.86 Pg C, respectively. Subtropical forests would have more CCC and CSP than other biomes. Consequently, relying on forests to uptake carbon by decreasing disturbance on forests would be an alternative approach for mitigating greenhouse gas concentration effects besides afforestation and reforestation.

Microscopic dynamics research on the "mature" process of dye-sensitized solar cells after injection of highly concentrated electrolyte.

PubMed

Liang, Zhongguan; Liu, Weiqing; Chen, Jun; Hu, Linhua; Dai, Songyuan

2015-01-21

After injection of electrolyte, the internal three-dimensional solid-liquid penetration system of dye-sensitized solar cells (DSCs) can take a period of time to reach "mature" state. This paper studies the changes of microscopic processes of DSCs including TiO2 energy-level movement, localized state distribution, charge accumulation, electron transport, and recombination dynamics, from the beginning of electrolyte injection to the time of reached mature state. The results show that the microscopic dynamics process of DSCs exhibited a time-dependent behavior and achieved maturity ∼12 h after injecting the electrolyte into DSCs. Within 0-12 h, several results were observed: (1) the conduction band edge of TiO2 moved slightly toward negative potential direction; (2) the localized states in the band gap of TiO2 was reduced according to the same distribution law; (3) the transport resistance in TiO2 film increased, and electron transport time was prolonged as the time of maturity went on, which indicated that the electron transport process is impeded gradually; (4) the recombination resistance at the TiO2/electrolyte (EL) interface increases, and electron lifetime gradually extends, therefore, the recombination process is continuously suppressed. Furthermore, results suggest that the parameters of EL/Pt-transparent conductive oxide (TCO) interface including the interfacial capacitance, electron-transfer resistance, and transfer time constant would change with time of maturity, indicating that the EL/Pt-TCO interface is a potential factor affecting the mature process of DSCs.

l-Ergothioneine improves the developmental potential of in vitro sheep embryos without influencing OCTN1-mediated cross-membrane transcript expression.

PubMed

Mishra, A; Reddy, I J; Dhali, A; Javvaji, P K

2018-04-02

SummaryThe objective of the study was to investigate the effect of l-ergothioneine (l-erg) (5 mM or 10 mM) supplementation in maturation medium on the developmental potential and OCTN1-dependant l-erg-mediated (10 mM) change in mRNA abundance of apoptotic (Bcl2, Bax, Casp3 and PCNA) and antioxidant (GPx, SOD1, SOD2 and CAT) genes in sheep oocytes and developmental stages of embryos produced in vitro. Oocytes matured with l-erg (10 mM) reduced their embryo toxicity by decreasing intracellular ROS and increasing intracellular GSH in matured oocytes that in turn improved developmental potential, resulting in significantly (P < 0.05) higher percentages of cleavage (53.72% vs 38.86, 46.56%), morulae (34.36% vs 20.62, 25.84%) and blastocysts (14.83% vs 6.98, 9.26%) compared with other lower concentrations (0 mM and 5 mM) of l-erg without change in maturation rate. l-Erg (10 mM) treatment did not influence the mRNA abundance of the majority of apoptotic and antioxidant genes studied in the matured oocytes and developmental stages of embryo. A gene expression study found that the SLC22A4 gene that encodes OCTN1, an integral membrane protein and specific transporter of l-erg was not expressed in oocytes and developmental stages of embryos. Therefore it was concluded from the study that although there was improvement in the developmental potential of sheep embryos by l-erg supplementation in maturation medium, there was no change in the expression of the majority of the genes studied due to the absence of the SLC22A4 gene in oocytes and embryos that encode OCTN1, which is responsible for transportation of l-erg across the membrane to alter gene expression.

Remote sensing of potential lunar resources. I - Near-side compositional properties

NASA Technical Reports Server (NTRS)

Johnson, Jeffrey R.; Larson, Stephen M.; Singer, Robert B.

1991-01-01

Using telescopic CCD multispectral images of the lunar near side and the results of 330-870 nm spectroscopy of selected regions, the compositional differences relevant to the locations of potential lunar resources (such as ilmenite, FeTiO3, and solar-wind-implanted He-3 and H) are estimated. The 400/560 nm CCD ratio images were converted to weight percent TiO2, and the values were used to construct a new TiO2 abundance map which can be used to estimate the areas potentially rich in ilmenite. A 950/560 nm CCD ratio mosaic of the full moon provides estimates of relative surface maturity. Since high He-3 concentrations correlate with mature ilmenite-rich soils, a combination of relative surface maturity maps and the TiO2 abundance maps can be used to estimate distributions of He-3 (and possibly H) on local scales.

Exploring life history characteristics of naturalized versus stocked chinook

USGS Publications Warehouse

Rogers, Mark W.; Kerns, Janice A; Bunnell, David B.; Claramunt, Randall M.; Collingsworth, Paris D.

2011-01-01

Naturalization of stocked populations can result in divergence of life-history traits from domestic stocks. Lake Michigan supports popular Chinook (Oncorhynchus tshawytscha) Salmon fisheries that have been sustained by stocking since the late 1960s. Natural recruitment of Chinook Salmon in Lake Michigan has increased in the last few decades and currently contributes over 50% of Chinook Salmon recruits. Samples collected as part of a lakewide mass-marking of Lake Michigan Chinook Salmon, starting with the 2006 year class, indicated hatchery fish average 30-mm longer and 130 grams heavier than naturalized fish at age-1. We hypothesized that selective forces differ for naturalized and hatchery populations resulting in divergent life-history characteristics with implications for Chinook Salmon population production and the Lake Michigan fishery. Specific life-history metrics of interest include: age- and size- at maturity, spawning run timing, fecundity, and sex ratio. Objectives: We evaluated life history characteristics between naturally recruited and stocked Chinook Salmon in Lake Michigan to help discern potential changes resulting from naturalization and implications for fisheries. A. Conduct an analysis of historical data to determine if life-history parameters changed through time as the Chinook Salmon population became increasingly naturalized. B. Conduct a two-year field study of naturalized and hatchery stocked Chinook Salmon spawning populations to quantify differences in life-history metrics of adults. C. Determine if reproductive potential differs between naturalized and hatchery stocked Chinook salmon by measuring egg thiamine levels.

Epigenetic profiling of ADHD symptoms trajectories: a prospective, methylome-wide study.

PubMed

Walton, E; Pingault, J-B; Cecil, C A M; Gaunt, T R; Relton, C L; Mill, J; Barker, E D

2017-02-01

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent developmental disorder, associated with a range of long-term impairments. Variation in DNA methylation, an epigenetic mechanism, is implicated in both neurobiological functioning and psychiatric health. However, the potential role of DNA methylation in ADHD symptoms is currently unclear. In this study, we examined data from the Avon Longitudinal Study of Parents and Children (ALSPAC)-specifically the subsample forming the Accessible Resource for Integrated Epigenomics Studies (ARIES)-that includes (1) peripheral measures of DNA methylation (Illumina 450k) at birth (n=817, 49% male) and age 7 (n=892, 50% male) and (2) trajectories of ADHD symptoms (7-15 years). We first employed a genome-wide analysis to test whether DNA methylation at birth associates with later ADHD trajectories; and then followed up at age 7 to investigate the stability of associations across early childhood. We found that DNA methylation at birth differentiated ADHD trajectories across multiple genomic locations, including probes annotated to SKI (involved in neural tube development), ZNF544 (previously implicated in ADHD), ST3GAL3 (linked to intellectual disability) and PEX2 (related to perixosomal processes). None of these probes maintained an association with ADHD trajectories at age 7. Findings lend novel insights into the epigenetic landscape of ADHD symptoms, highlighting the potential importance of DNA methylation variation in genes related to neurodevelopmental and peroxisomal processes that play a key role in the maturation and stability of cortical circuits.

CHARACTERIZATION OF SUBSETS OF HUMAN SPERMATOZOA AT DIFFERENT STAGES OF MATURATION: IMPLICATIONS IN THE DIAGNOSIS AND TREATMENT OF MALE INFERTILITY. (R827019)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Factors affecting bee communities in forest openings and adjacent mature forest

Treesearch

H. Patrick Roberts; David I. King; Joan Milam

2017-01-01

Anthropogenic disturbance of habitat is considered a contributing factor of pollinator declines, but some disturbances such as silviculture, may have positive implications for pollinator communities. Silviculture is a key source of disturbance in the eastern USA and thus, developing a better understanding of its ramifications for these keystone species is important for...

Investigation of the Functional Neuroanatomy of Single Word Reading and Its Development

ERIC Educational Resources Information Center

Palmer, Erica D.; Brown, Timothy T.; Petersen, Steven E.; Schlaggar, Bradley L.

2004-01-01

An understanding of the processing underlying single word reading will provide insight into how skilled reading is achieved, with important implications for reading education and impaired reading. Investigation of the functional neuroanatomy of both the mature and the developing systems will be critical for reaching this understanding. To this…

Contributions and Implications of the Medford, Oregon, Boys' Growth Study.

ERIC Educational Resources Information Center

Clarke, H. H.

The overall and long-range purposes of the Medford Boys' Growth Study are: (1) to construct physical and motor growth curves and growth acceleration curves of boys seven to 18 years old; (2) to relate these traits to physiological maturity, physique type, nutritional status, socio-personal adjustment, interests, and scholastic aptitude and…

New Discoveries from the Bilingual Brain and Mind across the Life Span: Implications for Education

ERIC Educational Resources Information Center

Petitto, Laura-Ann

2009-01-01

We discuss the fruits of educational neuroscience research from our laboratory and show how the typical maturational timing milestones in bilingual language acquisition provide educators with a tool for differentiating a bilingual child experiencing language and reading delay versus deviance. Further, early schooling in two languages…

Infant diet-related changes in syllable processing between 4 and 5 months: Implications for developing native language sensitivity

USDA-ARS?s Scientific Manuscript database

Since maturational processes triggering increased attunement to native language features in early infancy are sensitive to dietary factors, infant-diet related differences in brain processing of native-language speech stimuli might indicate variations in onset of this tuning process. We measured cor...

Bouncing Back by Moving Forward: Transactional Models of Risk and Resiliency. Revolutionary Studies in Child Psychology.

ERIC Educational Resources Information Center

Thurber, Christopher A.

2003-01-01

Four studies in child development show that children socialize parents as much as parents socialize children. Child development is a function of biological maturation and child-environment interaction. The most important determinants of resiliency are caregiver quality and socioeconomic status. Implications for camp are discussed, the most…

Working Memory Deficits, Increased Anxiety-Like Traits, and Seizure Susceptibility in BDNF Overexpressing Mice

ERIC Educational Resources Information Center

Papaleo, Francesco; Silverman, Jill L.; Aney, Jordan; Tian, Qingjun; Barkan, Charlotte L.; Chadman, Kathryn K.; Crawley, Jacqueline N.

2011-01-01

BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher…

Three Experiments Examining the Use of Electroencephalogram,Event-Related Potentials, and Heart-Rate Variability for Real-Time Human-Centered Adaptive Automation Design

NASA Technical Reports Server (NTRS)

Prinzel, Lawrence J., III; Parasuraman, Raja; Freeman, Frederick G.; Scerbo, Mark W.; Mikulka, Peter J.; Pope, Alan T.

2003-01-01

Adaptive automation represents an advanced form of human-centered automation design. The approach to automation provides for real-time and model-based assessments of human-automation interaction, determines whether the human has entered into a hazardous state of awareness and then modulates the task environment to keep the operator in-the-loop , while maintaining an optimal state of task engagement and mental alertness. Because adaptive automation has not matured, numerous challenges remain, including what the criteria are, for determining when adaptive aiding and adaptive function allocation should take place. Human factors experts in the area have suggested a number of measures including the use of psychophysiology. This NASA Technical Paper reports on three experiments that examined the psychophysiological measures of event-related potentials, electroencephalogram, and heart-rate variability for real-time adaptive automation. The results of the experiments confirm the efficacy of these measures for use in both a developmental and operational role for adaptive automation design. The implications of these results and future directions for psychophysiology and human-centered automation design are discussed.

Detection of Free-Living Amoebae Using Amoebal Enrichment in a Wastewater Treatment Plant of Gauteng Province, South Africa

PubMed Central

Muchesa, P.; Mwamba, O.; Barnard, T. G.; Bartie, C.

2014-01-01

Free-living amoebae pose a potential health risk in water systems as they may be pathogenic and harbor potential pathogenic bacteria known as amoebae resistant bacteria. Free-living amoebae were observed in 150 (87.2%) of the environmental water samples. In particular, Acanthamoeba sp. was identified in 22 (12.8%) using amoebal enrichment and confirmed by molecular analysis. FLA were isolated in all 8 stages of the wastewater treatment plant using the amoebal enrichment technique. A total of 16 (9.3%) samples were positive for FLA from influent, 20 (11.6%) from bioreactor feed, 16 (9.3%) from anaerobic zone, 16 (9.3%) from anoxic zone, 32 (18.6%) from aerators, 16 (9.3%) from bioreactor effluent, 11 (6.4%) from bioreactor final effluent, and 45 (26.2%) from maturation pond. This study provides baseline information on the occurrence of amoebae in wastewater treatment plant. This has health implications on receiving water bodies as some FLA are pathogenic and are also involved in the transmission and dissemination of pathogenic bacteria. PMID:25530964

The origin, type and hydrocarbon generation potential of organic matter in a marine-continental transitional facies shale succession (Qaidam Basin, China).

PubMed

Wang, Guo-Cang; Sun, Min-Zhuo; Gao, Shu-Fang; Tang, Li

2018-04-26

This organic-rich shale was analyzed to determine the type, origin, maturity and depositional environment of the organic matter and to evaluate the hydrocarbon generation potential of the shale. This study is based on geochemical (total carbon content, Rock-Eval pyrolysis and the molecular composition of hydrocarbons) and whole-rock petrographic (maceral composition) analyses. The petrographic analyses show that the shale penetrated by the Chaiye 2 well contains large amounts of vitrinite and sapropelinite and that the organic matter within these rocks is type III and highly mature. The geochemical analyses show that these rocks are characterized by high total organic carbon contents and that the organic matter is derived from a mix of terrestrial and marine sources and highly mature. These geochemical characteristics are consistent with the results of the petrographic analyses. The large amounts of organic matter in the Carboniferous shale succession penetrated by the Chaiye 2 well may be due to good preservation under hypersaline lacustrine and anoxic marine conditions. Consequently, the studied shale possesses very good hydrocarbon generation potential because of the presence of large amounts of highly mature type III organic matter.

Age-related changes in spatiotemporal characteristics of gait accompany ongoing lower limb linear growth in late childhood and early adolescence.

PubMed

Froehle, Andrew W; Nahhas, Ramzi W; Sherwood, Richard J; Duren, Dana L

2013-05-01

Walking gait is generally held to reach maturity, including walking at adult-like velocities, by 7-8 years of age. Lower limb length, however, is a major determinant of gait, and continues to increase until 13-15 years of age. This study used a sample from the Fels Longitudinal Study (ages 8-30 years) to test the hypothesis that walking with adult-like velocity on immature lower limbs results in the retention of immature gait characteristics during late childhood and early adolescence. There was no relationship between walking velocity and age in this sample, whereas the lower limb continued to grow, reaching maturity at 13.2 years in females and 15.6 years in males. Piecewise linear mixed models regression analysis revealed significant age-related trends in normalized cadence, initial double support time, single support time, base of support, and normalized step length in both sexes. Each trend reached its own, variable-specific age at maturity, after which the gait variables' relationships with age reached plateaus and did not differ significantly from zero. Offsets in ages at maturity occurred among the gait variables, and between the gait variables and lower limb length. The sexes also differed in their patterns of maturation. Generally, however, immature walkers of both sexes took more frequent and relatively longer steps than did mature walkers. These results support the hypothesis that maturational changes in gait accompany ongoing lower limb growth, with implications for diagnosing, preventing, and treating movement-related disorders and injuries during late childhood and early adolescence. Copyright © 2012 Elsevier B.V. All rights reserved.

Assessing the impact of adjusting for maturity in weight status classification in a cross-sectional sample of UK children.

PubMed

Gillison, Fiona; Cumming, Sean; Standage, Martyn; Barnaby, Catherine; Katzmarzyk, Peter

2017-06-26

To compare the weight categorisation of a cohort of UK children using standard procedures (ie, comparing body mass index (BMI) centiles to age-matched UK reference data) versus an approach adjusted for maturation status (ie, matching relative to biological age). Analysis of data collected from an observational study of UK primary school children. Schools in South West England. Four hundred and seven 9-11 year-old children (98% white British). Weight status was classified using BMI centiles using (1) sex and chronological age-matched referents and (2) sex and biological age-matched referents (based on % of predicted adult stature) relative to UK 1990 reference growth charts. For both approaches, children were classified as a normal weight if >2nd centile and <85thcentile, overweight if 85th and <95thcentiles, and obese if ≥95thcentile. Fifty-one children (12.5%) were overweight, and a further 51 obese (12.5%) according to standard chronological age-matched classifications. Adjustment for maturity resulted in 32% of overweight girls, and 15% of overweight boys being reclassified as a normal weight, and 11% and 8% of obese girls and boys, respectively, being reclassified as overweight. Early maturing children were 4.9 times more likely to be reclassified from overweight to normal weight than 'on-time' maturers (OR 95% CI 1.3 to 19). Incorporating assessments of maturational status into weight classification resulted in significant changes to the classification of early-maturing adolescents. Further research exploring the implications for objective health risk and well-being is needed. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The DNA Maturation Domain of gpA, the DNA Packaging Motor Protein of Bacteriophage Lambda, Contains an ATPase Site Associated with Endonuclease Activity

PubMed Central

Ortega, Marcos E.; Gaussier, Helene; Catalano, Carlos E.

2007-01-01

Summary Terminase enzymes are common to double-stranded DNA (dsDNA) viruses and are responsible for packaging viral DNA into the confines of an empty capsid shell. In bacteriophage lambda the catalytic terminase subunit is gpA, which is responsible for maturation of the genome end prior to packaging and subsequent translocation of the matured DNA into the capsid. DNA packaging requires an ATPase catalytic site situated in the N-terminus of the protein. A second ATPase catalytic site associated with the DNA maturation activities of the protein has been proposed; however, direct demonstration of this putative second site is lacking. Here we describe biochemical studies that define protease-resistant peptides of gpA and expression of these putative domains in E. coli. Biochemical characterization of gpA-ΔN179, a construct in which the N-terminal 179 residues of gpA have been deleted, indicates that this protein encompasses the DNA maturation domain of gpA. The construct is folded, soluble and possesses an ATP-dependent nuclease activity. Moreover, the construct binds and hydrolyzes ATP despite the fact that the DNA packaging ATPase site in the N-terminus of gpA has been deleted. Mutation of lysine 497, which alters the conserved lysine in a predicted Walker A “P-loop” sequence, does not affect ATP binding but severely impairs ATP hydrolysis. Further, this mutation abrogates the ATP-dependent nuclease activity of the protein. These studies provide direct evidence for the elusive nucleotide-binding site in gpA that is directly associated with the DNA maturation activity of the protein. The implications of these results with respect to the two roles of the terminase holoenzyme – DNA maturation and DNA packaging – are discussed. PMID:17870092

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

PubMed Central

Conrad, Kirk P.

2016-01-01

BACKGROUND Important roles for G-protein-coupled receptors (GPCRs) have been identified in the maternal physiological adaptations to pregnancy and in the pathogenesis of preeclampsia. On this basis, GPCRs are potential therapeutic targets for preeclampsia. OBJECTIVES AND RATIONALE In this review, vasopressin and apelin are initially considered in this context before the focus on the hormone relaxin and its cognate receptor, the relaxin/insulin-like family peptide receptor 1 (RXFP1). Based on both compelling scientific rationale and a promising safety profile, the relaxin ligand–receptor system is comprehensively evaluated as a potential therapeutic endpoint in preeclampsia. SEARCH METHODS The published literature relating to the topic was searched through January 2016 using PubMed. OUTCOMES Relaxin is a peptide hormone secreted by the corpus luteum; it circulates in the luteal phase and during pregnancy. Activation of RXFP1 is vasodilatory; thus, relaxin supplementation is expected to at least partly restore the fundamental vasodilatory changes of normal pregnancy, thereby alleviating maternal organ hypoperfusion, which is a major pathogenic manifestation of severe preeclampsia. Specifically, by exploiting its pleiotropic hemodynamic attributes in preeclampsia, relaxin administration is predicted to (i) reverse robust arterial myogenic constriction; (ii) blunt systemic and renal vasoconstriction in response to activation of the angiotensin II receptor, type 1; (iii) mollify the action of endogenous vasoconstrictors on uterine spiral arteries with failed remodeling and retained smooth muscle; (iv) increase arterial compliance; (v) enhance insulin-mediated glucose disposal by promoting skeletal muscle vasodilation and (vi) mobilize and activate bone marrow-derived angiogenic progenitor cells, thereby repairing injured endothelium and improving maternal vascularity in organs such as breast, uterus, pancreas, skin and fat. By exploiting its pleiotropic molecular attributes in preeclampsia, relaxin supplementation is expected to (i) enhance endothelial nitric oxide synthesis and bioactivity, as well as directly reduce vascular smooth muscle cytosolic calcium, thus promoting vasodilation; (ii) improve the local angiogenic balance by augmenting arterial vascular endothelial and placental growth factor (VEGF and PLGF) activities; (iii) ameliorate vascular inflammation; (iv) enhance placental peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PCG1α) expression, and hence, peroxisome proliferator-activated receptor gamma (PPAR-γ) activity and (v) confer cytotrophoblast and endothelial cytoprotection. Insofar as impaired endometrial maturation (decidualization) predisposes to the development of preeclampsia, relaxin administration in the late secretory phase and during early pregnancy would be anticipated to improve decidualization, and hence trophoblast invasion and spiral artery remodeling, thereby reducing the risk of preeclampsia. Relaxin has a favorable safety profile both in the non-pregnant condition and during pregnancy. WIDER IMPLICATIONS There is a strong scientific rationale for RXFP1 activation in severe preeclampsia by administration of relaxin, relaxin analogs or small molecule mimetics, in order to mollify the disease pathogenesis for safe prolongation of pregnancy, thus allowing time for more complete fetal maturation, which is a primary therapeutic endpoint in treating the disease. In light of recent data implicating deficient or defective decidualization as a potential etiological factor in preeclampsia and the capacity of relaxin to promote endometrial maturation, the prophylactic application of relaxin to reduce the risk of preeclampsia is a plausible therapeutic approach to consider. Finally, given its pleiotropic and beneficial attributes particularly in the cardiovascular system, relaxin, although traditionally considered as a ‘pregnancy’ hormone, is likely to prove salutary for several disease indications in the non-pregnant population. PMID:27385360

Evaluation of genetic variability among "Early Mature" Juglans regia using microsatellite markers and morphological traits.

PubMed

Ebrahimi, Aziz; Zarei, Abdolkarim; Zamani Fardadonbeh, Mojtaba; Lawson, Shaneka

2017-01-01

Limiting the juvenile phase and reducing tree size are the two main challenges for breeders to improve most fruit crops. Early maturation and dwarf cultivars have been reported for many fruit species. "Early mature" and low vigor walnut genotypes were found among seedlings of Persian walnut. Nine microsatellite markers were used to evaluate genetic diversity among "Early Mature" Persian walnut accessions and provide a comparison with "normal growth" accessions. Six maturation related characteristics were also measured in "Early Mature" samples. Phenotypic traits and diversity indices showed relatively high levels of genetic diversity in "Early Mature" seedlings and indicated high differentiation between individuals. Seedling height, the most diverse phenotypic trait, has an important role in the clustering of "Early Mature" accessions. The "Early Mature" type had higher number of alleles, number of effective allele, and Shannon index compared to the "Normal Growth" group. The two types of studied walnuts had different alleles, with more than half of produced alleles specific to a specific group. "Early Mature" and "Normal Growth" walnuts had 27 and 17 private alleles, respectively. Grouping with different methods separated "Early Mature" and "Normal Growth" samples entirely. The presence of moderate to high genetic diversity in "Early Mature" walnuts and high genetic differentiation with "Normal Growth" walnuts, indicated that "Early Mature" walnuts were more diverse and distinct from "Normal Growth" samples. Moreover, our results showed SSR markers were useful for differentiating between "Early Mature" and "Normal Growth" walnuts. A number of identified loci have potential in breeding programs for identification of "Early Mature" walnuts at the germination phase.

An examination of three theoretical models to explain the organ donation attitude--registration discrepancy among mature adults.

PubMed

Quick, Brian L; Anker, Ashley E; Feeley, Thomas Hugh; Morgan, Susan E

2016-01-01

An inconsistency in the research indicates positive attitudes toward organ donation do not map reliably onto organ donor registrations. Various models have sought to explain this inconsistency and the current analysis formally compared three models: the Bystander Intervention Model (BIM), the Organ Donor Model (ODM), and Vested Interest Theory (VIT). Mature (N = 688) adults between the ages of 50 to 64 years completed surveys related to organ donation. Results revealed that VIT accounted for the most variance in organ donation registrations followed by the BIM and ODM. The discussion emphasizes the importance of employing theories to explain a phenomenon as well as the practical implications of the findings.

Role of Wnt Signaling in the Control of Adult Hippocampal Functioning in Health and Disease: Therapeutic Implications

PubMed Central

Ortiz-Matamoros, Abril; Salcedo-Tello, Pamela; Avila-Muñoz, Evangelina; Zepeda, Angélica; Arias, Clorinda

2013-01-01

It is well recognized the role of the Wnt pathway in many developmental processes such as neuronal maturation, migration, neuronal connectivity and synaptic formation. Growing evidence is also demonstrating its function in the mature brain where is associated with modulation of axonal remodeling, dendrite outgrowth, synaptic activity, neurogenesis and behavioral plasticity. Proteins involved in Wnt signaling have been found expressed in the adult hippocampus suggesting that Wnt pathway plays a role in the hippocampal function through life. Indeed, Wnt ligands act locally to regulate neurogenesis, neuronal cell shape and pre- and postsynaptic assembly, events that are thought to underlie changes in synaptic function associated with long-term potentiation and with cognitive tasks such as learning and memory. Recent data have demonstrated the increased expression of the Wnt antagonist Dickkopf-1 (DKK1) in brains of Alzheimer´s disease (AD) patients suggesting that dysfunction of Wnt signaling could also contribute to AD pathology. We review here evidence of Wnt-associated molecules expression linked to physiological and pathological hippocampal functioning in the adult brain. The basic aspects of Wnt related mechanisms underlying hippocampal plasticity as well as evidence of how hippocampal dysfunction may rely on Wnt dysregulation is analyzed. This information would provide some clues about the possible therapeutic targets for developing treatments for neurodegenerative diseases associated with aberrant brain plasticity. PMID:24403870

Role of wnt signaling in the control of adult hippocampal functioning in health and disease: therapeutic implications.

PubMed

Ortiz-Matamoros, Abril; Salcedo-Tello, Pamela; Avila-Muñoz, Evangelina; Zepeda, Angélica; Arias, Clorinda

2013-09-01

It is well recognized the role of the Wnt pathway in many developmental processes such as neuronal maturation, migration, neuronal connectivity and synaptic formation. Growing evidence is also demonstrating its function in the mature brain where is associated with modulation of axonal remodeling, dendrite outgrowth, synaptic activity, neurogenesis and behavioral plasticity. Proteins involved in Wnt signaling have been found expressed in the adult hippocampus suggesting that Wnt pathway plays a role in the hippocampal function through life. Indeed, Wnt ligands act locally to regulate neurogenesis, neuronal cell shape and pre- and postsynaptic assembly, events that are thought to underlie changes in synaptic function associated with long-term potentiation and with cognitive tasks such as learning and memory. Recent data have demonstrated the increased expression of the Wnt antagonist Dickkopf-1 (DKK1) in brains of Alzheimer´s disease (AD) patients suggesting that dysfunction of Wnt signaling could also contribute to AD pathology. We review here evidence of Wnt-associated molecules expression linked to physiological and pathological hippocampal functioning in the adult brain. The basic aspects of Wnt related mechanisms underlying hippocampal plasticity as well as evidence of how hippocampal dysfunction may rely on Wnt dysregulation is analyzed. This information would provide some clues about the possible therapeutic targets for developing treatments for neurodegenerative diseases associated with aberrant brain plasticity.

Chymotrypsin C (Caldecrin) Is Associated with Enamel Development

PubMed Central

Lacruz, R.S.; Smith, C.E.; Smith, S.M.; Hu, P.; Bringas, P.; Sahin-Tóth, M.; Moradian-Oldak, J.; Paine, M.L.

2011-01-01

Two main proteases cleave enamel extracellular matrix proteins during amelogenesis. Matrix metalloprotease-20 (Mmp20) is the predominant enzyme expressed during the secretory stage, while kallikrein-related peptidase-4 (Klk4) is predominantly expressed during maturation. Mutations to both Mmp20 and Klk4 result in abnormal enamel phenotypes. During a recent whole-genome microarray analysis of rat incisor enamel organ cells derived from the secretory and maturation stages of amelogenesis, the serine protease chymotrypsin C (caldecrin, Ctrc) was identified as significantly up-regulated (> 11-fold) during enamel maturation. Prior reports indicate that Ctrc expression is pancreas-specific, albeit low levels were also noted in brain. We here report on the expression of Ctrc in the enamel organ. Quantitative PCR (qPCR) and Western blot analysis were used to confirm the expression of Ctrc in the developing enamel organ. The expression profile of Ctrc is similar to that of Klk4, increasing markedly during the maturation stage relative to the secretory stage, although levels of Ctrc mRNA are lower than for Klk4. The discovery of a new serine protease possibly involved in enamel development has important implications for our understanding of the factors that regulate enamel biomineralization. PMID:21828354

Hsp90: a novel target for the disruption of multiple signaling cascades.

PubMed

Bishop, Stephanie C; Burlison, Joseph A; Blagg, Brian S J

2007-06-01

The 90 kDa heat shock proteins (Hsp90) are proving to be an excellent target for the development of novel anti-cancer agents designed to selectively block the growth and proliferation of tumor cells. Since Hsp90 is a molecular chaperone and is responsible for folding numerous oncogenic proteins, its inhibition represents a novel approach toward the simultaneous disruption of multiple signaling cascades. This review summarizes recent literature implicating Hsp90 as a key facilitator for the maturation of proteins represented in all six hallmarks of cancer: 1) growth signal self-sufficiency, 2) anti-growth signal insensitivity, 3) evasion of apoptosis, 4) unlimited replicative potential, 5) metastasis and tissue invasion, and 6) sustained angiogenesis. Also described are recent advances towards the development of novel Hsp90 inhibitors via structure-based drug design that have contributed to the number of compounds undergoing clinical development.

Pubertal testosterone influences threat-related amygdala-orbitofrontal cortex coupling.

PubMed

Spielberg, Jeffrey M; Forbes, Erika E; Ladouceur, Cecile D; Worthman, Carol M; Olino, Thomas M; Ryan, Neal D; Dahl, Ronald E

2015-03-01

Growing evidence indicates that normative pubertal maturation is associated with increased threat reactivity, and this developmental shift has been implicated in the increased rates of adolescent affective disorders. However, the neural mechanisms involved in this pubertal increase in threat reactivity remain unknown. Research in adults indicates that testosterone transiently decreases amygdala-orbitofrontal cortex (OFC) coupling. Consequently, we hypothesized that increased pubertal testosterone disrupts amygdala-OFC coupling, which may contribute to developmental increases in threat reactivity in some adolescents. Hypotheses were tested in a longitudinal study by examining the impact of testosterone on functional connectivity. Findings were consistent with hypotheses and advance our understanding of normative pubertal changes in neural systems instantiating affect/motivation. Finally, potential novel insights into the neurodevelopmental pathways that may contribute to adolescent vulnerability to behavioral and emotional problems are discussed. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Learning about Environments: The Significance of Primal Landscapes

NASA Astrophysics Data System (ADS)

Measham, Thomas G.

2006-09-01

The way we learn about our environments—be they farms, forests, or tribal lands—has implications for the formulation of environmental policy. This article presents the findings of how residents learned about their environments in two rural case studies conducted in northern Queensland and relates these to the concept of “primal landscapes,” which is concerned with the interaction that occurs between children and the environments in which they mature. Rather than focusing specifically on built environments or natural environments, the article draws on an approach that conceptualizes environment as meaning-laden places in which we live and work, which integrate social, cultural, biological, physical, and economic dimensions. In drawing insights for environmental policy, the article draws attention to the timing of policy interventions, the significance of experiential environmental education, the potential to learn from place-based festivals, and the importance of learning from extreme events such as fires and floods.

Cross-Cultural Studies of Personality Traits and their Relevance to Psychiatry

PubMed Central

Terracciano, Antonio; McCrae, Robert R.

2009-01-01

Aims This article provides a brief review of recent cross-cultural research on personality traits at both individual and culture levels, highlighting the relevance of recent findings for psychiatry. Method In most cultures around the world, personality traits can be clearly summarized by the five broad dimensions of the Five-Factor Model (FFM), which makes it feasible to compare cultures on personality and psychopathology. Results Maturational patterns and sex differences in personality traits generally show cultural invariance, which generates the hypothesis that age of onset, clinical evolution, and sex differences in the prevalence of psychiatric disorders might follow similar universal patterns. The average personality profiles from 51 cultures show meaningful geographical distributions and associations with culture-level variables, but are clearly unrelated to national character stereotypes. Conclusions Aggregate personality scores can potentially be related to epidemiological data on psychiatric disorders, and dimensional personality models have implications for psychiatric diagnosis and treatment around the world. PMID:17128620

In vivo activation of Wnt signaling pathway enhances cognitive function of adult mice and reverses cognitive deficits in an Alzheimer's disease model.

PubMed

Vargas, Jessica Y; Fuenzalida, Marco; Inestrosa, Nibaldo C

2014-02-05

The role of the Wnt signaling pathway during synaptic development has been well established. In the adult brain, different components of Wnt signaling are expressed, but little is known about its role in mature synapses. Emerging in vitro studies have implicated Wnt signaling in synaptic plasticity. Furthermore, activation of Wnt signaling has shown to protect against amyloid-β-induced synaptic impairment. The present study provides the first evidence that in vivo activation of Wnt signaling improves episodic memory, increases excitatory synaptic transmission, and enhances long-term potentiation in adult wild-type mice. Moreover, the activation of Wnt signaling also rescues memory loss and improves synaptic dysfunction in APP/PS1-transgenic mice that model the amyloid pathology of Alzheimer's diseases. These findings indicate that Wnt signaling modulates cognitive function in the adult brain and could be a novel promising target for Alzheimer's disease therapy.

[In vitro activity of matrine against Candida albicans biofilms].

PubMed

Wu, Lan; Zhou, Zeng-tong; Zhou, Yong-mei; Wang, Hai-yan; Shi, Lin-jun

2009-08-01

To establish a model of Candida albicans biofilms and to examine the effect of matrine on C.albicans biofilms and ultrastructure. C. albicans collection strain ATCC76615 was obtained and propagated. Biofilms were formed in 96-well microtiter plates. Antifungal susceptibility testing of C. albicans biofilms were assessed with the tetrazolium salt (XTT) reduction assay. Confocal laser scanning microscopy (CLSM) and dead/live fluorescent staining technique were combined to detect the effects of Matrine on preformed C. albican biofilms' composition and ultrastructure. Matrine was active against different growth stages (early,middle,mature) of biofilms; The bioactivity and drug-resistance of C. albican biofilm increased with culturing time. CLSM showed that C. albicans biofilms were inhibited and growth were predominantly composed of yeast cells and pseudohyphae. This study demonstrates that Matrine has potent activity against C.albicans biofilms in vitro and potential therapeutic implication for biofilm-associated candidal infections.

Suppressing unsteady flow in arterio-venous fistulae

NASA Astrophysics Data System (ADS)

Grechy, L.; Iori, F.; Corbett, R. W.; Shurey, S.; Gedroyc, W.; Duncan, N.; Caro, C. G.; Vincent, P. E.

2017-10-01

Arterio-Venous Fistulae (AVF) are regarded as the "gold standard" method of vascular access for patients with end-stage renal disease who require haemodialysis. However, a large proportion of AVF do not mature, and hence fail, as a result of various pathologies such as Intimal Hyperplasia (IH). Unphysiological flow patterns, including high-frequency flow unsteadiness, associated with the unnatural and often complex geometries of AVF are believed to be implicated in the development of IH. In the present study, we employ a Mesh Adaptive Direct Search optimisation framework, computational fluid dynamics simulations, and a new cost function to design a novel non-planar AVF configuration that can suppress high-frequency unsteady flow. A prototype device for holding an AVF in the optimal configuration is then fabricated, and proof-of-concept is demonstrated in a porcine model. Results constitute the first use of numerical optimisation to design a device for suppressing potentially pathological high-frequency flow unsteadiness in AVF.

The sacroiliac joint: an overview of its anatomy, function and potential clinical implications

PubMed Central

Vleeming, A; Schuenke, M D; Masi, A T; Carreiro, J E; Danneels, L; Willard, F H

2012-01-01

This article focuses on the (functional) anatomy and biomechanics of the pelvic girdle and specifically the sacroiliac joints (SIJs). The SIJs are essential for effective load transfer between the spine and legs. The sacrum, pelvis and spine, and the connections to the arms, legs and head, are functionally interrelated through muscular, fascial and ligamentous interconnections. A historical overview is presented on pelvic and especially SIJ research, followed by a general functional anatomical overview of the pelvis. In specific sections, the development and maturation of the SIJ is discussed, and a description of the bony anatomy and sexual morphism of the pelvis and SIJ is debated. The literature on the SIJ ligaments and innervation is discussed, followed by a section on the pathology of the SIJ. Pelvic movement studies are investigated and biomechanical models for SIJ stability analyzed, including examples of insufficient versus excessive sacroiliac force closure. PMID:22994881

The minimalist architectures of viroporins and their therapeutic implications

PubMed Central

OuYang, Bo; Chou, James J.

2014-01-01

Many viral genomes encode small, integral membrane proteins that form homo-oligomeric channels in membrane, and they transport protons, cations, and other molecules across the membrane barrier to aid various steps of viral entry and maturation. These viral proteins, collectively named viroporins, are crucial for viral pathogenicity. In the past five years, structures obtained by nuclear magnetic resonance (NMR), X-ray crystallography, and electron microscopy (EM) showed that viroporins often adopt minimalist architectures to achieve their functions. A number of small molecules have been identified to interfere with their channel activity and thereby inhibit viral infection, making viroporins potential drug targets for therapeutic intervention. The known architectures and inhibition mechanisms of viroporins differ significantly from each other, but some common principles are shared between them. This review article summarizes the recent developments in the structural investigation of viroporins and their inhibition by antiviral compounds. PMID:24055819

Exposure to an obesogenic diet during adolescence leads to abnormal maturation of neural and behavioral substrates underpinning fear and anxiety.

PubMed

Vega-Torres, Julio David; Haddad, Elizabeth; Lee, Jeong Bin; Kalyan-Masih, Priya; Maldonado George, Wanda I; López Pérez, Leonardo; Piñero Vázquez, Darla M; Arroyo Torres, Yaría; Santiago Santana, José M; Obenaus, Andre; Figueroa, Johnny D

2018-05-01

Post-traumatic stress disorder (PTSD) and obesity are highly prevalent in adolescents. Emerging findings from our laboratory and others are consistent with the novel hypothesis that obese individuals may be predisposed to developing PTSD. Given that aberrant fear responses are pivotal in the pathogenesis of PTSD, the objective of this study was to determine the impact of an obesogenic Western-like high-fat diet (WD) on neural substrates associated with fear. Adolescent Lewis rats (n = 72) were fed with either the experimental WD (41.4% kcal from fat) or the control diet. The fear-potentiated startle paradigm was used to determine sustained and phasic fear responses. Diffusion tensor imaging metrics and T2 relaxation times were used to determine the structural integrity of the fear circuitry including the medial prefrontal cortex (mPFC) and the basolateral complex of the amygdala (BLA). The rats that consumed the WD exhibited attenuated fear learning and fear extinction. These behavioral impairments were associated with oversaturation of the fear circuitry and astrogliosis. The BLA T2 relaxation times were significantly decreased in the WD rats relative to the controls. We found elevated fractional anisotropy in the mPFC of the rats that consumed the WD. We show that consumption of a WD may lead to long-lasting damage to components of the fear circuitry. Our findings demonstrate that consumption of an obesogenic diet during adolescence has a profound impact in the maturation of the fear neurocircuitry. The implications of this research are significant as they identify potential biomarkers of risk for psychopathology in the growing obese population. Copyright © 2018 Elsevier Inc. All rights reserved.

Keratins as components of the enamel organic matrix

PubMed Central

Duverger, Olivier; Beniash, Elia; Morasso, Maria I.

2016-01-01

Dental enamel is a hardest tissue in the human body, and although it starts as a tissue rich in proteins, by the time of eruption of the tooth in the oral cavity only a small fraction of the protein remains. While this organic matrix of enamel represents less than 1% by weight it plays essential roles in improving both toughness and resilience to chemical attacks. Despite the fact that the first studies of the enamel matrix began in the 19th century its exact composition and mechanisms of its function remain poorly understood. It was proposed that keratin or a keratin-like primitive epithelial component exists in mature enamel, however due to the extreme insolubility of its organic matrix the presence of keratins there was never clearly established. We have recently identified expression of a number of hair keratins in ameloblasts, the enamel secreting cells, and demonstrated their incorporation into mature enamel. Mutation in epithelial hair keratin KRT75 leads to a skin condition called pseudofollicularis barbae. Carriers of this mutation have an altered enamel structure and mechanical properties. Importantly, these individuals have a much higher prevalence of caries. To the best of our knowledge, this is the first study showing a direct link between a mutation in a protein-coding region of a gene and increased caries rates. In this paper we present an overview of the evidence of keratin-like material in enamel that has accumulated over the last 150 years. Furthermore, we propose potential mechanisms of action of KTR75 in enamel and highlight the clinical implications of the link between mutations in KRT75 and caries. Finally, we discuss the potential use of keratins for enamel repair. PMID:26709044

Regulation of hippocampal synaptic plasticity by the tyrosine kinase receptor, REK7/EphA5, and its ligand, AL-1/Ephrin-A5.

PubMed

Gao, W Q; Shinsky, N; Armanini, M P; Moran, P; Zheng, J L; Mendoza-Ramirez, J L; Phillips, H S; Winslow, J W; Caras, I W

1998-08-01

The Eph-related tyrosine kinase receptor, REK7/EphA5, mediates the effects of AL-1/Ephrin-A5 and related ligands and is involved in the guidance of retinal, cortical, and hippocampal axons during development. The continued expression of REK7/EphA5 in the adult brain, in particular in areas associated with a high degree of synaptic plasticity such as the hippocampus, raises the question of its function in the mature nervous system. In this report we examined the role of REK7/EphA5 in synaptic remodeling by asking if agents that either block or activate REK7/EphA5 affect synaptic strength in hippocampal slices from adult mouse brain. We show that a REK7/EphA5 antagonist, soluble REK7/EphA5-IgG, impairs the induction of long-term potentiation (LTP) without affecting other synaptic parameters such as normal synaptic transmission or paired-pulse facilitation. In contrast, perfusion with AL-1/Ephrin-A5-IgG, an activator of REK7/EphA5, induces a sustained increase in normal synaptic transmission that partially mimics LTP. The sustained elevation of normal synaptic transmission could be attributable to a long-lasting binding of the AL-1/Ephrin-A5-IgG to the endogenous REK7/EphA5 receptor, as revealed by immunohistochemistry. Furthermore, maximal electrical induction of LTP occludes the potentiating effects of subsequent treatment with AL-1/Ephrin-A5-IgG. Taken together these results implicate REK7/EphA5 in the regulation of synaptic plasticity in the mature hippocampus and suggest that REK7/EphA5 activation is recruited in the LTP induced by tetanization. Copyright 1998 Academic Press.

