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An Extended Culture System that Supports Human Primordial Germ Cell-like Cell Survival and Initiation of DNA Methylation Erasure.
The development of an in vitro system in which human primordial germ cell-like cells (hPGCLCs) are generated from human pluripotent stem cells (hPSCs) has been invaluable to further our understanding of human primordial germ cell (hPGC) specification. However, the means to evaluate the next fundamental steps in germ cell development have not been well established. In this study we describe a two dimensional extended culture system that promotes proliferation of specified hPGCLCs, without reversion to a pluripotent state. We demonstrate that hPGCLCs in extended culture undergo partial epigenetic reprogramming, mirroring events described in hPGCs in vivo, including a genome-wide reduction in DNA methylation and maintenance of depleted H3K9me2. This extended culture system provides a new approach for expanding the number of hPGCLCs for downstream technologies, including transplantation, molecular screening, or possibly the differentiation of hPGCLCs into gametes by in vitro gametogenesis
Experience-dependent plasticity in an innate social behavior is mediated by hypothalamic LTP
All animals can perform certain survival behaviors without prior experience, suggesting a âhard wiringâ of underlying neural circuits. Experience, however, can alter the expression of innate behaviors. Where in the brain and how such plasticity occurs remains largely unknown. Previous studies have established the phenomenon of âaggression training,â in which the repeated experience of winning successive aggressive encounters across multiple days leads to increased aggressiveness. Here, we show that this procedure also leads to long-term potentiation (LTP) at an excitatory synapse, derived from the posteromedial part of the amygdalohippocampal area (AHiPM), onto estrogen receptor 1-expressing (Esr1âș) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl). We demonstrate further that the optogenetic induction of such LTP in vivo facilitates, while optogenetic long-term depression (LTD) diminishes, the behavioral effect of aggression training, implying a causal role for potentiation at AHiPMâVMHvl^(Esr1) synapses in mediating the effect of this training. Interestingly, âŒ25% of inbred C57BL/6 mice fail to respond to aggression training. We show that these individual differences are correlated both with lower levels of testosterone, relative to mice that respond to such training, and with a failure to exhibit LTP after aggression training. Administration of exogenous testosterone to such nonaggressive mice restores both behavioral and physiological plasticity. Together, these findings reveal that LTP at a hypothalamic circuit node mediates a form of experience-dependent plasticity in an innate social behavior, and a potential hormone-dependent basis for individual differences in such plasticity among genetically identical mice
Experience-dependent plasticity in an innate social behavior is mediated by hypothalamic LTP
All animals can perform certain survival behaviors without prior experience, suggesting a âhard wiringâ of underlying neural circuits. Experience, however, can alter the expression of innate behaviors. Where in the brain and how such plasticity occurs remains largely unknown. Previous studies have established the phenomenon of âaggression training,â in which the repeated experience of winning successive aggressive encounters across multiple days leads to increased aggressiveness. Here, we show that this procedure also leads to long-term potentiation (LTP) at an excitatory synapse, derived from the posteromedial part of the amygdalohippocampal area (AHiPM), onto estrogen receptor 1-expressing (Esr1âș) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl). We demonstrate further that the optogenetic induction of such LTP in vivo facilitates, while optogenetic long-term depression (LTD) diminishes, the behavioral effect of aggression training, implying a causal role for potentiation at AHiPMâVMHvl^(Esr1) synapses in mediating the effect of this training. Interestingly, âŒ25% of inbred C57BL/6 mice fail to respond to aggression training. We show that these individual differences are correlated both with lower levels of testosterone, relative to mice that respond to such training, and with a failure to exhibit LTP after aggression training. Administration of exogenous testosterone to such nonaggressive mice restores both behavioral and physiological plasticity. Together, these findings reveal that LTP at a hypothalamic circuit node mediates a form of experience-dependent plasticity in an innate social behavior, and a potential hormone-dependent basis for individual differences in such plasticity among genetically identical mice
TMSB4Y is a Candidate Tumor Suppressor on the Y Chromosome and is Deleted in Male Breast Cancer.