Follicular development and hormonal levels following highly purified or recombinant follicle-stimulating hormone administration in ovulatory women undergoing ovarian stimulation after pituitary suppression for in vitro fertilization: implications for implantation potential.

PubMed

Balasch, J; Fábregues, F; Creus, M; Peñarrubia, J; Vidal, E; Carmona, F; Puerto, B; Vanrell, J A

2000-01-01

The main goal in the present study was to compare follicular development and estradiol levels after ovarian stimulation in pituitary suppressed normally ovulating women undergoing IVF, using highly purified urinary follicle stimulating hormone (FSH) (u-FSH-HP) and recombinant FSH (rec-FSH). A secondary variable in our study was embryo implantation potential, which is closely related to appropriate follicular development and oocyte competence. For the main purpose of this study, 30 IVF patients (group 1) were treated during IVF consecutive cycles, using the same stimulation protocol, with u-FSH-HP in the first treatment study cycle and rec-FSH in the second one. As a control group (group 2) for implantation rates obtained in cycles treated with rec-FSH, 30 additional IVF patients were included who underwent a second IVF attempt again with u-FSH-HP. The total dose of FSH used and ovarian response obtained in terms of estradiol plasma levels and the total number of growing follicles on the day of human chronic gonadotropin (HCG) injection were similar in both treatment cycles in group 1 but better follicular dynamics and oocyte maturity were obtained with rec-FSH. The implantation rate was significantly higher in rec-FSH treated cycles in patients in group 1 than in control women (group 2). rec-FSH is more efficacious than u-FSH-HP when used in the same patient in inducing multiple follicular development in down-regulated cycles as indicated by ovarian performance and oocyte maturity. In addition, rec-FSH yields significantly higher implantation rates than u-FSH-HP when used in patients undergoing their second IVF attempt.

Glass Polyalkenoate Cements Designed for Cranioplasty Applications: An Evaluation of Their Physical and Mechanical Properties

PubMed Central

Khader, Basel A.; Curran, Declan J.; Peel, Sean; Towler, Mark R.

2016-01-01

Glass polyalkenoate cements (GPCs) have potential for skeletal cementation. Unfortunately, commercial GPCs all contain, and subsequently release, aluminum ions, which have been implicated in degenerative brain disease. The purpose of this research was to create a series of aluminum-free GPCs constructed from silicate (SiO2), calcium (CaO), zinc (ZnO) and sodium (Na2O)-containing glasses mixed with poly-acrylic acid (PAA) and to evaluate the potential of these cements for cranioplasty applications. Three glasses were formulated based on the SiO2-CaO-ZnO-Na2O parent glass (KBT01) with 0.03 mol % (KBT02) and 0.06 mol % (KBT03) germanium (GeO2) substituted for ZnO. Each glass was then mixed with 50 wt % of a patented SiO2-CaO-ZnO-strontium (SrO) glass composition and the resultant mixtures were subsequently reacted with aqueous PAA (50 wt % addition) to produce three GPCs. The incorporation of Ge in the glass phase was found to result in decreased working (142 s to 112 s) and setting (807 s to 448 s) times for the cements manufactured from them, likely due to the increase in crosslink formation between the Ge-containing glasses and the PAA. Compressive (σc) and biaxial flexural (σf) strengths of the cements were examined at 1, 7 and 30 days post mixing and were found to increase with both maturation and Ge content. The bonding strength of a titanium cylinder (Ti) attached to bone by the cements increased from 0.2 MPa, when placed, to 0.6 MPa, after 14 days maturation. The results of this research indicate that Germano-Silicate based GPCs have suitable handling and mechanical properties for cranioplasty fixation. PMID:27023623

Longitudinal maturation of auditory cortical function during adolescence.

PubMed

Fitzroy, Ahren B; Krizman, Jennifer; Tierney, Adam; Agouridou, Manto; Kraus, Nina

2015-01-01

Cross-sectional studies have demonstrated that the cortical auditory evoked potential (CAEP) changes substantially in amplitude and latency from childhood to adulthood, suggesting that these aspects of the CAEP continue to mature through adolescence. However, no study to date has longitudinally followed maturation of these CAEP measures through this developmental period. Additionally, no study has examined the trial-to-trial variability of the CAEP during adolescence. Therefore, we longitudinally tracked changes in the latency, amplitude, and variability of the P1, N1, P2, and N2 components of the CAEP in 68 adolescents from age 14 years to age 17 years. Latency decreased for N1 and N2, and did not change for P1 or P2. Amplitude decreased for P1 and N2, increased for N1, and did not change for P2. Variability decreased with age for all CAEP components. These findings provide longitudinal support for the view that the human auditory system continues to mature through adolescence. Continued auditory system maturation through adolescence suggests that CAEP neural generators remain plastic during this age range and potentially amenable to experience-based enhancement or deprivation.

Improving and accelerating the differentiation and functional maturation of human stem cell-derived neurons: role of extracellular calcium and GABA.

PubMed

Kemp, Paul J; Rushton, David J; Yarova, Polina L; Schnell, Christian; Geater, Charlene; Hancock, Jane M; Wieland, Annalena; Hughes, Alis; Badder, Luned; Cope, Emma; Riccardi, Daniela; Randall, Andrew D; Brown, Jonathan T; Allen, Nicholas D; Telezhkin, Vsevolod

2016-11-15

Neurons differentiated from pluripotent stem cells using established neural culture conditions often exhibit functional deficits. Recently, we have developed enhanced media which both synchronize the neurogenesis of pluripotent stem cell-derived neural progenitors and accelerate their functional maturation; together these media are termed SynaptoJuice. This pair of media are pro-synaptogenic and generate authentic, mature synaptic networks of connected forebrain neurons from a variety of induced pluripotent and embryonic stem cell lines. Such enhanced rate and extent of synchronized maturation of pluripotent stem cell-derived neural progenitor cells generates neurons which are characterized by a relatively hyperpolarized resting membrane potential, higher spontaneous and induced action potential activity, enhanced synaptic activity, more complete development of a mature inhibitory GABA A receptor phenotype and faster production of electrical network activity when compared to standard differentiation media. This entire process - from pre-patterned neural progenitor to active neuron - takes 3 weeks or less, making it an ideal platform for drug discovery and disease modelling in the fields of human neurodegenerative and neuropsychiatric disorders, such as Huntington's disease, Parkinson's disease, Alzheimer's disease and Schizophrenia. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Tooth enamel mineralization in ungulates: implications for recovering a primary isotopic time-series

NASA Astrophysics Data System (ADS)

Passey, Benjamin H.; Cerling, Thure E.

2002-09-01

Temporal changes in the carbon and oxygen isotopic composition of an animal are an environmental and behavioral input signal that is recorded into the enamel of developing teeth. In this paper, we evaluate changes in phosphorus content and density along the axial lengths of three developing ungulate teeth to illustrate the protracted nature of mineral accumulation in a volume of developing enamel. The least mature enamel in these teeth contains by volume about 25% of the mineral mass of mature enamel, and the remaining 75% of the mineral accumulates during maturation. Using data from one of these teeth (a Hippopotamus amphibius canine), we develop a model for teeth growing at constant rate that describes how an input signal is recorded into tooth enamel. The model accounts for both the temporal and spatial patterns of amelogenesis (enamel formation) and the sampling geometry. The model shows that input signal attenuation occurs as a result of time-averaging during amelogenesis when the maturation interval is long compared to the duration of features in the input signal. Sampling does not induce significant attenuation, provided that the sampling interval is several times shorter than the maturation interval. We present a detailed δ 13C and δ 18O record for the H. amphibius canine and suggest possible input isotope signals that may have given rise to the measured isotope signal.

Arteriovenous fistula maturation in patients with permanent access created prior to or after hemodialysis initiation.

PubMed

Duque, Juan C; Martinez, Laisel; Tabbara, Marwan; Dvorquez, Denise; Mehandru, Sushil K; Asif, Arif; Vazquez-Padron, Roberto I; Salman, Loay H

2017-05-15

Multiple factors and comorbidities have been implicated in the ability of arteriovenous fistulas (AVF) to mature, including vessel anatomy, advanced age, and the presence of coronary artery disease or peripheral vascular disease. However, little is known about the role of uremia on AVF primary failure. In this study, we attempt to evaluate the effect of uremia on AVF maturation by comparing AVF outcomes between pre-dialysis chronic kidney disease (CKD) stage five patients and those who had their AVF created after hemodialysis (HD) initiation. We included 612 patients who underwent AVF creation between 2003 and 2015 at the University of Miami Hospital and Jackson Memorial Hospital. Effects of uremia on primary failure were evaluated using univariate statistical comparisons and multivariate logistic regression analyses. Primary failure occurred in 28.1% and 26.3% of patients with an AVF created prior to or after HD initiation, respectively (p = 0.73). The time of HD initiation was not associated with AVF maturation in multivariate logistic regression analysis (p = 0.57). In addition, pre-operative blood urea nitrogen (p = 0.78), estimated glomerular filtration rate (p = 0.66), and serum creatinine levels (p = 0.14) were not associated with AVF primary failure in pre-dialysis patients. Our results show that clearance of uremia with regular HD treatments prior to AVF creation does not improve the frequency of vascular access maturation.

An endosomal syntaxin and the AP-3 complex are required for formation and maturation of candidate lysosome-related secretory organelles (mucocysts) in Tetrahymena thermophila

PubMed Central

Kaur, Harsimran; Sparvoli, Daniela; Osakada, Hiroko; Iwamoto, Masaaki; Haraguchi, Tokuko; Turkewitz, Aaron P.

2017-01-01

The ciliate Tetrahymena thermophila synthesizes large secretory vesicles called mucocysts. Mucocyst biosynthesis shares features with dense core granules (DCGs) in animal cells, including proteolytic processing of cargo proteins during maturation. However, other molecular features have suggested relatedness to lysosome-related organelles (LROs). LROs, which include diverse organelles in animals, are formed via convergence of secretory and endocytic trafficking. Here we analyzed Tetrahymena syntaxin 7-like 1 (Stx7l1p), a Qa-SNARE whose homologues in other lineages are linked with vacuoles/LROs. Stx7l1p is targeted to both immature and mature mucocysts and is essential in mucocyst formation. In STX7L1-knockout cells, the two major classes of mucocyst cargo proteins localize independently, accumulating in largely nonoverlapping vesicles. Thus initial formation of immature mucocysts involves heterotypic fusion, in which a subset of mucocyst proteins is delivered via an endolysosomal compartment. Further, we show that subsequent maturation requires AP-3, a complex widely implicated in LRO formation. Knockout of the µ-subunit gene does not impede delivery of any known mucocyst cargo but nonetheless arrests mucocyst maturation. Our data argue that secretory organelles in ciliates may represent a new class of LROs and reveal key roles of an endosomal syntaxin and AP-3 in the assembly of this complex compartment. PMID:28381425

Alternative life histories in Xiphophorus multilineatus: evidence for different ages at sexual maturity and growth responses in the wild.

PubMed

Bono, L M; Rios-Cardenas, O; Morris, M R

2011-05-01

In order to examine potential trade-offs in alternative life histories of the high-backed pygmy swordtail Xiphophorus multilineatus, otoliths were used from wild-caught males to determine if sneaker males had the advantage of maturing earlier in natural environments. The sneakers matured significantly earlier than courters, but there was no difference among the three courter variants. In addition, analyses suggested that the effect of the pituitary locus on size at sexual maturity and growth rates was a consequence of age at sexual maturity. Finally, one of the courter variants had a significantly different relationship between age and size at sexual maturity than the other variants, suggesting that in this variant, age at sexual maturity may be more closely related to size and therefore may be less plastic in its growth responses. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

Tectono-thermal History of the Southern Nenana Basin, Interior Alaska: Implications for Conventional and Unconventional Hydrocarbon Exploration

NASA Astrophysics Data System (ADS)

Dixit, N. C.; Hanks, C. L.

2014-12-01

The Tertiary Nenana basin of Interior Alaska is currently the focus of both new oil exploration and coalbed methane exploitation and is being evaluated as a potential CO2sequestration site. The basin first formed as a Late Paleocene extensional rift with the deposition of oil and gas-prone, coal-bearing non-marine sediments with excellent source potential. Basin inversion during the Early Eocene-Early Oligocene times resulted in folding and erosion of higher stratigraphic levels, forming excellent structural and stratigraphic traps. Initiation of active faulting on its eastern margin in the middle Oligocene caused slow tectonic subsidence that resulted in the deposition of reservoir and seal rocks of the Usibelli Group. Onset of rapid tectonic subsidence in Pliocene that continues to the present-day has provided significant pressure and temperature gradient for the source rocks. Apatite fission-track and vitrinite reflectance data reveals two major paleo-thermal episodes: Late Paleocene to Early Eocene (60 Ma to 54.8 Ma) and Late Miocene to present-day (7 Ma to present). These episodes of maximum paleotemperatures have implications for the evolution of source rock maturity within the basin. In this study, we are also investigating the potential for coalbed methane production from the Late Paleocene coals via injection of CO2. Our preliminary analyses demonstrate that 150 MMSCF of methane could be produced while 33000 tonnes of CO2 per injection well (base case of ~9 years) can be sequestered in the vicinity of existing infrastructure. However, these volumes of sequestered CO2and coal bed methane recovery are estimates and are sensitive to the reservoir's geomechanical and flow properties. Keywords: extensional rift, seismic, subsidence, thermal history, fission track, vitrinite reflectance, coal bed methane, Nenana basin, CO2 sequestration

Thermal maturity and organic composition of Pennsylvanian coals and carbonaceous shales, north-central Texas: Implications for coalbed gas potential

USGS Publications Warehouse

Hackley, P.C.; Guevara, E.H.; Hentz, T.F.; Hook, R.W.

2009-01-01

Thermal maturity was determined for about 120 core, cuttings, and outcrop samples to investigate the potential for coalbed gas resources in Pennsylvanian strata of north-central Texas. Shallow (< 600??m; 2000??ft) coal and carbonaceous shale cuttings samples from the Middle-Upper Pennsylvanian Strawn, Canyon, and Cisco Groups in Archer and Young Counties on the Eastern Shelf of the Midland basin (northwest and downdip from the outcrop) yielded mean random vitrinite reflectance (Ro) values between about 0.4 and 0.8%. This range of Ro values indicates rank from subbituminous C to high volatile A bituminous in the shallow subsurface, which may be sufficient for early thermogenic gas generation. Near-surface (< 100??m; 300??ft) core and outcrop samples of coal from areas of historical underground coal mining in the region yielded similar Ro values of 0.5 to 0.8%. Carbonaceous shale core samples of Lower Pennsylvanian strata (lower Atoka Group) from two deeper wells (samples from ~ 1650??m; 5400??ft) in Jack and western Wise Counties in the western part of the Fort Worth basin yielded higher Ro values of about 1.0%. Pyrolysis and petrographic data for the lower Atoka samples indicate mixed Type II/Type III organic matter, suggesting generated hydrocarbons may be both gas- and oil-prone. In all other samples, organic material is dominated by Type III organic matter (vitrinite), indicating that generated hydrocarbons should be gas-prone. Individual coal beds are thin at outcrop (< 1??m; 3.3??ft), laterally discontinuous, and moderately high in ash yield and sulfur content. A possible analog for coalbed gas potential in the Pennsylvanian section of north-central Texas occurs on the northeast Oklahoma shelf and in the Cherokee basin of southeastern Kansas, where contemporaneous gas-producing coal beds are similar in thickness, quality, and rank.

Leadership Development and Organizational Maturity.

ERIC Educational Resources Information Center

Iannuzzi, Patricia

1992-01-01

Urges the design and implementation of strategies in academic libraries for the development of leadership potential. Discusses the components of organizations that lead to organizational maturity, and calls for library leaders with vision, skill, and commitment to nurture an organizational culture that emphasizes leadership development. (20…

Effect of oxygen levels on the physiology of dendritic cells: implications for adoptive cell therapy.

PubMed

Futalan, Diahnn; Huang, Chien-Tze; Schmidt-Wolf, Ingo G H; Larsson, Marie; Messmer, Davorka

2011-01-01

Dendritic cell (DC)-based adoptive tumor immunotherapy approaches have shown promising results, but the incidence of tumor regression is low and there is an evident call for identifying culture conditions that produce DCs with a more potent Th1 potential. Routinely, DCs are differentiated in CO(2) incubators under atmospheric oxygen conditions (21% O(2)), which differ from physiological oxygen levels of only 3-5% in tissue, where most DCs reside. We investigated whether differentiation and maturation of DCs under physiological oxygen levels could produce more potent T-cell stimulatory DCs for use in adoptive immunotherapy. We found that immature DCs differentiated under physiological oxygen levels showed a small but significant reduction in their endocytic capacity. The different oxygen levels did not influence their stimuli-induced upregulation of cluster of differentiation 54 (CD54), CD40, CD83, CD86, C-C chemokine receptor type 7 (CCR7), C-X-C chemokine receptor type 4 (CXCR4) and human leukocyte antigen (HLA)-DR or the secretion of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10 in response to lipopolysaccharide (LPS) or a cytokine cocktail. However, DCs differentiated under physiological oxygen level secreted higher levels of IL-12(p70) after exposure to LPS or CD40 ligand. Immature DCs differentiated at physiological oxygen levels caused increased T-cell proliferation, but no differences were observed for mature DCs with regard to T-cell activation. In conclusion, we show that although DCs generated under atmospheric or physiological oxygen conditions are mostly similar in function and phenotype, DCs differentiated under physiological oxygen secrete larger amounts of IL-12(p70). This result could have implications for the use of ex vivo-generated DCs for clinical studies, since DCs differentiated at physiological oxygen could induce increased Th1 responses in vivo.

Circuit and synaptic mechanisms of repeated stress: Perspectives from differing contexts, duration, and development.

PubMed

Bath, Kevin G; Russo, Scott J; Pleil, Kristen E; Wohleb, Eric S; Duman, Ronald S; Radley, Jason J

2017-12-01

The current review is meant to synthesize research presented as part of a symposium at the 2016 Neurobiology of Stress workshop in Irvine California. The focus of the symposium was "Stress and the Synapse: New Concepts and Methods" and featured the work of several junior investigators. The presentations focused on the impact of various forms of stress (altered maternal care, binge alcohol drinking, chronic social defeat, and chronic unpredictable stress) on synaptic function, neurodevelopment, and behavioral outcomes. One of the goals of the symposium was to highlight the mechanisms accounting for how the nervous system responds to stress and their impact on outcome measures with converging effects on the development of pathological behavior. Dr. Kevin Bath's presentation focused on the impact of disruptions in early maternal care and its impact on the timing of hippocampus maturation in mice, finding that this form of stress drove accelerated synaptic and behavioral maturation, and contributed to the later emergence of risk for cognitive and emotional disturbance. Dr. Scott Russo highlighted the impact of chronic social defeat stress in adolescent mice on the development and plasticity of reward circuity, with a focus on glutamatergic development in the nucleus accumbens and mesolimbic dopamine system, and the implications of these changes for disruptions in social and hedonic response, key processes disturbed in depressive pathology. Dr. Kristen Pleil described synaptic changes in the bed nuclei of the stria terminalis that underlie the behavioral consequences of allostatic load produced by repeated cycles of alcohol binge drinking and withdrawal. Dr. Eric Wohleb and Dr. Ron Duman provided new data associating decreased mammalian target of rapamycin (mTOR) signaling and neurobiological changes in the synapses in response to chronic unpredictable stress, and highlighted the potential for the novel antidepressant ketamine to rescue synaptic and behavioral effects. In aggregate, these presentations showcased how divergent perspectives provide new insights into the ways in which stress impacts circuit development and function, with implications for understanding emergence of affective pathology.

Oils and hydrocarbon source rocks of the Baltic syneclise

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

Kanev, S.; Margulis, L.; Bojesen-Koefoed, J.A.

Prolific source rock horizons of varying thickness, having considerable areal extent, occur over the Baltic syneclise. These source sediments are rich and have excellent petroleum generation potential. Their state of thermal maturity varies form immature in the northeastern part of the syneclise to peak generation maturity in the southwestern part of the region-the main kitchen area. These maturity variations are manifest in petroleum composition in the region. Hence, mature oils occur in the Polish and Kaliningrad areas, immature oils in small accumulations in Latvian and central Lithuanian onshore areas, and intermediate oils in areas between these extremes. The oil accumulationsmore » probably result from pooling of petroleum generated from a number of different source rocks at varying levels of thermal maturity. Hence, no single source for petroleum occurrences in the Baltic syneclise may be identified. The paper describes the baltic syneclise, source rocks, thermal maturity and oils and extracts.« less

The characteristics and experiences of mature nursing students.

PubMed

Montgomery, Laura E A; Tansey, Etain A; Roe, Sean M

To explore the characteristics of mature nursing students, including how they perceive themselves, and to identify the problems they experience, which may influence whether they continue with their course. A sample of 239 students completed an anonymous questionnaire at the end of their first year of study for a diploma in nursing science. A question concerning age was included to enable identification of mature students, of which there were 90. Mature students as a group were desirable students, tending to perform better academically than their younger counterparts and bringing a wealth of caring experience to the course. However, mature students experienced additional pressures, for example financial concerns. When considering the potential benefits of educating mature students, the government and universities should be encouraging their recruitment and retention. An increase in the bursary and free or heavily subsidised childcare would help to alleviate financial concerns.

Organic petrology of the Aptian-age section in the downdip Mississippi Interior Salt Basin, Mississippi, USA: Observations and preliminary implications for thermal maturation history

USGS Publications Warehouse

Valentine, Brett J.; Hackley, Paul C.; Enomoto, Catherine B.; Bove, Alana M.; Dulong, Frank T.; Lohr, Celeste D.; Scott, Krystina R.

2014-01-01

This study identifies a thermal maturity anomaly within the downdip Mississippi Interior Salt Basin (MISB) of southern Mississippi, USA, through examination of bitumen reflectance data from Aptian-age strata (Sligo Formation, Pine Island Shale, James Limestone, and Rodessa Formation). U.S. Geological Survey (USGS) reconnaissance investigations conducted in 2011–2012 examined Aptian-age thermal maturity trends across the onshore northern Gulf of Mexico region and indicated that the section in the downdip MISB is approaching the wet gas/condensate window (Ro~1.2%). A focused study in 2012–2013 used 6 whole core, one sidewall core, and 49 high-graded cutting samples (depth range of 13,000–16,500 ft [3962.4–5029.2 m] below surface) collected from 15 downdip MISB wells for mineralogy, fluid inclusion, organic geochemistry, and organic petrographic analysis. Based on native solid bitumen reflectance (Ro generally > 0.8%; interpreted to be post-oil indigenous bitumens matured in situ), Ro values increase regionally across the MISB from the southeast to the northwest. Thermal maturity in the eastern half of the basin (Ro range 1.0 to 1.25%) appears to be related to present-day burial depth and shows a gradual increase with respect to depth. To the west, thermal maturity continues to increase even as the Aptian section shallows structurally on the Adams County High (Ro range 1.4 to > 1.8%). After evaluating the possible thermal agents responsible for increasing maturity at shallower depths (i.e., igneous activity, proximity to salt, variations in regional heat flux, and uplift), we tentatively propose that either greater paleoheat flow or deeper burial coupled with uplift in the western part of the MISB could be responsible for the thermal maturity anomaly. Further research and additional data are needed to determine the cause(s) of the thermal anomaly.

Effects of sexual maturation and Salmonella infection on the expression of Toll-like receptors in the chicken vagina.

PubMed

Michailidis, G; Theodoridis, A; Avdi, M

2011-02-01

Toll-like receptors (TLRs) are a critical component of the innate immune response in many vertebrates, including avian species. The recent findings of chicken TLRs (cTLRs) expression in ovarian follicles and in the chicken ovary in vivo, as well as the changes in their expression in response to lipopolysaccharide or Salmonella enteritidis (SE) infection, have broad implications for reproductive physiology and for the prevention of transmission of zoonotic diseases to humans through the consumption of contaminated poultry eggs. Because the main route of egg contamination is from infection of the oviduct and mainly from the vagina, the aim of this study was to investigate the expression of the ten cTLRs identified to date in the chicken oviduct in vivo, to determine whether sexual maturation affects their mRNA abundance and to investigate whether SE infection alters the expression of TLRs in the chicken vagina. RNA was extracted from the vagina of healthy prepubertal, sexually mature and aged birds, and from sexually mature and aged SE infected birds. RT-PCR analysis revealed that all types of cTLRs apart from TLR1-1 were expressed in the vagina of sexually mature birds. Quantitative real-time PCR analysis revealed that the mRNA abundance of TLR2-1, 2-2 and 4 differ with respect to sexual maturation in the chicken vagina. SE infection resulted in a significant induction of TLR5 and 15 in the vagina of sexually mature birds, and in a significant induction of TLR2-1, 4 and 15 in the vagina of aged birds, while a significant down-regulation was observed for TLR7 in the vagina of sexually mature birds. These findings suggest that a TLR mediated immune response mechanism exists in the chicken vagina, playing a crucial role in preventing microbial pathogens from being incorporated into newly forming eggs. Copyright © 2011 Elsevier B.V. All rights reserved.

Mammalian target of rapamycin (mTOR) signaling is required for a late-stage fusion process during skeletal myotube maturation.

PubMed

Park, In-Hyun; Chen, Jie

2005-09-09

Skeletal myogenesis is a well orchestrated cascade of events regulated by multiple signaling pathways, one of which is recently characterized by its sensitivity to the bacterial macrolide rapamycin. Previously we reported that the mammalian target of rapamycin (mTOR) regulates the initiation of the differentiation program in mouse C2C12 myoblasts by controlling the expression of insulin-like growth factor-II in a kinase-independent manner. Here we provide experimental evidence suggesting that a different mode of mTOR signaling regulates skeletal myogenesis at a later stage. In the absence of endogenous mTOR function in C2C12 cells treated with rapamycin, a kinase-inactive mTOR fully supports myogenin expression, but causes a delay in contractile protein expression. Myoblasts fuse to form nascent myotubes in the absence of kinase-active mTOR, whereas the formation of mature myotubes by further fusion requires the catalytic activity of mTOR. Therefore, the two stages of myocyte fusion are molecularly separable at the level of mTOR signaling. In addition, our data suggest that a factor secreted into the culture medium is responsible for mediating the function of mTOR in regulating the late-stage fusion leading to mature myotubes. Furthermore, taking advantage of the unique features of cells stably expressing a mutant mTOR, we have performed cDNA microarray analysis to compare global gene expression profiles between mature and nascent myotubes, the results of which have implicated classes of genes and revealed candidate regulators in myotube maturation or functions of mature myotubes.

The Number of Sexual Partners and Health-Risking Sexual Behavior: Prediction from High School Entry to High School Exit

PubMed Central

Van Ryzin, Mark J.; Johnson, Amber B.; Leve, Leslie D.; Hyoun, Kim K.

2013-01-01

Precursors to adolescent health-risking sexual behavior (HRSB) were examined in a normative sample of 373 adolescents (48.0% female, n = 178). Using a variable-oriented approach, we regressed the number of sexual partners at high school exit (age 17) on parental monitoring, association with delinquent peers, romantic relationship status, problem behavior, physical maturity, and tobacco and alcohol use at high school entry (age 14); all emerged as significant predictors except alcohol use and physical maturity (we found sex differences in physical maturity and romantic relationship status, with females being more advanced in both areas). Sexual experimentation at high school entry served to partially or fully mediate the impact of these factors. A person-oriented approach, using a broader measure of HRSB, found three subgroups of adolescents: abstainers, low-risk-takers, and high-risk-takers. Results predicting membership in these groups generally followed those from the variable-oriented analysis. Implications for the prevention of HRSB and future research directions are discussed. PMID:20703789

Modeling the clinical phenotype of BTK inhibition in the mature murine immune system.

PubMed

Benson, Micah J; Rodriguez, Varenka; von Schack, David; Keegan, Sean; Cook, Tim A; Edmonds, Jason; Benoit, Stephen; Seth, Nilufer; Du, Sarah; Messing, Dean; Nickerson-Nutter, Cheryl L; Dunussi-Joannopoulos, Kyri; Rankin, Andrew L; Ruzek, Melanie; Schnute, Mark E; Douhan, John

2014-07-01

Inhibitors of Bruton's tyrosine kinase (BTK) possess much promise for the treatment of oncologic and autoimmune indications. However, our current knowledge of the role of BTK in immune competence has been gathered in the context of genetic inactivation of btk in both mice and man. Using the novel BTK inhibitor PF-303, we model the clinical phenotype of BTK inhibition by systematically examining the impact of PF-303 on the mature immune system in mice. We implicate BTK in tonic BCR signaling, demonstrate dependence of the T3 B cell subset and IgM surface expression on BTK activity, and find that B1 cells survive and function independently of BTK. Although BTK inhibition does not impact humoral memory survival, Ag-driven clonal expansion of memory B cells and Ab-secreting cell generation are inhibited. These data define the role of BTK in the mature immune system and mechanistically predict the clinical phenotype of chronic BTK inhibition. Copyright © 2014 by The American Association of Immunologists, Inc.

Effects of nitric oxide on neuromuscular properties of developing zebrafish embryos.

PubMed

Jay, Michael; Bradley, Sophie; McDearmid, Jonathan Robert

2014-01-01

Nitric oxide is a bioactive signalling molecule that is known to affect a wide range of neurodevelopmental processes. However, its functional relevance to neuromuscular development is not fully understood. Here we have examined developmental roles of nitric oxide during formation and maturation of neuromuscular contacts in zebrafish. Using histochemical approaches we show that elevating nitric oxide levels reduces the number of neuromuscular synapses within the axial swimming muscles whilst inhibition of nitric oxide biosynthesis has the opposite effect. We further show that nitric oxide signalling does not change synapse density, suggesting that the observed effects are a consequence of previously reported changes in motor axon branch formation. Moreover, we have used in vivo patch clamp electrophysiology to examine the effects of nitric oxide on physiological maturation of zebrafish neuromuscular junctions. We show that developmental exposure to nitric oxide affects the kinetics of spontaneous miniature end plate currents and impacts the neuromuscular drive for locomotion. Taken together, our findings implicate nitrergic signalling in the regulation of zebrafish neuromuscular development and locomotor maturation.

Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies

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

Ovchinnikov, Victor; Louveau, Joy E.; Barton, John P.

Eliciting antibodies that are cross reactive with surface proteins of diverse strains of highly mutable pathogens (e.g., HIV, influenza) could be key for developing effective universal vaccines. Mutations in the framework regions of such broadly neutralizing antibodies (bnAbs) have been reported to play a role in determining their properties. We used molecular dynamics simulations and models of affinity maturation to study specific bnAbs against HIV. Our results suggest that there are different classes of evolutionary lineages for the bnAbs. If germline B cells that initiate affinity maturation have high affinity for the conserved residues of the targeted epitope, framework mutationsmore » increase antibody rigidity as affinity maturation progresses to evolve bnAbs. If the germline B cells exhibit weak/moderate affinity for conserved residues, an initial increase in flexibility via framework mutations may be required for the evolution of bnAbs. Subsequent mutations that increase rigidity result in highly potent bnAbs. Implications of our results for immunogen design are discussed.« less

Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies

DOE PAGES

Ovchinnikov, Victor; Louveau, Joy E.; Barton, John P.; ...

2018-02-14

Eliciting antibodies that are cross reactive with surface proteins of diverse strains of highly mutable pathogens (e.g., HIV, influenza) could be key for developing effective universal vaccines. Mutations in the framework regions of such broadly neutralizing antibodies (bnAbs) have been reported to play a role in determining their properties. We used molecular dynamics simulations and models of affinity maturation to study specific bnAbs against HIV. Our results suggest that there are different classes of evolutionary lineages for the bnAbs. If germline B cells that initiate affinity maturation have high affinity for the conserved residues of the targeted epitope, framework mutationsmore » increase antibody rigidity as affinity maturation progresses to evolve bnAbs. If the germline B cells exhibit weak/moderate affinity for conserved residues, an initial increase in flexibility via framework mutations may be required for the evolution of bnAbs. Subsequent mutations that increase rigidity result in highly potent bnAbs. Implications of our results for immunogen design are discussed.« less

Ubiquitination dynamics in the early-branching eukaryote Giardia intestinalis

PubMed Central

Niño, Carlos A; Chaparro, Jenny; Soffientini, Paolo; Polo, Simona; Wasserman, Moises

2013-01-01

Ubiquitination is a highly dynamic and versatile posttranslational modification that regulates protein function, stability, and interactions. To investigate the roles of ubiquitination in a primitive eukaryotic lineage, we utilized the early-branching eukaryote Giardia intestinalis. Using a combination of biochemical, immunofluorescence-based, and proteomics approaches, we assessed the ubiquitination status during the process of differentiation in Giardia. We observed that different types of ubiquitin modifications present specific cellular and temporal distribution throughout the Giardia life cycle from trophozoites to cyst maturation. Ubiquitin signal was detected in the wall of mature cysts, and enzymes implicated in cyst wall biogenesis were identified as substrates for ubiquitination. Interestingly, inhibition of proteasome activity did not affect trophozoite replication and differentiation, while it caused a decrease in cyst viability, arguing for proteasome involvement in cyst wall maturation. Using a proteomics approach, we identified around 200 high-confidence ubiquitinated candidates that vary their ubiquitination status during differentiation. Our results indicate that ubiquitination is critical for several cellular processes in this primitive eukaryote. PMID:23613346

Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies

PubMed Central

2018-01-01

Eliciting antibodies that are cross reactive with surface proteins of diverse strains of highly mutable pathogens (e.g., HIV, influenza) could be key for developing effective universal vaccines. Mutations in the framework regions of such broadly neutralizing antibodies (bnAbs) have been reported to play a role in determining their properties. We used molecular dynamics simulations and models of affinity maturation to study specific bnAbs against HIV. Our results suggest that there are different classes of evolutionary lineages for the bnAbs. If germline B cells that initiate affinity maturation have high affinity for the conserved residues of the targeted epitope, framework mutations increase antibody rigidity as affinity maturation progresses to evolve bnAbs. If the germline B cells exhibit weak/moderate affinity for conserved residues, an initial increase in flexibility via framework mutations may be required for the evolution of bnAbs. Subsequent mutations that increase rigidity result in highly potent bnAbs. Implications of our results for immunogen design are discussed. PMID:29442996

Seipin is required for converting nascent to mature lipid droplets

PubMed Central

Wang, Huajin; Becuwe, Michel; Housden, Benjamin E; Chitraju, Chandramohan; Porras, Ashley J; Graham, Morven M; Liu, Xinran N; Thiam, Abdou Rachid; Savage, David B; Agarwal, Anil K; Garg, Abhimanyu; Olarte, Maria-Jesus; Lin, Qingqing; Fröhlich, Florian; Hannibal-Bach, Hans Kristian; Upadhyayula, Srigokul; Perrimon, Norbert; Kirchhausen, Tomas; Ejsing, Christer S; Walther, Tobias C; Farese, Robert V

2016-01-01

How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation—the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs. DOI: http://dx.doi.org/10.7554/eLife.16582.001 PMID:27564575

The number of sexual partners and health-risking sexual behavior: prediction from high school entry to high school exit.

PubMed

Van Ryzin, Mark J; Johnson, Amber B; Leve, Leslie D; Kim, Hyoun K

2011-10-01

Precursors to adolescent health-risking sexual behavior (HRSB) were examined in a normative sample of 373 adolescents (48.0% female, n = 178). Using a variable-oriented approach, we regressed the number of sexual partners at high school exit (age 17) on parental monitoring, association with delinquent peers, romantic relationship status, problem behavior, physical maturity, and tobacco and alcohol use at high school entry (age 14); all emerged as significant predictors except alcohol use and physical maturity (we found sex differences in physical maturity and romantic relationship status, with females being more advanced in both areas). Sexual experimentation at high school entry served to partially or fully mediate the impact of these factors. A person-oriented approach, using a broader measure of HRSB, found three subgroups of adolescents: abstainers, low-risk-takers, and high-risk-takers. Results predicting membership in these groups generally followed those from the variable-oriented analysis. Implications for the prevention of HRSB and future research directions are discussed.

Kerogen maturation and incipient graphitization of hydrocarbon source rocks in the Arkoma Basin, Oklahoma and Arkansas: A combined petrographic and Raman spectrometric study

USGS Publications Warehouse

Spotl, C.; Houseknecht, D.W.; Jaques, R.C.

1998-01-01

Dispersed kerogen of the Woodford-Chattanooga and Atoka Formations from the subsurface of the Arkoma Basin show a wide range of thermal maturities (0.38 to 6.1% R(o)) indicating thermal conditions ranging from diagenesis to incipient rock metamorphism. Raman spectral analysis reveals systematic changes of both the first- and second-order spectrum with increasing thermal maturity. These changes include a pronounced increase in the D/O peak height ratio accompanied by a narrowing of the D peak, a gradual decrease in the D/O peak width ratio, and a shift of both peaks toward higher wave numbers. Second-order Raman peaks, though less intensive, also show systematic peak shifting as a function of R(o). These empirical results underscore the high potential of Raman spectrometry as a fast and reliable geothermometer of mature to supermature hydrocarbon source rocks, and as an indicator of thermal maturity levels within the anchizone.Dispersed kerogen of the Woodford-Chattanooga and Atoka Formations from the subsurface of the Arkoma Basin show a wide range of thermal maturities (0.38 to 6.1% Ro) indicating thermal conditions ranging from diagenesis to incipient rock metamorphism. Raman spectral analysis reveals systematic changes of both the first- and second-order spectrum with increasing thermal maturity. These changes include a pronounced increase in the D/O peak height ratio accompanied by a narrowing of the D peak, a gradual decrease in the D/O peak width ratio, and a shift of both peaks toward higher wave numbers. Second-order Raman peaks, though less intensive, also show systematic peak shifting as a function of Ro. These empirical results underscore the high potential of Raman spectrometry as a fast and reliable geothermometer of mature to supermature hydrocarbon source rocks, and as an indicator of thermal maturity levels within the anchizone.

How research in behavioral pharmacology informs behavioral science.

PubMed

Branch, Marc N

2006-05-01

Behavioral pharmacology is a maturing science that has made significant contributions to the study of drug effects on behavior, especially in the domain of drug-behavior interactions. Less appreciated is that research in behavioral pharmacology can have, and has had, implications for the experimental analysis of behavior, especially its conceptualizations and theory. In this article, I outline three general strategies in behavioral pharmacology research that have been employed to increase understanding of behavioral processes. Examples are provided of the general characteristics of the strategies and of implications of previous research for behavior theory. Behavior analysis will advance as its theories are challenged.

Bone Morphogenetic Protein 15 in the Pro-Mature Complex Form Enhances Bovine Oocyte Developmental Competence

PubMed Central

Sudiman, Jaqueline; Sutton-McDowall, Melanie L.; Ritter, Lesley J.; White, Melissa A.; Mottershead, David G.; Thompson, Jeremy G.; Gilchrist, Robert B.

2014-01-01

Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/− FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/− FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies. PMID:25058588

Bone morphogenetic protein 15 in the pro-mature complex form enhances bovine oocyte developmental competence.

PubMed

Sudiman, Jaqueline; Sutton-McDowall, Melanie L; Ritter, Lesley J; White, Melissa A; Mottershead, David G; Thompson, Jeremy G; Gilchrist, Robert B

2014-01-01

Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/- FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/- FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies.

The Significance of the Origin of Physical Chemistry for Physical Chemistry Education: The Case of Electrolyte Solution Chemistry

ERIC Educational Resources Information Center

de Berg, Kevin Charles

2014-01-01

Physical Chemistry's birth was fraught with controversy, a controversy about electrolyte solution chemistry which has much to say about how scientific knowledge originates, matures, and responds to challenges. This has direct implications for the way our students are educated in physical chemistry in particular and science in general. The…

Improving HEI Productivity and Performance through Project Management: Implications from a Benchmarking Case Study

ERIC Educational Resources Information Center

Bryde, David; Leighton, Diana

2009-01-01

As higher education institutions (HEIs) look to be more commercial in their outlook they are likely to become more dependent on the successful implementation of projects. This article reports a benchmarking survey of PM maturity in a HEI, with the purpose of assessing its capability to implement projects. Data were collected via questionnaires…

Coming of Age, Media and the Mature Audience. Media & Values 45.

ERIC Educational Resources Information Center

Thoman, Elizabeth, Ed.; Silver, Rosalind, Ed.

1989-01-01

This issue of "Media & Values" explores the influence of mass media on the perceptions about aging in our society. The essays present various interpretations of that influence and the implications for the society. Articles in the "Awareness/Analysis" section include: (1) "Granny Bashing: New Myth Recasts Elders as Villains" (Ronald F. Pollack);…

"Mass Effect 2": A Case Study in the Design of Game Narrative

ERIC Educational Resources Information Center

Bizzocchi, Jim; Tanenbaum, Joshua

2012-01-01

Digital games have matured substantially as a narrative medium in the last decade. However, there is still much work to be done to more fully understand the poetics of story-based-games. Game narrative remains an important issue with significant cultural, economic and scholarly implications. In this article, we undertake a critical analysis of the…

The use of hoop nets seeded with mature brook trout to capture conspecifics

Treesearch

James A. Lamansky; Ernest R. Keeley; Michael K. Young; Kevin A. Meyer

2009-01-01

The brook trout Salvelinus fontinalis, a native of eastern North America, is considered an invasive species in the western United States because it has been implicated in the decline of many native trout species there. Current methods for controlling brook trout are usually time-consuming and expensive and are sometimes harmful to nontarget species....

Adorno and Horkheimer: Diasporic Philosophy, Negative Theology, and Counter-Education

ERIC Educational Resources Information Center

Gur-Ze'ev, Ilan

2010-01-01

The later Horkheimer presents mature Critical Theory as a Jewish Negative Theology. This change carries major educational implications hegemonic critical pedagogy has not yet dared to address until now and much less in the present era of the new anti-Semitism as the meta-narrative of the progressive circles. In Horkheimer's work the change from a…

ADHD Delays, Rather Than Alters, Brain Development. Science Briefs

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2008

2008-01-01

"Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This brief reports on the study "Attention-deficit/Hyperactivity Disorder is Characterized by a Delay in Cortical Maturation" (P. Shaw; K. Eckstrand; W. Sharp; J. Blumenthal; J. P. Lerch; D. Greenstein; L. Clasen; A. Evans; J. Giedd;…

Mobile Technology in 2020: Predictions and Implications for K-12 Education

ERIC Educational Resources Information Center

Norris, Cathleen A.; Soloway, Elliot

2015-01-01

While "mobile learning" has gained recognition in K-12 as a category in educational technology, the authors argue that, between 2010 and 2015, at least, its impact hasn't matched the hype. But between 2015 and 2020, hardware, software, and network technologies will mature sufficiently such that educational technology's Holy…

The Implications of Adult Identity for Educational and Work Attainment in Young Adulthood

ERIC Educational Resources Information Center

Benson, Janel E.; Johnson, Monica Kirkpatrick; Elder, Glen H., Jr.