Male breast cancer comprises less than 1% of breast cancer diagnoses. Although estrogen exposure has been causally linked to the development of female breast cancers, the etiology of male breast cancer is unclear. Here, we show via fluorescence in situ hybridization (FISH) and droplet digital PCR (ddPCR) that the Y chromosome was clonally lost at a frequency of ~16% (5/31) in two independent cohorts of male breast cancer patients. We also show somatic loss of the Y chromosome gene TMSB4Y in a male breast tumor, confirming prior reports of loss at this locus in male breast cancers. To further understand the function of TMSB4Y, we created inducible cell lines of TMSB4Y in the female human breast epithelial cell line MCF-10A. Expression of TMSB4Y resulted in aberrant cellular morphology and reduced cell proliferation, with a corresponding reduction in the fraction of metaphase cells. We further show that TMSB4Y interacts directly with ÎČ-actin, the main component of the actin cytoskeleton and a cell cycle modulator. Taken together, our results suggest that clonal loss of the Y chromosome may contribute to male breast carcinogenesis, and that the TMSB4Y gene has tumor suppressor properties
Respiratory Symptoms in Relation to Residential Coal Burning and Environmental Tobacco Smoke Among Early Adolescents in Wuhan, China: A Cross-Sectional Study
Background
Cigarette smoking and coal burning are the primary sources of indoor air pollution in Chinese households. However, effects of these exposures on Chinese children\u27s respiratory health are not well characterized. Methods
Seventh grade students (N = 5051) from 22 randomly selected schools in the greater metropolitan area of Wuhan, China, completed an in-class self-administered questionnaire on their respiratory health and home environment. Results
Coal burning for cooking and/or heating increased odds of wheezing with colds [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.07â2.29] and without colds (OR = 1.44, 95% CI: 1.05â1.97). For smoking in the home, the strongest associations were seen for cough (OR = 1.74, 95% CI: 1.17â2.60) and phlegm production (OR = 2.25, 95% CI: 1.36â3.72) without colds among children who lived with two or more smokers. Conclusions
Chinese children living with smokers or in coal-burning homes are at increased risk for respiratory impairment. While economic development in China may decrease coal burning by providing cleaner fuels for household energy use, the increasing prevalence of cigarette smoking is a growing public health concern due to its effects on children. Adverse effects of tobacco smoke exposure were seen despite the low rates of maternal smoking (3.6%) in this population
Self-Assembled Molecular-Electronic Films Controlled by Room Temperature Quantum Interference
If single-molecule, room-temperature, quantum interference (QI) effects could be translated into massively parallel arrays of molecules located between planar electrodes, QI-controlled molecular transistors would become available as building blocks for future electronic devices. Here, we demonstrate unequivocal signatures of room-temperature QI in vertical tunneling transistors, formed from self-assembled monolayers (SAMs), with stable room-temperature switching operations. As a result of constructive QI effects, the conductances of the junctions formed from anthanthrene-based molecules with two different connectivities differ by a factor of 34, which can further increase to 173 by controlling the molecule-electrode interface with different terminal groups. Field-effect control is achieved using an ionic liquid gate, whose strong vertical electric field penetrates through the graphene layer and tunes the energy levels of the SAMs. The resulting room-temperature on-off current ratio of the lowest-conductance SAMs can reach up to 306, about one order of magnitude higher than that of the highest-conductance SAMs
Modeling the Response of Cardiac Troponin C to Calcium on the Thin Filament: Effects of Disease-Related and Post-Translational Modifications
Mobile Service Clouds: A self-managing infrastructure for autonomic mobile computing services
Abstract. We recently introduced Service Clouds, a distributed infrastructure designed to facilitate rapid prototyping and deployment of autonomic communication services. In this paper, we propose a model that extends Service Clouds to the wireless edge of the Internet. This model, called Mobile Service Clouds, enables dynamic instantiation, composition, configuration, and reconfiguration of services on an overlay network to support mobile computing. We have implemented a prototype of this model and applied it to the problem of dynamically instantiating and migrating proxy services for mobile hosts. We conducted a case study involving data streaming across a combination of PlanetLab nodes, local proxies, and wireless hosts. Results are presented demonstrating the effectiveness of the prototype in establishing new proxies and migrating their functionality in response to node failures.
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