2012-01-01

This study investigates the relation of young adult identities (ages 18-22 years), reflecting subjective age and psychosocial maturity, to educational and career attainment in young adulthood (ages 25-29 years). Add Health data show that having an older subjective age alone does not curtail attainment; the critical issue is the level of…

Making the Grade: The Quest for Validity in Admissions Decisions.

ERIC Educational Resources Information Center

Pelech, William; Stalker, Carol A.; Regehr, Cheryl; Jacobs, Marilyn

1999-01-01

A study found that students having problems in a graduate social-work program are more likely to be older, be male, have lower undergraduate grades, have more experience in social service-related work, and be rated lower in emotional maturity based on personal statements. Implications for provision of support for such students are discussed.…

Clearcutting and natural regeneration: management implications for the northern Sierra Nevada

Treesearch

Philip M. McDonald

1983-01-01

In the young-mature mixed-conifer and hardwood forests of north-central California, a dense and persistent hardwood understory competes with the conifers for space, nutrients, and water. Clear-cutting with intensive site preparation often is the most appropriate silvicultural regeneration method. This report, the result of 20 years of research on the Challenge...

Selective effect of hydroxyapatite nanoparticles on osteoporotic and healthy bone formation correlates with intracellular calcium homeostasis regulation.

PubMed

Zhao, Rui; Xie, Pengfei; Zhang, Kun; Tang, Zhurong; Chen, Xuening; Zhu, Xiangdong; Fan, Yujiang; Yang, Xiao; Zhang, Xingdong

2017-09-01

Adequate bone substitutes osseointegration has been difficult to achieve in osteoporosis. Hydroxyapatite of the osteoporotic bone, secreted by pathologic osteoblasts, had a smaller crystal size and lower crystallinity than that of the normal. To date, little is known regarding the interaction of synthetic hydroxyapatite nanoparticles (HANPs) with osteoblasts born in bone rarefaction. The present study investigated the biological effects of HANPs on osteoblastic cells derived from osteoporotic rat bone (OVX-OB), in comparison with the healthy ones (SHM-OB). A selective effect of different concentrations of HANPs on the two cell lines was observed that the osteoporotic osteoblasts had a higher tolerance. Reductions in cell proliferation, ALP activity, collagen secretion and osteoblastic gene expressions were found in the SHM-OB when administered with HANPs concentration higher than 25µg/ml. In contrast, those of the OVX-OB suffered no depression but benefited from 25 to 250µg/ml HANPs in a dose-dependent manner. We demonstrated that the different effects of HANPs on osteoblasts were associated with the intracellular calcium influx into the endoplasmic reticulum. The in vivo bone defect model further confirmed that, with a critical HANPs concentration administration, the osteoporotic rats had more and mechanically matured new bone formation than the non-treated ones, whilst the sham rats healed no better than the natural healing control. Collectively, the observed epigenetic regulation of osteoblastic cell function by HANPs has significant implication on defining design parameters for a potential therapeutic use of nanomaterials. In this study, we investigated the biological effects of hydroxyapatite nanoparticles (HANPs) on osteoporotic rat bone and the derived osteoblast. Our findings revealed a previously unrecognized phenomenon that the osteoporotic individuals could benefit from higher concentrations of HANPs, as compared with the healthy individuals. The in vivo bone defect model confirmed that, with a critical HANPs concentration administration, the osteoporotic rats had more mechanically matured new bone formation than the non-treated ones, whilst the sham rats healed no better than the natural healing control. The selective effect of HANPs might be associated with the intracellular calcium influx into the endoplasmic reticulum. Collectively, the observed epigenetic regulation by HANPs has significant implication on defining design parameters for a potential therapeutic use of nanomaterials in a pathological condition. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The human sperm epigenome and its potential role in embryonic development.

PubMed

Carrell, Douglas T; Hammoud, Saher Sue

2010-01-01

Along with many of the genome-wide transitions in chromatin composition throughout spermatogenesis, epigenetic modifications on histone tails and DNA are continuously modified to ensure stage specific gene expression in the maturing spermatid. Recent findings have suggested that the repertoire of epigenetic modifications in the mature sperm may have a potential role in the developing embryo and alterations in the epigenetic profile have been associated with infertility. These changes include DNA demethylation and the retention of modified histones at important developmental, signaling and micro-RNA genes, which resemble the epigenetic state of an embryonic stem cell. This review assesses the significance of epigenetic changes during spermatogenesis, and provides insight on recent associations made between altered epigenetic profiles in the mature sperm and its relationship to infertility.

Predicting the Timing of Maturational Spurts in Skeletal Age

PubMed Central

Nahhas, Ramzi W.; Sherwood, Richard J.; Chumlea, Wm. Cameron; Towne, Bradford; Duren, Dana L.

2014-01-01

Measures of maturity provide windows into the timing and tempo of childhood growth and maturation. Delayed maturation in a single child, or systemically in a population, can result from either genetic or environmental factors. In terms of the skeleton, delayed maturation may result in short stature or indicate another underlying issue. Thus, prediction of the timing of a maturational spurt is often desirable in order to determine the likelihood that a child will catch up to their chronological age peers. Serial data from the Fels Longitudinal Study were used to predict future skeletal age conditional on current skeletal age and to predict the timing of maturational spurts. For children who were delayed relative to their chronological age peers, the like-lihood of catch-up maturation increased through the average age of onset of puberty and decreased prior to the average age of peak height velocity. For boys, the probability of an imminent maturational spurt was higher for those who were less mature. For girls aged 11 to 13 years, however, this probability was higher for those who were more mature, potentially indicating the presence of a skeletal maturation plateau between multiple spurts. The prediction model, available on the web, is most relevant to children of European ancestry living in the Midwestern US. Our model may also provide insight into the tempo of maturation for children in other populations, but must be applied with caution if those populations are known to have high burdens of environmental stressors not typical of the Midwestern US. Am J Phys Anthropol 150:68–75, 2013. PMID:23283666

Donor Selection for Adult- to- Adult Living Donor Liver Transplantation: Well Begun is Half Done

PubMed Central

Sharma, Amit; Ashworth, April; Behnke, Martha; Cotterell, Adrian; Posner, Marc; Fisher, Robert A.

2012-01-01

Background Donor selection criteria for adult-to-adult living donor liver transplantation vary with the medical center of evaluation. Living donor evaluation utilizes considerable resources and the non-maturation of potential into actual donors may sometimes prove fatal for patients with end stage liver disease. On the contrary, a thorough donor evaluation process is mandatory to ensure safe outcomes in otherwise healthy donors. We aimed to study the reasons for non-maturation of potential right lobe liver donors at our transplant center. Methods A retrospective data analysis of all potential living liver donors evaluated at our center from 1998 to 2010 was done. Results Overall 324 donors were evaluated for 219 potential recipients and 171 (52.7%) donors were disqualified. Common reasons for donor non-maturation included: (1) Donor reluctance, 21% (2) >10% macro-vesicular steatosis, 16% (3) assisted donor withdrawal, 14% (4) inadequate remnant liver volume, 13% (5) psychosocial issues, 7% and thrombophilia, 7%. Ten donors (6%) were turned down due to anatomical variations (8 biliary and 2 arterial anomalies). Donors older than 50 years and those with BMI over 25 were less likely to be accepted for donation. Conclusions We conclude that donor reluctance, hepatic steatosis and assisted donor withdrawal are major reasons for non-maturation of potential into actual donors. Anatomical variations and underlying medical conditions were not a major cause of donor rejection. A system in practice to recognize these factors early in the course of donor evaluation to improve the efficiency of the selection process and ensure donor safety is proposed. PMID:23128999

Insulin-like growth factor I: a biologic maturation indicator.

PubMed

Ishaq, Ramy Abdul Rahman; Soliman, Sanaa Abou Zeid; Foda, Manal Yehya; Fayed, Mona Mohamed Salah

2012-11-01

Determination of the maturation level and the subsequent evaluation of growth potential during preadolescence and adolescence are important for optimal orthodontic treatment planning and timing. This study was undertaken to evaluate the applicability of insulin-like growth factor I (IGF-I) blood level as a maturation indicator by correlating it to the cervical vertebral maturation index. The study was conducted with 120 subjects, equally divided into 60 males (ages, 10-18 years) and 60 females (ages, 8-16 years). A lateral cephalometric radiograph and a blood sample were taken from each subject. For each subject, cervical vertebral maturation and IGF-I serum level were assessed. Mean values of IGF-I in each stage of cervical vertebral maturation were calculated, and the means in each stage were statistically compared with those of the other stages. The IGF-I mean value at each cervical vertebral maturation stage was statistically different from the mean values at the other stages. The highest mean values were observed in stage 4, followed by stage 5 in males and stage 3 in females. IGF-I serum level is a reliable maturation indicator that could be applied in orthodontic diagnosis. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Inference on energetics of deep-sea fish that cannot be aged: The case of the hagfish

NASA Astrophysics Data System (ADS)

van der Meer, Jaap; Kooijman, Sebastiaan (Bas) A. L. M.

2014-11-01

Dynamic Energy Budget (DEB) theory is used to estimate maximum growth rates and age at maturity for two hagfish species, the Atlantic hagfish Myxine glutinosa and the Pacific hagfish Eptatretus stoutii. Neither direct measurements on growth nor aging methods are available for these species. Only limited information on, for example, length and mass at birth and at puberty, and on oxygen consumption versus mass is available. For the Atlantic hagfish, but not for the Pacific hagfish, estimated growth rates are much higher and estimated age at maturity is much lower than previously thought, which may have implications for fisheries management. Yet, whether or not these results are due to erroneous oxygen consumption measurements remains to be seen.

When Can the Child Speak for Herself? The Limits of Parental Consent in Data Protection Law for Health Research.

PubMed

Taylor, Mark J; Dove, Edward S; Laurie, Graeme; Townend, David

2017-11-13

Draft regulatory guidance suggests that if the processing of a child's personal data begins with the consent of a parent, then there is a need to find and defend an enduring consent through the child's growing capacity and on to their maturity. We consider the implications for health research of the UK Information Commissioner's Office's (ICO) suggestion that the relevant test for maturity is the Gillick test, originally developed in the context of medical treatment. Noting the significance of the welfare principle to this test, we examine the implications for the responsibilities of a parent to act as proxy for their child. We argue, contrary to draft ICO guidance, that a data controller might legitimately continue to rely upon parental consent as a legal basis for processing after a child is old enough to provide her own consent. Nevertheless, we conclude that data controllers should develop strategies to seek fresh consent from children as soon as practicable after the data controller has reason to believe they are mature enough to consent independently. Techniques for effective communication, recommended to address challenges associated with Big Data analytics, might have a role here in addressing the dynamic relationship between data subject and processing. Ultimately, we suggest that fair and lawful processing of a child's data will be dependent upon data controllers taking seriously the truism that consent is ongoing, rather than a one-time event: the core associated responsibility is to continue to communicate with a data subject regarding the processing of personal data. © The Author 2017. Published by Oxford University Press.

The complexity of selection at the major primate beta-defensin locus.

PubMed

Semple, Colin A M; Maxwell, Alison; Gautier, Philippe; Kilanowski, Fiona M; Eastwood, Hayden; Barran, Perdita E; Dorin, Julia R

2005-05-18

We have examined the evolution of the genes at the major human beta-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on beta-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific beta-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of beta-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. Identification of these putatively functional sites has important implications for our understanding of beta-defensin function and for novel antibiotic design.

Insect outbreak shifts the direction of selection from fast to slow growth rates in the long-lived conifer Pinus ponderosa.

PubMed

de la Mata, Raul; Hood, Sharon; Sala, Anna

2017-07-11

Long generation times limit species' rapid evolution to changing environments. Trees provide critical global ecosystem services, but are under increasing risk of mortality because of climate change-mediated disturbances, such as insect outbreaks. The extent to which disturbance changes the dynamics and strength of selection is unknown, but has important implications on the evolutionary potential of tree populations. Using a 40-y-old Pinus ponderosa genetic experiment, we provide rare evidence of context-dependent fluctuating selection on growth rates over time in a long-lived species. Fast growth was selected at juvenile stages, whereas slow growth was selected at mature stages under strong herbivory caused by a mountain pine beetle ( Dendroctonus ponderosae ) outbreak. Such opposing forces led to no net evolutionary response over time, thus providing a mechanism for the maintenance of genetic diversity on growth rates. Greater survival to mountain pine beetle attack in slow-growing families reflected, in part, a host-based life-history trade-off. Contrary to expectations, genetic effects on tree survival were greatest at the peak of the outbreak and pointed to complex defense responses. Our results suggest that selection forces in tree populations may be more relevant than previously thought, and have implications for tree population responses to future environments and for tree breeding programs.

Molecular Characterization of Caveolin-induced Membrane Curvature*

PubMed Central

Ariotti, Nicholas; Rae, James; Leneva, Natalya; Ferguson, Charles; Loo, Dorothy; Okano, Satomi; Hill, Michelle M.; Walser, Piers; Collins, Brett M.; Parton, Robert G.

2015-01-01

The generation of caveolae involves insertion of the cholesterol-binding integral membrane protein caveolin-1 (Cav1) into the membrane, however, the precise molecular mechanisms are as yet unknown. We have speculated that insertion of the caveolin scaffolding domain (CSD), a conserved amphipathic region implicated in interactions with signaling proteins, is crucial for caveola formation. We now define the core membrane-juxtaposed region of Cav1 and show that the oligomerization domain and CSD are protected by tight association with the membrane in both mature mammalian caveolae and a model prokaryotic system for caveola biogenesis. Cryoelectron tomography reveals the core membrane-juxtaposed domain to be sufficient to maintain oligomerization as defined by polyhedral distortion of the caveolar membrane. Through mutagenesis we demonstrate the importance of the membrane association of the oligomerization domain/CSD for defined caveola biogenesis and furthermore, highlight the functional significance of the intramembrane domain and the CSD for defined caveolin-induced membrane deformation. Finally, we define the core structural domain of Cav1, constituting only 66 amino acids and of great potential to nanoengineering applications, which is required for caveolin-induced vesicle formation in a bacterial system. These results have significant implications for understanding the role of Cav1 in caveola formation and in regulating cellular signaling events. PMID:26304117

Molecular Characterization of Caveolin-induced Membrane Curvature.

PubMed

Ariotti, Nicholas; Rae, James; Leneva, Natalya; Ferguson, Charles; Loo, Dorothy; Okano, Satomi; Hill, Michelle M; Walser, Piers; Collins, Brett M; Parton, Robert G

2015-10-09

The generation of caveolae involves insertion of the cholesterol-binding integral membrane protein caveolin-1 (Cav1) into the membrane, however, the precise molecular mechanisms are as yet unknown. We have speculated that insertion of the caveolin scaffolding domain (CSD), a conserved amphipathic region implicated in interactions with signaling proteins, is crucial for caveola formation. We now define the core membrane-juxtaposed region of Cav1 and show that the oligomerization domain and CSD are protected by tight association with the membrane in both mature mammalian caveolae and a model prokaryotic system for caveola biogenesis. Cryoelectron tomography reveals the core membrane-juxtaposed domain to be sufficient to maintain oligomerization as defined by polyhedral distortion of the caveolar membrane. Through mutagenesis we demonstrate the importance of the membrane association of the oligomerization domain/CSD for defined caveola biogenesis and furthermore, highlight the functional significance of the intramembrane domain and the CSD for defined caveolin-induced membrane deformation. Finally, we define the core structural domain of Cav1, constituting only 66 amino acids and of great potential to nanoengineering applications, which is required for caveolin-induced vesicle formation in a bacterial system. These results have significant implications for understanding the role of Cav1 in caveola formation and in regulating cellular signaling events. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

White Matter Development in Adolescence: The Influence of Puberty and Implications for Affective Disorders

PubMed Central

Ladouceur, Cecile D.; Peper, Jiska S.; Crone, Eveline A.; Dahl, Ronald E.

2011-01-01

There have been rapid advances in understanding a broad range of changes in brain structure and function during adolescence, and a growing interest in identifying which of these neurodevelopmental changes are directly linked with pubertal maturation—at least in part because of their potential to provide insights into the numerous emotional and behavioral health problems that emerge during this developmental period. This review focuses on what is known about the influence of puberty on white matter development in adolescence. We focus on white matter because of its role in providing the structural architectural organization of the brain and as a structural correlate of communication within complex neural systems. We begin with a review of studies that report sex differences or sex by age interactions in white matter development as these findings can provide, although indirectly, information relevant to puberty-related changes. Studies are also critically reviewed based on methodological procedures used to assess pubertal maturation and relations with white matter changes. Findings are discussed in light of their implications for the development of neural systems underlying the regulation of emotion and behavior and how alterations in the development of these systems may mediate risk for affective disorders in vulnerable adolescents. PMID:22247751

Approaches for targeting self-renewal pathways in cancer stem cells: implications for hematological treatments.

PubMed

Horne, Gillian A; Copland, Mhairi

2017-05-01

Self-renewal is considered a defining property of stem cells. Self-renewal is essential in embryogenesis and normal tissue repair and homeostasis. However, in cancer, self-renewal pathways, e.g. WNT, NOTCH, Hedgehog and BMP, frequently become de-regulated in stem cells, or more mature progenitor cells acquire self-renewal properties, resulting in abnormal tissue growth and tumorigenesis. Areas covered: This review considers the conserved embryonic self-renewal pathways, including WNT, NOTCH, Hedgehog and BMP. The article describes recent advances in our understanding of these pathways in leukemia and, more specifically, leukemia stem cells (LSC), how these pathways cross-talk and interact with the LSC microenvironment, and discusses the clinical implications and potential therapeutic strategies, both in preclinical and in clinical trials for hematological malignancies. Expert opinion: The conserved embryonic self-renewal pathways are frequently de-regulated in cancer stem cells (CSC), including LSCs. There is significant cross-talk between self-renewal pathways, and their downstream targets, and the microenvironment. Effective targeting of these pathways is challenging due to cross-talk, and importantly, because these pathways are important for normal stem cells as well as CSC, adverse effects on normal tissues may mean a therapeutic window cannot be identified. Nonetheless, several agents targeting these pathways are currently in clinical trials in hematological malignancies.

Interfacing theories of program with theories of evaluation for advancing evaluation practice: Reductionism, systems thinking, and pragmatic synthesis.

PubMed

Chen, Huey T

2016-12-01

Theories of program and theories of evaluation form the foundation of program evaluation theories. Theories of program reflect assumptions on how to conceptualize an intervention program for evaluation purposes, while theories of evaluation reflect assumptions on how to design useful evaluation. These two types of theories are related, but often discussed separately. This paper attempts to use three theoretical perspectives (reductionism, systems thinking, and pragmatic synthesis) to interface them and discuss the implications for evaluation practice. Reductionism proposes that an intervention program can be broken into crucial components for rigorous analyses; systems thinking view an intervention program as dynamic and complex, requiring a holistic examination. In spite of their contributions, reductionism and systems thinking represent the extreme ends of a theoretical spectrum; many real-world programs, however, may fall in the middle. Pragmatic synthesis is being developed to serve these moderate- complexity programs. These three theoretical perspectives have their own strengths and challenges. Knowledge on these three perspectives and their evaluation implications can provide a better guide for designing fruitful evaluations, improving the quality of evaluation practice, informing potential areas for developing cutting-edge evaluation approaches, and contributing to advancing program evaluation toward a mature applied science. Copyright © 2016 Elsevier Ltd. All rights reserved.

On the widespread capacity for, and functional significance of, extreme inbreeding in ferns.

PubMed

Sessa, Emily B; Testo, Weston L; Watkins, James E

2016-08-01

Homosporous vascular plants utilize three different mating systems, one of which, gametophytic selfing, is an extreme form of inbreeding only possible in homosporous groups. This mating system results in complete homozygosity in all progeny and has important evolutionary and ecological implications. Ferns are the largest group of homosporous land plants, and the significance of extreme inbreeding for fern evolution has been a subject of debate for decades. We cultured gametophytes in the laboratory and quantified the relative frequencies of sporophyte production from isolated and paired gametophytes, and examined associations between breeding systems and several ecological and evolutionary traits. The majority of fern species studied show a capacity for gametophytic selfing, producing sporophytes from both isolated and paired gametophytes. While we did not follow sporophytes to maturity to investigate potential detrimental effects of homozygosity at later developmental stages, our results suggest that gametophytic selfing may have greater significance for fern evolution and diversification than has previously been realized. We present evidence from the largest study of mating behavior in ferns to date that the capacity for extreme inbreeding is prevalent in this lineage, and we discuss its implications and relevance and make recommendations for future studies of fern mating systems. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Age-related differences in articular cartilage wound healing: a potential role for transforming growth factor beta1 in adult cartilage repair.

PubMed

Bos, P K; Verhaar, J A N; van Osch, G J V M

2006-01-01

Objective of this study was to investigate the early wound healing reactions of immature and mature articular cartilage on experimental wound healing in the New Zealand White rabbit. The proliferation potential and glycosaminoglycan production of isolated chondrocytes of these animals was studied in an alginate culture system. A band of tissue with death chondrocytes was observed at wound edges of immature articular cartilage, whereas mature cartilage showed a significant smaller amount of dead chondrocytes. A general increase in TGFbeta1, FGF2 and IGF1 was observed throughout cartilage tissue with the exception of lesion edges. The observed immunonegative area appeared to correlate with the observed cell death in lesion edges. Repair in immature cartilage was indicated by chondrocyte proliferation in clusters and a decrease in defect size. No repair response was observed in mature articular cartilage defects. The alginate culture experiment demonstrated a higher proliferation rate of immature chondrocytes. Addition of recombinant TGFbeta1 increased proliferation rate and GAG production of mature chondrocytes. We were not able to further stimulate immature chondrocytes. These results indicate that TGFbeta1 addition may contribute to induce cartilage repair responses in mature cartilage as observed in immature, developing cartilage.

Developmental potential of elongating and elongated spermatids obtained after in-vitro maturation of isolated round spermatids.

PubMed

Cremades, N; Sousa, M; Bernabeu, R; Barros, A

2001-09-01

Round spermatid injections are associated with disappointing clinical outcomes, and although these cells have been shown to mature into late spermatids in vitro, the developmental potential of such gametes remains to be demonstrated. Round spermatids were isolated from 12 testicle samples of patients with obstructive azoospermia, hypoplasia, complete maturation arrest, and incomplete Sertoli cell-only syndrome. They were cultured for 7 days at 32 degrees C, 5% CO(2)in air, in microdrops of Vero cell-conditioned medium containing 10% synthetic serum substitute. From the 238 round spermatids cultured, 25.2% attained the elongating and 5.5% the elongated spermatid stage (3-4 days per step). Relatively higher maturation rates were found in cases with obstructive azoospermia, but differences were significant only for elongated spermatids (9.3%). No differences were found in maturation rates between cases with non-obstructive azoospermia (4.3% of elongated spermatids). Experimental microinjections with elongating and elongated spermatids revealed a low fertilization rate (40.9%) but a normal blastocyst formation rate (60%). Late spermatids resulting from in-vitro culture of round spermatids in conditioned medium, either in controls in cases with a spermiogenetic block, appeared able to successfully fertilize the human oocyte and elicit normal embryo development.

Atlantic wolf-fish Anarhichas lupus population diversity: growth and maturation.

PubMed

Gunnarsson, Á

2014-02-01

Biological data from 1125 female Atlantic wolf-fish Anarhichas lupus were collected during 2002-2006 at their main spawning and fishing grounds in Iceland. The results demonstrated substantial annual variation in growth and maturity of female A. lupus. The fast growing females mature earlier than the slow growing ones. In addition, females mature at a larger size and greater age in warmer temperatures than colder ones. There was a strong negative relationship between temperature and growth, which may indicate that the sea temperature west of Iceland has risen above the optimum for growth of female A. lupus and thereby reduced the reproductive potential of the species. © 2014 The Fisheries Society of the British Isles.

Cannabidiol Exposure During Neuronal Differentiation Sensitizes Cells Against Redox-Active Neurotoxins.

PubMed

Schönhofen, Patrícia; de Medeiros, Liana M; Bristot, Ivi Juliana; Lopes, Fernanda M; De Bastiani, Marco A; Kapczinski, Flávio; Crippa, José Alexandre S; Castro, Mauro Antônio A; Parsons, Richard B; Klamt, Fábio

2015-08-01

Cannabidiol (CBD), one of the most abundant Cannabis sativa-derived compounds, has been implicated with neuroprotective effect in several human pathologies. Until now, no undesired side effects have been associated with CBD. In this study, we evaluated CBD's neuroprotective effect in terminal differentiation (mature) and during neuronal differentiation (neuronal developmental toxicity model) of the human neuroblastoma SH-SY5Y cell line. A dose-response curve was performed to establish a sublethal dose of CBD with antioxidant activity (2.5 μM). In terminally differentiated SH-SY5Y cells, incubation with 2.5 μM CBD was unable to protect cells against the neurotoxic effect of glycolaldehyde, methylglyoxal, 6-hydroxydopamine, and hydrogen peroxide (H2O2). Moreover, no difference in antioxidant potential and neurite density was observed. When SH-SY5Y cells undergoing neuronal differentiation were exposed to CBD, no differences in antioxidant potential and neurite density were observed. However, CBD potentiated the neurotoxicity induced by all redox-active drugs tested. Our data indicate that 2.5 μM of CBD, the higher dose tolerated by differentiated SH-SY5Y neuronal cells, does not provide neuroprotection for terminally differentiated cells and shows, for the first time, that exposure of CBD during neuronal differentiation could sensitize immature cells to future challenges with neurotoxins.

Geology, thermal maturation, and source rock geochemistry in a volcanic covered basin: San Juan sag, south-central Colorado

USGS Publications Warehouse

Gries, R.R.; Clayton, J.L.; Leonard, C.

1997-01-01

The San Juan sag, concealed by the vast San Juan volcanic field of south-central Colorado, has only recently benefited from oil and gas wildcat drilling and evaluations. Sound geochemical analyses and maturation modeling are essential elements for successful exploration and development. Oil has been produced in minor quantities from an Oligocene sill in the Mancos Shale within the sag, and major oil and gas production occurs from stratigraphically equivalent rocks in the San Juan basin to the south-west and in the Denver basin to the northeast. The objectives of this study were to identify potential source rocks, assess thermal maturity, and determine hydrocarbon-source bed relationships. Source rocks are present in the San Juan sag in the upper and lower Mancos Shale (including the Niobrara Member), which consists of about 666 m (2184 ft) of marine shale with from 0.5 to 3.1 wt. % organic carbon. Pyrolysis yields (S1 + S2 = 2000-6000 ppm) and solvent extraction yields (1000-4000 ppm) indicate that some intervals within the Mancos Shale are good potential source rocks for oil, containing type II organic matter, according to Rock-Eval pyrolysis assay. Oils produced from the San Juan sag and adjacent part of the San Juan basin are geochemically similar to rock extracts obtained from these potential source rock intervals. Based on reconstruction of the geologic history of the basin integrated with models of organic maturation, we conclude that most of the source rock maturation occurred in the Oligocene and Miocene. Little to no maturation took place during Laramide subsidence of the basin, when the Animas and Blanco Basin formations were deposited. The timing of maturation is unlike that of most Laramide basins in the Rocky Mountain region, where maturation occurred as a result of Paleocene and Eocene basin fill. The present geothermal gradient in the San Juan sag is slightly higher (average 3.5??C/100 m; 1.9??F/100 ft) than the regional average for southern Rocky Mountain basins; however, although the sag contains intrusives and a volcanic cover, the gradient is significantly lower than that reported for parts of the adjacent San Juan basin (4.7??C/100 m; 2.6??F/100 ft). Burial depth appears to be a more important controlling factor in the thermal history of the source rocks than local variations in the geothermal gradient due to volcanic activity. Interestingly, the thick overburden of volcanic rocks appears to have provided the necessary burial depth for maturation.

An automated technique for potential differentiation of ovarian mature teratomas from other benign tumours using neural networks classification of 2D ultrasound static images: a pilot study

NASA Astrophysics Data System (ADS)

Al-karawi, Dhurgham; Sayasneh, A.; Al-Assam, Hisham; Jassim, Sabah; Page, N.; Timmerman, D.; Bourne, T.; Du, Hongbo

2017-05-01

Ovarian cysts are a common pathology in women of all age groups. It is estimated that 5-10% of women have a surgical intervention to remove an ovarian cyst in their lifetime. Given this frequency rate, characterization of ovarian masses is essential for optimal management of patients. Patients with benign ovarian masses can be managed conservatively if they are asymptomatic. Mature teratomas are common benign ovarian cysts that occur, in most cases, in premenopausal women. These ovarian cysts can contain different types of human tissue including bone, cartilage, fat, hair, or other tissue. If they are causing no symptoms, they can be harmless and may not require surgery. Subjective assessment by ultrasound examiners has a high diagnostic accuracy when characterising mature teratomas from other types of tumours. The aim of this study is to develop a computerised technique with the potential to characterise mature teratomas and distinguish them from other types of benign ovarian tumours. Local Binary Pattern (LBP) was applied to extract texture features that are specific in distinguishing teratomas. Neural Networks (NN) was then used as a classifier for recognising mature teratomas. A pilot sample set of 130 B-mode static ovarian ultrasound images (41 mature teratomas tumours and 89 other types of benign tumours) was used to test the effectiveness of the proposed technique. Test results show an average accuracy rate of 99.4% with a sensitivity of 100%, specificity of 98.8% and positive predictive value of 98.9%. This study demonstrates that the NN and LBP techniques can accurately classify static 2D B-mode ultrasound images of benign ovarian masses into mature teratomas and other types of benign tumours.

In vitro maturation of human oocytes for assisted reproduction.

PubMed

Jurema, Marcus W; Nogueira, Daniela

2006-11-01

To describe and evaluate the current practice of in vitro maturation of oocytes for assisted reproduction. Review of the available and relevant literature regarding in vitro maturation of oocytes. In vitro maturation of human oocytes retrieved from antral ovarian follicles is an emerging procedure quickly being incorporated into the realm of assisted reproductive technologies. This new technology has several potential advantages over traditional controlled ovarian hyperstimulation for IVF, such as reduction of costs by minimizing gonadotropin and GnRH analogue use, elimination of ovarian hyperstimulation syndrome, and simplicity of protocol. In vitro maturation of oocytes for assisted reproduction in human beings still is undergoing refinement but currently is providing efficacy and safety outcome comparable to that of traditional IVF in recent selected studies. Implementing in vitro maturation into an established IVF practice is feasible and requires only a few simple adjustments. Crucial to the advancement and optimization of the technology is a better understanding of how to maximize immature oocyte developmental competence and endometrial receptivity.

Development of visual evoked potentials in neonates. A study using light emitting diode goggles.

PubMed Central

Chin, K C; Taylor, M J; Menzies, R; Whyte, H

1985-01-01

We used a signal averager with light emitting diode goggles as the photostimulator to study the development of the visual evoked potentials in 40 normal neonates of between 23 and 42 weeks' gestation. All except two infants of less than 24 weeks' gestation had replicable visual evoked potentials. A negative peak of latency (mean (SD), 308 (21) msec) was present in all infants, but the development of the primary positive peak depended on maturity. Only infants of 37 weeks or more had a consistent positive peak of latency (mean (SD), 220 (22) msec). The practical simplicity and reliability of this technique has distinct advantages over previous conventional recording systems. Neonatal visual evoked potentials are shown to change with maturity. PMID:4091582

Histomorphometric and microchemical characterization of maturing dental enamel in rats fed a boron-deficient diet

USDA-ARS?s Scientific Manuscript database

Few reports are available in the literature on enamel formation under nutritional deficiencies. Continuously erupting rodent incisors have considerable potential to serve as a model system for amelogenesis. Thus, we performed a study to determine the effects of boron (B) deficiency on the maturing d...

Comparison of Growth Efficiency of Mature Longleaf and Slash Pine Trees

Treesearch

Steven B. Jack; Mary Carol P. Sheffield; Daniel J. McConville

2002-01-01

Variation in aboveground biomass partitioning (between the stem, branches, and foliage) of mature trees is a key determinant of growth potential. Investment of photosynthate in crown components generally results in greater overall biomass production of longer duration. The increased production of crown components may be an investment in longterm aboveground production...

Exploring the Decision Process of "School Leavers" and "Mature Students" in University Choice.

ERIC Educational Resources Information Center

Harker, Debra; Slade, Peter; Harker, Michael

2001-01-01

Examined potential differences in how Australian mature entrants and those who have just left school undertake the decision to attend a new university. Found differences between the two groups in terms of their need for public transportation and scheduling convenience, emphasis on program quality, and college search strategies. (EV)

Maturing Brain Mechanisms and Developing Behavioral Language Skills

ERIC Educational Resources Information Center

Friedrich, Manuela; Friederici, Angela D.

2010-01-01

The relation between the maturation of brain mechanisms responsible for the N400 elicitation in the event-related brain potential (ERP) and the development of behavioral language skills was investigated in 12-month-old infants. ERPs to words presented in a picture-word priming paradigm were analyzed according to the infants' production and…

Registration of oilseed sunflower restorer germplasms RHA 476 and RHA 477, adapted for short season environments

USDA-ARS?s Scientific Manuscript database

Northward expansion and double crop use of sunflower (Helianthus annuus L.) is limited by the lack of commercial hybrids with early maturity. We seek to provide the sunflower industry with new, early maturing restorer inbred germplasms with high yield potential and favorable agronomic and seed oil t...

Functional Tooth Regeneration Using a Bioengineered Tooth Unit as a Mature Organ Replacement Regenerative Therapy

PubMed Central

Imamura, Aya; Ogawa, Miho; Yasukawa, Masato; Yamazaki, Hiromichi; Morita, Ritsuko; Ikeda, Etsuko; Nakao, Kazuhisa; Takano-Yamamoto, Teruko; Kasugai, Shohei; Saito, Masahiro; Tsuji, Takashi

2011-01-01

Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy. PMID:21765896

Receiver operating characteristic analysis of age-related changes in lineup performance.

PubMed

Humphries, Joyce E; Flowe, Heather D

2015-04-01

In the basic face memory literature, support has been found for the late maturation hypothesis, which holds that face recognition ability is not fully developed until at least adolescence. Support for the late maturation hypothesis in the criminal lineup identification literature, however, has been equivocal because of the analytic approach that has been used to examine age-related changes in identification performance. Recently, receiver operator characteristic (ROC) analysis was applied for the first time in the adult eyewitness memory literature to examine whether memory sensitivity differs across different types of lineup tests. ROC analysis allows for the separation of memory sensitivity from response bias in the analysis of recognition data. Here, we have made the first ROC-based comparison of adults' and children's (5- and 6-year-olds and 9- and 10-year-olds) memory performance on lineups by reanalyzing data from Humphries, Holliday, and Flowe (2012). In line with the late maturation hypothesis, memory sensitivity was significantly greater for adults compared with young children. Memory sensitivity for older children was similar to that for adults. The results indicate that the late maturation hypothesis can be generalized to account for age-related performance differences on an eyewitness memory task. The implications for developmental eyewitness memory research are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Possible role of the microbiome in the development of acute malnutrition and implications for food-based strategies to prevent and treat acute malnutrition

USDA-ARS?s Scientific Manuscript database

A pattern of changes in the microbiome composition have been observed in the normal maturation of the human gut. Perturbations from this pattern have been described in malnourished humans and reproduced in animal models of severe malnutrition. Treatment and prevention of malnutrition in the future m...

Early infant diet and the omega 3 fatty acid DHA: effects on resting cardiovascular activity and behavioral development during the first half-year of life

USDA-ARS?s Scientific Manuscript database

The course of postnatal maturation of cardiac control has implications for cognitive development, but the influence of early nutrition on underlying processes is still being defined. This investigation evaluated the effects of different diets on interactions among these variables during the first ha...

Soluble soil aluminum alters the relative uptake of mineral nitrogen forms by six mature temperate broadleaf tree species: possible implications for watershed nitrate retention

Treesearch

Mark B. Burnham; Jonathan R. Cumming; Mary Beth Adams; William T. Peterjohn

2017-01-01

Increased availability of monomeric aluminum ( Al3+) in forest soils is an important adverse effect of acidic deposition that reduces root growth and inhibits nutrient uptake. There is evidence that Al3+ exposure interferes with NO3− uptake. If true for overstory trees, the...

Germinating a New SEAD: The Implications of Executing the SEAD Mission in a UCAV

DTIC Science & Technology

2001-06-01

20 SEAD FROM BIRTH TO MATURITY...reader must understand those differences in order to understand the weight in the argument. The first group of related terms has to do with unmanned...higher flying were ordered in mass numbers. However, these RPVs were strictly for target practice. None was intended for combat.12 At the onset

2016: Signaling Breakthroughs of the Year.

PubMed

Adler, Elizabeth M

2017-01-03

Signaling breakthroughs of 2016 clustered mainly in the areas of neuroscience, immunology, and metabolism, with excursions into plant hormone signaling and bacterial manipulation of host signaling pathways. Perhaps reflecting the growing maturity of the discipline of cell signaling, many of this year's breakthroughs have implications for the pathogenesis or treatment of human disease. Copyright © 2017, American Association for the Advancement of Science.

The silvicultural implications of age patterns in two southern pine stands after 72 years of uneven-aged management

Treesearch

Don C. Bragg; James M. Guldin

2015-01-01

A randomized sample of 250 loblolly (Pinus taeda L.) and shortleaf (Pinus echinata Mill.) pine ring counts was collected from the Good and Poor Farm Forestry compartments on the Crossett Experimental Forest. These mature, pine-dominated stands have been managed using uneven-aged silviculture since 1937. Our sample shows that both...

Carbon nanotube scaffolds as emerging nanoplatform for myocardial tissue regeneration: A review of recent developments and therapeutic implications.

PubMed

Gorain, Bapi; Choudhury, Hira; Pandey, Manisha; Kesharwani, Prashant; Abeer, Muhammad Mustafa; Tekade, Rakesh Kumar; Hussain, Zahid

2018-08-01

Myocardial infarction (cardiac tissue death) is among the most prevalent causes of death among the cardiac patients due to the inability of self-repair in cardiac tissues. Myocardial tissue engineering is regarded as one of the most realistic strategies for repairing damaged cardiac tissue. However, hindrance in transduction of electric signals across the cardiomyocytes due to insulating properties of polymeric materials worsens the clinical viability of myocardial tissue engineering. Aligned and conductive scaffolds based on Carbon nanotubes (CNT) have gained remarkable recognition due to their exceptional attributes which provide synthetic but viable microenvironment for regeneration of engineered cardiomyocytes. This review presents an overview and critical analysis of pharmaceutical implications and therapeutic feasibility of CNT based scaffolds in improving the cardiac tissue regeneration and functionality. The expository analysis of the available evidence revealed that inclusion of single- or multi-walled CNT into fibrous, polymeric, and elastomeric scaffolds results in significant improvement in electrical stimulation and signal transduction through cardiomyocytes. Moreover, incorporation of CNT in engineering scaffolds showed a greater potential of augmenting cardiomyocyte proliferation, differentiation, and maturation and has improved synchronous beating of cardiomyocytes. Despite promising ability of CNT in promoting functionality of cardiomyocytes, their presence in scaffolds resulted in substantial improvement in mechanical properties and structural integrity. Conclusively, this review provides new insight into the remarkable potential of CNT aligned scaffolds in improving the functionality of engineered cardiac tissue and signifies their feasibility in cardiac tissue regenerative medicines and stem cell therapy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Goosefish Lophius americanus fecundity and spawning frequency, with implications for population reproductive potential.

PubMed

McBride, R S; Johnson, A K; Lindsay, E K; Walsh, H J; Richards, R A

2017-05-01

To improve knowledge of goosefish Lophius americanus' reproductive biology, females were collected during 2009-2012 from the Mid-Atlantic Bight shelf region of the U.S. east coast. Batch fecundity increased with total length (L T ), from 229 100 to 2 243 300 mature oocytes per female (L T range: 55·5-112 cm; n = 54). This estimate of fecundity at L T is lower than one derived from a sample collected during 1982-1985. Examination of whole oocyte diameters in different months indicated that L. americanus is a serial spawner, releasing more than one egg veil per spawning season, as suspected or observed for other Lophius species. Seasonality of spawning was evident from whole oocytes and gonad histology, and from larval fish surveys spanning the U.S. north-east shelf, and confirmed a protracted (c. 6 months) spawning period. Peak spawning activity progressed northward from spring to autumn. The population-level implications of these results were explored by estimating population reproductive potential (P RP ), which considered the value of both current and future per capita reproduction using decade-specific age structure and fecundity at length. P RP is now more than 50% lower compared with the historical period (1982-1985), a result of the lower proportions of large females and reduced fecundity across all sizes. Mechanisms that could explain this loss of stock productivity are fishing-induced size-age truncation or regime shifts in egg production caused by changes in energy density of common forage species. © 2017 The Fisheries Society of the British Isles.

Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

PubMed Central

Brunert, Daniela; Kurtenbach, Stefan; Isik, Sonnur; Benecke, Heike; Gisselmann, Günter; Schuhmann, Wolfgang; Hatt, Hanns; Wetzel, Christian H.

2009-01-01

The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis. PMID:19430528

Quantitative Evaluation of Collagen Crosslinks and Corresponding Tensile Mechanical Properties in Mouse Cervical Tissue during Normal Pregnancy

PubMed Central

Yoshida, Kyoko; Jiang, Hongfeng; Kim, MiJung; Vink, Joy; Cremers, Serge; Paik, David; Wapner, Ronald; Mahendroo, Mala; Myers, Kristin

2014-01-01

The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery. Cervical collagens are known to remodel extensively in mice with progressing gestation leading to a soft cervix at term. During this process, mature crosslinked collagens are hypothesized to be replaced with immature less crosslinked collagens to facilitate cervical softening and ripening. To determine the mechanical role of collagen crosslinks during normal mouse cervical remodeling, tensile load-to-break tests were conducted for the following time points: nonpregnant (NP), gestation day (d) 6, 12, 15, 18 and 24 hr postpartum (PP) of the 19-day gestation period. Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). There were no significant changes in the total immature crosslink density (HLNL+DHLNL mol per collagen mol) throughout normal mouse gestation (range: 0.31–0.49). Total mature crosslink density (PYD+DPD mol per collagen mol) decreased significantly in early softening from d6 to d15 (d6: 0.17, d12: 0.097, d15: 0.026) and did not decrease with further gestation. The maturity ratio (total mature to total immature crosslinks) significantly decreased in early softening from d6 to d15 (d6: 0.2, d15: 0.074). All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL. This data provides quantitative evidence to support the hypothesis that as mature crosslinked collagens decline, they are replaced by immature collagens to facilitate increased tissue compliance in the early softening period from d6 to d15. PMID:25397407

Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies

PubMed Central

Hwang, Joyce K.; Wang, Chong; Du, Zhou; Meyers, Robin M.; Kepler, Thomas B.; Neuberg, Donna; Kwong, Peter D.; Mascola, John R.; Joyce, M. Gordon; Bonsignori, Mattia; Haynes, Barton F.; Yeap, Leng-Siew; Alt, Frederick W.

2017-01-01

Variable regions of Ig chains provide the antigen recognition portion of B-cell receptors and derivative antibodies. Ig heavy-chain variable region exons are assembled developmentally from V, D, J gene segments. Each variable region contains three antigen-contacting complementarity-determining regions (CDRs), with CDR1 and CDR2 encoded by the V segment and CDR3 encoded by the V(D)J junction region. Antigen-stimulated germinal center (GC) B cells undergo somatic hypermutation (SHM) of V(D)J exons followed by selection for SHMs that increase antigen-binding affinity. Some HIV-1–infected human subjects develop broadly neutralizing antibodies (bnAbs), such as the potent VRC01-class bnAbs, that neutralize diverse HIV-1 strains. Mature VRC01-class bnAbs, including VRC-PG04, accumulate very high SHM levels, a property that hinders development of vaccine strategies to elicit them. Because many VRC01-class bnAb SHMs are not required for broad neutralization, high overall SHM may be required to achieve certain functional SHMs. To elucidate such requirements, we used a V(D)J passenger allele system to assay, in mouse GC B cells, sequence-intrinsic SHM-targeting rates of nucleotides across substrates representing maturation stages of human VRC-PG04. We identify rate-limiting SHM positions for VRC-PG04 maturation, as well as SHM hotspots and intrinsically frequent deletions associated with SHM. We find that mature VRC-PG04 has low SHM capability due to hotspot saturation but also demonstrate that generation of new SHM hotspots and saturation of existing hotspot regions (e.g., CDR3) does not majorly influence intrinsic SHM in unmutated portions of VRC-PG04 progenitor sequences. We discuss implications of our findings for bnAb affinity maturation mechanisms. PMID:28747530

Endogenous antigen tunes the responsiveness of naive B cells but not T cells

PubMed Central

Zikherman, Julie; Parameswaran, Ramya; Weiss, Arthur

2012-01-01

In humans up to 75% of newly generated B cells and about 30% of mature B cells exhibit some degree of autoreactivity1. Yet, how B cells establish and maintain tolerance in the face of autoantigen exposure during and after development is not certain. Studies of model BCR transgenic systems have highlighted the critical role played by functional unresponsiveness or ‘anergy’2,3. Unlike T cells, evidence suggests that receptor editing and anergy, rather than deletion, account for much of B cell tolerance4,5. However, it remains unclear whether the mature diverse B cell repertoire of mice contains anergic autoreactive B cells, and if so, whether antigen was encountered during or after their development. By taking advantage of a reporter mouse in which B cell antigen receptor (BCR) signaling rapidly and robustly induces GFP expression under the control of the Nur77 regulatory region, antigen-dependent and – independent BCR signaling events in vivo during B cell maturation were visualized. Here we show that B cells encounter antigen during development in the spleen, and that this antigen exposure in turn tunes the responsiveness of BCR signaling in B cells at least partly by down-modulating expression of surface IgM but not IgD BCRs, and by modifying basal calcium levels. By contrast, no analogous process occurs in naive mature T cells. Our data demonstrate not only that autoreactive B cells persist in the mature repertoire, but that functional unresponsiveness or ‘anergy’ exists in the mature B cell repertoire along a continuum, a fact that has long been suspected, but never yet shown. These results have important implications for understanding how tolerance in T and B cells is differently imposed, and how these processes might go awry in disease. PMID:22902503

Structures of Coxsackievirus A16 Capsids with Native Antigenicity: Implications for Particle Expansion, Receptor Binding, and Immunogenicity.

PubMed

Ren, Jingshan; Wang, Xiangxi; Zhu, Ling; Hu, Zhongyu; Gao, Qiang; Yang, Pan; Li, Xuemei; Wang, Junzhi; Shen, Xinliang; Fry, Elizabeth E; Rao, Zihe; Stuart, David I

2015-10-01

Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the primary causes of the epidemics of hand-foot-and-mouth disease (HFMD) that affect more than a million children in China each year and lead to hundreds of deaths. Although there has been progress with vaccines for EV71, the development of a CVA16 vaccine has proved more challenging, and the EV71 vaccine does not give useful cross-protection, despite the capsid proteins of the two viruses sharing about 80% sequence identity. The structural details of the expanded forms of the capsids, which possess nonnative antigenicity, are now well understood, but high resolution information for the native antigenic form of CVA16 has been missing. Here, we remedy this with high resolution X-ray structures of both mature and natural empty CVA16 particles and also of empty recombinant viruslike particles of CVA16 produced in insect cells, a potential vaccine antigen. All three structures are unexpanded native particles and antigenically identical. The recombinant particles have recruited a lipid moiety to stabilize the native antigenic state that is different from the one used in a natural virus infection. As expected, the mature CVA16 virus is similar to EV71; however, structural and immunogenic comparisons highlight differences that may have implications for vaccine production. Hand-foot-and-mouth disease is a serious public health threat to children in Asian-Pacific countries, resulting in millions of cases. EV71 and CVA16 are the two dominant causative agents of the disease that, while usually mild, can cause severe neurological complications, leading to hundreds of deaths. EV71 vaccines do not provide protection against CVA16. A CVA16 vaccine or bivalent EV71/CVA16 vaccine is therefore urgently needed. We report atomic structures for the mature CVA16 virus, a natural empty particle, and a recombinant CVA16 virus-like particle that does not contain the viral genome. All three particles have similar structures and identical antigenicity. The recombinant particles, produced in insect cells (a system suitable for making vaccine antigen), are stabilized by recruiting from the insect cells a small molecule that is different from that used by the virus in a normal infection. We present structural and immunogenic comparisons with EV71 to facilitate structure-based drug design and vaccine development. Copyright © 2015, Ren et al.

A rare case report of squamous-cell carcinoma arising from mature cystic teratoma of ovary.

PubMed

Kalampokas, E; Boutas, I; Kairi-Vasilatou, E; Salakos, N; Panoulis, K; Aravantinos, L; Damaskos, C; Kalampokas, T; Deligeoroglou, E

2014-01-01

The most frequent ovarian germ cell tumors are mature cystic teratomas (MCTs), composing 10-25% of all ovarian neoplasms. MCTs have the potential of undergoing malignant transformation, typically in postmenopausal women, with a frequency of 0.17-3%, with squamous cell carcinoma being the most common malignant tumor arising from MCT. We present the rare clinical entity of a squamous cell carcinoma arising from a mature cystic teratoma in a 56-year-old premenopausal woman as well as diagnostic and therapeutic route followed.

Potential anthelmintic: D-psicose inhibits motility, growth and reproductive maturity of L1 larvae of Caenorhabditis elegans.

PubMed

Sato, Masashi; Kurose, Hiroyuki; Yamasaki, Toru; Izumori, Ken

2008-04-01

No anthelmintic sugars have yet been identified. Eight ketohexose stereoisomers (D- and L-forms of psicose, fructose, tagatose and sorbose), along with D-galactose and D-glucose, were examined for potency against L1 stage Caenorhabditis elegans fed Escherichia coli. Of the sugars, D-psicose specifically inhibited the motility, growth and reproductive maturity of the L1 stage. D-Psicose probably interferes with the nematode nutrition. The present results suggest that D-psicose, one of the rare sugars, is a potential anthelmintic.

Fog interception by Sequoia sempervirens (D. Don) crowns decouples physiology from soil water deficit.

PubMed

Simonin, Kevin A; Santiago, Louis S; Dawson, Todd E

2009-07-01

Although crown wetting events can increase plant water status, leaf wetting is thought to negatively affect plant carbon balance by depressing photosynthesis and growth. We investigated the influence of crown fog interception on the water and carbon relations of juvenile and mature Sequoia sempervirens trees. Field observations of mature trees indicated that fog interception increased leaf water potential above that of leaves sheltered from fog. Furthermore, observed increases in leaf water potential exceeded the maximum water potential predicted if soil water was the only available water source. Because field observations were limited to two mature trees, we conducted a greenhouse experiment to investigate how fog interception influences plant water status and photosynthesis. Pre-dawn and midday branchlet water potential, leaf gas exchange and chlorophyll fluorescence were measured on S. sempervirens saplings exposed to increasing soil water deficit, with and without overnight canopy fog interception. Sapling fog interception increased leaf water potential and photosynthesis above the control and soil water deficit treatments despite similar dark-acclimated leaf chlorophyll fluorescence. The field observations and greenhouse experiment show that fog interception represents an overlooked flux into the soil-plant-atmosphere continuum that temporarily, but significantly, decouples leaf-level water and carbon relations from soil water availability.

Chlorogenic acid supplementation during in vitro maturation improves maturation, fertilization and developmental competence of porcine oocytes.

PubMed

Nguyen, T-V; Tanihara, F; Do, Ltk; Sato, Y; Taniguchi, M; Takagi, M; Van Nguyen, T; Otoi, T

2017-12-01

Chlorogenic acid (CGA) is a quinic acid conjugate of caffeic acid, and a phytochemical found in many fruits and beverages that acts as an antioxidant. The present study investigated the effects of CGA supplementation during in vitro maturation (IVM), on in vitro development of porcine oocytes, to improve the porcine in vitro production (IVP) system. Oocytes were matured either without (control) or with CGA (10, 50, 100 and 200 μM). Subsequently, the matured oocytes were fertilized and cultured in vitro for 7 day. The rates of maturation, fertilization and blastocyst formation of oocytes matured with 50 μM CGA were significantly (p < .05) higher than those of the control oocytes. Hydrogen peroxide (H 2 O 2 ) is one of the reactive oxygen species and induces DNA damage in porcine oocytes. When oocytes were matured with 1 mM H 2 O 2 to assess the protective effect of CGA, 50 μM CGA supplementation improved the maturation rate and the proportion of DNA-fragmented nuclei in oocytes compared with control oocytes matured without CGA. Moreover, when oocytes were matured with either 50 μM CGA (control) or caffeic acid (10, 50 and 100 μM), the rates of maturation, fertilization and the blastocyst formation of oocytes matured with 50 μM CGA were similar to those of oocytes matured with 10 and 50 μM caffeic acid. Our results suggest that CGA has comparable effects to caffeic acid, and IVM with 50 μM CGA is particularly beneficial to IVP of porcine embryos and protects oocytes from DNA damage induced by oxidative stress. Supplementation of CGA to the maturation medium has a potential to improve porcine IVP system. © 2017 Blackwell Verlag GmbH.

Characterization of 16S rRNA Processing with Pre-30S Subunit Assembly Intermediates from E. coli.

PubMed

Smith, Brian A; Gupta, Neha; Denny, Kevin; Culver, Gloria M

2018-06-08

Ribosomal RNA (rRNA) is a major component of ribosomes and is fundamental to the process of translation. In bacteria, 16S rRNA is a component of the small ribosomal subunit and plays a critical role in mRNA decoding. rRNA maturation entails the removal of intervening spacer sequences contained within the pre-rRNA transcript by nucleolytic enzymes. Enzymatic activities involved in maturation of the 5'-end of 16S rRNA have been identified, but those involved in 3'-end maturation of 16S rRNA are more enigmatic. Here, we investigate molecular details of 16S rRNA maturation using purified in vivo-formed small subunit (SSU) assembly intermediates (pre-SSUs) from wild-type Escherichia coli that contain precursor 16S rRNA (17S rRNA). Upon incubation of pre-SSUs with E. coli S100 cell extracts or purified enzymes implicated in 16S rRNA processing, the 17S rRNA is processed into additional intermediates and mature 16S rRNA. These results illustrate that exonucleases RNase R, RNase II, PNPase, and RNase PH can process the 3'-end of pre-SSUs in vitro. However, the endonuclease YbeY did not exhibit nucleolytic activity with pre-SSUs under these conditions. Furthermore, these data demonstrate that multiple pathways facilitate 16S rRNA maturation with pre-SSUs in vitro, with the dominant pathways entailing complete processing of the 5'-end of 17S rRNA prior to 3'-end maturation or partial processing of the 5'-end with concomitant processing of the 3'-end. These results reveal the multifaceted nature of SSU biogenesis and suggest that E. coli may be able to escape inactivation of any one enzyme by using an existing complementary pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Low-Threshold Calcium Channel Cav3.2 Mediates Burst Firing of Mature Dentate Granule Cells

PubMed Central

Dumenieu, Mael; Senkov, Oleg; Mironov, Andrey; Bourinet, Emmanuel; Kreutz, Michael R; Dityatev, Alexander; Heine, Martin; Bikbaev, Arthur

2018-01-01

Abstract Mature granule cells are poorly excitable neurons that were recently shown to fire action potentials, preferentially in bursts. It is believed that the particularly pronounced short-term facilitation of mossy fiber synapses makes granule cell bursting a very effective means of properly transferring information to CA3. However, the mechanism underlying the unique bursting behavior of mature granule cells is currently unknown. Here, we show that Cav3.2 T-type channels at the axon initial segment are responsible for burst firing of mature granule cells in rats and mice. Accordingly, Cav3.2 knockout mice fire tonic spikes and exhibit impaired bursting, synaptic plasticity and dentate-to-CA3 communication. The data show that Cav3.2 channels are strong modulators of bursting and can be considered a critical molecular switch that enables effective information transfer from mature granule cells to the CA3 pyramids. PMID:29790938

Chronic nitrate exposure alters reproductive physiology in fathead minnows.

PubMed

Kellock, Kristen A; Moore, Adrian P; Bringolf, Robert B

2018-01-01

Nitrate is a ubiquitous aquatic pollutant that is commonly associated with eutrophication and dead zones in estuaries around the world. At high concentrations nitrate is toxic to aquatic life but at environmental concentrations it has also been purported as an endocrine disruptor in fish. To investigate the potential for nitrate to cause endocrine disruption in fish, we conducted a lifecycle study with fathead minnows (Pimephales promelas) exposed to nitrate (0, 11.3, and 56.5 mg/L (total nitrate-nitrogen (NO 3 -N)) from <24 h post hatch to sexual maturity (209 days). Body mass, condition factor, gonadal somatic index (GSI), incidence of intersex, and vitellogenin induction were determined in mature male and female fish and plasma 11-keto testosterone (11-KT) was measured in males only. In nitrate-exposed males both 11-KT and vitellogenin were significantly induced when compared with controls. No significant differences occurred for body mass, condition factor, or GSI among males and intersex was not observed in any of the nitrate treatments. Nitrate-exposed females also had significant increases in vitellogenin compared to controls but no significant differences for mass, condition factor, or GSI were observed in nitrate exposed groups. Estradiol was used as a positive control for vitellogenin induction. Our findings suggest that environmentally relevant nitrate levels may disrupt steroid hormone synthesis and/or metabolism in male and female fish and may have implications for fish reproduction, watershed management, and regulation of nutrient pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tet2 Regulates Osteoclast Differentiation by Interacting with Runx1 and Maintaining Genomic 5-Hydroxymethylcytosine (5hmC).

PubMed

Chu, Yajing; Zhao, Zhigang; Wayne Sant, David; Zhu, Ganqian; Greenblatt, Sarah M; Liu, Lin; Wang, Jinhuan; Cao, Zeng; Cheng Tho, Jeanette; Chen, Shi; Liu, Xiaochen; Zhang, Peng; Maciejewski, Jaroslaw P; Nimer, Stephen; Wang, Gaofeng; Yuan, Weiping; Yang, Feng-Chun; Xu, Mingjiang

2018-06-13

As a dioxygenase, Ten-eleven translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. Tet2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 -/- mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (5hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities. Copyright © 2018. Production and hosting by Elsevier B.V.

The preconditioning role of Tropical Atlantic Variability in the development of the ENSO teleconnection: implications for the prediction of Nordeste rainfall

NASA Astrophysics Data System (ADS)

Giannini, A.; Saravanan, R.; Chang, P.

A comparison of rainfall variability in the semi-arid Brazilian Nordeste in observations and in two sets of model simulations leads to the conclusion that the evolving interaction between Tropical Atlantic Variability (TAV) and the El Niño-Southern Oscillation (ENSO) phenomenon can explain two puzzling features of ENSO's impact on the Nordeste: (1) the event-to-event unpredictability of ENSO's impact; (2) the greater impact of cold rather than warm ENSO events during the past 50 years. The explanation is in the `preconditioning' role of Tropical Atlantic Variability. When, in seasons prior to the mature phase of ENSO, the tropical Atlantic happens to be evolving consistently with the development expected of the ENSO teleconnection, ENSO and TAV add up to force large anomalies in Nordeste rainfall. When it happens to be evolving in opposition to the canonical development of ENSO, then the net outcome is less obvious, but also less anomalous. The more frequent occurrence of tropical Atlantic conditions consistent with those that develop during a cold ENSO event, i.e. of a negative meridional sea surface temperature gradient, explains the weaker warm ENSO and stronger cold ENSO anomalies in Nordeste rainfall of the latter part of the twentieth century. Close monitoring of the evolution of the tropical Atlantic in seasons prior to the mature phase of ENSO should lead to an enhanced forecast potential.

Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca) with Time after Birth--Three Phases in Early Lactation and Progressive Individual Differences.

PubMed

Zhang, Tong; Zhang, Rong; Zhang, Liang; Zhang, Zhihe; Hou, Rong; Wang, Hairui; Loeffler, I Kati; Watson, David G; Kennedy, Malcolm W

2015-01-01

Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1-6 (Phase 1), days 7-20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth.

In vitro activity of xanthorrhizol isolated from the rhizome of Javanese turmeric (Curcuma xanthorrhiza Roxb.) against Candida albicans biofilms.

PubMed

Rukayadi, Yaya; Hwang, Jae-Kwan

2013-07-01

The purpose of this study was to investigate the activity of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. on Candida albicans biofilms at adherent, intermediate, and mature phase of growth. C. albicans biofilms were formed in flat-bottom 96-well microtiter plates. The biofilms of C. albicans at different phases of development were exposed to xanthorrhizol at different concentrations (0.5 µg/mL-256 µg/mL) for 24 h. The metabolic activity of cells within the biofilms was quantified using the XTT reduction assay. Sessile minimum inhibitory concentrations (SMICs) were determined at 50% and 80% reduction in the biofilm OD₄₉₀ compared to the control wells. The SMIC₅₀ and SMIC₈₀ of xanthorrhizol against 18 C. albicans biofilms were 4--16 µg/mL and 8--32 µg/mL, respectively. The results demonstrated that the activity of xanthorrhizol in reducing C. albicans biofilms OD₄₉₀ was dependent on the concentration and the phase of growth of biofilm. Xanthorrhizol at concentration of 8 µg/mL completely reduced in biofilm referring to XTT-colorimetric readings at adherent phase, whereas 32 µg/mL of xanthorrhizol reduced 87.95% and 67.48 % of biofilm referring to XTT-colorimetric readings at intermediate and mature phases, respectively. Xanthorrhizol displayed potent activity against C. albicans biofilms in vitro and therefore might have potential therapeutic implication for biofilm-associated candidal infections. Copyright © 2012 John Wiley & Sons, Ltd.

Chronic Fluoride Toxicity: Dental Fluorosis

PubMed Central

DenBesten, Pamela; Li, Wu

2012-01-01

Dental fluorosis occurs as a result of excess fluoride ingestion during tooth formation. Enamel fluorosis and primary dentin fluorosis can only occur when teeth are forming, and therefore fluoride exposure (as it relates to dental fluorosis) occurs during childhood. In the permanent dentition, this would begin with the lower incisors, which complete mineralization at approximately 2–3 years of age, and end after mineralization of the third molars. The white opaque appearance of fluorosed enamel is caused by a hypomineralized enamel subsurface; with more severe dental fluorosis, pitting and a loss of the enamel surface occurs, leading to secondary staining (appearing as a brown color). Many of the changes caused by fluoride are related to cell/matrix/mineral interactions as the teeth are forming. At the early maturation stage, the relative quantity of amelogenin protein is increased in fluorosed enamel in a dose-related manner. This appears to result from a delay in the removal of amelogenins as the enamel matures. In vitro, when fluoride is incorporated into the mineral, more protein binds to the forming mineral, and protein removal by proteinases is delayed. This suggests that altered protein/mineral interactions are in part responsible for retention of amelogenins and the resultant hypomineralization that occurs in fluorosed enamel. Fluoride also appears to enhance mineral precipitation in forming teeth, resulting in hypermineralized bands of enamel, which are then followed by hypomineralized bands. Enhanced mineral precipitation with local increases in matrix acidity may affect maturation stage ameloblast modulation, potentially explaining the doserelated decrease in cycles of ameloblast modulation from ruffleended to smooth-ended cells that occur with fluoride exposure in rodents. Specific cellular effects of fluoride have been implicated, but more research is needed to determine which of these changes are relevant to the formation of fluorosed teeth. As further studies are done, we will better understand the mechanisms responsible for dental fluorosis. PMID:21701193

Chronic fluoride toxicity: dental fluorosis.

PubMed

Denbesten, Pamela; Li, Wu

2011-01-01

Dental fluorosis occurs as a result of excess fluoride ingestion during tooth formation. Enamel fluorosis and primary dentin fluorosis can only occur when teeth are forming, and therefore fluoride exposure (as it relates to dental fluorosis) occurs during childhood. In the permanent dentition, this would begin with the lower incisors, which complete mineralization at approximately 2-3 years of age, and end after mineralization of the third molars. The white opaque appearance of fluorosed enamel is caused by a hypomineralized enamel subsurface. With more severe dental fluorosis, pitting and a loss of the enamel surface occurs, leading to secondary staining (appearing as a brown color). Many of the changes caused by fluoride are related to cell/matrix interactions as the teeth are forming. At the early maturation stage, the relative quantity of amelogenin protein is increased in fluorosed enamel in a dose-related manner. This appears to result from a delay in the removal of amelogenins as the enamel matures. In vitro, when fluoride is incorporated into the mineral, more protein binds to the forming mineral, and protein removal by proteinases is delayed. This suggests that altered protein/mineral interactions are in part responsible for retention of amelogenins and the resultant hypomineralization that occurs in fluorosed enamel. Fluoride also appears to enhance mineral precipitation in forming teeth, resulting in hypermineralized bands of enamel, which are then followed by hypomineralized bands. Enhanced mineral precipitation with local increases in matrix acidity may affect maturation stage ameloblast modulation, potentially explaining the dose-related decrease in cycles of ameloblast modulation from ruffle-ended to smooth-ended cells that occur with fluoride exposure in rodents. Specific cellular effects of fluoride have been implicated, but more research is needed to determine which of these changes are relevant to the formation of fluorosed teeth. As further studies are done, we will better understand the mechanisms responsible for dental fluorosis. Copyright © 2011 S. Karger AG, Basel.

A short protocol using dexamethasone and monophosphoryl lipid A generates tolerogenic dendritic cells that display a potent migratory capacity to lymphoid chemokines

PubMed Central

2013-01-01

Background Generation of tolerogenic dendritic cells (TolDCs) for therapy is challenging due to its implications for the design of protocols suitable for clinical applications, which means not only using safe products, but also working at defining specific biomarkers for TolDCs identification, developing shorter DCs differentiation methods and obtaining TolDCs with a stable phenotype. We describe here, a short-term protocol for TolDCs generation, which are characterized in terms of phenotypic markers, cytokines secretion profile, CD4+ T cell-stimulatory ability and migratory capacity. Methods TolDCs from healthy donors were generated by modulation with dexamethasone plus monophosphoryl lipid A (MPLA-tDCs). We performed an analysis of MPLA-tDCs in terms of yield, viability, morphology, phenotypic markers, cytokines secretion profile, stability, allogeneic and antigen-specific CD4+ T-cell stimulatory ability and migration capacity. Results After a 5-day culture, MPLA-tDCs displayed reduced expression of costimulatory and maturation molecules together to an anti-inflammatory cytokines secretion profile, being able to maintain these tolerogenic features even after the engagement of CD40 by its cognate ligand. In addition, MPLA-tDCs exhibited reduced capabilities to stimulate allogeneic and antigen-specific CD4+ T cell proliferation, and induced an anti-inflammatory cytokine secretion pattern. Among potential tolerogenic markers studied, only TLR-2 was highly expressed in MPLA-tDCs when compared to mature and immature DCs. Remarkable, like mature DCs, MPLA-tDCs displayed a high CCR7 and CXCR4 expression, both chemokine receptors involved in migration to secondary lymphoid organs, and even more, in an in vitro assay they exhibited a high migration response towards CCL19 and CXCL12. Conclusion We describe a short-term protocol for TolDC generation, which confers them a stable phenotype and migratory capacity to lymphoid chemokines, essential features for TolDCs to be used as therapeutics for autoimmunity and prevention of graft rejection. PMID:23706017

Functional Interactions between Newborn and Mature Neurons Leading to Integration into Established Neuronal Circuits.

PubMed

Boulanger-Weill, Jonathan; Candat, Virginie; Jouary, Adrien; Romano, Sebastián A; Pérez-Schuster, Verónica; Sumbre, Germán

2017-06-19

From development up to adulthood, the vertebrate brain is continuously supplied with newborn neurons that integrate into established mature circuits. However, how this process is coordinated during development remains unclear. Using two-photon imaging, GCaMP5 transgenic zebrafish larvae, and sparse electroporation in the larva's optic tectum, we monitored spontaneous and induced activity of large neuronal populations containing newborn and functionally mature neurons. We observed that the maturation of newborn neurons is a 4-day process. Initially, newborn neurons showed undeveloped dendritic arbors, no neurotransmitter identity, and were unresponsive to visual stimulation, although they displayed spontaneous calcium transients. Later on, newborn-labeled neurons began to respond to visual stimuli but in a very variable manner. At the end of the maturation period, newborn-labeled neurons exhibited visual tuning curves (spatial receptive fields and direction selectivity) and spontaneous correlated activity with neighboring functionally mature neurons. At this developmental stage, newborn-labeled neurons presented complex dendritic arbors and neurotransmitter identity (excitatory or inhibitory). Removal of retinal inputs significantly perturbed the integration of newborn neurons into the functionally mature tectal network. Our results provide a comprehensive description of the maturation of newborn neurons during development and shed light on potential mechanisms underlying their integration into a functionally mature neuronal circuit. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Age, psychological maturity, and the transition to motherhood among English-speaking Australian women in a metropolitan area.

PubMed

Camberis, Anna-Lisa; McMahon, Catherine A; Gibson, Frances L; Boivin, Jacky

2014-08-01

In the context of the trend toward delayed parenthood, this study examines whether older maternal age is associated with greater psychological maturity and whether greater psychological maturity provides any adaptive benefit during the transition to motherhood. A sample of 240 predominantly English-speaking Australian women in a metropolitan area expecting their 1st baby (mean age = 32.81 years; 41% conceived after fertility treatment) completed measures of psychological maturity (hardiness, ego development, and ego resiliency) and pregnancy adaptation (maternal fetal attachment and formation of a maternal identity) in the 3rd trimester of pregnancy and a measure of postnatal adjustment at 4-6 months postpartum. Structural equation modeling showed age was positively associated with a latent construct of psychological maturity, and psychological maturity was associated with more optimal adaptation in pregnancy and early motherhood. Both psychological maturity and pregnancy adaptation predicted positive postnatal adjustment. Age was indirectly related to adaptation through its relationship with psychological maturity. The relationships in the model applied regardless of mode of conception (fertility treatment or spontaneous). Potentially confounding contextual factors associated with older age at motherhood, higher education, and maternal and child health were included in the model. These results suggest that psychological maturity is a benefit of motherhood at older ages. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Calcium Signaling enhancement during oocyte maturation

NASA Astrophysics Data System (ADS)

Jung, Peter; Ullah, Ghanim; Machaca, Khaled

2006-03-01

A Ca2+ signal with a special spatial and temporal characteristic universally removes cell-cycle arrest after fertilization of a mature egg cell. The Ca2+ signal is characterized by a fast rise of intracellular Ca2+ and a slow decay on the time scale of minutes. We use computational modeling of Ca2+ release on the microscale (Ca2+ puffs) and cell-scale in conjunction with experimental knowledge of the changes in the Ca2+ signaling apparatus during oocyte maturation and changing signaling patterns to explore the relationship between organization and sensitivity of IP3 receptors and SERCA pumps and the resulting signaling patterns. We hypothesize that potentiation of the IP3 receptors during oocyte maturation is the main cause for the differentiation in the signaling patterns.

Genetic transformation of mature citrus plants.

PubMed

Cervera, Magdalena; Juárez, José; Navarro, Luis; Peña, Leandro

2005-01-01

Most woody fruit species have long juvenile periods that drastically prolong the time required to analyze mature traits. Evaluation of characteristics related to fruits is a requisite to release any new variety into the market. Because of a decline in regenerative and transformation potential, genetic transformation procedures usually employ juvenile material as the source of plant tissue, therefore resulting in the production of juvenile plants. Direct transformation of mature material could ensure the production of adult transgenic plants, bypassing in this way the juvenile phase. Invigoration of the source adult material, establishment of adequate transformation and regeneration conditions, and acceleration of plant development through grafting allowed us to produce transgenic mature sweet orange trees flowering and bearing fruits in a short time period.

Eruption of the permanent maxillary canines in relation to mandibular second molar maturity.

PubMed

Perinetti, Giuseppe; Callovi, Marilena; Salgarello, Stefano; Biasotto, Matteo; Contardo, Luca

2013-07-01

To evaluate the timing of spontaneous maxillary canine eruption in relation to stages of mandibular second molar maturation. Potential confounding effects from such factors as age, growth phase, and facial features were also explored. A sample of 106 healthy subjects (48 females and 58 males; age range, 9.4-14.3 years) with both permanent maxillary canines during the final phase of intraoral eruption were included. Mandibular second molar maturation (stages E to H) was assessed according to the method of Demirjian. Skeletal maturity was determined using the cervical vertebral maturational (CVM) method. Facial vertical and sagittal relationships were evaluated by recording the Sella-Nasion/mandibular plane (SN/MP) angle and the ANB angle. An ordered multiple logistic regression was run to evaluate adjusted correlation of each parameter with the mandibular second molar maturational stage. Overall, the prevalence of the different second molar maturational stages was 36.8%, 37.8%, and 27.4% for stages E, F and G, respectively. According to the regression model, this relation was not influenced by sex, CVM stage, SN/MP angle, and ANB angle. Irrespective of sex, growth phase, and facial features, the maturational stage of the mandibular second molar may be a reliable indicator for the timing of spontaneous eruption of the maxillary canine.

Maturity-Associated Variation in Functional Characteristics Of Elite Youth Tennis Players.

PubMed

Myburgh, Gillian K; Cumming, Sean P; Silva, Manuel Coelho E; Cooke, Karl; Malina, Robert M

2016-11-01

To evaluate relationships among skeletal maturity, body size, and functional capacities of elite junior tennis players. Participants were 88 elite British Junior tennis players (44 male; 44 female), 8-16 years of age (12.4 } 1.9 years). Skeletal age estimated maturty. Anthropometry, grip strength, countermovement jump, squat jump, forehand agility, backhand agility, Yo-Yo, 5-m, 10-m and 20-m sprints were measured. Comparative analysis for each sex was performed, relating advanced maturers (Male: 15; Female: 29) to a combination of on-time and late maturers (Male: 29; Female: 31). ANCOVAs were used to determine absolute differences between male and female players and between the 2 maturity subgroups, with chronological age as the covariate. Advanced maturity afforded male players advantages in absolute measures of grip strength, speed, upper and lower body power but not in acceleration, agility or aerobic endurance. Male players were significantly taller than females in the U13-U16 age group. Advanced maturity in female players afforded advantages in absolute measures of grip strength, agility and overhead power, but not in backhand agility, aerobic endurance or squat jump power. It is important that talent identification protocols consider the maturity of youth athletes to more satisfactorily address athletic potential rather than transient physical capabilities.

Predicting the influence of liposomal lipid composition on liposome size, zeta potential and liposome-induced dendritic cell maturation using a design of experiments approach.

PubMed

Soema, Peter C; Willems, Geert-Jan; Jiskoot, Wim; Amorij, Jean-Pierre; Kersten, Gideon F

2015-08-01

In this study, the effect of liposomal lipid composition on the physicochemical characteristics and adjuvanticity of liposomes was investigated. Using a design of experiments (DoE) approach, peptide-containing liposomes containing various lipids (EPC, DOPE, DOTAP and DC-Chol) and peptide concentrations were formulated. Liposome size and zeta potential were determined for each formulation. Moreover, the adjuvanticity of the liposomes was assessed in an in vitro dendritic cell (DC) model, by quantifying the expression of DC maturation markers CD40, CD80, CD83 and CD86. The acquired data of these liposome characteristics were successfully fitted with regression models, and response contour plots were generated for each response factor. These models were applied to predict a lipid composition that resulted in a liposome with a target zeta potential. Subsequently, the expression of the DC maturation factors for this lipid composition was predicted and tested in vitro; the acquired maturation responses corresponded well with the predicted ones. These results show that a DoE approach can be used to screen various lipids and lipid compositions, and to predict their impact on liposome size, charge and adjuvanticity. Using such an approach may accelerate the formulation development of liposomal vaccine adjuvants. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Emerald ash borer biocontrol in ash saplings: The potential for early stage recovery of North American ash trees

Treesearch

Jian J. Duan; Leah S. Bauer; Roy G. Van Driesche

2017-01-01

In many parts of North America, ash (Fraxinus) stands have been reduced by the emerald ash borer (Agrilus planipennis) invasion to a few surviving mature trees, saplings, basal sprouts, and seedlings. Without a soil seed bank for Fraxinus spp., tree recovery will require survival and maturation of these...

Emerald ash borer biocontrol in ash saplings: the potential for early stage recovery of North American ash

USDA-ARS?s Scientific Manuscript database

In many parts of North America, ash stands have been reduced by the emerald ash borer (Agrilus planipennis) invasion to a few surviving mature trees and young basal sprouts, saplings, and seedlings. Without a seed bank, ash tree recovery will require survival and maturation of these younger cohorts...

Psychosocial Correlates of Adolescent Drug Dealing in the Inner City: Potential Roles of Opportunity, Conventional Commitments, and Maturity

ERIC Educational Resources Information Center

Little, Michelle; Steinberg, Laurence

2006-01-01

This study examined a model of the simultaneous and interactive influence of social context, psychosocial attitudes, and individual maturity on the prediction of urban adolescent drug dealing. Five factors were found to significantly increase adolescents' opportunity for drug selling: low parental monitoring, poor neighborhood conditions, low…

Petroleum geochemistry of oil and gas from Barbados: Implications for distribution of Cretaceous source rocks and regional petroleum prospectivity

USGS Publications Warehouse

Hill, R.J.; Schenk, C.J.

2005-01-01

Petroleum produced from the Barbados accretionary prism (at Woodbourne Field on Barbados) is interpreted as generated from Cretaceous marine shale deposited under normal salinity and dysoxic conditions rather than from a Tertiary source rock as previously proposed. Barbados oils correlate with some oils from eastern Venezuela and Trinidad that are positively correlated to extracts from Upper Cretaceous La Luna-like source rocks. Three distinct groups of Barbados oils are recognized based on thermal maturity, suggesting petroleum generation occurred at multiple levels within the Barbados accretionary prism. Biodegradation is the most significant process affecting Barbados oils resulting in increased sulfur content and decreased API gravity. Barbados gases are interpreted as thermogenic, having been co-generated with oil, and show mixing with biogenic gas is limited. Gas biodegradation occurred in two samples collected from shallow reservoirs at the Woodbourne Field. The presence of Cretaceous source rocks within the Barbados accretionary prism suggests that greater petroleum potential exists regionally, and perhaps further southeast along the passive margin of South America. Likewise, confirmation of a Cretaceous source rock indicates petroleum potential exists within the Barbados accretionary prism in reservoirs that are deeper than those from Woodbourne Field.

How does mindfulness modulate self-regulation in pre-adolescent children? An integrative neurocognitive review.

PubMed

Kaunhoven, Rebekah Jane; Dorjee, Dusana

2017-03-01

Pre-adolescence is a key developmental period in which complex intrinsic volitional methods of self-regulation are acquired as a result of rapid maturation within the brain networks underlying the self-regulatory processes of attention control and emotion regulation. Fostering adaptive self-regulation skills during this stage of development has strong implications for physical health, emotional and socio-economic outcomes during adulthood. There is a growing interest in mindfulness-based programmes for pre-adolescents with initial findings suggesting self-regulation improvements, however, neurodevelopmental studies on mindfulness with pre-adolescents are scarce. This analytical review outlines an integrative neuro-developmental approach, which combines self-report and behavioural assessments with event related brain potentials (ERPs) to provide a systemic multilevel understanding of the neurocognitive mechanisms of mindfulness in pre-adolescence. We specifically focus on the N2, error related negativity (ERN), error positivity (Pe), P3a, P3b and late positive potential (LPP) ERP components as indexes of mindfulness related modulations in non-volitional bottom-up self-regulatory processes (salience detection, stimulus driven orienting and mind wandering) and volitional top-down self-regulatory processes (endogenous orienting and executive attention). Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Acute Kidney Injury and Big Data.

PubMed

Sutherland, Scott M; Goldstein, Stuart L; Bagshaw, Sean M

2018-01-01

The recognition of a standardized, consensus definition for acute kidney injury (AKI) has been an important milestone in critical care nephrology, which has facilitated innovation in prevention, quality of care, and outcomes research among the growing population of hospitalized patients susceptible to AKI. Concomitantly, there have been substantial advances in "big data" technologies in medicine, including electronic health records (EHR), data registries and repositories, and data management and analytic methodologies. EHRs are increasingly being adopted, clinical informatics is constantly being refined, and the field of EHR-enabled care improvement and research has grown exponentially. While these fields have matured independently, integrating the two has the potential to redefine and integrate AKI-related care and research. AKI is an ideal condition to exploit big data health care innovation for several reasons: AKI is common, increasingly encountered in hospitalized settings, imposes meaningful risk for adverse events and poor outcomes, has incremental cost implications, and has been plagued by suboptimal quality of care. In this concise review, we discuss the potential applications of big data technologies, particularly modern EHR platforms and health data repositories, to transform our capacity for AKI prediction, detection, and care quality. © 2018 S. Karger AG, Basel.

Holocene Paleoearthquake History on the Qingchuan Fault in the Northeastern Segment of the Longmenshan Thrust Zone and Its Implications

NASA Astrophysics Data System (ADS)

Sun, H.; He, H.; Ikeda, Y.; Kano, K.; Shi, F.; Gao, W.; Echigo, T.; Okada, S.

2017-12-01

Although much work has been performed for faults with high slip-rates, little attention has been paid to low slip-rate faults, such as the Longmenshan Thrust Zone (LTZ). The LTZ is a long and matured fault that evolved during the Mesozoic as a structural boundary, but its Quaternary activity had been considered insignificant. The Wenchuan earthquake and the following Lushan earthquake on the central and southwestern segments of the LTZ not only demonstrate its capability for strong earthquakes but also illustrate the necessity of assessing the regional seismic potential around its northeastern extension. The sparse seismicity along the northeastern segment of the LTZ relative to the very seismically active Minshan Uplift seems to have suggested that the slip on the central LTZ transfers northeastward to the Minshan Uplift, so that its northeastern segment is inactive. However, the Wenchuan earthquake surface rupture and aftershocks extended beyond the Minshan Uplift, and revealed that the break both at and below the ground surface may have reached the northeastern segment of the LTZ raising a question that whether or not this fault segment is active. Although several studies had been carried out on the northeastern segment of the LTZ, little is known about its activity and seismic potential. To solve these problems, we conducted paleoseismological trench excavations on the Qingchuan fault (QF) in the northeastern LTZ and identified one (and the latest) event occurred in the Holocene. Based on radiocarbon dating, the event is constrained to occur between 4115-3820 B.C., and a long recurrence interval is thus estimated. Judging from the matured fault structure of the QF, the latest event was likely to have ruptured the full length of the QF, and was estimated to be Mw 7.6-7.9 according to empirical scaling laws. Using the slip rate and the elapsed time since the last event, it is estimated an accumulated seismic moment equivalent to Mw 7.5 on the QF. Considering the increased Coulomb failure stress and the shortened time of earthquake recurrence triggered by the Wenchuan earthquake, it is suggested a high seismic risk along the QF and its neighboring area. Furthermore, the slow strain buildup, unadapted geometry, and matured fault structure of the LTZ may be the reason why it produces rare but large intraplate earthquakes.

Human face processing is tuned to sexual age preferences

PubMed Central

Ponseti, J.; Granert, O.; van Eimeren, T.; Jansen, O.; Wolff, S.; Beier, K.; Deuschl, G.; Bosinski, H.; Siebner, H.

2014-01-01

Human faces can motivate nurturing behaviour or sexual behaviour when adults see a child or an adult face, respectively. This suggests that face processing is tuned to detecting age cues of sexual maturity to stimulate the appropriate reproductive behaviour: either caretaking or mating. In paedophilia, sexual attraction is directed to sexually immature children. Therefore, we hypothesized that brain networks that normally are tuned to mature faces of the preferred gender show an abnormal tuning to sexual immature faces in paedophilia. Here, we use functional magnetic resonance imaging (fMRI) to test directly for the existence of a network which is tuned to face cues of sexual maturity. During fMRI, participants sexually attracted to either adults or children were exposed to various face images. In individuals attracted to adults, adult faces activated several brain regions significantly more than child faces. These brain regions comprised areas known to be implicated in face processing, and sexual processing, including occipital areas, the ventrolateral prefrontal cortex and, subcortically, the putamen and nucleus caudatus. The same regions were activated in paedophiles, but with a reversed preferential response pattern. PMID:24850896

RNA Surveillance: Molecular Approaches in Transcript Quality Control and their Implications in Clinical Diseases

PubMed Central

Moraes, Karen CM

2010-01-01

Production of mature mRNAs that encode functional proteins involves highly complex pathways of synthesis, processing and surveillance. At numerous steps during the maturation process, the mRNA transcript undergoes scrutiny by cellular quality control machinery. This extensive RNA surveillance ensures that only correctly processed mature mRNAs are translated and precludes production of aberrant transcripts that could encode mutant or possibly deleterious proteins. Recent advances in elucidating the molecular mechanisms of mRNA processing have demonstrated the existence of an integrated network of events, and have revealed that a variety of human diseases are caused by disturbances in the well-coordinated molecular equilibrium of these events. From a medical perspective, both loss and gain of function are relevant, and a considerable number of different diseases exemplify the importance of the mechanistic function of RNA surveillance in a cell. Here, mechanistic hallmarks of mRNA processing steps are reviewed, highlighting the medical relevance of their deregulation and how the understanding of such mechanisms can contribute to the development of therapeutic strategies. PMID:19829759

Distinct features of multivesicular body-lysosome fusion revealed by a new cell-free content-mixing assay.

PubMed

Karim, Mahmoud Abdul; Samyn, Dieter Ronny; Mattie, Sevan; Brett, Christopher Leonard

2018-02-01

When marked for degradation, surface receptor and transporter proteins are internalized and delivered to endosomes where they are packaged into intralumenal vesicles (ILVs). Many rounds of ILV formation create multivesicular bodies (MVBs) that fuse with lysosomes exposing ILVs to hydrolases for catabolism. Despite being critical for protein degradation, the molecular underpinnings of MVB-lysosome fusion remain unclear, although machinery underlying other lysosome fusion events is implicated. But how then is specificity conferred? And how is MVB maturation and fusion coordinated for efficient protein degradation? To address these questions, we developed a cell-free MVB-lysosome fusion assay using Saccharomyces cerevisiae as a model. After confirming that the Rab7 ortholog Ypt7 and the multisubunit tethering complex HOPS (homotypic fusion and vacuole protein sorting complex) are required, we found that the Qa-SNARE Pep12 distinguishes this event from homotypic lysosome fusion. Mutations that impair MVB maturation block fusion by preventing Ypt7 activation, confirming that a Rab-cascade mechanism harmonizes MVB maturation with lysosome fusion. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Maturation of neuronal form and function in a mouse thalamo-cortical circuit.

PubMed

Warren, R A; Jones, E G

1997-01-01

Postnatal development of physiological properties underlying slow intrathalamic oscillations was studied by whole-cell recording from synaptically coupled neurons of the reticular nucleus (RTN) and ventral posterior nucleus (VPN) of mouse brain slices in vitro and compared with the morphological development of dye-injected cells. Between postnatal days 3 and 11 (P3-P11), progressive changes in RTN and VPN neurons included shortening of the membrane time constant, decreasing input resistance, and lowering of the resting membrane potential (RMP). Low-threshold Ca2+ spikes (LTS) were present from P3, but their capacity to sustain multispike bursts was limited before P11. Synaptic responses were evoked in RTN and VPN neurons by electrical stimulation of the internal capsule from P3. Younger RTN neurons responded with a single spike, but their capacity to fire bursts gradually improved as the RMP reached levels below the LTS activation potential. Concomitantly, as the reversal potential of the inhibitory postsynaptic potential in VPN neurons became more negative, its capacity to deinactivate the LTS increased, and rebound bursts that could maintain oscillations were produced; sustained oscillations became the typical response to internal capsule stimulation at P12. The functional maturation of the intrathalamic circuitry, particularly between P10 and P14, occurs in parallel with the morphological maturation (size, dendritic growth, and dendritic field structure) of individual RTN and VPN neurons, as studied by confocal microscopy. Maturation of RTN cells led that of VPN cells by 2-3 d. The appearance of intrathalamic oscillations is probably correlated with the appearance of slow-wave sleep in postnatal animals.

Rate of egg maturation in marine turtles exhibits 'universal temperature dependence'.

PubMed

Weber, Sam B; Blount, Jonathan D; Godley, Brendan J; Witt, Matthew J; Broderick, Annette C

2011-09-01

1. The metabolic theory of ecology (MTE) predicts that, after correcting for body mass variation among organisms, the rates of most biological processes will vary as a universal function of temperature. However, empirical support for 'universal temperature dependence' (UTD) is currently equivocal and based on studies of a limited number of traits. 2. In many ectothermic animals, the rate at which females produce mature eggs is temperature dependent and may be an important factor in determining the costs of reproduction. 3. We tested whether the rate of egg maturation in marine turtles varies with environmental temperature as predicted by MTE, using the time separating successive clutches of individual females to estimate the rate at which eggs are formed. We also assessed the phenotypic contribution to this rate, by using radio telemetry to make repeated measurements of interclutch intervals for individual green turtles (Chelonia mydas). 4. Rates of egg maturation increased with seasonally increasing water temperatures in radio-tracked green turtles, but were not repeatable for individual females, and did not vary according to maternal body size or reproductive investment (number and size of eggs produced). 5. Using a collated data set from several different populations and species of marine turtles, we then show that a single relationship with water temperature explains most of the variation in egg maturation rates, with a slope that is statistically indistinguishable from the UTD predicted by MTE. However, several alternative statistical models also described the relationship between temperature and egg maturation rates equally parsimoniously. 6. Our results offer novel support for the MTE's predicted UTD of biological rates, although the underlying mechanisms require further study. The strong temperature dependence of egg maturation combined with the apparently weak phenotypic contribution to this rate has interesting behavioural implications in ectothermic animals. We suggest that maternal thermoregulatory behaviour in marine turtles, and many other reptiles, is consistent with a strategy of adaptively increasing body temperatures to accelerate egg maturation. © 2011 The Authors. Journal of Animal Ecology © 2011 British Ecological Society.

Double probing of human spermatozoa for persistent histones, surplus cytoplasm, apoptosis and DNA fragmentation.

PubMed

Sati, Leyla; Ovari, Laszlo; Bennett, David; Simon, Stephen D; Demir, Ramazan; Huszar, Gabor

2008-04-01

Individual spermatozoa were assessed with pairs of probes for persistent histones and cytoplasmic retention, persistent histones and DNA fragmentation, and persistent histones and apoptotic markers. The individual spermatozoa were treated sequentially with combinations of probes for these cytoplasmic and nuclear biochemical markers. Sperm fields were recorded with computer-assisted imaging, and staining patterns with the two probes in the same spermatozoa were examined and scored as light, intermediate or dark (mature to arrested-maturity spermatozoa). The effects of arrested sperm maturation were similar with respect to the cytoplasmic and nuclear characteristics of spermatozoa in 84% of cells, indicating that cytoplasmic and nuclear attributes of arrested sperm maturation are related. However, there were moderate (intermediate-dark or intermediate-light patterns, 14.5% of cells) or major (light-dark patterns, 1.6% of cells) discrepancies in the intensity of the double staining patterns. Thus, testing with single maturity markers may not be fully reliable. These findings are important with respect to: (i) arrested sperm maturation; (ii) potential efficacy of antioxidant and similar therapeutic strategies in subfertile men, as spermatozoa with infrastructure defects due to mismaturation or maturation arrest are unlikely to respond to interventions; and (iii) detection of adverse male environmental exposures.

Identification of differentially expressed genes in the zebrafish hypothalamus - pituitary axis

PubMed Central

Toro, Sabrina; Wegner, Jeremy; Muller, Marc; Westerfield, Monte; Varga, Zoltan M.

2009-01-01

The vertebrate hypothalamic-pituitary axis (HP) is the main link between the central nervous system and endocrine system. Although several signal pathways and regulatory genes have been implicated in adenohypophysis ontogenesis, little is known about hypothalamic and neurohypophysial development or when the HP matures and becomes functional. To identify markers of the HP, we constructed subtractive cDNA libraries between adult zebrafish hypothalamus and pituitary. We identified previously published genes and ESTs and novel zebrafish genes, some of which were predicted by genomic database analysis. We also analyzed expression patterns of these genes and found that several are expressed in the embryonic and larval hypothalamus, neurohypophysis, and/or adenohypophysis. Expression at these stages makes these genes useful markers to study HP maturation and function. PMID:19166982

Magnetic properties of Apollo samples and implications for regolith formation

NASA Technical Reports Server (NTRS)

Pearce, G. W.; Strangway, D. W.; Gose, W. A.

1974-01-01

The magnetic properties of a number of Apollo 17 samples have been measured and confirm that regoliths of mare sites (Apollo 11, 12, 15 valley, and 17 valley) differ markedly from those of highland sites (Apollo 14, 16, and 17 massif) in the ratio of content of metallic to ferrous iron and in the grain size of metallic iron. The ratio of metallic to ferrous iron is correlated with mean particle size, a parameter representing maturity, for soils of Apollo 16 and roughly correlated with the age of the sites for soils of different sites. It is suggested that the ratio of metallic to ferrous iron may be an effective indicator of relative soil maturity for any one site and of the age of the soil material for any sites.

In-vitro maturation of germinal vesicle and metaphase I eggs prior to cryopreservation optimizes reproductive potential in patients undergoing fertility preservation.

PubMed

Lee, Joseph A; Sekhon, Lucky; Grunfeld, Lawrence; Copperman, Alan B

2014-06-01

To evaluate current and previous findings related to a timely implementation of in-vitro maturation (IVM) of germinal vesicle, metaphase I and metaphase II oocytes with an optimal cryopreservation to determine whether IVM should be attempted prior to (fresh IVM) or IVM after cryopreservation (postthaw IVM). Mitochondrion, chromatin and spindle formation in both groups were interpreted from referenced studies to establish best management of all oocytes. The postthaw survival of germinal vesicle, metaphase I, fresh IVM-metaphase II and control metaphase II oocytes did not differ significantly [83.3% (n=9), 86.7% (n=12), 83% (n=57) and 86% (n=68), respectively]. Overall, combined survival and maturation were significantly higher (P<0.05) in the fresh IVM group at 63.8% (44 of 69) compared with the postthaw IVM group at 33.3% (nine of 27). Conservation of retrieved immature oocytes after vaginal oocyte retrieval has become a major concern for patients, as they strive to maximize the reproductive viability of all oocytes obtained during treatment. Oocyte cryopreservation is important for patients at risk of ovarian cancer, elective fertility preservation and potentially for ovum donation. The superior maturation rate of germinal vesicle and metaphase I oocytes in the fresh IVM vs. postthaw groups provides strong impetus to mature oocytes to the metaphase II stage prior to cryopreservation.

Geochemical evaluation of upper cretaceous fruitland formation coals, San Juan Basin, New Mexico and Colorado

USGS Publications Warehouse

Michael, G.E.; Anders, D.E.; Law, B.E.

1993-01-01

Geochemical analyses of coal samples from the Upper Cretaceous Fruitland Formation in the San Juan Basin of New Mexico and Colorado were used to determine thermal maturity, type of kerogen, and hydrocarbon generation potential. Mean random vitrinite reflectance (%Rm) of the Fruitland coal ranges from 0.42 to 1.54%. Rock-Eval pyrolysis data and saturated to aromatic hydrocarbon ratio indicate that the onset of thermal hydrocarbon generation begins at about 0.60% Rm and peak generation occurs at about 0.85% Rm. Several samples have hydrogen index values between 200 and 400, indicating some potential for liquid hydrocarbon generation and a mixed Type III and II kerogen. Pentacyclic and tricyclic terpanes, steranes, aromatic steroids and methylphenanthrene maturity parameters were observed through the complete range of thermal maturity in the Fruitland coals. Aromatic pentacyclic terpanes, similar to those found in brown coals of Australia, were observed in low maturity samples, but not found above 0.80% Rm. N-alkane depleted coal samples, which occur at a thermal maturity of approx. 0.90% Rm, paralleling peak hydrocarbon generation, are fairly widespread throughout the basin. Depletion of n-alkanes in these samples may be due to gas solution stripping and migration fromthe coal seams coincident with the development of pressure induced fracturing due to hydrocarbon generation; however, biodegradation may also effect these samples. ?? 1993.

Time and temperature in petroleum formation: application of Lopatin's method to petroleum exploration

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

Waples, D.W.

1980-06-01

N.V. Lopatin in the Soviet Union has developed a method for taking both time and temperature into account as factors in thermal maturation of kerogen. Lopatin's time-temperature index of maturity (TTI) values correlate with the thermal regimes corresponding to generation and preservation of hydrocarbons. Because such information is potentially of great interest for oil exploration, a calibration and evaluation have been made of Lopatin's method. Within the limitations of the date presently available the following statements can be made: 1. The rate of the chemical reactions involved in thermal maturation of organic material appears to double with every 10/sup 0/Cmore » (18/sup 0/F) rise in temperature. 2. Threshold values of Lopatin's time-temperature index of maturity (TTI) are: 15 onset of oil generation; 75 peak oil generation; 160 end oil generation; approx. 500 40/sup 0/ oil preservation deadline; approx. 1000 50/sup 0/ oil preservation deadline; approx. 1500 wet gas preservation deadline; and > 65,000 dry gas preservation deadline. 3. TTI values calculated from Lopatin reconstructions consistently agree with other maturation parameters commonly used by petroleum geochemists. Potential applications of Lopatin's method for oil exploration include timing of oil generation, calculation of volume of hydrocarbons generated within a basin, and determination of economic deadlines. 13 figures, 5 tables.« less

Role of ataxia-telangiectasia mutated (ATM) in porcine oocyte in vitro maturation.

PubMed

Lin, Zi-Li; Kim, Nam-Hyung

2015-06-01

Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germinal vesicle breakdown (GVBD) and first polar body extrusion. KU-55933 also decreased the expression of DNA damage-related genes (breast cancer 1, budding uninhibited by benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and other cell cycle-regulated genes that are predominantly expressed during G2/M phase, including bone morphogenetic protein 15, growth differentiation factor 9, cell division cycle protein 2, cyclinB1, and AKT. KU-55933 treatment decreased the developmental potential of blastocysts following parthenogenetic activation and increased the level of apoptosis. Together, these data suggested that ATM influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially by decreasing their sensitivity to DNA strand breaks, stimulating the AKT pathway, and/or altering the expression of other maternal genes. © 2015 International Federation for Cell Biology.

Mobilization and Defense Management Technical Reports Series. The Impact of OSHA (Occupational Safety and Health Administration) and EPA (Environmental Protection Agency) on Defense Industry and the Implications for Mobilization.

DTIC Science & Technology

1983-05-01

mat of the voluntary standards thean in existence (JASI and NVA standards, for wcmmle). fwue affected the broad spectrum of Nm rican industry. As OBIA ...have been funded. As OMA matured, programs, standards, and inspections were significantly improved and gained industry aeptance. OBIA has deleted many

Steady State Staff Planning: The Experience of a "Mature" Liberal Arts College and Its Implications.

ERIC Educational Resources Information Center

Lamson, George; And Others

The end of faculty growth in higher education has led to near panic predictions of aging, highly tenured, more costly, steady-state faculties as the "growth bulge" hired in the 1960's age. This study discusses two models for simulating the behavior over time of indices of faculty health such as average age and salary, annual new hires,…

Quantifying sources of variation in the frequency of fungi associated with spruce beetles: implications for hypothesis testing and sampling methodology in bark beetle-symbiont relationships.

Treesearch

Brian H. Aukema; Richard A. Werner; Kirsten E. Haberkern; Barbara L. Illman; Murray K. Clayton; Kenneth F. Raffa

2005-01-01

The spruce beetle, Dendroctonus rufipennis (Kirby), causes landscape level mortality to mature spruce (Picea spp.) throughout western and northern North America. As with other bark beetles, this beetle is associated with a variety of fungi, whose ecological functions are largely unknown. It has been proposed that the relative...

Credentialism, Adults, and Part-Time Higher Education in the United Kingdom: An Account of Rising Take Up and Some Implications for Policy.

ERIC Educational Resources Information Center

Fuller, Alison

2001-01-01

Explains the growing importance of higher-level qualifications for adults in the UK, highlighting statistical trends in commitment to learning and qualifying-the result of taking part-time courses in higher education. Most part-time undergraduates fund their own tuition. Mature students' backgrounds and perspectives partly account for their rising…

Maturational changes in the thermoalgesic system in humans from childhood to adulthood revealed by CO(2) laser evoked brain potentials following cutaneous heat stimuli.

PubMed

Opsommer, E; Plaghki, L

2001-12-28

Possible maturational changes in the thermoalgesic system were studied by reaction times (RT) and late (Adelta-fibre) laser evoked potentials (LEPs) following CO(2) laser heat stimulation of the hand in healthy children (n=12) and young adults (n=12). In children (10+/-2 years) LEPs presented a negative-positive complex with maximum amplitude (peak-to-peak 71+/-35 microV) at the vertex and latencies of 248+/-82 and 433+/-104 ms, respectively. As compared to adults (24+/-3 years), children had a significant increased peak-to-peak amplitude (+25.7 microV; P=0.03) although no difference in latencies and topography. Median RT (710 ms) was also significantly increased (+312 ms; P<0.005) in children. A decrease in RT and late LEP amplitude from childhood to adulthood may reflect aspects of maturation in sensory processing of the thermoalgesic system.

Deletion or underexpression of the Y-chromosome genes CDY2 and HSFY is associated with maturation arrest in American men with nonobstructive azoospermia.

PubMed

Stahl, Peter J; Mielnik, Anna N; Barbieri, Christopher E; Schlegel, Peter N; Paduch, Darius A

2012-09-01

Maturation arrest (MA) refers to failure of germ cell development leading to clinical nonobstructive azoospermia. Although the azoospermic factor (AZF) region of the human Y chromosome is clearly implicated in some cases, thus far very little is known about which individual Y-chromosome genes are important for complete male germ cell development. We sought to identify single genes on the Y chromosome that may be implicated in the pathogenesis of nonobstructive azoospermia associated with MA in the American population. Genotype-phenotype analysis of 132 men with Y-chromosome microdeletions was performed. Protein-coding genes associated with MA were identified by visual analysis of a genotype-phenotype map. Genes associated with MA were selected as those genes within a segment of the Y chromosome that, when completely or partially deleted, were always associated with MA and absence of retrievable testicular sperm. Expression of each identified gene transcript was then measured with quantitative RT-PCR in testicular tissue from separate cohorts of patients with idiopathic MA and obstructive azoospermia. Ten candidate genes for association with MA were identified within an 8.4-Mb segment of the Y chromosome overlapping the AZFb region. CDY2 and HSFY were the only identified genes for which differences in expression were observed between the MA and obstructive azoospermia cohorts. Men with obstructive azoospermia had 12-fold higher relative expression of CDY2 transcript (1.33 ± 0.40 vs. 0.11 ± 0.04; P=0.0003) and 16-fold higher expression of HSFY transcript (0.78 ± 0.32 vs. 0.05 ± 0.02; P=0.0005) compared to men with MA. CDY2 and HSFY were also underexpressed in patients with Sertoli cell only syndrome. These data indicate that CDY2 and HSFY are located within a segment of the Y chromosome that is important for sperm maturation, and are underexpressed in testicular tissue derived from men with MA. These observations suggest that impairments in CDY2 or HSFY expression could be implicated in the pathogenesis of MA.

Contextual amplification or attenuation of the impact of pubertal timing on Mexican-origin boys' mental health symptoms.

PubMed

White, Rebecca M B; Deardorff, Julianna; Liu, Yu; Gonzales, Nancy A

2013-12-01

To examine the role of neighborhood contextual variation in the putative association between pubertal timing and internalizing and externalizing symptoms among Mexican-origin boys. In a sample of seventh-grade Mexican-origin boys (N = 353; x¯age=12.8years) we assessed a range of secondary sexual characteristics, internalizing, and externalizing symptoms. Reports on all secondary sexual characteristics were collapsed and age-standardized to represent total pubertal timing. We also distinguished between the timing of physical changes driven by adrenal versus gonadal maturation. Boys' residential addresses were geocoded and American Community Survey data were used to describe neighborhoods along two dimensions: ethnic concentration and socioeconomic disadvantage. Three years later (in 10th grade) we re-assessed internalizing and externalizing symptoms. We examined the moderating influence of neighborhood ethnic concentration and neighborhood socioeconomic disadvantage on the prospective associations between puberty timing (total, gonadal, adrenal) and internalizing and externalizing symptoms. Earlier total pubertal timing predicted increases in externalizing symptoms, but only when Mexican-origin boys lived in neighborhoods low on ethnic concentration. Total timing results for externalizing symptoms were replicated for adrenal timing. Furthermore, early adrenal timing predicted increases in internalizing symptoms, but again, only when boys lived in neighborhoods low on ethnic concentration. No effects were observed for gonadal timing specifically. Early pubertal timing, especially advanced physical changes initiated and regulated by adrenal maturation, have important implications for Mexican-origin boys' internalizing and externalizing symptoms, but these implications depend on neighborhood characteristics. Ethnically concentrated neighborhoods are protective for early-maturing Mexican-origin boys. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Monitoring fetal maturation—objectives, techniques and indices of autonomic function*

PubMed Central

Hoyer, Dirk; Żebrowski, Jan; Cysarz, Dirk; Gonçalves, Hernâni; Pytlik, Adelina; Amorim-Costa, Célia; Bernardes, João; Ayres-de-Campos, Diogo; Witte, Otto W; Schleußner, Ekkehard; Stroux, Lisa; Redman, Christopher; Georgieva, Antoniya; Payne, Stephen; Clifford, Gari; Signorini, Maria G; Magenes, Giovanni; Andreotti, Fernando; Malberg, Hagen; Zaunseder, Sebastian; Lakhno, Igor; Schneider, Uwe

2017-01-01

Objective Monitoring the fetal behavior does not only have implications for acute care but also for identifying developmental disturbances that burden the entire later life. The concept, of ‘fetal programming’, also known as ‘developmental origins of adult disease hypothesis’, e.g. applies for cardiovascular, metabolic, hyperkinetic, cognitive disorders. Since the autonomic nervous system is involved in all of those systems, cardiac autonomic control may provide relevant functional diagnostic and prognostic information. Approach The fetal heart rate patterns (HRP) are one of the few functional signals in the prenatal period that relate to autonomic control and, therefore, is key to fetal autonomic assessment. The development of sensitive markers of fetal maturation and its disturbances requires the consideration of physiological fundamentals, recording technology and HRP parameters of autonomic control. Main Results Based on the ESGCO2016 special session on monitoring the fetal maturation we herein report the most recent results on: (i) functional fetal autonomic brain age score (fABAS), Recurrence Quantitative Analysis and Binary Symbolic Dynamics of complex HRP resolve specific maturation periods, (ii) magnetocardiography (MCG) based fABAS was validated for cardiotocography (CTG), (iii) 30 min recordings are sufficient for obtaining episodes of high variability, important for intrauterine growth restriction (IUGR) detection in handheld Doppler, (iv) novel parameters from PRSA to identify Intra IUGR fetuses, (v) evaluation of fetal electrocardiographic (ECG) recordings, (vi) correlation between maternal and fetal HRV is disturbed in pre-eclampsia. Significance The reported novel developments significantly extend the possibilities for the established CTG methodology. Novel HRP indices improve the accuracy of assessment due to their more appropriate consideration of complex autonomic processes across the recording technologies (CTG, handheld Doppler, MCG, ECG). The ultimate objective is their dissemination into routine practice and studies of fetal developmental disturbances with implications for programming of adult diseases. PMID:28186000

Evidence the U.S. autism epidemic initiated by acetaminophen (Tylenol) is aggravated by oral antibiotic amoxicillin/clavulanate (Augmentin) and now exponentially by herbicide glyphosate (Roundup).

PubMed

Good, Peter

2018-02-01

Because certain hereditary diseases show autistic behavior, and autism often runs in families, researchers seek genes underlying the pathophysiology of autism, thus core behaviors. Other researchers argue environmental factors are decisive, citing compelling evidence of an autism epidemic in the United States beginning about 1980. Recognition that environmental factors influence gene expression led to synthesis of these views - an 'epigenetic epidemic' provoked by pervasive environmental agents altering expression of vulnerable genes, inducing characteristic autistic biochemistries in many mothers and infants. Two toxins most implicated in the U.S. autism epidemic are analgesic/antipyretic acetaminophen (Tylenol) and oral antibiotic amoxicillin/clavulanate (Augmentin). Recently herbicide glyphosate (Roundup) was exponentially implicated. What do these toxins have in common? Acetaminophen depletes sulfate and glutathione required to detoxify it. Oral antibiotics kill and glyphosate inhibits intestinal bacteria that synthesize methionine (precursor of sulfate and glutathione, and required to methylate DNA), bacteria that synthesize tryptophan (sole precursor of neuroinhibitor serotonin), and bacteria that restrain ammonia-generating anaerobes. Sulfate plus glutathione normally sulfate fetal adrenal androgen dehydroepiandrosterone to DHEAS - major precursor of placental/postnatal estrogens. Glyphosate (and heavy metals) also inhibit aromatase that turns androgens to estrogens. Placental/postnatal estrogens dehydrate/mature brain myelin sheaths, mature corpus callosum and left hemisphere preferentially, dilate brain blood vessels, and elevate brain serotonin and oxytocin. Stress-induced weak androgens and estrogen depletion coherently explain white matter asymmetry and dysconnection in autism, extreme male brain, low brain blood flow, hyperexcitability, social anxiety, and insufficient maternal oxytocin at birth to limit fetal brain chloride/water and mature GABA. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Diosgenin promotes oligodendrocyte progenitor cell differentiation through estrogen receptor-mediated ERK1/2 activation to accelerate remyelination.

PubMed

Xiao, Lin; Guo, Dazhi; Hu, Chun; Shen, Weiran; Shan, Lei; Li, Cui; Liu, Xiuyun; Yang, Wenjing; Zhang, Weidong; He, Cheng

2012-07-01

Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is a prerequisite for remyelination after demyelination, and impairment of this process is suggested to be a major reason for remyelination failure. Diosgenin, a plant-derived steroid, has been implicated for therapeutic use in many diseases, but little is known about its effect on the central nervous system. In this study, using a purified rat OPC culture model, we show that diosgenin significantly and specifically promotes OPC differentiation without affecting the viability, proliferation, or migration of OPC. Interestingly, the effect of diosgenin can be blocked by estrogen receptor (ER) antagonist ICI 182780 but not by glucocorticoid and progesterone receptor antagonist RU38486, nor by mineralocorticoid receptor antagonist spirolactone. Moreover, it is revealed that both ER-alpha and ER-beta are expressed in OPC, and diosgenin can activate the extracellular signal-regulated kinase 1/2 (ERK1/2) in OPC via ER. The pro-differentiation effect of diosgenin can also be obstructed by the ERK inhibitor PD98059. Furthermore, in the cuprizone-induced demyelination model, it is demonstrated that diosgenin administration significantly accelerates/enhances remyelination as detected by Luxol fast blue stain, MBP immunohistochemistry and real time RT-PCR. Diosgenin also increases the number of mature oligodendrocytes in the corpus callosum while it does not affect the number of OPCs. Taking together, our results suggest that diosgenin promotes the differentiation of OPC into mature oligodendrocyte through an ER-mediated ERK1/2 activation pathway to accelerate remyelination, which implicates a novel therapeutic usage of this steroidal natural product in demyelinating diseases such as multiple sclerosis (MS). Copyright © 2012 Wiley Periodicals, Inc.

The capsid-spacer peptide 1 Gag processing intermediate is a dominant-negative inhibitor of HIV-1 maturation.

PubMed

Checkley, Mary Ann; Luttge, Benjamin G; Soheilian, Ferri; Nagashima, Kunio; Freed, Eric O

2010-04-25

The human immunodeficiency virus type 1 (HIV-1) maturation inhibitor bevirimat disrupts virus replication by inhibiting the cleavage of the capsid-spacer peptide 1 (CA-SP1) Gag processing intermediate to mature CA. The observation that bevirimat delays but does not completely block CA-SP1 processing suggests that the presence of uncleaved CA-SP1 may disrupt the maturation process in trans. In this study, we validate this hypothesis by using a genetic approach to demonstrate that a non-cleavable CA-SP1 mutant exerts a dominant-negative effect on maturation of wild-type HIV-1. In contrast, a mutant in which cleavage can occur internally within SP1 is significantly less potent as a dominant-negative inhibitor. We also show that bevirimat blocks processing at both the major CA-SP1 cleavage site and the internal site. These data underscore the importance of full CA-SP1 processing for HIV-1 maturation and highlight the therapeutic potential of inhibitors that target this Gag cleavage event. Published by Elsevier Inc.

ADP-ribosylation Factor 6 (ARF6) Bidirectionally Regulates Dendritic Spine Formation Depending on Neuronal Maturation and Activity*

PubMed Central

Kim, Yoonju; Lee, Sang-Eun; Park, Joohyun; Kim, Minhyung; Lee, Boyoon; Hwang, Daehee; Chang, Sunghoe

2015-01-01

Recent studies have reported conflicting results regarding the role of ARF6 in dendritic spine development, but no clear answer for the controversy has been suggested. We found that ADP-ribosylation factor 6 (ARF6) either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation increased the spine formation in developing neurons, whereas it decreased spine density in mature neurons. Genome-wide microarray analysis revealed that ARF6 activation in each stage leads to opposite patterns of expression of a subset of genes that are involved in neuronal morphology. ARF6-mediated Rac1 activation via the phospholipase D pathway is the coincident factor in both stages, but the antagonistic RhoA pathway becomes involved in the mature stage. Furthermore, blocking neuronal activity in developing neurons using tetrodotoxin or enhancing the activity in mature neurons using picrotoxin or chemical long term potentiation reversed the effect of ARF6 on each stage. Thus, activity-dependent dynamic changes in ARF6-mediated spine structures may play a role in structural plasticity of mature neurons. PMID:25605715

Zoledronic acid modulates maturation of human monocyte-derived dendritic cells.

PubMed

Orsini, Giulia; Failli, Alessandra; Legitimo, Annalisa; Adinolfi, Barbara; Romanini, Antonella; Consolini, Rita

2011-12-01

Zoledronic acid (ZA) is a drug of the bisphosphonate class, which is widely used for the treatment of both osteoporosis and skeletal metastasis. Besides its main bone antiresorptive activity, ZA displays antitumor properties, by triggering the expansion and activation of γδ T-cells, which exert an antitumor effect through dendritic cells (DCs). Several studies have reported the interaction between ZA and γδ T-cells, but the potential immunoregulatory activity of this drug on DCs has scarcely been investigated. Therefore, in this paper, we evaluated the effects of a therapeutic dose of ZA on the in vitro generation and maturation of DCs derived from peripheral blood monocytes of healthy adult donors. We demonstrate that ZA treatment did not affect DC differentiation, but inhibited DC maturation on lipopolysaccharide activation, as shown by the impaired expression of maturation surface markers and reduced ability to induce allogeneic T-cell proliferation. Interestingly, IL-10 secretion by mature DCs was significantly lower in ZA-treated cells than in controls. We conclude that ZA exerts its immunological in vitro activity also by modulating the maturation of DCs.

GnRHa to trigger final oocyte maturation: a time to reconsider.

PubMed

Humaidan, P; Papanikolaou, E G; Tarlatzis, B C

2009-10-01

Recently GnRH antagonist protocols for the prevention of a premature LH surge were introduced, allowing final oocyte maturation to be triggered with a single bolus of a GnRH agonist (GnRHa). GnRHa is as effective as hCG for the induction of ovulation, and apart from the LH surge a FSH surge is also induced. Until recently, prospective randomized studies reported a poor clinical outcome when GnRHa was used to trigger final oocyte maturation in IVF/ICSI antagonist protocols, presumably due to a luteal phase deficiency, despite standard luteal phase supplementation with progesterone and estradiol. As GnRHa triggering of final oocyte maturation could possess advantages over hCG triggering in terms of a reduced if not eliminated risk of ovarian hyperstimulation syndrome (OHSS) and the retrieval of more mature oocytes, the challenge has been to rescue the luteal phase. In the literature now several studies report a luteal phase rescue with a reproductive outcome comparable to that of hCG induced final oocyte maturation. Although more research is needed, GnRHa triggering is now a valid alternative with potential benefits.

Prediction of brain maturity based on cortical thickness at different spatial resolutions.

PubMed

Khundrakpam, Budhachandra S; Tohka, Jussi; Evans, Alan C

2015-05-01

Several studies using magnetic resonance imaging (MRI) scans have shown developmental trajectories of cortical thickness. Cognitive milestones happen concurrently with these structural changes, and a delay in such changes has been implicated in developmental disorders such as attention-deficit/hyperactivity disorder (ADHD). Accurate estimation of individuals' brain maturity, therefore, is critical in establishing a baseline for normal brain development against which neurodevelopmental disorders can be assessed. In this study, cortical thickness derived from structural magnetic resonance imaging (MRI) scans of a large longitudinal dataset of normally growing children and adolescents (n=308), were used to build a highly accurate predictive model for estimating chronological age (cross-validated correlation up to R=0.84). Unlike previous studies which used kernelized approach in building prediction models, we used an elastic net penalized linear regression model capable of producing a spatially sparse, yet accurate predictive model of chronological age. Upon investigating different scales of cortical parcellation from 78 to 10,240 brain parcels, we observed that the accuracy in estimated age improved with increased spatial scale of brain parcellation, with the best estimations obtained for spatial resolutions consisting of 2560 and 10,240 brain parcels. The top predictors of brain maturity were found in highly localized sensorimotor and association areas. The results of our study demonstrate that cortical thickness can be used to estimate individuals' brain maturity with high accuracy, and the estimated ages relate to functional and behavioural measures, underscoring the relevance and scope of the study in the understanding of biological maturity. Copyright © 2015 Elsevier Inc. All rights reserved.

Maturation delay for the predators can enhance stable coexistence for a class of prey-predator models.

PubMed

Banerjee, Malay; Takeuchi, Yasuhiro

2017-01-07

Maturation time delay for the predators is introduced in prey-predator models to implicitly model the stage-structure of predators. Most of the prey-predator models with maturation delay are known to exhibit destabilization of coexistence steady-state. Discrete time delay induced destabilization is a common finding, however, this is due to the introduction of time delay with lack of ecological justification. The main objective of the present work is to show the stabilizing role of maturation delay for a class of delayed prey-predator model. To be specific, we consider prey-predator models with strong and weak Allee effects in prey growth and Michaelis-Menten type functional response. We provide ecological justification for the introduction of maturation delay parameter in predator's growth equation. We obtain the conditions for stable and oscillatory coexistence of prey and their specialist predator in case of strong as well as weak Allee effect for non-delayed and delayed models. Apart from the analytical results for the models under consideration, we perform extensive numerical simulations to construct the relevant bifurcation diagrams. Our analytical and supportive numerical findings reveal that delay is not always a destabilizing factor rather the stable coexistence in the presence of time delay depends upon the formulation of the delayed model. The biological implications of the current investigation are provided in the conclusion section. We also explain the validity of obtained results for other types of prey-predator models with a specialist predator. Copyright © 2016 Elsevier Ltd. All rights reserved.

Towards a theory of PACS deployment: an integrative PACS maturity framework.

PubMed

van de Wetering, Rogier; Batenburg, Ronald

2014-06-01

Owing to large financial investments that go along with the picture archiving and communication system (PACS) deployments and inconsistent PACS performance evaluations, there is a pressing need for a better understanding of the implications of PACS deployment in hospitals. We claim that there is a gap in the research field, both theoretically and empirically, to explain the success of the PACS deployment and maturity in hospitals. Theoretical principles are relevant to the PACS performance; maturity and alignment are reviewed from a system and complexity perspective. A conceptual model to explain the PACS performance and a set of testable hypotheses are then developed. Then, structural equation modeling (SEM), i.e. causal modeling, is applied to validate the model and hypotheses based on a research sample of 64 hospitals that use PACS, i.e. 70 % of all hospitals in the Netherlands. Outcomes of the SEM analyses substantiate that the measurements of all constructs are reliable and valid. The PACS alignment-modeled as a higher-order construct of five complementary organizational dimensions and maturity levels-has a significant positive impact on the PACS performance. This result is robust and stable for various sub-samples and segments. This paper presents a conceptual model that explains how alignment in deploying PACS in hospitals is positively related to the perceived performance of PACS. The conceptual model is extended with tools as checklists to systematically identify the improvement areas for hospitals in the PACS domain. The holistic approach towards PACS alignment and maturity provides a framework for clinical practice.

Potential residual biomass in mature pine stands of the Midsouth, U.S.A.

Treesearch

J.F. Rosson

1989-01-01

The extent, location, and ownership of residual woody biomass available on mature pine timberland prior to the harvest of log-size pine was determined for the Midsouth States. Most of this residual is on non-industrial private timberland. Sweetgum (Liquidambar styraciflua L.) and loblolly pine (Pinus taeda L.) are the dominant species in the residual. Stems of all...

(Br-SCMM) Brazilian Smart City Maturity Model: A Perspective from the Health Domain.

PubMed

Afonso, Ricardo Alexandre; dos Santos Brito, Kellyton; Holanda do Nascimento, Clóvis; Campos da Costa, Luciana; Álvaro, Alexandre; Cardoso Garcia, Vinicius

2015-01-01

The term definition "Smart City" still allows various interpretations, and this causes some difficulty in establishing parameters to measure how smart the cities can be. This paper presents a Maturity Model that uses a set of minimum domains and indicators that aim to encourage cities of different sizes to identify their potential and improve processes and public policies.

[Age-related characteristics of the surface bioelectrical potential of human, canine and rat teeth and features of its distribution over the surface of the crown].

PubMed

Donskiĭ, G I; Pavliuchenko, O N; Palamarchuk, Iu N; Makarova, N Ia

1989-01-01

Using a digital electron voltmeter, bioelectrical potentials (BEPs) of dental crowns have been recorded in 180 patients, 36 dogs, and 93 white non-inbred rats. It has been established that the surface BEP is a marker of dental enamel maturation and does not depend on the species of mammals. On the other hand maturation processes differ in their rate on the cutting edge, equator, and neck: with advancing age algebraic difference between the magnitudes of surface BEPs decreases in humans and increases in dogs and rats.

Microclimate, Water Potential, Transpiration, and Bole Dielectric Constant of Coniferous and Deciduous Tree Species in the Continental Boreal Ecotone of Central Alaska

NASA Technical Reports Server (NTRS)

Zimmermann, R.; McDonald, K.; Way, J.; Oren, R.

1994-01-01

Tree canopy microclimate, xylem water flux and xylem dielectric constant have been monitored in situ since June 1993 in two adjacent natural forest stands in central Alaska. The deciduous stand represents a mature balsam poplar site on the Tanana River floodplain, while the coniferous stand consists of mature white spruce with some black spruce mixed in. During solstice in June and later in summer, diurnal changes of xylem water potential were measured to investigate the occurrence and magnitude of tree transpiration and dielectric constant changes in stems.

Identification of Human Islet Amyloid Polypeptide as a BACE2 Substrate

PubMed Central

Rulifson, Ingrid C.; Cao, Ping; Miao, Li; Kopecky, David; Huang, Linda; White, Ryan D.; Samayoa, Kim; Gardner, Jonitha; Wu, Xiaosu; Chen, Kui; Tsuruda, Trace; Homann, Oliver; Baribault, Helene; Yamane, Harvey; Carlson, Tim; Wiltzius, Jed; Li, Yang

2016-01-01

Pancreatic amyloid formation by islet amyloid polypeptide (IAPP) is a hallmark pathological feature of type 2 diabetes. IAPP is stored in the secretory granules of pancreatic beta-cells and co-secreted with insulin to maintain glucose homeostasis. IAPP is innocuous under homeostatic conditions but imbalances in production or processing of IAPP may result in homodimer formation leading to the rapid production of cytotoxic oligomers and amyloid fibrils. The consequence is beta-cell dysfunction and the accumulation of proteinaceous plaques in and around pancreatic islets. Beta-site APP-cleaving enzyme 2, BACE2, is an aspartyl protease commonly associated with BACE1, a related homolog responsible for amyloid processing in the brain and strongly implicated in Alzheimer’s disease. Herein, we identify two distinct sites of the mature human IAPP sequence that are susceptible to BACE2-mediated proteolytic activity. The result of proteolysis is modulation of human IAPP fibrillation and human IAPP protein degradation. These results suggest a potential therapeutic role for BACE2 in type 2 diabetes-associated hyperamylinaemia. PMID:26840340

The sacroiliac joint: an overview of its anatomy, function and potential clinical implications.

PubMed

Vleeming, A; Schuenke, M D; Masi, A T; Carreiro, J E; Danneels, L; Willard, F H

2012-12-01

This article focuses on the (functional) anatomy and biomechanics of the pelvic girdle and specifically the sacroiliac joints (SIJs). The SIJs are essential for effective load transfer between the spine and legs. The sacrum, pelvis and spine, and the connections to the arms, legs and head, are functionally interrelated through muscular, fascial and ligamentous interconnections. A historical overview is presented on pelvic and especially SIJ research, followed by a general functional anatomical overview of the pelvis. In specific sections, the development and maturation of the SIJ is discussed, and a description of the bony anatomy and sexual morphism of the pelvis and SIJ is debated. The literature on the SIJ ligaments and innervation is discussed, followed by a section on the pathology of the SIJ. Pelvic movement studies are investigated and biomechanical models for SIJ stability analyzed, including examples of insufficient versus excessive sacroiliac force closure. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

Extracellular and intracellular cleavages of proBDNF required at two distinct stages of late-phase LTP

NASA Astrophysics Data System (ADS)

Pang, Petti T.; Nagappan, Guhan; Guo, Wei; Lu, Bai

2016-05-01

Although late-phase long-term potentiation (L-LTP) is implicated in long-term memory, its molecular mechanisms are largely unknown. Here we provide evidence that L-LTP can be divided into two stages: an induction stage (I) and a maintenance stage (II). Both stages require mature brain-derived neurotrophic factor (mBDNF), but involve distinct underlying mechanisms. Stage I requires secretion of existing proBDNF followed by extracellular cleavage by tPA/plasmin. Stage II depends on newly synthesized BDNF. Surprisingly, mBDNF at stage II is derived from intracellular cleavage of proBDNF by furin/PC1. Moreover, stage I involves BDNF-TrkB signaling mainly through MAP kinase, whereas all three signaling pathways (phospholipase C-γ, PI3 kinase, and MAP kinase) are required for the maintenance of L-LTP at stage II. These results reveal the molecular basis for two temporally distinct stages in L-LTP, and provide insights on how BDNF modulates this long-lasting synaptic alternation at two critical time windows.

Structural disorder of graphite and implications for graphite thermometry

NASA Astrophysics Data System (ADS)

Kirilova, Martina; Toy, Virginia; Rooney, Jeremy S.; Giorgetti, Carolina; Gordon, Keith C.; Collettini, Cristiano; Takeshita, Toru

2018-02-01

Graphitization, or the progressive maturation of carbonaceous material, is considered an irreversible process. Thus, the degree of graphite crystallinity, or its structural order, has been calibrated as an indicator of the peak metamorphic temperatures experienced by the host rocks. However, discrepancies between temperatures indicated by graphite crystallinity versus other thermometers have been documented in deformed rocks. To examine the possibility of mechanical modifications of graphite structure and the potential impacts on graphite thermometry, we performed laboratory deformation experiments. We sheared highly crystalline graphite powder at normal stresses of 5 and 25 megapascal (MPa) and aseismic velocities of 1, 10 and 100 µm s-1. The degree of structural order both in the starting and resulting materials was analyzed by Raman microspectroscopy. Our results demonstrate structural disorder of graphite, manifested as changes in the Raman spectra. Microstructural observations show that brittle processes caused the documented mechanical modifications of the aggregate graphite crystallinity. We conclude that the calibrated graphite thermometer is ambiguous in active tectonic settings.

Characteristics of organic soil in black spruce forests: Implications for the application of land surface and ecosystem models in cold regions

USGS Publications Warehouse

Yi, S.; Manies, K.; Harden, J.; McGuire, A.D.

2009-01-01

Soil organic layers (OL) play an important role in landatmosphere exchanges of water, energy and carbon in cold environments. The proper implementation of OL in land surface and ecosystem models is important for predicting dynamic responses to climate warming. Based on the analysis of OL samples of black spruce (Picea mariana), we recommend that implementation of OL for cold regions modeling: (1) use three general organic horizon types (live, fibrous, and amorphous) to represent vertical soil heterogeneity; (2) implement dynamics of OL over the course of disturbance, as there are significant differences of OL thickness between young and mature stands; and (3) use two broad drainage classes to characterize spatial heterogeneity, as there are significant differences in OL thickness between dry and wet sites. Implementation of these suggestions into models has the potential to substantially improve how OL dynamics influence variability in surface temperature and soil moisture in cold regions. Copyright 2009 by the American Geophys.ical Union.

Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch

PubMed Central

Hwang, Yung; Futran, Melinda; Hidalgo, Daniel; Pop, Ramona; Iyer, Divya Ramalingam; Scully, Ralph; Rhind, Nicholas; Socolovsky, Merav

2017-01-01

Cell cycle regulators are increasingly implicated in cell fate decisions, such as the acquisition or loss of pluripotency and self-renewal potential. The cell cycle mechanisms that regulate these cell fate decisions are largely unknown. We studied an S phase–dependent cell fate switch, in which murine early erythroid progenitors transition in vivo from a self-renewal state into a phase of active erythroid gene transcription and concurrent maturational cell divisions. We found that progenitors are dependent on p57KIP2-mediated slowing of replication forks for self-renewal, a novel function for cyclin-dependent kinase inhibitors. The switch to differentiation entails rapid down-regulation of p57KIP2 with a consequent global increase in replication fork speed and an abruptly shorter S phase. Our work suggests that cell cycles with specialized global DNA replication dynamics are integral to the maintenance of specific cell states and to cell fate decisions. PMID:28560351

Gap junctional communication in the male reproductive system.

PubMed

Pointis, Georges; Fiorini, Céline; Defamie, Norah; Segretain, Dominique

2005-12-20

Male fertility is a highly controlled process that allows proliferation, meiosis and differentiation of male germ cells in the testis, final maturation in the epididymis and also requires functional male accessory glands: seminal vesicles, prostate and corpus cavernosum. In addition to classical endocrine and paracrine controls, mainly by gonadotropins LH and FSH and steroids, there is now strong evidence that all these processes are dependent upon the presence of homocellular or heterocellular junctions, including gap junctions and their specific connexins (Cxs), between the different cell types that structure the male reproductive tract. The present review is focused on the identification of Cxs, their distribution in the testis and in different structures of the male genital tract (epididymis, seminal vesicle, prostate, corpus cavernosum), their crucial role in the control of spermatogenesis and their implication in the function of the male accessory glands, including functional smooth muscle tone. Their potential dysfunctions in some testis (spermatogenic arrest, seminoma) and prostate (benign hyperplasia, adenocarcinoma) diseases and in the physiopathology of the human erectile function are also discussed.

Nanotechnology and bone healing.

PubMed

Harvey, Edward J; Henderson, Janet E; Vengallatore, Srikar T

2010-03-01

Nanotechnology and its attendant techniques have yet to make a significant impact on the science of bone healing. However, the potential benefits are immediately obvious with the result that hundreds of researchers and firms are performing the basic research needed to mature this nascent, yet soon to be fruitful niche. Together with genomics and proteomics, and combined with tissue engineering, this is the new face of orthopaedic technology. The concepts that orthopaedic surgeons recognize are fabrication processes that have resulted in porous implant substrates as bone defect augmentation and medication-carrier devices. However, there are dozens of applications in orthopaedic traumatology and bone healing for nanometer-sized entities, structures, surfaces, and devices with characteristic lengths ranging from 10s of nanometers to a few micrometers. Examples include scaffolds, delivery mechanisms, controlled modification of surface topography and composition, and biomicroelectromechanical systems. We review the basic science, clinical implications, and early applications of the nanotechnology revolution and emphasize the rich possibilities that exist at the crossover region between micro- and nanotechnology for developing new treatments for bone healing.

Convergence of nanotechnology with radiation therapy—insights and implications for clinical translation

PubMed Central

Chatterjee, Dev Kumar; Wolfe, Tatiana; Lee, Jihyoun; Brown, Aaron P; Singh, Pankaj Kumar; Bhattarai, Shanta Raj; Diagaradjane, Parmeswaran; Krishnan, Sunil

2014-01-01

Improvements in accuracy and efficacy in treating tumors with radiation therapy (RT) over the years have been fueled by parallel technological and conceptual advances in imaging and image-guidance techniques, radiation treatment machines, computational methods, and the understanding of the biology of tumor response to RT. Recent advances in our understanding of the hallmarks of cancer and the emergence of strategies to combat these traits of cancer have resulted in an expanding repertoire of targeted therapeutics, many of which can be exploited for enhancing the efficacy of RT. Complementing this advent of new treatment options is the evolution of our knowledge of the interaction between nanoscale materials and human tissues (nanomedicine). As with the changes in RT paradigms when the field has encountered newer and maturing disciplines, the incorporation of nanotechnology innovations into radiation oncology has the potential to refine or redefine its principles and revolutionize its practice. This review provides a summary of the principles, applications, challenges and outlook for the use of metallic nanoparticles in RT. PMID:25279336

Neurobiology of Adolescent Substance Use and Addictive Behaviors: Prevention and Treatment Implications

PubMed Central

Hammond, Christopher J.; Mayes, Linda C.; Potenza, Marc N.

2015-01-01

Psychoactive substance and nonsubstance/behavioral addictions are major public health concerns associated with significant societal cost. Adolescence is a period of dynamic biologic, psychological, and behavioral changes. Adolescence is also associated with an increased risk for substance use and addictive disorders. During adolescence, developmental changes in neural circuitry of reward processing, motivation, cognitive control, and stress may contribute to vulnerability for increased levels of engagement in substance use and nonsubstance addictive behaviors. Current biologic models of adolescent vulnerability for addictions incorporate existing data on allostatic changes in function and structure of the midbrain dopaminergic system, stress-associated neuroplasticity, and maturational imbalances between cognitive control and reward reactivity. When characterizing adolescent vulnerability, identifying subgroups of adolescents at high risk for addictive behaviors is a major goal of the addiction field. Genetics, epigenetics, and intermediate phenotypes/endophenotypes may assist in characterizing children and adolescents at risk. Improved understanding of the neurobiology of adolescence and addiction vulnerability has the potential to refine screening, enhance prevention and intervention strategies, and inform public policy. PMID:25022184

Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma

PubMed Central

Rastogi, Deepa; Suzuki, Masako; Greally, John M.

2013-01-01

While DNA methylation plays a role in T-helper (Th) cell maturation, its potential dysregulation in the non-atopic Th1-polarized systemic inflammation observed in obesity-associated asthma is unknown. We studied DNA methylation epigenome-wide in peripheral blood mononuclear cells (PBMCs) from 8 obese asthmatic pre-adolescent children and compared it to methylation in PBMCs from 8 children with asthma alone, obesity alone and healthy controls. Differentially methylated loci implicated certain biologically relevant molecules and pathways. PBMCs from obese asthmatic children had distinctive DNA methylation patterns, with decreased promoter methylation of CCL5, IL2RA and TBX21, genes encoding proteins linked with Th1 polarization, and increased promoter methylation of FCER2, a low-affinity receptor for IgE, and of TGFB1, inhibitor of Th cell activation. T-cell signaling and macrophage activation were the two primary pathways that were selectively hypomethylated in obese asthmatics. These findings suggest that dysregulated DNA methylation is associated with non-atopic inflammation observed in pediatric obesity-associated asthma. PMID:23857381

Impairment of pneumococcal antigen specific isotype-switched Igg memory B-cell immunity in HIV infected Malawian adults.

PubMed

Iwajomo, Oluwadamilola H; Finn, Adam; Ogunniyi, Abiodun D; Williams, Neil A; Heyderman, Robert S

2013-01-01

Pneumococcal disease is associated with a particularly high morbidity and mortality amongst adults in HIV endemic countries. Our previous findings implicating a B-cell defect in HIV-infected children from the same population led us to comprehensively characterize B-cell subsets in minimally symptomatic HIV-infected Malawian adults and investigate the isotype-switched IgG memory B-cell immune response to the pneumococcus. We show that similar to vertically acquired HIV-infected Malawian children, horizontally acquired HIV infection in these adults is associated with IgM memory B-cell (CD19(+) CD27(+) IgM(+) IgD(+)) depletion, B-cell activation and impairment of specific IgG B-cell memory to a range of pneumococcal proteins. Our data suggest that HIV infection affects both T-cell independent and T-cell dependent B-cell maturation, potentially leading to impairment of humoral responses to extracellular pathogens such as the pneumococcus, and thus leaving this population susceptible to invasive disease.

Control of Spine Maturation and Pruning through ProBDNF Synthesized and Released in Dendrites

PubMed Central

Orefice, Lauren L.; Shih, Chien-Cheng; Xu, Haifei; Waterhouse, Emily G.; Xu, Baoji

2015-01-01

Excess synapses formed during early postnatal development are pruned over an extended period, while the remaining synapses mature. Synapse pruning is critical for activity-dependent refinement of neuronal connections and its dysregulation has been found in neurodevelopmental disorders such as autism spectrum disorders; however, the mechanism underlying synapse pruning remains largely unknown. As dendritic spines are the postsynaptic sites for the vast majority of excitatory synapses, spine maturation and pruning are indicators for maturation and elimination of these synapses. Our previous studies have found that dendritically localized mRNA for brain-derived neurotrophic factor (BDNF) regulates spine maturation and pruning. Here we investigated the mechanism by which dendritic Bdnf mRNA, but not somatically restricted Bdnf mRNA, promotes spine maturation and pruning. We found that neuronal activity stimulates both translation of dendritic Bdnf mRNA and secretion of its translation product mainly as proBDNF. The secreted proBDNF promotes spine maturation and pruning, and its effect on spine pruning is in part mediated by the p75NTR receptor via RhoA activation. Furthermore, some proBDNF is extracellularly converted to mature BDNF and then promotes maturation of stimulated spines by activating Rac1 through the TrkB receptor. In contrast, translation of somatic Bdnf mRNA and the release of its translation product mainly as mature BDNF are independent of action potentials. These results not only reveal a biochemical pathway regulating synapse pruning, but also suggest that BDNF synthesized in the soma and dendrites is released through distinct secretory pathways. PMID:26705735

Phaeodarian radiolarians as potential indicators of thermal maturation

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

Casey, R.E.

1986-04-01

Phaeodarian radiolarian skeletons contain large amounts of organic matter, and discolored phaeodarian skeletons are observed in the fossil record, which suggests that the skeletons may be useful as thermal maturation indicators. Such a maturation index would be useful in Monterey-type rocks that are difficult to interpret with conventional thermal maturation indexes. Phaeodarians extracted from plankton samples, Holocene Santa Barbara and Orca basin sediments, and Neogene Monterey rocks with siliceous facies were subjected to different temperatures of varying duration in pyrolysis experiments. To calibrate the observed phaeodarian color changes with a known standard, Holocene pine pollen were subjected to the samemore » treatment. These phaeodarian go through the same color change spectrum as do the pollen, but they appear to lag slightly behind the pollen color changes.« less

Whatever happened to "What might have been"? Regrets, happiness, and maturity.

PubMed

King, Laura A; Hicks, Joshua A

2007-10-01

Although lost opportunities and mistaken expectations are unpleasant to think and talk about, these experiences may have a role to play in personality development. Drawing on research using narratives of lost possible selves, the authors review the relations of regrettable experiences to 2 important and independent aspects of maturity, happiness and complexity. Thinking about a lost possible self is related to concurrent regrets, distress, and lowered well-being; however, elaborating on a lost possible self is related, concurrently, to complexity and predicts complexity, prospectively, over time. In this article, the authors describe the role that regrettable experiences have in promoting both happiness and complexity. Finally, expanding on previous work, the authors examine potential affordances of happy maturity and suggest psychological capacities that may promote happy maturity. Copyright 2007 APA, all rights reserved.

Neuroticism developmental courses--implications for depression, anxiety and everyday emotional experience; a prospective study from adolescence to young adulthood.

PubMed

Aldinger, Maren; Stopsack, Malte; Ulrich, Ines; Appel, Katja; Reinelt, Eva; Wolff, Sebastian; Grabe, Hans Jörgen; Lang, Simone; Barnow, Sven

2014-08-06

Neuroticism is frequently discussed as a risk factor for psychopathology. According to the maturity principle, neuroticism decreases over the course of life, but not uniformly across individuals. However, the implications of differences in personality maturation on mental health have not been well studied so far. Hence, we hypothesized that different forms of neuroticism development from adolescence to young adulthood are associated with differences in depression, anxiety and everyday emotional experience at the age of 25. A sample of 266 adolescents from the general population was examined three times over ten years (age at T0: 15, T1: 20 and T2: 25) using questionnaires, interviews and ecological momentary assessment (EMA). At all measurement points, neuroticism was assessed with the NEO inventory. At T2, diagnoses of major depression and anxiety disorders were captured with a structured clinical interview (M-CIDI). Phone-based EMA was used to assess emotional experience and affective instability over a two-week period at T2. The best fitting model was a latent class growth analysis with two groups of neuroticism development. Most individuals (n = 205) showed moderate values whereas 61 participants were clustered into a group with elevated neuroticism levels. In both groups neuroticism significantly changed during the ten year period with a peak at the age of 20. Individuals with a higher absolute level were at 14-fold increased risk for depression and 7-fold risk for anxiety disorders at the age of 25. In EMA, increased negative affect and arousal as well as decreased positive emotions were found in this high group. Other than expected, personality did not mature in our sample. However, there was a significant change of neuroticism values from adolescence to young adulthood. Further, over 20% of our participants showed a neuroticism development which was associated with adverse outcomes such as negatively toned emotional experience and a heightened risk to suffer from depressive and anxiety disorders in young adulthood. These high-risk persons need to be identified early to provide interventions supporting continuous personality maturation.

Identification and characterization of long noncoding RNAs and mRNAs expression profiles related to postnatal liver maturation of breeder roosters using Ribo-zero RNA sequencing.

PubMed

Wu, Shengru; Liu, Yanli; Guo, Wei; Cheng, Xi; Ren, Xiaochun; Chen, Si; Li, Xueyuan; Duan, Yongle; Sun, Qingzhu; Yang, Xiaojun

2018-06-27

The liver is mainly hematopoietic in the embryo, and converts into a major metabolic organ in the adult. Therefore, it is intensively remodeled after birth to adapt and perform adult functions. Long non-coding RNAs (lncRNAs) are involved in organ development and cell differentiation, likely they have potential roles in regulating postnatal liver development. Herein, in order to understand the roles of lncRNAs in postnatal liver maturation, we analyzed the lncRNAs and mRNAs expression profiles in immature and mature livers from one-day-old and adult (40 weeks of age) breeder roosters by Ribo-Zero RNA-Sequencing. Around 21,939 protein-coding genes and 2220 predicted lncRNAs were expressed in livers of breeder roosters. Compared to protein-coding genes, the identified chicken lncRNAs shared fewer exons, shorter transcript length, and significantly lower expression levels. Notably, in comparison between the livers of newborn and adult breeder roosters, a total of 1570 mRNAs and 214 lncRNAs were differentially expressed with the criteria of log 2 fold change > 1 or < - 1 and P values < 0.05, which were validated by qPCR using randomly selected five mRNAs and five lncRNAs. Further GO and KEGG analyses have revealed that the differentially expressed mRNAs were involved in the hepatic metabolic and immune functional changes, as well as some biological processes and pathways including cell proliferation, apoptotic and cell cycle that are implicated in the development of liver. We also investigated the cis- and trans- regulatory effects of differentially expressed lncRNAs on its target genes. GO and KEGG analyses indicated that these lncRNAs had their neighbor protein coding genes and trans-regulated genes associated with adapting of adult hepatic functions, as well as some pathways involved in liver development, such as cell cycle pathway, Notch signaling pathway, Hedgehog signaling pathway, and Wnt signaling pathway. This study provides a catalog of mRNAs and lncRNAs related to postnatal liver maturation of chicken, and will contribute to a fuller understanding of biological processes or signaling pathways involved in significant functional transition during postnatal liver development that differentially expressed genes and lncRNAs could take part in.

The Influence of Sex and Maturation on Knee Mechanics during Side-Step Cutting

PubMed Central

Sigward, Susan M.; Pollard, Christine D.; Havens, Kathryn L.; Powers, Christopher M.

2012-01-01

Introduction Females have been reported to have a 3-5 times greater incidence of non-contact ACL injury when compared to their male counterparts. Previous research suggests that physical maturation is one factor that is associated with the development of potentially injurious lower extremity biomechanics in female athletes. Purpose To determine if lower extremity biomechanics differ between male and female soccer athletes during a cutting maneuver across different stages of maturational development. Methods One hundred and fifty six soccer players (76 male and 80 females) between the ages of 9 and 23 participated. Subjects were classified based on maturation as pre-pubertal, pubertal, post-pubertal or young adult. Lower extremity kinematics, kinetics and ground reaction forces (GRF) were obtained during a 45 degree side-step cutting maneuver. Differences between sex and maturation were assessed for peak knee valgus angle, knee adductor moments and GRF's (vertical, posterior and lateral) during weight acceptance using a 2 factor ANCOVA (controlling for approach velocity). Results No sex × maturation interactions were found for any variable of interest. On average, females exhibited greater knee abduction and adductor moments than males. Pre-pubertal athletes demonstrated greater knee adductor moments and GRFs than all other groups. Conclusion Biomechanical differences between males and females were evident across all stages of maturation. On average, less mature athletes exhibit biomechanical patterns during cutting that may place them at greater risk for injury than their more mature counterparts. PMID:22330027

A Molecular Approach Designed to Limit the Replication of Mature DENV2 in Host Cells.

PubMed

Raheel, Ummar; Jamal, Muhsin; Zaidi, Najam Us Sahar Sadaf

2015-09-01

Dengue virus (DENV) is an arthropod-borne virus, which belongs to the Flaviviridae family, and completes its life cycle in two hosts: humans and mosquitoes. For DENV maturation, the surface pre-membrane (prM) protein is cleaved to form a mature membrane protein (M) by furin, which is a cellular enzyme subsequently releasing the mature virus from the host dendritic cell. The objective of the current study was to inhibit mature DENV isotype 2 (DENV2) by RNA-interference in a Vero-81 cell line. Mature DENV2 was propagated in and isolated from U937 cells expressing dendritic cell-specific intracellular adhesion molecule-3-grabbing non-integrin. Maturation of DENV2 was confirmed by Western blot analysis, where virus stock lacking prM was considered mature. Inhibition studies were carried out by transfection of Vero-81 cells with six synthetic siRNAs along with a control siRNA. Reduction in cellular DENV2 was observed also by focus-reduction assay, immunofluorescence assay (IFA), and real-time quantitative polymerase chain reaction (RT-qPCR). Cells transfected with DENV2SsiRNA2, which was targeting the structural region M of mature DENV2, was able to reduce DENV2 titer by up to 85% in focus reduction assays. A significant reduction in mature DENV2 RNA load was observed by RT-qPCR, confirming the previous findings. IFA also revealed reduced levels of cellular DENV2. These results demonstrated that mature DENV2 can be effectively inhibited by synthetic siRNA targeting the structural region of the genome. Mature DENV2 can be successfully inhibited by siRNAs, and specifically high knock-down efficiency is observed by siRNAs against M region of mature DENV2. This study shows that M represents a potential target for RNAi based inhibitory approaches.

Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation

PubMed Central

Zallocchi, Marisa; Meehan, Daniel T.; Delimont, Duane; Rutledge, Joseph; Gratton, Michael Anne; Flannery, John; Cosgrove, Dominic

2012-01-01

The molecular mechanisms underlying hair cell synaptic maturation are not well understood. Cadherin-23 (CDH23), protocadherin-15 (PCDH15) and the very large G-protein coupled receptor 1 (VLGR1) have been implicated in the development of cochlear hair cell stereocilia, while clarin-1 has been suggested to also play a role in synaptogenesis. Mutations in CDH23, PCDH15, VLGR1 and clarin-1 cause Usher syndrome, characterized by congenital deafness, vestibular dysfunction and retinitis pigmentosa. Here we show developmental expression of these Usher proteins in afferent spiral ganglion neurons and hair cell synapses. We identify a novel synaptic Usher complex comprised of clarin-1 and specific isoforms of CDH23, PCDH15 and VLGR1. To establish the in vivo relevance of this complex, we performed morphological and quantitative analysis of the neuronal fibers and their synapses in the Clrn1−/− mouse, which was generated by incomplete deletion of the gene. These mice showed a delay in neuronal/synaptic maturation by both immunostaining and electron microscopy. Analysis of the ribbon synapses in Ames waltzerav3J mice also suggests a delay in hair cell synaptogenesis. Collectively, these results show that, in addition to the well documented role for Usher proteins in stereocilia development, Usher protein complexes comprised of specific protein isoforms likely function in synaptic maturation as well. PMID:22363448

GLABROUS INFLORESCENCE STEMS modulates the regulation by gibberellins of epidermal differentiation and shoot maturation in Arabidopsis.

PubMed

Gan, Yinbo; Kumimoto, Rod; Liu, Chang; Ratcliffe, Oliver; Yu, Hao; Broun, Pierre

2006-06-01

As a plant shoot matures, it transitions through a series of growth phases in which successive aerial organs undergo distinct developmental changes. This process of phase change is known to be influenced by gibberellins (GAs). We report the identification of a putative transcription factor, GLABROUS INFLORESCENCE STEMS (GIS), which regulates aspects of shoot maturation in Arabidopsis thaliana. GIS loss-of-function mutations affect the epidermal differentiation of inflorescence organs, causing a premature decrease in trichome production on successive leaves, stem internodes, and branches. Overexpression has the opposite effect on trichome initiation and causes other heterochronic phenotypes, affecting flowering and juvenile-adult leaf transition and inducing the formation of rosette leaves on inflorescence stems. Genetic and gene expression analyses suggest that GIS acts in a GA-responsive pathway upstream of the trichome initiation regulator GLABROUS1 (GL1) and downstream of the GA signaling repressor SPINDLY (SPY). GIS mediates the induction of GL1 expression by GA in inflorescence organs and is antagonized in its action by the DELLA repressor GAI. The implication of GIS in the broader regulation of phase change is further suggested by the delay in flowering caused by GIS loss of function in the spy background. The discovery of GIS reveals a novel mechanism in the control of shoot maturation, through which GAs regulate cellular differentiation in plants.

The autism associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain

PubMed Central

Peng, Yun; Lu, Zhongming; Li, Guohui; Piechowicz, Mariel; Anderson, Miranda; Uddin, Yasin; Wu, Jie; Qiu, Shenfeng

2015-01-01

The human MET gene imparts a replicated risk for autism spectrum disorder (ASD), and is implicated in the structural and functional integrity of brain. MET encodes a receptor tyrosine kinase, MET, which plays a pleiotropic role in embryogenesis and modifies a large number of neurodevelopmental events. Very little is known, however, on how MET signaling engages distinct cellular events to collectively affect brain development in ASD-relevant disease domains. Here, we show that MET protein expression is dynamically regulated and compartmentalized in developing neurons. MET is heavily expressed in neuronal growth cones at early developmental stages and its activation engages small GTPase Cdc42 to promote neuronal growth, dendritic arborization, and spine formation. Genetic ablation of MET signaling in mouse dorsal pallium leads to altered neuronal morphology indicative of early functional maturation. In contrast, prolonged activation of MET represses the formation and functional maturation of glutamatergic synapses. Moreover, manipulating MET signaling levels in vivo in the developing prefrontal projection neurons disrupts the local circuit connectivity made onto these neurons. Therefore, normal time-delimited MET signaling is critical in regulating the timing of neuronal growth, glutamatergic synapse maturation and cortical circuit function. Dysregulated MET signaling may lead to pathological changes in forebrain maturation and connectivity, and thus contribute to the emergence of neurological symptoms associated with ASD. PMID:26728565

Raman spectroscopy as a tool to understand Kerogen production potential

NASA Astrophysics Data System (ADS)

Khatibi, S.; Ostadhassan, M.; Mohammed, R. A.; Alexeyev, A.

2017-12-01

A lot attention has given to unconventional reservoirs specifically oil shale in North America during the last decades. Understanding Kerogen properties in terms of maturity and production potential are crucial for unconventional reservoir. Since, the amount of hydrocarbon generation is a function of kerogen type and content in the formation, and the magnitude and duration in which heat and pressure were applied. This study presents a non-destructive and fast method to determine Kerogen properties in terms of Rock-Eval parameters by means of Raman Spectroscopy. Samples were gathered from upper and lower Bakken formation, with different maturities at different depth. Raman spectroscopy as a powerful nondestructive analytical tool for molecular reconstruction was employed to find Raman spectra of different samples. In the next step, Rock-Eval was performed for each sample and different measurements were made. Then in an original approach, correlation between Rock-Eval parameters with Raman Spectroscopy results was established to fully understand how kerogen productivity potentials can be reflected on the Raman response. Results showed, maturity related parameters (RO, Tmax), S1 (already generated oil in the rock), S2 (potential hydrocarbon) and OSI (oil saturation index as indication of potential oil flow zones) can be correlated to band separation, D band intensity, G band intensity and G/D intensity, respectively. Proposed method provide a fast nondestructive method to evaluate Kerogen quality even at field without any special sample preparation.

Immature, Semi-Mature, and Fully Mature Dendritic Cells: Toward a DC-Cancer Cells Interface That Augments Anticancer Immunity

PubMed Central

Dudek, Aleksandra M.; Martin, Shaun; Garg, Abhishek D.; Agostinis, Patrizia

2013-01-01

Dendritic cells (DCs) are the sentinel antigen-presenting cells of the immune system; such that their productive interface with the dying cancer cells is crucial for proper communication of the “non-self” status of cancer cells to the adaptive immune system. Efficiency and the ultimate success of such a communication hinges upon the maturation status of the DCs, attained following their interaction with cancer cells. Immature DCs facilitate tolerance toward cancer cells (observed for many apoptotic inducers) while fully mature DCs can strongly promote anticancer immunity if they secrete the correct combinations of cytokines [observed when DCs interact with cancer cells undergoing immunogenic cell death (ICD)]. However, an intermediate population of DC maturation, called semi-mature DCs exists, which can potentiate either tolerogenicity or pro-tumorigenic responses (as happens in the case of certain chemotherapeutics and agents exerting ambivalent immune reactions). Specific combinations of DC phenotypic markers, DC-derived cytokines/chemokines, dying cancer cell-derived danger signals, and other less characterized entities (e.g., exosomes) can define the nature and evolution of the DC maturation state. In the present review, we discuss these different maturation states of DCs, how they might be attained and which anticancer agents or cell death modalities (e.g., tolerogenic cell death vs. ICD) may regulate these states. PMID:24376443

Objective evaluation of cervical vertebral bone age' its reliability in comparison with hand-wrist bone age: by TW3 method.

PubMed

Prasad, Cms Krishna; Reddy, Vamsi Nilay; Sreedevi, Gojja; Ponnada, Swaroopa Rani; Priya, K Padma; Naik, B Raveendra

2013-09-01

The aim of this study was to establish the validity of a new method for evaluating skeletal maturation by assessing the 3rd and 4th cervical vertebrae seen in the cephalometric radiograph. This study consisted of a sample of 50 patients in the age group of 8 to 14 years of age. Chronologically, they were divided into six groups, based on the age consisting of a minimum of six to a maximum of 10 subjects. All the patients included in the study were females. The selected subjects were clinically examined and then age and date of birth of the patient in years and months was noted. Then lateral cephalograms and hand-wrist radiographs of the patient were taken on the same day with good clarity and contrast. The results suggested that cervical vertebral bone age on cephalometric radiographs calculated with this method is as reliable at estimating bone age as is the Tanner-Whitehouse 3 (TW3) method on hand-wrist radiographs. By determining the cervical vertebral bone age, skeletal maturity can be evaluated in a detailed and objective manner with cephalometric radiographs. The ability to accurately appraise skeletal maturity from cervical vertebral maturation, without the need for additional radiographs, has the potential to improve orthodontic diagnostic and therapeutic decisions. The technique's simplicity and ease of use should encourage this method as a frst level diagnostic tool to assess skeletal maturation. Clinical signifcance: This study revealed that the timing and sequence of ossifcation of the bones in hand and wrist and cervical vertebrae were able to relate the skeletal development of the various skeletal maturity indicators to a child's development. This method provided a mean with which one can determine the skeletal maturity of a person and thereby determine whether the possibility of potential growth existed.

Male sexual enhancement after methoprene treatment in Anastrepha fraterculus (Diptera: Tephritidae): A sustained response that does not fade away after sexual maturation.

PubMed

Bachmann, G E; Devescovi, F; Nussenbaum, A L; Cladera, J L; Fernández, P C; Vera, M T; Teal, P E A; Segura, D F

2017-08-01

The juvenile hormone (JH) of insects triggers physiological changes related to reproduction in adults of both sexes. Methoprene is a sesquiterpene with some effects that are analogous to those of JH. Treatments with methoprene accelerate sexual maturation in males of the South American fruit fly Anastrepha fraterculus, giving young males a mating advantage over non-treated males of the same age. Here, we evaluated the effects of methoprene treatment on A. fraterculus males after the sexual maturation phase and tested whether this compound provides a long-term mating advantage. Moreover, we took the first step to unravel the mechanisms that underlie male sexual enhancement. We treated males 1day or 8days after adult emergence and compared mate choice between recently matured (young) females and females that had been mature for ca. 10days (aged females). We also addressed methoprene treatment effects on male sexual signalling. We found that methoprene treatment enhanced male sexual competitiveness even after the sexual maturation phase, and the effect did not decrease until males were older than 20days. However, when methoprene treatment was carried out close to sexual maturity, the mating enhancement was no longer observed, suggesting a non-immediate effect and excluding the possibility that methoprene acts as a pheromonal compound. Young and aged females tended to mate more frequently with treated-males. This might indicate that in a context of sexual selection, the potential benefits associated with reproductive success would be similar for females of both ages. Treated males released larger amounts of pheromonal compounds than non-treated males, but their courtship behaviour was not altered to the same extent, suggesting that methoprene treatment may accelerate differently the components of male courtship. We discuss potential benefits of using methoprene to increase the efficiency of the sterile insect technique, which is an environmentally safe method to control this important South American fruit pest. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trauma center maturity measured by an analysis of preventable and potentially preventable deaths: there is always something to be learned….

PubMed

Matsumoto, Shokei; Jung, Kyoungwon; Smith, Alan; Coimbra, Raul

2018-06-23

To establish the preventable and potentially preventable death rates in a mature trauma center and to identify the causes of death and highlight the lessons learned from these cases. We analyzed data from a Level-1 Trauma Center Registry, collected over a 15-year period. Data on demographics, timing of death, and potential errors were collected. Deaths were judged as preventable (PD), potentially preventable (PPD), or non-preventable (NPD), following a strict external peer-review process. During the 15-year period, there were 874 deaths, 15 (1.7%) and 6 (0.7%) of which were considered PPDs and PDs, respectively. Patients in the PD and PPD groups were not sicker and had less severe head injury than those in the NPD group. The time-death distribution differed according to preventability. We identified 21 errors in the PD and PPD groups, but only 61 (7.3%) errors in the NPD group (n = 853). Errors in judgement accounted for the majority and for 90.5% of the PD and PPD group errors. Although the numbers of PDs and PPDs were low, denoting maturity of our trauma center, there are important lessons to be learned about how errors in judgment led to deaths that could have been prevented.

Size-Dependent Effects of Gold Nanoparticles Uptake on Maturation and Antitumor Functions of Human Dendritic Cells In Vitro

PubMed Central

Tomić, Sergej; Đokić, Jelena; Vasilijić, Saša; Ogrinc, Nina; Rudolf, Rebeka; Pelicon, Primož; Vučević, Dragana; Milosavljević, Petar; Janković, Srđa; Anžel, Ivan; Rajković, Jelena; Rupnik, Marjan Slak; Friedrich, Bernd; Čolić, Miodrag

2014-01-01

Gold nanoparticles (GNPs) are claimed as outstanding biomedical tools for cancer diagnostics and photo-thermal therapy, but without enough evidence on their potentially adverse immunological effects. Using a model of human dendritic cells (DCs), we showed that 10 nm- and 50 nm-sized GNPs (GNP10 and GNP50, respectively) were internalized predominantly via dynamin-dependent mechanisms, and they both impaired LPS-induced maturation and allostimulatory capacity of DCs, although the effect of GNP10 was more prominent. However, GNP10 inhibited LPS-induced production of IL-12p70 by DCs, and potentiated their Th2 polarization capacity, while GNP50 promoted Th17 polarization. Such effects of GNP10 correlated with a stronger inhibition of LPS-induced changes in Ca2+ oscillations, their higher number per DC, and more frequent extra-endosomal localization, as judged by live-cell imaging, proton, and electron microscopy, respectively. Even when released from heat-killed necrotic HEp-2 cells, GNP10 inhibited the necrotic tumor cell-induced maturation and functions of DCs, potentiated their Th2/Th17 polarization capacity, and thus, impaired the DCs' capacity to induce T cell-mediated anti-tumor cytotoxicity in vitro. Therefore, GNP10 could potentially induce more adverse DC-mediated immunological effects, compared to GNP50. PMID:24802102

Properties of a Novel pH-dependent Ca2+ Permeation Pathway Present in Male Germ Cells with Possible Roles in Spermatogenesis and Mature Sperm Function

PubMed Central

Santi, Celia M.; Santos, Teresa; Hernández-Cruz, Arturo; Darszon, Alberto

1998-01-01

Rises of intracellular Ca2+ ([Ca2+]i) are key signals for cell division, differentiation, and maturation. Similarly, they are likely to be important for the unique processes of meiosis and spermatogenesis, carried out exclusively by male germ cells. In addition, elevations of [Ca2+]i and intracellular pH (pHi) in mature sperm trigger at least two events obligatory for fertilization: capacitation and acrosome reaction. Evidence implicates the activity of Ca2+ channels modulated by pHi in the origin of these Ca2+ elevations, but their nature remains unexplored, in part because work in individual spermatozoa are hampered by formidable experimental difficulties. Recently, late spermatogenic cells have emerged as a model system for studying aspects relevant for sperm physiology, such as plasmalemmal ion fluxes. Here we describe the first study on the influence of controlled intracellular alkalinization on [Ca2+]i on identified spermatogenic cells from mouse adult testes. In BCECF [(2′,7′)-bis(carboxymethyl)- (5,6)-carboxyfluorescein]-AM-loaded spermatogenic cells, a brief (30–60 s) application of 25 mM NH4Cl increased pHi by ∼1.3 U from a resting pHi ∼6.65. A steady pHi plateau was maintained during NH4Cl application, with little or no rebound acidification. In fura-2-AM-loaded cells, alkalinization induced a biphasic response composed of an initial [Ca2+]i drop followed by a two- to threefold rise. Maneuvers that inhibit either Ca2+ influx or intracellular Ca2+ release demonstrated that the majority of the Ca2+ rise results from plasma membrane Ca2+ influx, although a small component likely to result from intracellular Ca2+ release was occasionally observed. Ca2+ transients potentiated with repeated NH4Cl applications, gradually obliterating the initial [Ca2+]i drop. The pH-sensitive Ca2+ permeation pathway allows the passage of other divalents (Sr2+, Ba2+, and Mn2+) and is blocked by inorganic Ca2+ channel blockers (Ni2+ and Cd2+), but not by the organic blocker nifedipine. The magnitude of these Ca2+ transients increased as maturation advanced, with the largest responses being recorded in testicular sperm. By extrapolation, these findings suggest that the pH-dependent Ca2+ influx pathway could play significant roles in mature sperm physiology. Its pharmacology and ion selectivity suggests that it corresponds to an ion channel different from the voltage-gated T-type Ca2+ channel also present in spermatogenic cells. We postulate that the Ca2+ permeation pathway regulated by pHi, if present in mature sperm, may be responsible for the dihydropyridine-insensitive Ca2+ influx required for initiating the acrosome reaction and perhaps other important sperm functions. PMID:9649582

The effect of local and landscape-level characteristics on the abundance of forest birds in early-successional habitats during the post-fledging season in western Massachusetts

Treesearch

Michelle A. Labbe; David I. King; Tim A. Mousseau

2014-01-01

Many species of mature forest-nesting birds ("forest birds") undergo a pronounced shift in habitat use during the post-fledging period and move from their forest nesting sites into areas of early-successional vegetation. Mortality is high during this period, thus understanding the resource requirements of post-fledging birds has implications for conservation...

Stomata open at night in pole-sized and mature ponderosa pine: implications for O3 exposure metrics

Treesearch

Nancy Grulke; R. Alonso; T. Nguyen; C. Cascio; W. Dobrowolski

2004-01-01

Ponderosa pine (Pinus ponderosa Dougl. exLaws.) is widely distributed in the western USA.We report the lack of stomatal closure at night in early summer for ponderosa pine at two of three sites investigated. Trees at a third site with lower nitrogen dioxide and nitric acid exposure, but greater drought stress, had slightly open stomata at night in...

Development of the Potential for Cyanogenesis in Maturing Black Cherry (Prunus serotina Ehrh.) Fruits 1

PubMed Central

Swain, Elisabeth; Li, Chun Ping; Poulton, Jonathan E.

1992-01-01

Biochemical changes related to cyanogenesis (hydrogen cyanide production) were monitored during maturation of black cherry (Prunus serotina Ehrh.) fruits. At weekly intervals from flowering until maturity, fruits (or selected parts thereof) were analyzed for (a) fresh and dry weights, (b) prunasin and amygdalin levels, and (c) levels of the catabolic enzymes amygdalin hydrolase, prunasin hydrolase, and mandelonitrile lyase. During phase I (0-28 days after flowering [DAF]), immature fruits accumulated prunasin (mean: 3 micromoles/fruit) but were acyanogenic because they lacked the above enzymes. Concomitant with cotyledon development during mid-phase II, the seeds began accumulating both amygdalin (mean: 3 micromoles/seed) and the catabolic enzymes and were highly cyanogenic upon tissue disruption. Meanwhile, prunasin levels rapidly declined and were negligible by maturity. During phases II (29-65 DAF) and III (66-81 DAF), the pericarp also accumulated amygdalin, whereas its prunasin content declined toward maturity. Lacking the catabolic enzymes, the pericarp remained acyanogenic throughout all developmental stages. ImagesFigure 2Figure 4 PMID:16668810

Comparative proteomics of milk fat globule membrane in goat colostrum and mature milk.

PubMed

Lu, Jing; Liu, Lu; Pang, Xiaoyang; Zhang, Shuwen; Jia, Zhenhu; Ma, Changlu; Zhao, Lili; Lv, Jiaping

2016-10-15

As an important nutrient source in large area of world, the composition and nutritional value of goat milk are not well deliberated. Detailed annotation of protein composition is essential to address the physiological and nutritional value of goat milk. In the present study, 423 colostrum and mature goat milk fat globule membrane (MFGM) proteins were identified. The abundance of 189 proteins was significantly different between colostrums and mature milk MFGM. The acute phase proteins were higher in colostrums MFGM than those in mature milk MFGM which protected newborns at the beginning of life. Proteins related to synthesis and secretion were conserved through lactation to ensure the milk production. Of note, long term depression (LTD) proteins were observed in colostrum and mature milk MFGM. Milk LTD proteins could be potential biomarkers for diagnosis of lactation related depressive syndromes and should be taken into considerations of their effects on newborns. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of creosote on vitellogenin production in rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

Sherry, J.P.; Whyte, J.J.; Karrow, N.A.; Gamble, A.; Boerman, H.J.; Bol, N.C.; Dixon, D.G.; Solomon, K.R.

2006-01-01

As part of a broader investigation into the effects of creosote treatments on the aquatic biota in pond microcosms, we examined the possible implications for vitellogenin (Vtg) production in Oncorhynchus mykiss [rainbow trout (RT)]. Vtg is the precursor of egg yolk protein and has emerged as a useful biomarker of exposure to estrogenic substances. Our a priori intent was to assess the ability of the creosote treatments (nominal cresoste concentrations were 0, 3, and 10 ??l/L immediately after the last subsurface addition) to induce estrogenic responses in RT. The data showed no evidence of an estrogenic response in the treated fish. During the course of the experiment, however, the fish matured and began to produce Vtg, probably in response to endogenous estrogen. A posteriori analysis of the Vtg data from the maturing fish showed that after 28 days, the plasma Vtg concentrations were about 15-fold lower in fish from the creosote-treated microcosms compared with fish from the reference microcosm. Although the experiment design does not permit mechanistic insights, our observation suggests that exposure of female fish to PAH mixtures such as creosote can impair the production of Vtg with possible health implications for embryos and larvae. ?? 2006 Springer Science+Business Media, Inc.

Identification of CD22 Ligands on Bone Marrow Sinusoidal Endothelium Implicated in CD22-dependent Homing of Recirculating B Cells

PubMed Central

Nitschke, Lars; Floyd, Helen; Ferguson, David J.P.; Crocker, Paul R.

1999-01-01

CD22 is a B cell–specific transmembrane protein known to function as a negative regulator of B cell signaling. It has also been implicated in cell adhesion through recognition of α2,6-linked sialic acids on glycans of target cells. Previous studies showed that CD22-deficient mice had a strongly reduced population of mature recirculating B cells in the bone marrow despite normal B cell development. Using a soluble recombinant form of the receptor (CD22-Fc), we demonstrate here that sialylated ligands for CD22 are expressed on sinusoidal endothelial cells of murine bone marrow but not on endothelial cells in other tissues examined. Injection of CD22-Fc revealed that the CD22 ligands in the bone marrow were accessible to the circulation. Treatment of mice with either CD22-Fc or affinity-purified anti-CD22 antibody led to an ∼50% reduction in mature recirculating B cells in the bone marrow without affecting numbers in the spleen. Finally, consistent with the notion that CD22 is a homing receptor, we show that compared with wild-type mice, CD22-deficient animals have a lower number of immunoglobulin M–secreting plasma cells in the bone marrow. PMID:10224292

Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies

PubMed Central

Brydges, Susannah D.; Broderick, Lori; McGeough, Matthew D.; Pena, Carla A.; Mueller, James L.; Hoffman, Hal M.

2013-01-01

The inflammasome is a cytoplasmic multiprotein complex that promotes proinflammatory cytokine maturation in response to host- and pathogen-derived signals. Missense mutations in cryopyrin (NLRP3) result in a hyperactive inflammasome that drives overproduction of the proinflammatory cytokines IL-1β and IL-18, leading to the cryopyrin-associated periodic syndromes (CAPS) disease spectrum. Mouse lines harboring CAPS-associated mutations in Nlrp3 have elevated levels of IL-1β and IL-18 and closely mimic human disease. To examine the role of inflammasome-driven IL-18 in murine CAPS, we bred Nlrp3 mutations onto an Il18r-null background. Deletion of Il18r resulted in partial phenotypic rescue that abolished skin and visceral disease in young mice and normalized serum cytokines to a greater extent than breeding to Il1r-null mice. Significant systemic inflammation developed in aging Nlrp3 mutant Il18r-null mice, indicating that IL-1 and IL-18 drive pathology at different stages of the disease process. Ongoing inflammation in double-cytokine knockout CAPS mice implicated a role for caspase-1–mediated pyroptosis and confirmed that CAPS is inflammasome dependent. Our results have important implications for patients with CAPS and residual disease, emphasizing the need to explore other NLRP3-mediated pathways and the potential for inflammasome-targeted therapy. PMID:24084736

Gene expression profiles of prohibitin in testes of Octopus tankahkeei (ot-phb) revealing its possible role during spermiogenesis.

PubMed

Mao, Hai-Tao; Wang, Da-Hui; Lan, Zhou; Zhou, Hong; Yang, Wan-Xi

2012-05-01

Prohibitin is essential for intracellular homeostasis and stabilization of mitochondrial respiratory chain complexes. To explore its functions during spermiogenesis of Octopus tankahkeei (O. tankahkeei), we have cloned and sequenced the cDNA of this mammalian PHB homologue (termed ot-PHB) from the testes of O. tankahkeei. The 1165 bp ot-phb cDNA contains a 100 bp 5' UTR, a 882 bp open reading frame and a 183 bp 3' UTR. The putative ot-PHB protein owns a transmembrane domain from 6 to 31 amino acid (aa) and a putative PHB domain from 26 to 178 aa. Protein alignment demonstrated that ot-PHB had 73.3, 73.6, 74.0, 75.1, and 45.4% identity with its homologues in Homo sapiens, Mus muculus, Danio rerio, Xenopus tropicalis and Trypanosoma brucei, respectively. Tissue distribution profile analysis revealed its presence in all the tissues examined. In situ hybridization in spermiogenic cells demonstrated that ot-phb was expressed moderately at the beginning of the spermiogenesis. The abundance of transcripts increased in intermediate spermatids and in drastically remodeling final spermatids. In mature spermatozoa, the residuary transcripts concentrated around the chondriosomal mantle where mitochondria assemble around. In summary, the expression of ot-phb during spermiogenesis implicates a potential function of this protein during mitochondrial ubiquitination. It is the first time to implicate the role of prohibitin in cephalopod spermiogenesis.

Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain.

PubMed

Santoro, Antonietta; Spinelli, Chiara Carmela; Martucciello, Stefania; Nori, Stefania Lucia; Capunzo, Mario; Puca, Annibale Alessandro; Ciaglia, Elena

2018-03-01

Ongoing studies evidence cellular senescence in undifferentiated and specialized cells from tissues of all ages. Although it is believed that senescence plays a wider role in several stress responses in the mature age, its participation in certain physiological and pathological processes throughout life is coming to light. The "senescence machinery" has been observed in all brain cell populations, including components of innate immunity (e.g., microglia and astrocytes). As the beneficial versus detrimental implications of senescence is an open question, we aimed to analyze the contribution of immune responses in regulatory mechanisms governing its distinct functions in healthy (development, organogenesis, danger patrolling events) and diseased brain (glioma, neuroinflammation, neurodeneration), and the putative connection between cellular and molecular events governing the 2 states. Particularly this review offers new insights into the complex roles of senescence both as a chronological event as age advances, and as a molecular mechanism of brain homeostasis through the important contribution of innate immune responses and their crosstalk with neighboring cells in brain parenchyma. We also highlight the impact of the recently described glymphatic system and brain lymphatic vasculature in the interplay between peripheral and central immune surveillance and its potential implication during aging. This will open new ways to understand brain development, its deterioration during aging, and the occurrence of several oncological and neurodegenerative diseases. ©2018 Society for Leukocyte Biology.

Insect outbreak shifts the direction of selection from fast to slow growth rates in the long-lived conifer Pinus ponderosa

PubMed Central

Sala, Anna

2017-01-01

Long generation times limit species’ rapid evolution to changing environments. Trees provide critical global ecosystem services, but are under increasing risk of mortality because of climate change-mediated disturbances, such as insect outbreaks. The extent to which disturbance changes the dynamics and strength of selection is unknown, but has important implications on the evolutionary potential of tree populations. Using a 40-y-old Pinus ponderosa genetic experiment, we provide rare evidence of context-dependent fluctuating selection on growth rates over time in a long-lived species. Fast growth was selected at juvenile stages, whereas slow growth was selected at mature stages under strong herbivory caused by a mountain pine beetle (Dendroctonus ponderosae) outbreak. Such opposing forces led to no net evolutionary response over time, thus providing a mechanism for the maintenance of genetic diversity on growth rates. Greater survival to mountain pine beetle attack in slow-growing families reflected, in part, a host-based life-history trade-off. Contrary to expectations, genetic effects on tree survival were greatest at the peak of the outbreak and pointed to complex defense responses. Our results suggest that selection forces in tree populations may be more relevant than previously thought, and have implications for tree population responses to future environments and for tree breeding programs. PMID:28652352

Cell-autonomous inactivation of the Reelin pathway impairs adult neurogenesis in the hippocampus

PubMed Central

Teixeira, Catia M.; Kron, Michelle M.; Masachs, Nuria; Zhang, Helen; Lagace, Diane C.; Martinez, Albert; Reillo, Isabel; Duan, Xin; Bosch, Carles; Pujadas, Lluis; Brunso, Lucas; Song, Hongjun; Eisch, Amelia J.; Borrell, Victor; Howell, Brian W.; Parent, Jack M.; Soriano, Eduardo

2012-01-01

Adult hippocampal neurogenesis is thought to be essential for learning and memory and has been implicated in the pathogenesis of several disorders. Although recent studies have identified key factors regulating neuroprogenitor proliferation in the adult hippocampus, the mechanisms that control the migration and integration of adult-born neurons into circuits are largely unknown. Reelin is an extracellular matrix protein that is vital for neuronal development. Activation of the Reelin cascade leads to phosphorylation of disabled-1 (Dab1), an adaptor protein required for Reelin signaling. Here we used transgenic mouse and retroviral reporters along with Reelin signaling gain- and loss-of-function studies to show that the Reelin pathway regulates migration and dendritic development of adult-generated hippocampal neurons. Whereas overexpression of Reelin accelerated dendritic maturation, inactivation of the Reelin signaling pathway specifically in adult neuroprogenitor cells resulted in aberrant migration, decreased dendrite development, formation of ectopic dendrites in the hilus and the establishment of aberrant circuits. Our findings support a cell-autonomous and critical role for the Reelin pathway in regulating dendritic development and the integration of adult-generated granule cells and point to this pathway as a key regulator of adult neurogenesis. Moreover, our data reveal a novel role of the Reelin cascade in adult brain function with potential implications for the pathogenesis of several neurological and psychiatric disorders. PMID:22933789

Evidence of metachronous development of ovarian teratomas: a case report of bilateral mature cystic teratomas of the ovaries and systematic literature review.

PubMed

Wang, Wen-Chung; Lai, Yen-Chein

2017-03-14

Mature cystic teratomas are usually found in the ovaries. They are bilateral in 10 to 15% of cases and multiple cystic teratomas may be present in one ovary. The aim of this study is to clarify if development of mature cystic teratomas of the ovaries in a single host is metachronous or due to autoimplant or recurrence. We report a woman with bilateral mature cystic teratomas of the ovaries. DNA profiles of these teratomas were investigated via short tandem repeat (STR) analysis and methylation statuses were determined via methylation sensitive multiplex ligation-dependent probe amplification methods. The results showed that the cystic teratomas originated from different stages of oogonia or primary oocyte before germinal vesicle stage failure of meiosis I in female gametogenesis. Potentially relevant literature was searched in PubMed database. Cases of bilateral or multiple mature cystic teratomas of the ovaries were analyzed. To date, there has been no reported case of multiple mature cystic teratomas in which clarification of the origin was achieved using molecular genetic methods. The results of this case study provide evidence of metachronous development of mature cystic teratomas of the ovaries and may serve as a reference in the management of patients following laparoscopic cystectomy.

Neogene evolution of the North New Guinea basin, Papua New Guinea: New constraints from seismic and subsidence analysis and implications for hydrocarbon exploration

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

Cullen, A.B.; Pigott, J.D.

1990-06-01

The present-day North New Guinea basin is a Plio-Pleistocene successor basin that formed subsequent to accretion of the Finisterre volcanic arc to the Australian Plate. The Ramu, Sepik, and Piore infrabasins formed in a forearc setting relative to the continental Maramuni magmatic arc. The evolution of these infrabasins was strongly influenced by accretion of the composite Torricelli-Prince Alexander terrane to the Australian Plate. Regional reflection seismic data and tectonic subsidence-subsidence rate calculations for seven wells drilled in the North New Guinea basin reveal a complex history. The timing and magnitude of subsidence and changes in subsidence rates differ between eachmore » of the Miocene infrabasins. A diachronous middle to late Miocene unconformity generally truncates infrabasin sequences. The Nopan No. 1 in the Sepik basin, however, has a complete middle Miocene to Pleistocene sedimentary record. This well records late Miocene negative subsidence rates documenting that the Nopan anticline grew as erosion occurred elsewhere in the region. This circumstance suggests that the major, sequence-bounding unconformity results from regional uplift and deformation, rather than changes in global sea level. The Plio-Pleistocene evolution of the North New Guinea basin has two profound implications regarding hydrocarbon exploration. First, the late Pliocene structural inversion of parts of the basin hinders stratigraphic and facies correlation inferred from the present setting. The recognition of basin inversion is particularly important in the Piore basin for predicting the distribution of potential reservoir facies in the Miocene carbonates. Second, the subsidence data suggest that although potential source rocks may be thermally within the oil window, these rocks may not have had sufficient time to mature owing to their recent burial.« less

CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.

PubMed

Sunday, M E; Hua, J; Torday, J S; Reyes, B; Shipp, M A

1992-12-01

The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth.

Importance of disturbance history on net primary productivity in the world's most productive forests and implications for the global carbon cycle.

PubMed

Volkova, Liubov; Roxburgh, Stephen H; Weston, Christopher J; Benyon, Richard G; Sullivan, Andrew L; Polglase, Philip J

2018-05-14

Analysis of growth and biomass turnover in natural forests of Eucalyptus regnans, the world's tallest angiosperm, reveals it is also the world's most productive forest type, with fire disturbance an important mediator of net primary productivity (NPP). A comprehensive empirical database was used to calculate the averaged temporal pattern of NPP from regeneration to 250 years age. NPP peaks at 23.1 ± 3.8 (95% interquantile range) Mg C ha -1  year -1 at age 14 years, and declines gradually to about 9.2 ± 0.8 Mg C ha -1  year -1 at 130 years, with an average NPP over 250 years of 11.4 ± 1.1 Mg C ha -1  year -1 , a value similar to the most productive temperate and tropical forests around the world. We then applied the age-class distribution of E. regnans resulting from relatively recent historical fires to estimate current NPP for the forest estate. Values of NPP were 40% higher (13 Mg C ha -1  year -1 ) than if forests were assumed to be at maturity (9.2 Mg C ha -1  year -1 ). The empirically derived NPP time series for the E. regnans estate was then compared against predictions from 21 global circulation models, showing that none of them had the capacity to simulate a post-disturbance peak in NPP, as found in E. regnans. The potential importance of disturbance impacts on NPP was further tested by applying a similar approach to the temperate forests of conterminous United States and of China. Allowing for the effects of disturbance, NPP summed across both regions was on average 11% (or 194 Tg C/year) greater than if all forests were assumed to be in a mature state. The results illustrate the importance of accounting for past disturbance history and growth stage when estimating forest primary productivity, with implications for carbon balance modelling at local to global scales. © 2018 John Wiley & Sons Ltd.

Application and Validation of Concept Maturity Assessment Framework

DTIC Science & Technology

2011-03-01

process. The following chapter will discuss a proposed methodology for validation of the concept maturity framwork and its Concept Evaluation and...of each contractor‟s conceptual solution and any gaps in information that may have been overlooked. The organization also commented that the... conceptual and does not have a specific system tied to it is often vulnerable to losing interest and potentially funding from decision makers. However

A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells.

PubMed

Gunhanlar, N; Shpak, G; van der Kroeg, M; Gouty-Colomer, L A; Munshi, S T; Lendemeijer, B; Ghazvini, M; Dupont, C; Hoogendijk, W J G; Gribnau, J; de Vrij, F M S; Kushner, S A

2018-05-01

Progress in elucidating the molecular and cellular pathophysiology of neuropsychiatric disorders has been hindered by the limited availability of living human brain tissue. The emergence of induced pluripotent stem cells (iPSCs) has offered a unique alternative strategy using patient-derived functional neuronal networks. However, methods for reliably generating iPSC-derived neurons with mature electrophysiological characteristics have been difficult to develop. Here, we report a simplified differentiation protocol that yields electrophysiologically mature iPSC-derived cortical lineage neuronal networks without the need for astrocyte co-culture or specialized media. This protocol generates a consistent 60:40 ratio of neurons and astrocytes that arise from a common forebrain neural progenitor. Whole-cell patch-clamp recordings of 114 neurons derived from three independent iPSC lines confirmed their electrophysiological maturity, including resting membrane potential (-58.2±1.0 mV), capacitance (49.1±2.9 pF), action potential (AP) threshold (-50.9±0.5 mV) and AP amplitude (66.5±1.3 mV). Nearly 100% of neurons were capable of firing APs, of which 79% had sustained trains of mature APs with minimal accommodation (peak AP frequency: 11.9±0.5 Hz) and 74% exhibited spontaneous synaptic activity (amplitude, 16.03±0.82 pA; frequency, 1.09±0.17 Hz). We expect this protocol to be of broad applicability for implementing iPSC-based neuronal network models of neuropsychiatric disorders.

Evo-devo of human adolescence: beyond disease models of early puberty

PubMed Central

2013-01-01

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research. PMID:23627891

Leaf development in Xylopia aromatica (Lam) Mart. (Annonaceae): implications for palatability to Stenoma scitiorella Walker 1864 (Lepidoptera: Elachistidae).

PubMed

Varanda, E M; Costa, A A; Barosela, J R

2008-11-01

Variations in specific foliar mass and water content, nitrogen, soluble carbohydrates and tannins were studied during the growth and maturation processes of the Xylopia aromatica leaves, to determine the effects of such alterations on the herbivory of Stenoma scitiorella caterpillars. This work was carried out in the physiognomy of the typical cerrado of the Parque Estadual de Vassununga, Gleba Pé-de Gigante, Santa Rita do Passa Quatro, São Paulo State, Brazil. While nutritional quality (water and nitrogen) decreases during expansion and maturation of Xylopia aromatica leaves, the chemical (tannins) and physical (sclerophylly) defenses are raised. In agreement with the observations on herbivory, the results support the hypothesis that the reduction in palatability and increase in chemical defenses of Xylopia aromatica leaves account for the caterpillars' preference for young expanding leaves.

Ontogeny and the fossil record: what, if anything, is an adult dinosaur?

PubMed

Hone, David W E; Farke, Andrew A; Wedel, Mathew J

2016-02-01

Identification of the ontogenetic status of an extinct organism is complex, and yet this underpins major areas of research, from taxonomy and systematics to ecology and evolution. In the case of the non-avialan dinosaurs, at least some were reproductively mature before they were skeletally mature, and a lack of consensus on how to define an 'adult' animal causes problems for even basic scientific investigations. Here we review the current methods available to determine the age of non-avialan dinosaurs, discuss the definitions of different ontogenetic stages, and summarize the implications of these disparate definitions for dinosaur palaeontology. Most critically, a growing body of evidence suggests that many dinosaurs that would be considered 'adults' in a modern-day field study are considered 'juveniles' or 'subadults' in palaeontological contexts. © 2016 The Author(s).

Ontogeny and the fossil record: what, if anything, is an adult dinosaur?

PubMed Central

2016-01-01

Identification of the ontogenetic status of an extinct organism is complex, and yet this underpins major areas of research, from taxonomy and systematics to ecology and evolution. In the case of the non-avialan dinosaurs, at least some were reproductively mature before they were skeletally mature, and a lack of consensus on how to define an ‘adult’ animal causes problems for even basic scientific investigations. Here we review the current methods available to determine the age of non-avialan dinosaurs, discuss the definitions of different ontogenetic stages, and summarize the implications of these disparate definitions for dinosaur palaeontology. Most critically, a growing body of evidence suggests that many dinosaurs that would be considered ‘adults’ in a modern-day field study are considered ‘juveniles’ or ‘subadults’ in palaeontological contexts. PMID:26888916

Managing produced water from coal seam gas projects: implications for an emerging industry in Australia.

PubMed

Davies, Peter J; Gore, Damian B; Khan, Stuart J

2015-07-01

This paper reviews the environmental problems, impacts and risks associated with the generation and disposal of produced water by the emerging coal seam gas (CSG) industry and how it may be relevant to Australia and similar physical settings. With only limited independent research on the potential environmental impacts of produced water, is it necessary for industry and government policy makers and regulators to draw upon the experiences of related endeavours such as mining and groundwater extraction accepting that the conclusions may not always be directly transferrable. CSG is widely touted in Australia as having the potential to provide significant economic and energy security benefits, yet the environmental and health policies and the planning and regulatory setting are yet to mature and are continuing to evolve amidst ongoing social and environmental concerns and political indecision. In this review, produced water has been defined as water that is brought to the land surface during the process of recovering methane gas from coal seams and includes water sourced from CSG wells as well as flowback water associated with drilling, hydraulic fracturing and gas extraction. A brief overview of produced water generation, its characteristics and environmental issues is provided. A review of past lessons and identification of potential risks, including disposal options, is included to assist in planning and management of this industry.

Long-term reproductive and behavioral toxicity of anthracene to fish in the presence of solar ultraviolet radiation

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

Hall, A.T.; Oris, J.T.

1994-12-31

The long-term, low-level effects of anthracene in the presence of solar ultraviolet radiation (SUVR) were examined in the fathead minnow (Pimephales promelas). Adult fish exposed to anthracene exhibited reduced egg laying capacity, with altered oocyte maturation as a potential mechanism of action. Eggs and larvae maternally exposed to anthracene exhibited reduced hatching success and severe developmental abnormalities when incubated under SUVR. The combination of reduced egg output and developmental effects resulted in an inhibition in reproductive capacity in the range of 70--100%. Maternal transfer of anthracene to eggs was efficient; the BCF was 717 for maternally exposed eggs. However, anthracenemore » deputation from eggs after oviposition with only maternal PAH exposure was rapid; anthracene half-life from eggs equaled 1.3 days. Exposure to anthracene under SUVR altered locomotor activity patterns in fathead minnows by inducing hyperactivity or hypoactivity during the light or dark phases of the photoperiod, respectively. Altered activity patterns indicated potential effects of anthracene on the nervous system and/or pineal gland. These alterations disrupted normal activity patterns and reproductive behaviors, and thus have major implications on a fish`s ability to survive and reproduce. Anthracene, a model phototoxic PAH, has many potential sites of toxic action, and any organism exposed to such contaminants will be an considerable SUVR-enhanced risk in the environment.« less

HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat.

PubMed

Fun, Axel; van Maarseveen, Noortje M; Pokorná, Jana; Maas, Renée Em; Schipper, Pauline J; Konvalinka, Jan; Nijhuis, Monique

2011-08-24

Maturation inhibitors are an experimental class of antiretrovirals that inhibit Human Immunodeficiency Virus (HIV) particle maturation, the structural rearrangement required to form infectious virus particles. This rearrangement is triggered by the ordered cleavage of the precursor Gag polyproteins into their functional counterparts by the viral enzyme protease. In contrast to protease inhibitors, maturation inhibitors impede particle maturation by targeting the substrate of protease (Gag) instead of the protease enzyme itself. Direct cross-resistance between protease and maturation inhibitors may seem unlikely, but the co-evolution of protease and its substrate, Gag, during protease inhibitor therapy, could potentially affect future maturation inhibitor therapy. Previous studies showed that there might also be an effect of protease inhibitor resistance mutations on the development of maturation inhibitor resistance, but the exact mechanism remains unclear. We used wild-type and protease inhibitor resistant viruses to determine the impact of protease inhibitor resistance mutations on the development of maturation inhibitor resistance. Our resistance selection studies demonstrated that the resistance profiles for the maturation inhibitor bevirimat are more diverse for viruses with a mutated protease compared to viruses with a wild-type protease. Viral replication did not appear to be a major factor during emergence of bevirimat resistance. In all in vitro selections, one of four mutations was selected: Gag V362I, A364V, S368N or V370A. The impact of these mutations on maturation inhibitor resistance and viral replication was analyzed in different protease backgrounds. The data suggest that the protease background affects development of HIV-1 resistance to bevirimat and the replication profiles of bevirimat-selected HIV-1. The protease-dependent bevirimat resistance and replication levels can be explained by differences in CA/p2 cleavage processing by the different proteases. These findings highlight the complicated interactions between the viral protease and its substrate. By providing a better understanding of these interactions, we aim to help guide the development of second generation maturation inhibitors.

Regulation of Fatty Acid Oxidation in Mouse Cumulus-Oocyte Complexes during Maturation and Modulation by PPAR Agonists

PubMed Central

Dunning, Kylie R.; Anastasi, Marie R.; Zhang, Voueleng J.; Russell, Darryl L.; Robker, Rebecca L.

2014-01-01

Fatty acid oxidation is an important energy source for the oocyte; however, little is known about how this metabolic pathway is regulated in cumulus-oocyte complexes. Analysis of genes involved in fatty acid oxidation showed that many are regulated by the luteinizing hormone surge during in vivo maturation, including acyl-CoA synthetases, carnitine transporters, acyl-CoA dehydrogenases and acetyl-CoA transferase, but that many are dysregulated when cumulus-oocyte complexes are matured under in vitro maturation conditions using follicle stimulating hormone and epidermal growth factor. Fatty acid oxidation, measured as production of 3H2O from [3H]palmitic acid, occurs in mouse cumulus-oocyte complexes in response to the luteinizing hormone surge but is significantly reduced in cumulus-oocyte complexes matured in vitro. Thus we sought to determine whether fatty acid oxidation in cumulus-oocyte complexes could be modulated during in vitro maturation by lipid metabolism regulators, namely peroxisome proliferator activated receptor (PPAR) agonists bezafibrate and rosiglitazone. Bezafibrate showed no effect with increasing dose, while rosiglitazone dose dependently inhibited fatty acid oxidation in cumulus-oocyte complexes during in vitro maturation. To determine the impact of rosiglitazone on oocyte developmental competence, cumulus-oocyte complexes were treated with rosiglitazone during in vitro maturation and gene expression, oocyte mitochondrial activity and embryo development following in vitro fertilization were assessed. Rosiglitazone restored Acsl1, Cpt1b and Acaa2 levels in cumulus-oocyte complexes and increased oocyte mitochondrial membrane potential yet resulted in significantly fewer embryos reaching the morula and hatching blastocyst stages. Thus fatty acid oxidation is increased in cumulus-oocyte complexes matured in vivo and deficient during in vitro maturation, a known model of poor oocyte quality. That rosiglitazone further decreased fatty acid oxidation during in vitro maturation and resulted in poor embryo development points to the developmental importance of fatty acid oxidation and the need for it to be optimized during in vitro maturation to improve this reproductive technology. PMID:24505284

Organic geochemistry of resins from modern Agathis australis and Eocene resins from New Zealand: Diagenetic and taxonomic implications

USGS Publications Warehouse

Lyons, P.C.; Mastalerz, Maria; Orem, W.H.

2009-01-01

A maturation series of resins and fossil resins from New Zealand, ranging in age from Modern to Eocene and ranging from uncoalified to high volatile C bituminous coal, were analyzed by elemental, pyrolysis-gas chromatography (Py-GC), Fourier Transform infrared (FTir), and solid-state 13C nuclear magnetic resonance (13C NMR) techniques. For comparison, four resin samples from the Latrobe Valley, Australia, were analyzed. All of the resins and fossil resins of this study show very high H/C atomic ratios, and are characterized by dominant peaks in the 10-60??ppm range of solid-state 13C NMR spectra and prominent bands in the aliphatic stretching region (2800-3000??cm- 1) of FTir spectra, all indicating a highly aliphatic molecular structure. The 13C NMR and FTir data indicate a diterpenoid structure for these resins. There is an abrupt loss of oxygen that occurs at the Lignite A/Subbituminous C stage, which is attributed to a dramatic loss of carboxyl (COOH) from the diterpenoid molecule. This is a new finding in the diagenesis of resins. This important loss in oxygenated functional groups is attributed to a maturation change. Also, there is a progressive loss of exomethylene (CH2) groups with increasing degree of maturation, as shown by both 13C NMR and FTir data. This change has been noted by previous investigators. Exomethylene is absent in the fossil resins from the Eocene high volatile C bituminous coals. This progressive loss is characteristic of Class I resinites. FTir data indicate that the oxygenated functional groups are strong in all the resin samples except the fossil resin from high volatile C bituminous coal. This important change in oxygenated functional groups is attributed to maturation changes. The 13C NMR and FTir data indicate there are minor changes in the Agathis australis resin from the living tree and soil, which suggests that alteration of A. australis resins begins shortly after deposition in the soil for as little as 1000??years. The Morwell and Yallourn fossil resins from brown coal (lignite B) Australia do not have some of the FTir characteristics of the New Zealand resins, which most likely indicates they have a different plant source because different degrees of oxidation and weathering and changes due to fires (i.e., charring) can be ruled out. Our results have implications for studies of the maturation, provenance, and botanical sources of fossil resins and resinites in Eocene and Miocene coals and sediments of New Zealand and Australia. ?? 2009 Elsevier B.V. All rights reserved.

The Permeability Transition Pore Controls Cardiac Mitochondrial Maturation and Myocyte Differentiation

PubMed Central

Hom, Jennifer R.; Quintanilla, Rodrigo A.; Hoffman, David L.; Karen L., de Mesy Bentley; Molkentin, Jeffery D.; Sheu, Shey-Shing; Porter, George A.

2011-01-01

SUMMARY Although mature myocytes rely on mitochondria as the primary source of energy, the role of mitochondria in the developing heart is not well known. Here, we find closure of the mitochondrial permeability transition pore (mPTP) drives maturation of mitochondrial structure and function and myocyte differentiation. Cardiomyocytes at embryonic day (E) 9.5, when compared to E13.5, displayed fragmented mitochondria with few cristae, a less polarized mitochondrial membrane potential, higher reactive oxygen species (ROS) levels, and an open mPTP. Pharmacologic and genetic closing of the mPTP yielded maturation of mitochondrial structure and function, lowered ROS, and increased myocyte differentiation (measured by counting Z-bands). Furthermore, myocyte differentiation was inhibited and enhanced with oxidant and antioxidant treatment, respectively, suggesting that redox signaling pathways lie downstream of mitochondria to regulate cardiac myocyte differentiation. PMID:21920313

N-hexane alters the maturation of oocytes and induces apoptosis in mice.

PubMed

Liu, Jin; Huang, Lei; Sun, Yan; Li, Yu Chen; Zhu, Jian Lin; Wang, Wen Xiang; Zhang, Wen Chang

2013-09-01

This study was aimed to determine the effects of n-hexane on the maturation of mouse oocytes. Cell culture was used to observe the maturation of mouse oocytes and CLSM was employed to determine their apoptosis. Germinal vesicle breakdown (GVBD) and extrusion of the first polar body in mouse oocytes were significantly inhibited by n-hexane. After fertilization, the number of eggs in the mouse was significantly reduced by n-hexane. Mitochondrial membrane potentials (ΔΨm) were altered in mouse oocytes that were leading to apoptosis of the oocytes. N-hexane might have affected the maturation of oocytes, causing alteration of ΔΨm and leading to apoptosis which maybe one of the most important mechanisms. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Effect of collection-maturation interval time and pregnancy status of donor mares on oocyte developmental competence in horse cloning.

PubMed

Gambini, A; Andrés, G; Jarazo, J; Javier, J; Karlanian, F; Florencia, K; De Stéfano, A; Salamone, D F

2014-02-01

The current limitations for obtaining ovaries from slaughterhouses and the low efficiency of in vivo follicular aspiration necessitate a complete understanding of the variables that affect oocyte developmental competence in the equine. For this reason, we assessed the effect on equine oocyte meiotic competence and the subsequent in vitro cloned embryo development of 1) the time interval between ovary collection and the onset of oocyte in vitro maturation (collection-maturation interval time) and 2) the pregnancy status of the donor mares. To define the collection-maturation interval time, collected oocytes were classified according to the slaughtering time and the pregnancy status of the mare. Maturation rate was recorded and some matured oocytes of each group were used to reconstruct zona free cloned embryos. Nuclear maturation rates were lower when the collection-maturation interval time exceeded 10 h as compared to 4 h (32/83 vs. 76/136, respectively; P = 0.0128) and when the donor mare was pregnant as compared to nonpregnant (53/146 vs. 177/329, respectively; P = 0.0004). Low rates of cleaved embryos were observed when the collection-maturation interval time exceeded 10 h as compared to 6 to 10 h (11/27 vs. 33/44, respectively; P = 0.0056), but the pregnancy status of donor mares did not affect cloned equine blastocyst development (3/49 vs. 1/27 for blastocyst rates of nonpregnant and pregnant groups, respectively; P = 1.00). These results indicate that, to apply assisted reproductive technologies in horses, oocytes should be harvested within approximately 10 h after ovary collection. Also, even though ovaries from pregnant mares are a potential source of oocytes, they should be processed at the end of the collection routine due to the lower collection and maturation rate in this group.

Business-IT Alignment in Trade Facilitation: A Case Study

NASA Astrophysics Data System (ADS)

Adaba, Godfried; Rusu, Lazar; El-Mekawy, Mohamed

In the information age, no organization can thrive without harnessing the power of IT. The effective deployment of IT to achieve business goals and gain competitive advantage requires the alignment of business and IT strategies of organizations. Using the Strategic Alignment Maturity model, this paper evaluates strategic alignment maturity of Customs Excise Preventive service, a frontline public organization charged with trade facilitation in Ghana. Strategic alignment maturity is at level 3; which implies the existence of an established process to leverage IT for efficiency and effectiveness. Efforts are required to strengthen alignment and fully harness the potential of IT to facilitate trade in Ghana.

The complexity of selection at the major primate β-defensin locus

PubMed Central

Semple, Colin AM; Maxwell, Alison; Gautier, Philippe; Kilanowski, Fiona M; Eastwood, Hayden; Barran, Perdita E; Dorin, Julia R

2005-01-01

Background We have examined the evolution of the genes at the major human β-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. Results We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on β-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific β-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of β-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. Conclusions Identification of these putatively functional sites has important implications for our understanding of β-defensin function and for novel antibiotic design. PMID:15904491

On gonadic maturation and reproductive strategy in deep-sea benthic octopus Graneledone macrotyla

NASA Astrophysics Data System (ADS)

Guerra, Ángel; Sieiro, María Pilar; Roura, Álvaro; Portela, Julio M.; del Río, José Luís

2013-09-01

The new information reported in this paper is based on five maturing and mature females of the large-tuberculate octopus Graneledone macrotyla. These specimens were caught in bottom trawl surveys ATLANTIS 2009 (February 24 to April 1, 2009) and ATLANTIS 2010 (March 9 to April 5, 2010) carried out off the Argentinean Economic Exclusive Zone. Capture depth ranged from 475 to 921 m and sea bottom temperature between 2.8 and 3.1 °C. Development of the complex ovary, oviducts, and oviducal glands during gonadic maturation is described. The absence of spermathecae in the oviducal glands and the presence of fertilized eggs inside the ovary suggested that fertilization took place within the ovary. Histological techniques showed the presence of four types of oocytes. Maturing oocyte size-frequency distribution was polymodal. Fluorescence reaction showed that atresia occurred in both early and later oocyte maturation stages. Atresia affected 48-55 % of the initial number of oocytes. The maximum observed potential fecundity was estimated at 250-300 eggs. G. macrotyla showed a group-synchronous ovulation pattern, regulative atresia, and a batching spawning pattern with a few egg batches spawned intermittently over an extended period of spawning.

Characterization of cyanidin- and quercetin-derived flavonoids and other phenolics in mature saskatoon fruits (Amelanchier alnifolia Nutt.).

PubMed

Ozga, Jocelyn A; Saeed, Asma; Wismer, Wendy; Reinecke, Dennis M

2007-12-12

In order to further characterize the anthocyanins, flavonols, and other phenolics present in mature saskatoon ( Amelanchier alnifolia Nutt.) fruit, extracts were characterized using high-performance liquid chromatography, gas chromatography, and liquid chromatography-mass spectrometry. Cyanidin 3-O-galactoside, cyanidin 3-O-glucoside, cyanidin 3-O-arabinoside, and cyanidin 3-O-xyloside were identified as the four major anthocyanins in the mature fruit. The quercetin-derived flavonols, quercetin 3-O-glucoside, quercetin 3-O-galactoside, quercetin 3-O-arabinoside, quercetin 3-O-xyloside, quercetin 3-O-arabinoglucoside, quercetin 3-O-robinobioside, and quercetin 3-O-rutinoside were also identified in mature fruit extracts. In addition, two chlorogenic acid isomers (hydroxycinnamates), 3-O-caffeoylquinic acid and 5-O-caffeoylquinic acid were detected. The total content of the anthocyanin-, flavonol-, and hydroxycinnamate-type phenolics detected in mature 'Smoky' saskatoon fruit was 140, 25, and 96 mg/100 g fresh weight, respectively. These data further our knowledge of the phenolic composition of mature saskatoon fruit, and as anthocyanins, flavonols, and hydroxycinnamates exhibit antioxidant activities, the presence and levels of these classes of phenolics will aid in the understanding of the potential health-beneficial effects of saskatoon fruits in the human diet.

Clay minerals and metal oxides strongly influence the structure of alkane-degrading microbial communities during soil maturation.

PubMed

Steinbach, Annelie; Schulz, Stefanie; Giebler, Julia; Schulz, Stephan; Pronk, Geertje J; Kögel-Knabner, Ingrid; Harms, Hauke; Wick, Lukas Y; Schloter, Michael

2015-07-01

Clay minerals, charcoal and metal oxides are essential parts of the soil matrix and strongly influence the formation of biogeochemical interfaces in soil. We investigated the role of these parental materials for the development of functional microbial guilds using the example of alkane-degrading bacteria harbouring the alkane monooxygenase gene (alkB) in artificial mixtures composed of different minerals and charcoal, sterile manure and a microbial inoculum extracted from an agricultural soil. We followed changes in abundance and community structure of alkane-degrading microbial communities after 3 and 12 months of soil maturation and in response to a subsequent 2-week plant litter addition. During maturation we observed an overall increasing divergence in community composition. The impact of metal oxides on alkane-degrading community structure increased during soil maturation, whereas the charcoal impact decreased from 3 to 12 months. Among the clay minerals illite influenced the community structure of alkB-harbouring bacteria significantly, but not montmorillonite. The litter application induced strong community shifts in soils, maturated for 12 months, towards functional guilds typical for younger maturation stages pointing to a resilience of the alkane-degradation function potentially fostered by an extant 'seed bank'.

Clay minerals and metal oxides strongly influence the structure of alkane-degrading microbial communities during soil maturation

PubMed Central

Steinbach, Annelie; Schulz, Stefanie; Giebler, Julia; Schulz, Stephan; Pronk, Geertje J; Kögel-Knabner, Ingrid; Harms, Hauke; Wick, Lukas Y; Schloter, Michael

2015-01-01

Clay minerals, charcoal and metal oxides are essential parts of the soil matrix and strongly influence the formation of biogeochemical interfaces in soil. We investigated the role of these parental materials for the development of functional microbial guilds using the example of alkane-degrading bacteria harbouring the alkane monooxygenase gene (alkB) in artificial mixtures composed of different minerals and charcoal, sterile manure and a microbial inoculum extracted from an agricultural soil. We followed changes in abundance and community structure of alkane-degrading microbial communities after 3 and 12 months of soil maturation and in response to a subsequent 2-week plant litter addition. During maturation we observed an overall increasing divergence in community composition. The impact of metal oxides on alkane-degrading community structure increased during soil maturation, whereas the charcoal impact decreased from 3 to 12 months. Among the clay minerals illite influenced the community structure of alkB-harbouring bacteria significantly, but not montmorillonite. The litter application induced strong community shifts in soils, maturated for 12 months, towards functional guilds typical for younger maturation stages pointing to a resilience of the alkane-degradation function potentially fostered by an extant ‘seed bank'. PMID:25535940

The Effect of Skeletal Maturity on the Regenerative Function of Intrinsic ACL Cells

PubMed Central

Mastrangelo, Ashley N.; Magarian, Elise M.; Palmer, Matthew P.; Vavken, Patrick; Murray, Martha M.

2010-01-01

Anterior cruciate ligament (ACL) injuries are an important clinical problem, particularly for adolescent patients. The effect of skeletal maturity on the potential for ACL healing is as yet unknown. In this study, we hypothesized that fibroblastic cells from the ACLs of skeletally immature animals would proliferate and migrate more quickly than cells from adolescent and adult animals. ACL tissue from skeletally immature, adolescent, and adult pigs and sheep were obtained and cells obtained using explant culture. Cell proliferation within a collagen–platelet scaffold was measured at days 2, 7, and 14 of culture using AMMTT assay. Cellular migration was measured at 4 and 24 h using a modified Boyden chamber assay, and cell outgrowth from the explants also measured at 1 week. ACL cells from skeletally immature animals had higher proliferation between 7 and 14 days (p < 0.01 for all comparisons) and higher migration potential at all time points in both species (p < 0.01 for all comparisons).ACL cells from skeletally immature animals have greater cellular proliferation and migration potential than cells from adolescent or adult animals. These experiments suggest that skeletal maturity may influence the biologic repair capacity of intrinsic ACL cells. PMID:19890988

The cancer paradigms of mammalian regeneration: can mammals regenerate as amphibians?

PubMed

Sarig, Rachel; Tzahor, Eldad

2017-04-01

Regeneration in mammals is restricted to distinct tissues and occurs mainly by expansion and maturation of resident stem cells. During regeneration, even subtle mutations in the proliferating cells may cause a detrimental effect by eliciting abnormal differentiation or malignant transformation. Indeed, cancer in mammals has been shown to arise through deregulation of stem cells maturation, which often leads to a differentiation block and cell transformation. In contrast, lower organisms such as amphibians retain a remarkable regenerative capacity in various organs, which occurs via de- and re-differentiation of mature cells. Interestingly, regenerating amphibian cells are highly resistant to oncogenic transformation. Therapeutic approaches to improve mammalian regeneration mainly include stem-cell transplantations; but, these have proved unsuccessful in non-regenerating organs such as the heart. A recently developed approach is to induce de-differentiation of mature cardiomyocytes using factors that trigger their re-entry into the cell cycle. This novel approach raises numerous questions regarding the balance between transformation and regeneration induced by de-differentiation of mature mammalian somatic cells. Can this balance be controlled artificially? Do de-differentiated cells acquire the protection mechanisms seen in regenerating cells of lower organisms? Is this model unique to the cardiac tissue, which rarely develops tumors? This review describes regeneration processes in both mammals and lower organisms and, particularly, the ability of regenerating cells to avoid transformation. By comparing the characteristics of mammalian embryonic and somatic cells, we discuss therapeutic strategies of using various cell populations for regeneration. Finally, we describe a novel cardiac regeneration approach and its implications for regenerative medicine. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Host Reticulocytes Provide Metabolic Reservoirs That Can Be Exploited by Malaria Parasites

PubMed Central

Srivastava, Anubhav; Creek, Darren J.; Evans, Krystal J.; De Souza, David; Schofield, Louis; Müller, Sylke; Barrett, Michael P.; McConville, Malcolm J.; Waters, Andrew P.

2015-01-01

Human malaria parasites proliferate in different erythroid cell types during infection. Whilst Plasmodium vivax exhibits a strong preference for immature reticulocytes, the more pathogenic P. falciparum primarily infects mature erythrocytes. In order to assess if these two cell types offer different growth conditions and relate them to parasite preference, we compared the metabolomes of human and rodent reticulocytes with those of their mature erythrocyte counterparts. Reticulocytes were found to have a more complex, enriched metabolic profile than mature erythrocytes and a higher level of metabolic overlap between reticulocyte resident parasite stages and their host cell. This redundancy was assessed by generating a panel of mutants of the rodent malaria parasite P. berghei with defects in intermediary carbon metabolism (ICM) and pyrimidine biosynthesis known to be important for P. falciparum growth and survival in vitro in mature erythrocytes. P. berghei ICM mutants (pbpepc-, phosphoenolpyruvate carboxylase and pbmdh-, malate dehydrogenase) multiplied in reticulocytes and committed to sexual development like wild type parasites. However, P. berghei pyrimidine biosynthesis mutants (pboprt-, orotate phosphoribosyltransferase and pbompdc-, orotidine 5′-monophosphate decarboxylase) were restricted to growth in the youngest forms of reticulocytes and had a severe slow growth phenotype in part resulting from reduced merozoite production. The pbpepc-, pboprt- and pbompdc- mutants retained virulence in mice implying that malaria parasites can partially salvage pyrimidines but failed to complete differentiation to various stages in mosquitoes. These findings suggest that species-specific differences in Plasmodium host cell tropism result in marked differences in the necessity for parasite intrinsic metabolism. These data have implications for drug design when targeting mature erythrocyte or reticulocyte resident parasites. PMID:26042734

Mettl3 Mutation Disrupts Gamete Maturation and Reduces Fertility in Zebrafish.

PubMed

Xia, Hui; Zhong, Chengrong; Wu, Xingxing; Chen, Ji; Tao, Binbin; Xia, Xiaoqin; Shi, Mijuan; Zhu, Zuoyan; Trudeau, Vance L; Hu, Wei

2018-02-01

N 6 -methyladenosine (m 6 A), catalyzed by Mettl3 methyltransferase, is a highly conserved epigenetic modification in eukaryotic messenger RNA (mRNA). Previous studies have implicated m 6 A modification in multiple biological processes, but the in vivo function of m 6 A has been difficult to study, because mettl3 mutants are embryonic lethal in both mammals and plants. In this study, we have used transcription activator-like effector nucleases and generated viable zygotic mettl3 mutant, Z mettl3 m/m , in zebrafish. We find that the oocytes in Z mettl3 m/m adult females are stalled in early development and the ratio of full-grown stage (FG) follicles is significantly lower than that of wild type. Human chorionic gonadotropin-induced ovarian germinal vesicle breakdown in vitro and the numbers of eggs ovulated in vivo are both decreased as well, while the defects of oocyte maturation can be rescued by sex hormone in vitro and in vivo In Z mettl3 m/m adult males, we find defects in sperm maturation and sperm motility is significantly reduced. Further study shows that 11-ketotestosterone (11-KT) and 17β-estradiol (E2) levels are significantly decreased in Z mettl3 m/m , and defective gamete maturation is accompanied by decreased overall m 6 A modification levels and disrupted expression of genes critical for sex hormone synthesis and gonadotropin signaling in Z mettl3 m/m Thus, our study provides the first in vivo evidence that loss of Mettl3 leads to failed gamete maturation and significantly reduced fertility in zebrafish. Mettl3 and m 6 A modifications are essential for optimal reproduction in vertebrates. Copyright © 2018 by the Genetics Society of America.

An endosomal syntaxin and the AP-3 complex are required for formation and maturation of candidate lysosome-related secretory organelles (mucocysts) in Tetrahymena thermophila.

PubMed

Kaur, Harsimran; Sparvoli, Daniela; Osakada, Hiroko; Iwamoto, Masaaki; Haraguchi, Tokuko; Turkewitz, Aaron P

2017-06-01

The ciliate Tetrahymena thermophila synthesizes large secretory vesicles called mucocysts. Mucocyst biosynthesis shares features with dense core granules (DCGs) in animal cells, including proteolytic processing of cargo proteins during maturation. However, other molecular features have suggested relatedness to lysosome-related organelles (LROs). LROs, which include diverse organelles in animals, are formed via convergence of secretory and endocytic trafficking. Here we analyzed Tetrahymena syntaxin 7-like 1 (Stx7l1p), a Qa-SNARE whose homologues in other lineages are linked with vacuoles/LROs. Stx7l1p is targeted to both immature and mature mucocysts and is essential in mucocyst formation. In STX7L1 -knockout cells, the two major classes of mucocyst cargo proteins localize independently, accumulating in largely nonoverlapping vesicles. Thus initial formation of immature mucocysts involves heterotypic fusion, in which a subset of mucocyst proteins is delivered via an endolysosomal compartment. Further, we show that subsequent maturation requires AP-3, a complex widely implicated in LRO formation. Knockout of the µ-subunit gene does not impede delivery of any known mucocyst cargo but nonetheless arrests mucocyst maturation. Our data argue that secretory organelles in ciliates may represent a new class of LROs and reveal key roles of an endosomal syntaxin and AP-3 in the assembly of this complex compartment. © 2017 Kaur et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

On/off TLR signaling decides proinflammatory or tolerogenic dendritic cell maturation upon CD1d-mediated interaction with invariant NKT cells.

PubMed

Caielli, Simone; Conforti-Andreoni, Cristina; Di Pietro, Caterina; Usuelli, Vera; Badami, Ester; Malosio, Maria Luisa; Falcone, Marika

2010-12-15

Invariant NKT (iNKT) cells play an effector/adjuvant function during antimicrobial and antitumoral immunity and a regulatory role to induce immune tolerance and prevent autoimmunity. iNKT cells that differentially modulate adaptive immunity do not bear a unique phenotype and/or specific cytokine secretion profile, thus opening questions on how a single T cell subset can exert opposite immunological tasks. In this study, we show that iNKT cells perform their dual roles through a single mechanism of action relying on the cognate interaction with myeloid dendritic cells (DCs) and leading to opposite effects depending on the presence of other maturation stimuli simultaneously acting on DCs. The contact of murine purified iNKT cells with immature autologous DCs directly triggers the tolerogenic maturation of DCs, rendering them able to induce regulatory T cell differentiation and prevent autoimmune diabetes in vivo. Conversely, the interaction of the same purified iNKT cells with DCs, in the presence of simultaneous TLR4 stimulation, significantly enhances proinflammatory DC maturation and IL-12 secretion. The different iNKT cell effects are mediated through distinct mechanisms and activation of different molecular pathways within the DC: CD1d signaling and activation of the ERK1/2 pathway for the tolerogenic action, and CD40-CD40L interaction and NF-κB activation for the adjuvant effect. Our data suggest that the DC decision to undergo proinflammatory or tolerogenic maturation results from the integration of different signals received at the time of iNKT cell contact and could have important therapeutic implications for exploiting iNKT cell adjuvant/regulatory properties in autoimmune diseases, infections, and cancer.

Detailed immunophenotyping of B-cell precursors in regenerating bone marrow of acute lymphoblastic leukaemia patients: implications for minimal residual disease detection.

PubMed

Theunissen, Prisca M J; Sedek, Lukasz; De Haas, Valerie; Szczepanski, Tomasz; Van Der Sluijs, Alita; Mejstrikova, Ester; Nováková, Michaela; Kalina, Tomas; Lecrevisse, Quentin; Orfao, Alberto; Lankester, Arjan C; van Dongen, Jacques J M; Van Der Velden, Vincent H J

2017-07-01

Flow cytometric detection of minimal residual disease (MRD) in children with B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) requires immunophenotypic discrimination between residual leukaemic cells and B-cell precursors (BCPs) which regenerate during therapy intervals. In this study, EuroFlow-based 8-colour flow cytometry and innovative analysis tools were used to first characterize the immunophenotypic maturation of normal BCPs in bone marrow (BM) from healthy children, resulting in a continuous multiparametric pathway including transition stages. This pathway was subsequently used as a reference to characterize the immunophenotypic maturation of regenerating BCPs in BM from children treated for BCP-ALL. We identified pre-B-I cells that expressed low or dim CD34 levels, in contrast to the classical CD34 high pre-B-I cell immunophenotype. These CD34 -dim pre-B-I cells were relatively abundant in regenerating BM (11-85% within pre-B-I subset), while hardly present in healthy control BM (9-13% within pre-B-I subset; P = 0·0037). Furthermore, we showed that some of the BCP-ALL diagnosis immunophenotypes (23%) overlapped with CD34 -dim pre-B-I cells. Our results indicate that newly identified CD34 -dim pre-B-I cells can be mistaken for residual BCP-ALL cells, potentially resulting in false-positive MRD outcomes. Therefore, regenerating BM, in which CD34 -dim pre-B-I cells are relatively abundant, should be used as reference frame in flow cytometric MRD measurements. © 2017 John Wiley & Sons Ltd.

Fetal cerebrovascular acclimatization responses to high-altitude, long-term hypoxia: a model for prenatal programming of adult disease?

PubMed

Longo, Lawrence D; Pearce, William J

2005-01-01

During the past several decades, many risk factors for cerebrovascular and cardiovascular disease have been identified. More recently, it has been appreciated that inadequate nutrition and/or other intrauterine factors during fetal development may play an important role in the genesis of these conditions. An additional stress factor that may "program" the fetus for disease later in life is chronic hypoxia. In studies originally designed to examine the function of developing cerebral arterial function in response to long-term hypoxia (LTH), it has become clear that many cellular and subcellular changes may have important implications for later life. Here we review some of the significant alterations in fetal cerebral artery structure and function induced by high-altitude (3,820 m, 12,470 ft) LTH ( approximately 110 days). LTH is associated with augmentation or upregulation of presynaptic functions, including responses to perivascular (i.e., sympathetic) nerve stimulation, and structural maturational changes. In contrast, many postsynaptic functions related to the Ca(2+)-dependent contractile pathway tend to be downregulated, whereas elements of the Ca(2+)-independent contraction pathway are upregulated. The results emphasize the role of high-altitude LTH in modulating many aspects of electromechanical and pharmacomechanical coupling in the developing cerebral vasculature. A complicating factor is that the regulation of cerebrovascular tone by Ca(2+)-dependent and Ca(2+)-independent pathways changes significantly as a function of maturational age. In addition to highlighting independent regulation of various elements of the signal transduction cascade, the studies demonstrate the potential for LTH to program the fetus for cerebrovascular and other disease as an adult.

Low level exposure to inorganic mercury interferes with B cell receptor signaling in transitional type 1 B cells.

PubMed

Gill, R; McCabe, M J; Rosenspire, A J

2017-09-01

Mercury (Hg) has been implicated as a factor contributing to autoimmune disease in animal models and humans. However the mechanism by which this occurs has remained elusive. Since the discovery of B cells it has been appreciated by immunologists that during the normal course of B cell development, some immature B cells must be generated that produce immunoglobulin reactive to self-antigens (auto-antibodies). However in the course of normal development, the vast majority of immature auto-reactive B cells are prevented from maturing by processes collectively known as tolerance. Autoimmune disease arises when these mechanisms of tolerance are disrupted. In the B cell compartment, it is firmly established that tolerance depends in part upon negative selection of self-reactive immature (transitional type 1) B cells. In these cells negative selection depends upon signals generated by the B Cell Receptor (BCR), in the sense that those T1 B cells who's BCRs most strongly bind to, and so generate the strongest signals to self-antigens are neutralized. In this report we have utilized multicolor phosphoflow cytometry to show that in immature T1 B cells Hg attenuates signal generation by the BCR through mechanisms that may involve Lyn, a key tyrosine kinase in the BCR signal transduction pathway. We suggest that exposure to low, environmentally relevant levels of Hg, disrupts tolerance by interfering with BCR signaling in immature B cells, potentially leading to the appearance of mature auto-reactive B cells which have the ability to contribute to auto-immune disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Anthropometric growth study of the ear in a Chinese population.

PubMed

Zhao, Shichun; Li, Dianguo; Liu, Zhenzhong; Wang, Yibiao; Liu, Lei; Jiang, Duyin; Pan, Bo

2018-04-01

A large number of anthropometric studies of the auricle have been reported in different nations, but little data were available in the Chinese population. The aim of this study was to analyze growth changes in the ear by measuring the width and length of ears in a Chinese population. A total of 480 participants were enrolled and classified into 1-, 3-, 5-, 7-, 9-, 12-, 14-, and 18-year groups (half were boys and half were girls in each group). Ear length, ear width, body weight, and body length were measured and recorded; ear index was calculated according to ear length and ear width. The growth of auricle and differences between genders were analyzed. Growth of ear in relation to body height and weight and the degree of emphasis on the length and width of the auricle were also analyzed. Ear length and width increased with age. Ear length achieved its mature size in both 14-year-old males and females. Ear width reached its mature size in males at 7 years and in females at 5 years. Different trends of ear index were shown between males and females. People in this population paid more attention to the length than the width of the auricle. The data indicated that ear development followed increase in age. There were gender and ethnic difference in the development of ear. These results may have potential implications for the diagnosis of congenital malformations, syndromes, and planning of ear reconstruction surgery. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca) with Time after Birth – Three Phases in Early Lactation and Progressive Individual Differences

PubMed Central

Zhang, Tong; Zhang, Rong; Zhang, Liang; Zhang, Zhihe; Hou, Rong; Wang, Hairui; Loeffler, I. Kati; Watson, David G.; Kennedy, Malcolm W.

2015-01-01

Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1–6 (Phase 1), days 7–20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth. PMID:26630345

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

Burwood, R.; Fortems, G.; Mycke, B.

Deposited under lacustrine conditions during the rift-phase opening of the southern Atlantic, the lower Congo Bucomazi Formation is a highly productive source rock sequence. Reaching considerable thickness (1.8 km), a heterogeneous organofacies reflects both rapid accumulation and changing conditions during Early Cretaceous Barremian sedimentation. As a component of organofacies, low resolution studies showed kerogen kinetic parameters (Ea/A) varied widely according to the gross paleoenvironmental conditions prevailing during deposition. As a a general trend, refractory (type I, higher Ea) kerogens of the [open quotes]basin fill[close quotes] Organic Rich Zone (ORZ) give way to more labile (type II, lower Ea) assemblages inmore » the up-section [open quotes]sheet drape[close quotes] sediments. At higher resolution, a considerable fine structure in Ea fluctuation, presumably reflecting micropaleoenvironment control, becomes evident. Using Ea values assembled for the Bucomazi type section, subsidence modeling for a Ponta Vermelha depocenter section showed a wide disparity in behavior. Being more representative of the sheet-drape episode, type II assemblages matured earlier, at lesser overburdens, and provided the initial hydrocarbon charge. For the ORZ assemblages, the dominant type I component was of retarded maturation, only becoming productive at commensurately greater overburdens. Cumulatively, these events merge to provide an extended period of hydrocarbon generation with implications for production of aggregate oils of varied emplacement histories. Significantly, the net effect of the observed Ea contrast results in the less prolific (but more labile) uppermost Bucomazi assuming a more important charging role than the ORZ of superior source richness. The latter can only realize its full potential under the greatest overburdens attainable in the most subsident depocenters.« less

In-cell NMR reveals potential precursor of toxic species from SOD1 fALS mutants

NASA Astrophysics Data System (ADS)

Luchinat, Enrico; Barbieri, Letizia; Rubino, Jeffrey T.; Kozyreva, Tatiana; Cantini, Francesca; Banci, Lucia

2014-11-01

Mutations in the superoxide dismutase 1 (SOD1) gene are related to familial cases of amyotrophic lateral sclerosis (fALS). Here we exploit in-cell NMR to characterize the protein folding and maturation of a series of fALS-linked SOD1 mutants in human cells and to obtain insight into their behaviour in the cellular context, at the molecular level. The effect of various mutations on SOD1 maturation are investigated by changing the availability of metal ions in the cells, and by coexpressing the copper chaperone for SOD1, hCCS. We observe for most of the mutants the occurrence of an unstructured SOD1 species, unable to bind zinc. This species may be a common precursor of potentially toxic oligomeric species, that are associated with fALS. Coexpression of hCCS in the presence of copper restores the correct maturation of the SOD1 mutants and prevents the formation of the unstructured species, confirming that hCCS also acts as a molecular chaperone.

Chemical profile of mango (Mangifera indica L.) using electrospray ionisation mass spectrometry (ESI-MS).

PubMed

Oliveira, Bruno G; Costa, Helber B; Ventura, José A; Kondratyuk, Tamara P; Barroso, Maria E S; Correia, Radigya M; Pimentel, Elisângela F; Pinto, Fernanda E; Endringer, Denise C; Romão, Wanderson

2016-08-01

Mangifera indica L., mango fruit, is consumed as a dietary supplement with purported health benefits; it is widely used in the food industry. Herein, the chemical profile of the Ubá mango at four distinct maturation stages was evaluated during the process of growth and maturity using negative-ion mode electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry (ESI(-)FT-ICR MS) and physicochemical characterisation analysis (total titratable acidity (TA), total soluble solids (TSS), TSS/TA ratio, and total polyphenolic content). Primary (organic acids and sugars) and secondary metabolites (polyphenolic compounds) were mostly identified in the third maturation stage, thus indicating the best stage for harvesting and consuming the fruit. In addition, the potential cancer chemoprevention of the secondary metabolites (phenolic extracts obtained from mango samples) was evaluated using the induction of quinone reductase activity, concluding that fruit polyphenols have the potential for cancer chemoprevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reversal of hippocampal neuronal maturation by serotonergic antidepressants

PubMed Central

Kobayashi, Katsunori; Ikeda, Yumiko; Sakai, Atsushi; Yamasaki, Nobuyuki; Haneda, Eisuke; Miyakawa, Tsuyoshi; Suzuki, Hidenori

2010-01-01

Serotonergic antidepressant drugs have been commonly used to treat mood and anxiety disorders, and increasing evidence suggests potential use of these drugs beyond current antidepressant therapeutics. Facilitation of adult neurogenesis in the hippocampal dentate gyrus has been suggested to be a candidate mechanism of action of antidepressant drugs, but this mechanism may be only one of the broad effects of antidepressants. Here we show a distinct unique action of the serotonergic antidepressant fluoxetine in transforming the phenotype of mature dentate granule cells. Chronic treatments of adult mice with fluoxetine strongly reduced expression of the mature granule cell marker calbindin. The fluoxetine treatment induced active somatic membrane properties resembling immature granule cells and markedly reduced synaptic facilitation that characterizes the mature dentate-to-CA3 signal transmission. These changes cannot be explained simply by an increase in newly generated immature neurons, but best characterized as “dematuration” of mature granule cells. This granule cell dematuration developed along with increases in the efficacy of serotonin in 5-HT4 receptor-dependent neuromodulation and was attenuated in mice lacking the 5-HT4 receptor. Our results suggest that serotonergic antidepressants can reverse the established state of neuronal maturation in the adult hippocampus, and up-regulation of 5-HT4 receptor-mediated signaling may play a critical role in this distinct action of antidepressants. Such reversal of neuronal maturation could affect proper functioning of the mature hippocampal circuit, but may also cause some beneficial effects by reinstating neuronal functions that are lost during development. PMID:20404165

New method for evaluation of cervical vertebral maturation based on angular measurements.

PubMed

Alhadlaq, Adel M; Al-Shayea, Eman I

2013-04-01

To investigate the validity of a new approach to assess the cervical vertebral maturation based on angular measurements of the lower border concavity of cervical vertebral bodies. Hand-wrist and lateral cephalometric radiographs of 197 male subjects with age range of 10-15 years attending the orthodontic clinic at King Saud University, Riyadh, Kingdom of Saudi Arabia were utilized. The study was carried out between September 2009 and May 2011. The study sample was divided into 6 groups (group 1: 10 years to group 6: 15 years) based on the chronological age of the subject. The skeletal age of the subjects was determined using Greulich and Pyle's standard radiographic atlas, and skeletal maturation was assessed by Fishman's skeletal maturity indicators. The cervical vertebral maturation (CVM) of subjects was determined using angular measurements of the second, third, and fourth cervical vertebral bodies. The validity of the newly developed method was assessed by examining the correlation between CVM stages determined by the angular measurements and the skeletal maturation level as determined by the standard hand-wrist methods. A significant correlation (r=0.94) was found between the angular CVM stages and the skeletal age determined by Greulich and Pyle's atlas from hand-wrist radiographs. Also, a high correlation (r=0.94) was found between the angular CVM stages and the Fishman's hand-wrist skeletal maturity indicators. The new angular measurement approach to determine CVM is valid and has the potential to be applied in assessing skeletal maturity level in growing male children.

Contributions of Function-Altering Variants in Genes Implicated in Pubertal Timing and Body Mass for Self-Limited Delayed Puberty.

PubMed

Howard, Sasha R; Guasti, Leonardo; Poliandri, Ariel; David, Alessia; Cabrera, Claudia P; Barnes, Michael R; Wehkalampi, Karoliina; O'Rahilly, Stephen; Aiken, Catherine E; Coll, Anthony P; Ma, Marcella; Rimmington, Debra; Yeo, Giles S H; Dunkel, Leo

2018-02-01

Self-limited delayed puberty (DP) is often associated with a delay in physical maturation, but although highly heritable the causal genetic factors remain elusive. Genome-wide association studies of the timing of puberty have identified multiple loci for age at menarche in females and voice break in males, particularly in pathways controlling energy balance. We sought to assess the contribution of rare variants in such genes to the phenotype of familial DP. We performed whole-exome sequencing in 67 pedigrees (125 individuals with DP and 35 unaffected controls) from our unique cohort of familial self-limited DP. Using a whole-exome sequencing filtering pipeline one candidate gene [fat mass and obesity-associated gene (FTO)] was identified. In silico, in vitro, and mouse model studies were performed to investigate the pathogenicity of FTO variants and timing of puberty in FTO+/- mice. We identified potentially pathogenic, rare variants in genes in linkage disequilibrium with genome-wide association studies of age at menarche loci in 283 genes. Of these, five genes were implicated in the control of body mass. After filtering for segregation with trait, one candidate, FTO, was retained. Two FTO variants, found in 14 affected individuals from three families, were also associated with leanness in these patients with DP. One variant (p.Leu44Val) demonstrated altered demethylation activity of the mutant protein in vitro. Fto+/- mice displayed a significantly delayed timing of pubertal onset (P < 0.05). Mutations in genes implicated in body mass and timing of puberty in the general population may contribute to the pathogenesis of self-limited DP. Copyright © 2017 Endocrine Society

Applications of psychophysical models to the study of auditory development

NASA Astrophysics Data System (ADS)

Werner, Lynne

2003-04-01

Psychophysical models of listening, such as the energy detector model, have provided a framework from which to characterize the function of the mature auditory system and to explore how mature listeners make use of auditory information in sound identification. The application of such models to the study of auditory development has similarly provided insight into the characteristics of infant hearing and listening. Infants intensity, frequency, temporal and spatial resolution have been described at least grossly and some contributions of immature listening strategies to infant hearing have been identified. Infants psychoacoustic performance is typically poorer than adults under identical stimulus conditions. However, the infant's performance typically varies with stimulus condition in a way that is qualitatively similar to the adult's performance. In some cases, though, infants perform in a qualitatively different way from adults in psychoacoustic experiments. Further, recent psychoacoustic studies of children suggest that the classic models of listening may be inadequate to describe the children's performance. The characteristics of a model that might be appropriate for the immature listener will be outlined and the implications for models of mature listening will be discussed. [Work supported by NIH grants DC00396 and by DC04661.

Endoplasmic Reticulum Stress Induces Myostatin High Molecular Weight Aggregates and Impairs Mature Myostatin Secretion.

PubMed

Sachdev, Rishibha; Kappes-Horn, Karin; Paulsen, Lydia; Duernberger, Yvonne; Pleschka, Catharina; Denner, Philip; Kundu, Bishwajit; Reimann, Jens; Vorberg, Ina

2018-03-15

Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disorder in the elderly with no defined etiology or effective therapy. Endoplasmic reticulum stress and deposition of myostatin, a secreted negative regulator of muscle growth, have been implicated in disease pathology. The myostatin signaling pathway has emerged as a major target for symptomatic treatment of muscle atrophy. Here, we systematically analyzed the maturation and secretion of myostatin precursor MstnPP and its metabolites in a human muscle cell line. We find that increased MsntPP protein levels induce ER stress. MstnPP metabolites were predominantly retained within the endoplasmic reticulum (ER), also evident in sIBM histology. MstnPP cleavage products formed insoluble high molecular weight aggregates, a process that was aggravated by experimental ER stress. Importantly, ER stress also impaired secretion of mature myostatin. Reduced secretion and aggregation of MstnPP metabolites were not simply caused by overexpression, as both events were also observed in wildtype cells under ER stress. It is tempting to speculate that reduced circulating myostatin growth factor could be one explanation for the poor clinical efficacy of drugs targeting the myostatin pathway in sIBM.

Preformation in vegetative buds of pistachio (Pistacia vera): relationship to shoot morphology, crown structure and rootstock vigor.

PubMed

Spann, Timothy M; Beede, Robert H; Dejong, Theodore M

2007-08-01

Effects of rootstock, shoot carbohydrate status, crop load and crown position on the number of preformed leaf primordia in the dormant terminal and lateral buds of mature and immature 'Kerman' pistachio (Pistacia vera L.) trees were investigated to determine if rootstock vigor is associated with greater shoot preformation. There was no significant variation in preformation related to the factors studied, suggesting strong genetic control of preformation in 'Kerman' pistachio. The growth differences observed among trees on different rootstocks were associated with greater stimulation of neoformed growth in trees on the more vigorous rootstocks. However, most annual extension growth in mature tree crowns was preformed, contrasting with the relatively high rate of neoformation found in young tree crowns. Large amounts of neoformed growth in young trees may allow the trees to become established quickly and secure resources, whereas predominantly preformed growth in mature trees may allow for continued crown expansion without outgrowing available resources. We hypothesized that the stimulation of neoformed growth by the more vigorous rootstocks is associated with greater resource uptake or transport, or both. Understanding the source of variation in shoot extension growth on different rootstocks has important implications for orchard management practices.

Human face processing is tuned to sexual age preferences.

PubMed

Ponseti, J; Granert, O; van Eimeren, T; Jansen, O; Wolff, S; Beier, K; Deuschl, G; Bosinski, H; Siebner, H

2014-05-01

Human faces can motivate nurturing behaviour or sexual behaviour when adults see a child or an adult face, respectively. This suggests that face processing is tuned to detecting age cues of sexual maturity to stimulate the appropriate reproductive behaviour: either caretaking or mating. In paedophilia, sexual attraction is directed to sexually immature children. Therefore, we hypothesized that brain networks that normally are tuned to mature faces of the preferred gender show an abnormal tuning to sexual immature faces in paedophilia. Here, we use functional magnetic resonance imaging (fMRI) to test directly for the existence of a network which is tuned to face cues of sexual maturity. During fMRI, participants sexually attracted to either adults or children were exposed to various face images. In individuals attracted to adults, adult faces activated several brain regions significantly more than child faces. These brain regions comprised areas known to be implicated in face processing, and sexual processing, including occipital areas, the ventrolateral prefrontal cortex and, subcortically, the putamen and nucleus caudatus. The same regions were activated in paedophiles, but with a reversed preferential response pattern. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Harnessing Sphingosine-1-Phosphate Signaling and Nanotopographical Cues To Regulate Skeletal Muscle Maturation and Vascularization.

PubMed

Tsui, Jonathan H; Janebodin, Kajohnkiart; Ieronimakis, Nicholas; Yama, David M P; Yang, Hee Seok; Chavanachat, Rakchanok; Hays, Aislinn L; Lee, Haeshin; Reyes, Morayma; Kim, Deok-Ho

2017-12-26

Despite possessing substantial regenerative capacity, skeletal muscle can suffer from loss of function due to catastrophic traumatic injury or degenerative disease. In such cases, engineered tissue grafts hold the potential to restore function and improve patient quality of life. Requirements for successful integration of engineered tissue grafts with the host musculature include cell alignment that mimics host tissue architecture and directional functionality, as well as vascularization to ensure tissue survival. Here, we have developed biomimetic nanopatterned poly(lactic-co-glycolic acid) substrates conjugated with sphingosine-1-phosphate (S1P), a potent angiogenic and myogenic factor, to enhance myoblast and endothelial maturation. Primary muscle cells cultured on these functionalized S1P nanopatterned substrates developed a highly aligned and elongated morphology and exhibited higher expression levels of myosin heavy chain, in addition to genes characteristic of mature skeletal muscle. We also found that S1P enhanced angiogenic potential in these cultures, as evidenced by elevated expression of endothelial-related genes. Computational analyses of live-cell videos showed a significantly improved functionality of tissues cultured on S1P-functionalized nanopatterns as indicated by greater myotube contraction displacements and velocities. In summary, our study demonstrates that biomimetic nanotopography and S1P can be combined to synergistically regulate the maturation and vascularization of engineered skeletal muscles.

Influence of age, body weight and body condition score before mating start date on the pubertal rate of maiden Holstein-Friesian heifers and implications for subsequent cow performance and profitability.

PubMed

Archbold, H; Shalloo, L; Kennedy, E; Pierce, K M; Buckley, F

2012-07-01

The aim of this study was to assess the influence of age, body weight (BW) and body condition score (BCS) of maiden Holstein-Friesian heifers before mating start date (MSD) on the rate of puberty, subsequent production and longevity and their implications with regard to farm profitability. Data were available on 871 Holstein-Friesian heifers from 48 herds. BW was recorded electronically and BCS was recorded by a single operator on a scale of 1 to 5. Heifer age was calculated as the number of days from birth to the day of visit. All of the independent variables of interest were grouped into three or four categories. Three age categories (thirtiles), four BW categories (quartiles) and four BCS categories (≤ 2.75, 3.00, 3.25 and ≥ 3.50) were formed. Heifers with an identifiable corpus lutuem (CL) in the presence or absence of large follicles and peri-ovulatory signs and with a plasma progesterone (P4) concentration ≥ 1 ng/ml were classified as pubertal. In addition, heifers without an identifiable CL in the presence or absence of large follicles and peri-ovulatory signs but with a P4 concentration ≥ 1 ng/ml were also classified as pubertal. Age, BW and BCS at MSD were all found to be significantly associated with pubertal rate (P < 0.05). Age was shown to have no practical implications on subsequent cow performance. BW at MSD was favourably associated with subsequent calving date (P < 0.05), subsequent cow BW (P < 0.001) and potential (305 days) milk fat plus protein yield (P < 0.001). BCS at MSD was found to be favourably associated with milk fat plus protein yield potential (P < 0.05) and BCS (P < 0.001) during lactation. The economic analysis undertaken indicated that larger, well-grown heifers will be more profitable because of superior production potential, all else being equal. However, because of the finding of poorer reproductive efficiency in heifers grown to more than 343 kg at MSD, heifers at ∼330 kg at MSD are deemed optimal. This will correspond to mature cow BW of ∼550 kg.

Magnetic Field Applications in Semiconductor Crystal Growth and Metallurgy

NASA Technical Reports Server (NTRS)

Mazuruk, Konstantin; Ramachandran, Narayanan; Grugel, Richard; Curreri, Peter A. (Technical Monitor)

2002-01-01

The Traveling Magnetic Field (TMF) technique, recently proposed to control meridional flow in electrically conducting melts, is reviewed. In particular, the natural convection damping capability of this technique has been numerically demonstrated with the implication of significantly improving crystal quality. Advantages of the traveling magnetic field, in comparison to the more mature rotating magnetic field method, are discussed. Finally, results of experiments with mixing metallic alloys in long ampoules using TMF is presented

I've Got the Music in Me: A Study of Peak Musical Memory Age and the Implications for Future Advertising

ERIC Educational Resources Information Center

Gerlich, R. Nicholas; Browning, Leigh; Westermann, Lori

2010-01-01

Neuropsychologists have demonstrated the effect music has on the human brain, and that a peak "musical memory age" occurs around 14, when normal bodily maturation is in progress. A group of 114 college students between the ages of 19 and 25 was exposed to short clips of the top 20 songs from each of the 11 years during their youth;…

CAN WE COMPETE?--The Implications of the Proposed Revised New Jersey Statewide Testing Program for Vocational Students.

ERIC Educational Resources Information Center

Merkel-Keller, Claudia

The State of New Jersey has proposed moving its competency test of basic skills from the 9th to the 11th grade, in order to allow for more content learning, more maturity, and more test-taking skills on the part of students. Since vocational students are more likely than other students to score low on the basic skills competency test, having the…

Fatty Acid β-Oxidation Is Essential in Leptin-Mediated Oocytes Maturation of Yellow Catfish Pelteobagrus fulvidraco.

PubMed

Song, Yu-Feng; Tan, Xiao-Ying; Pan, Ya-Xiong; Zhang, Li-Han; Chen, Qi-Liang

2018-05-14

Although several studies have been conducted to study leptin function, information is very scarce on the molecular mechanism of leptin in fatty acid β-oxidation and oocytes maturation in fish. In this study, we investigated the potential role of fatty acid β-oxidation in leptin-mediated oocytes maturation in Pelteobagrus fulvidraco . Exp. 1 investigated the transcriptomic profiles of ovary and the differential expression of genes involved in β-oxidation and oocytes maturation following rt-hLEP injection; rt-hLEP injection was associated with significant changes in the expression of genes, including twenty-five up-regulated genes ( CPT1 , Acsl , Acadl , Acadm , Hadhb , Echsl , Hsd17b4 , Acca , PPARα , CYP8B1 , ACOX1 , ACBP , MAPK , RINGO , Cdc2 , MEK1 , IGF-1R , APC/C, Cdk2 , GnRHR, STAG3 , SMC1 , FSHβ and C-Myc ) and ten down-regulated gene ( PPARγ , FATCD36 , UBC , PDK1 , Acads , Raf , Fizzy , C3H-4 , Raf and PKC ), involved in fatty acid β-oxidation and oocytes maturation. In Exp. 2, rt-hLEP and specific inhibitors AG490 (JAK-STAT inhibitor) were used to explore whether leptin induced oocytes maturation, and found that leptin incubation increased the diameters of oocytes and percentage of germinal vesicle breakdown (GVBD)-MII oocytes, up-regulated mRNA levels of genes involved in oocytes maturation and that leptin-induced oocyte maturation was related to activation of JAK-STAT pathway. In Exp. 3, primary oocytes of P. fulvidraco were treated with (R)-(+)-etomoxir (an inhibitor of β-oxidation) or l-carnitine (an enhancer of β-oxidation) for 48 h under rt-hLEP incubation. Exp. 3 indicated that the inhibition of fatty acid β-oxidation resulted in the down-regulation of gene expression involved in oocytes maturation, and repressed the leptin-induced up-regulation of these gene expression. Activation of fatty acid β-oxidation improved the maturation rate and mean diameter of oocytes, and up-regulated gene expression involved in oocytes maturation. Leptin is one of the main factors that links fatty acid β-oxidation with oocyte maturation; β-oxidation is essential for leptin-mediated oocyte maturation in fish.

Deforestation for oil palm alters the fundamental balance of the soil N cycle

NASA Astrophysics Data System (ADS)

Hamilton, Liz; Trimmer, Mark; Bradley, Chris; Pinay, Gilles

2016-04-01

Expansion of commercial agriculture in equatorial regions has significant implications for regional nitrogen (N) budgets, particularly nitrous oxide (N2O) and nitric oxide (NO) emissions, produced largely by microbial nitrification and denitrification. However, current estimates of soil N turnover are poorly constrained in Southeast Asia for nitrogen gas (N2) production and lesser known N transformations such as nitrate ammonification (DNRA) and anaerobic ammonium oxidation (anammox). We investigated changes in N availability and turnover following replacement of tropical forest with oil palm plantations along a chronosequence of oil palm maturity (3-months to 15-year-old stands) and secondary to primary forest succession in Sabah, Malaysian Borneo. Samples were taken from ten sites during March and April 2012. Using 15N tracing techniques, we measured rates of gross ammonium (NH4+) and nitrate (NO3-) production (mineralisation and nitrification) and consumption (n= 8), potential denitrification, DNRA and anammox (n= 12) in soil cores and slurries respectively. Gross mineralisation rates (0.05 - 3.08 g N m-2 d-1) remained unchanged in oil palm relative to forests. However, a significant reduction in gross nitrification (0.04 - 2.31 g N m-2 d-1) and an increase in NH4+ immobilisation disrupt the pathway to N2 production substantially reducing (by > 90%) rates of denitrification and anammox in recently planted oil palm relative to primary forest. In forests, N2 produced via anammox was ˜30% of that from denitrification highlighting the potential for anammox to contribute significantly to N2 production. NH4+ production rates from DNRA were over two orders of magnitude less than N2 production rates indicating that denitrification is the primary dissimilatory nitrate consumption process in these soils. Potential N2O emissions were greater than potential N2 production, remaining unchanged across the chronosequence and indicating an increased N2O:N2 emission ratio when soils were first disturbed. These results are an important precursor to studies providing improved estimates of regional N turnover and loss in Southeast Asia which will have global implications for N biogeochemical cycling.

The maturity index as a tool to facilitate the interpretation of changes in vitellogenin production and sex ratio in the Fish Sexual Development Test.

PubMed

Baumann, Lisa; Holbech, Henrik; Keiter, Susanne; Kinnberg, Karin Lund; Knörr, Susanne; Nagel, Tina; Braunbeck, Thomas

2013-03-15

In July 2011, the Fish Sexual Development Test (FSDT) has officially been adopted as OECD test guideline 234 for the detection of endocrine disrupting chemicals (EDCs). Sex ratio and vitellogenin (VTG) induction are the mandatory endocrine endpoints within this test, whereas gonad staging is only included as an option. In the present study, five FSDTs with zebrafish (Danio rerio) were conducted with EDCs with different modes of action (17α-ethinylestradiol, dihydrotestosterone, 17β-trenbolone, prochloraz and 4-tert-pentylphenol). Results document that not only sex ratio and VTG production of the exposed fish were massively affected, but also gonad maturation. As a novel approach for the quantification of gonad maturation in zebrafish, the maturity index was developed to allow not only an improved assessment of dose-dependent EDC-related effects on gonad maturation, but also statistical analysis of histological data. VTG induction and maturity index showed an excellent correlation for all five EDCs tested. Most importantly, the maturity index often helped to find appropriate interpretations for results that seemed contradictory at first sight. Results show that histological analyses and their predictive power for population fitness are currently underestimated and should become a standard component in the evaluation of potential EDCs. Copyright © 2012 Elsevier B.V. All rights reserved.

The immunoglobulin family member dendrite arborization and synapse maturation 1 (Dasm1) controls excitatory synapse maturation

PubMed Central

Shi, Song-Hai; Cheng, Tong; Jan, Lily Yeh; Jan, Yuh-Nung

2004-01-01

In the developing mammalian brain, a large fraction of excitatory synapses initially contain only N-methyl-d-aspartate receptor and thus are “silent” at the resting membrane potential. As development progresses, synapses acquire α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-Rs). Although this maturation of excitatory synapses has been well characterized, the molecular basis for this developmental change is not known. Here, we report that dendrite arborization and synapse maturation 1 (Dasm1), an Ig superfamily member, controls excitatory synapse maturation. Dasm1 is localized at the excitatory synapses. Suppression of Dasm1 expression by using RNA interference or expression of dominant negative deletion mutants of Dasm1 in hippocampal neurons at late developmental stage specifically impairs AMPA-R-mediated, but not N-methyl-d-aspartate receptor-mediated, synaptic transmission. The ability of Dasm1 to regulate synaptic AMPA-Rs requires its intracellular C-terminal PDZ domain-binding motif, which interacts with two synaptic PDZ domain-containing proteins involved in spine/synapse maturation, Shank and S-SCAM. Moreover, expression of dominant negative deletion mutants of Dasm1 leads to more immature silent synapses. These results suggest that Dasm1, as a transmembrane molecule, likely provides a link to bridge extracellular signals and intracellular signaling complexes in controlling excitatory synapse maturation. PMID:15340156

A positive correlation between serum levels of mature brain-derived neurotrophic factor and negative symptoms in schizophrenia.

PubMed

Niitsu, Tomihisa; Ishima, Tamaki; Yoshida, Taisuke; Hashimoto, Tasuku; Matsuzawa, Daisuke; Shirayama, Yukihiko; Nakazato, Michiko; Shimizu, Eiji; Hashimoto, Kenji; Iyo, Masaomi

2014-02-28

A meta-analysis study reported serum brain-derived neurotrophic factor (BDNF) levels as a potential biomarker for schizophrenia. However, at the time, commercially available human ELISA kits were unable to distinguish between pro-BDNF (precursor BDNF) and mature BDNF, because of limited antibody specificity. Here, we used new ELISA kits, to examine serum levels of mature BDNF and matrix metalloproteinase-9 (MMP-9), which converts pro-BDNF to mature BDNF in schizophrenia. Sixty-three patients with chronic schizophrenia and 52 age- and sex-matched healthy controls were enrolled. Patients were evaluated using the Brief Psychiatry Rating Scale, the Scale for the Assessment of Negative Symptoms (SANS) and neuropsychological tests. Neither serum mature BDNF nor MMP-9 levels differed between patients and controls. In male subgroups, serum MMP-9 levels of smoking patients were higher than those of non-smoking patients, but this was not observed in male controls or the female subgroup. In patients, serum mature BDNF levels were associated with SANS total scores and the Information subtest scores of the Wechsler Adult Intelligence Scale Revised (WAIS-R), while serum MMP-9 levels were associated with smoking and category fluency scores. These findings suggest that neither mature BDNF nor MMP-9 is a suitable biomarker for schizophrenia, although further studies using large samples are needed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Insight into phagocytosis of mature sexual (gametocyte) stages of Plasmodium falciparum using a human monocyte cell line.

PubMed

Bansal, Geetha P; Weinstein, Corey S; Kumar, Nirbhay

2016-05-01

During natural infection malaria parasites are injected into the bloodstream of a human host by the bite of an infected female Anopheles mosquito. Both asexual and mature sexual stages of Plasmodium circulate in the blood. Asexual forms are responsible for clinical malaria while sexual stages are responsible for continued transmission via the mosquitoes. Immune responses generated against various life cycle stages of the parasite have important roles in resistance to malaria and in reducing malaria transmission. Phagocytosis of free merozoites and erythrocytic asexual stages has been well studied, but very little is known about similar phagocytic clearance of mature sexual stages, which are critical for transmission. We evaluated phagocytic uptake of mature sexual (gametocyte) stage parasites by a human monocyte cell line in the absence of immune sera. We found that intact mature stages do not undergo phagocytosis, unless they are either killed or freed from erythrocytes. In view of this observation, we propose that the inability of mature gametocytes to be phagocytized may actually result in malaria transmission advantage. On the other hand, mature gametocytes that are not transmitted to mosquitoes during infection will eventually die and undergo phagocytosis, initiating immune responses that may have transmission blocking potential. A better understanding of early phagocytic clearance and immune responses to gametocytes may identify additional targets for transmission blocking strategies. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuropsychological assessment of executive functions following pediatric traumatic brain injury.

PubMed

Gaines, K Drorit; Soper, Henry V

2018-01-01

Assessment of executive functions in the adult is best captured at the stage where full maturation of brain development occurs. Assessment of executive functions of children, however, is considerably more complicated. First, assessment of executive functioning in children represents a snapshot of these developing functions at a particular time linked stage, which may have implications for further development. Second, neuropsychological measures available to assess executive functions in children are limited in number and scope and may not be sensitive to the gradual developmental changes. The present article provides an overview of the salient neurodevelopmental stages of executive functioning and discusses the utilization of recently developed neuropsychological measures to assess these stages. Comments on clinical implications of these findings regarding Traumatic Brain Injury will be provided.

Recent advances in lineage differentiation from stem cells: hurdles and opportunities?

PubMed Central

Terryn, Joke; Tricot, Tine; Gajjar, Madhavsai; Verfaillie, Catherine

2018-01-01

Pluripotent stem cells have the property of long-term self-renewal and the potential to give rise to descendants of the three germ layers and hence all mature cells in the human body. Therefore, they hold the promise of offering insight not only into human development but also for human disease modeling and regenerative medicine. However, the generation of mature differentiated cells that closely resemble their in vivo counterparts remains challenging. Recent advances in single-cell transcriptomics and computational modeling of gene regulatory networks are revealing a better understanding of lineage commitment and are driving modern genome editing approaches. Additional modification of the chemical microenvironment, as well as the use of bioengineering tools to recreate the cellular, extracellular matrix, and physical characteristics of the niche wherein progenitors and mature cells reside, is now being used to further improve the maturation and functionality of stem cell progeny. PMID:29552337

Length oscillation induces force potentiation in infant guinea pig airway smooth muscle.

PubMed

Wang, Lu; Chitano, Pasquale; Murphy, Thomas M

2005-12-01

Deep inspiration counteracts bronchospasm in normal subjects but triggers further bronchoconstriction in hyperresponsive airways. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in force-generating ability of airway smooth muscle after mechanical oscillation. It is known that healthy immature airways of both humans and animals exhibit hyperresponsiveness. We hypothesize that the profile of active force generation after mechanical oscillation changes with maturation and that this change contributes to the expression of airway hyperresponsiveness in juveniles. We examined the effect of an acute sinusoidal length oscillation on the force-generating ability of tracheal smooth muscle from 1 wk, 3 wk, and 2- to 3-mo-old guinea pigs. We found that the length oscillation produced 15-20% initial reduction in active force equally in all age groups. This was followed by a force recovery profile that displayed striking maturation-specific features. Unique to tracheal strips from 1-wk-old animals, active force potentiated beyond the maximal force generated before oscillation. We also found that actin polymerization was required in force recovery and that prostanoids contributed to the maturation-specific force potentiation in immature airway smooth muscle. Our results suggest a potentiated mechanosensitive contractile property of hyperresponsive airway smooth muscle. This can account for further bronchoconstriction triggered by deep inspiration in hyperresponsive airways.

Dynamic distribution of spindlin in nucleoli, nucleoplasm and spindle from primary oocytes to mature eggs and its critical function for oocyte-to-embryo transition in gibel carp.

PubMed

Sun, Min; Li, Zhi; Gui, Jian-Fang

2010-10-01

Spindlin (Spin) was thought as a maternal-effect factor associated with meiotic spindle. Its role for the oocyte-to-embryo transition was suggested in mouse, but its direct evidence for the function had been not obtained in other vertebrates. In this study, we used the CagSpin-specific antibody to investigate CagSpin expression pattern and distribution during oogenesis of gibel carp (Carassius auratus gibelio). First, the oocyte-specific expression pattern and dynamic distribution was revealed in nucleoli, nucleoplasm, and spindle from primary oocytes to mature eggs by immunofluorescence localization. In primary oocytes and growth stage oocytes, CagSpin accumulates in nucleoli in increasing numbers along with the oocyte growth, and its disassembly occurs in vitellogenic oocytes, which implicates that CagSpin may be a major component of a large number of nucleoli in fish growth oocytes. Then, co-localization of CagSpin and β-tubulin was revealed in meiotic spindle of mature egg, indicating that CagSpin is one spindle-associated factor. Moreover, microinjection of CagSpin-specific antibody into the fertilized eggs blocked the first cleavage, and found that the CagSpin depletion resulted in spindle assembly disturbance. Thereby, our study provided the first direct evidence for the critical oocyte-to-embryo transition function of Spin in vertebrates, and confirmed that Spin is one important maternal-effect factor that participates in oocyte growth, oocyte maturation, and oocyte-to-embryo transition.

THE INFLUENCE OF SEX AND MATURATION ON LANDING BIOMECHANICS: IMPLICATIONS FOR ACL INJURY

PubMed Central

Sigward, S. M.; Pollard, C. D.; Powers, C. M.

2010-01-01

During landing and cutting, females exhibit greater frontal plane moments at the knee (internal knee adductor moments or external knee abduction moments) and favor use of the knee extensors over the hip extensors to attenuate impact forces when compared to males. However, it is not known when this biomechanical profile emerges. The purpose of this study was to compare landing biomechanics between sexes across maturation levels. One hundred and nineteen male and female soccer players (9–22 years) participated. Subjects were grouped based on maturational development. Lower extremity kinematics and kinetics were obtained during a drop-land task. Dependent variables included the average internal knee adductor moment and sagittal plane knee/hip moment and energy absorption ratios during the deceleration phase of landing. When averaged across maturation levels, females demonstrated greater internal knee adductor moments (0.06±0.03 vs. 0.01±0.02 Nm/kg*m; P<0.005), knee/hip extensor moment ratios (2.0±0.1 vs. 1.4±0.1 Nm/kg*m; P<0.001), and knee/hip energy absorption ratios (2.9±0.1 vs. 1.96±0.1 Nm/kg*m; P<0.001) compared to males. Higher knee adductor moments combined with disproportionate use of knee extensors relative to hip extensors observed in females reflects a biomechanical pattern that increases ACL loading. This biomechanical strategy already was established in pre-pubertal female athletes. PMID:21210853