Notes

Sleep quality and also cortical amyloid-β deposition throughout postmenopausal females in the Kronos earlier estrogen prevention review.
Bacteria generally live in species-rich communities, such as the gut microbiota. Yet little is known about bacterial evolution in natural ecosystems. Here, we followed the long-term evolution of commensal Escherichia coli in the mouse gut. We observe the emergence of mutation rate polymorphism, ranging from wild-type levels to 1,000-fold higher. By combining experiments, whole-genome sequencing, and in silico simulations, we identify the molecular causes and explore the evolutionary conditions allowing these hypermutators to emerge and coexist within the microbiota. The hypermutator phenotype is caused by mutations in DNA polymerase III proofreading and catalytic subunits, which increase mutation rate by approximately 1,000-fold and stabilise hypermutator fitness, respectively. Strong mutation rate variation persists for >1,000 generations, with coexistence between lineages carrying 4 to >600 mutations. The in vivo molecular evolution pattern is consistent with fitness effects of deleterious mutations sd ≤ 10istent with the pattern of genetic polymorphism that is emerging from metagenomics studies of the human gut microbiota, suggesting that we have identified key evolutionary processes shaping the genetic composition of this community.BACKGROUND Globally, few studies compare progress toward the Joint United Nations Program on HIV/AIDS (UNAIDS) Fast-Track targets among migrant populations. Fast-Track targets are aligned to the HIV diagnosis and care cascade and entail achieving 90-90-90 (90% of people living with HIV [PLHIV] diagnosed, 90% of those diagnosed on treatment, and 90% of those on treatment with viral suppression [VS]) by 2020 and 95-95-95 by 2030. We compared cascades between migrant and nonmigrant populations in Australia. METHODS AND FINDINGS We conducted a serial cross-sectional survey for HIV diagnosis and care cascades using modelling estimates for proportions diagnosed combined with a clinical database for proportions on treatment and VS between 2013-2017. We estimated the number of PLHIV and number diagnosed using New South Wales (NSW) and Victorian (VIC) data from the Australian National HIV Registry. Cascades were stratified by migration status, sex, HIV exposure, and eligibility for subsidised healthcare in Australia (opposed to using all individuals diagnosed to calculate the proportions on ART. CONCLUSIONS HIV diagnosis and care cascades improved overall between 2013 and 2017 in NSW and VIC. Cascades for migrants had larger gaps compared with nonmigrants, particularly among key migrant populations. Tracking subpopulation cascades enables gaps to be identified and addressed early to facilitate achievement of Fast-Track targets.Epithelial-to-mesenchymal transition (EMT) is a fundamental cellular process and plays an essential role in development, tissue regeneration, and cancer metastasis. Interestingly, EMT is not a binary process but instead proceeds with multiple partial intermediate states. However, the functions of these intermediate states are not fully understood. Here, we focus on a general question about how the number of partial EMT states affects cell transformation. First, by fitting a hidden Markov model of EMT with experimental data, we propose a statistical mechanism for EMT in which many unobservable microstates may exist within one of the observable macrostates. Furthermore, we find that increasing the number of intermediate states can accelerate the EMT process and that adding parallel paths or transition layers may accelerate the process even further. Last, a stabilized intermediate state traps cells in one partial EMT state. This work advances our understanding of the dynamics and functions of EMT plasticity during cancer metastasis.The global incidence of arboviral diseases transmitted by Aedes mosquitoes, including dengue, chikungunya, yellow fever, and Zika, has increased dramatically in recent decades. The release of Aedes aegypti carrying the maternally inherited symbiont Wolbachia as an intervention to control arboviruses is being trialled in several countries. However, these efforts are compromised in many endemic regions due to the co-localization of the secondary vector Aedes albopictus, the Asian tiger mosquito. Ae. albopictus has an expanding global distribution following incursions into a number of new territories. To date, only the wMel and wPip strains of Wolbachia have been reported to be transferred into and characterized in this vector. A Wolbachia strain naturally infecting Drosophila simulans, wAu, was selected for transfer into a Malaysian Ae. albopictus line to create a novel triple-strain infection. The newly generated line showed self-compatibility, moderate fitness cost and complete resistance to Zika and dengue infections.BACKGROUND As conscientious vaccination exemption (CVE) percentages rise across the United States, so does the risk and occurrence of outbreaks of vaccine-preventable diseases such as measles. In the state of Texas, the median CVE percentage across school systems more than doubled between 2012 and 2018. During this period, the proportion of schools surpassing a CVE percentage of 3% rose from 2% to 6% for public schools, 20% to 26% for private schools, and 17% to 22% for charter schools. The aim of this study was to investigate this phenomenon at a fine scale. METHODS AND FINDINGS Here, we use beta regression models to study the socioeconomic and geographic drivers of CVE trends in Texas. Using annual counts of CVEs at the school system level from the 2012-2013 to the 2017-2018 school year, we identified county-level predictors of median CVE percentage among public, private, and charter schools, the proportion of schools below a high-risk threshold for vaccination coverage, and five-year trends in CVEs. Since ve this risk threshold. The major limitations of this study are inconsistent school-system-level CVE reporting during the study period and a lack of geographic and socioeconomic data for individual private schools. CONCLUSIONS In this study, we have identified high-risk communities that are typically obscured in county-level risk assessments and found that public schools, like private schools, are exhibiting predictable increases in vaccination exemption percentages. As public health agencies confront the reemerging threat of measles and other vaccine-preventable diseases, findings such as ours can guide targeted interventions and surveillance within schools, cities, counties, and sociodemographic subgroups.Most modeling in systems neuroscience has been descriptive where neural representations such as 'receptive fields', have been found by statistically correlating neural activity to sensory input. In the traditional physics approach to modelling, hypotheses are represented by mechanistic models based on the underlying building blocks of the system, and candidate models are validated by comparing with experiments. Until now validation of mechanistic cortical network models has been based on comparison with neuronal spikes, found from the high-frequency part of extracellular electrical potentials. In this computational study we investigated to what extent the low-frequency part of the signal, the local field potential (LFP), can be used to validate and infer properties of mechanistic cortical network models. In particular, we asked the question whether the LFP can be used to accurately estimate synaptic connection weights in the underlying network. We considered the thoroughly analysed Brunel network comprising an excitatory and an inhibitory population of recurrently connected integrate-and-fire (LIF) neurons. This model exhibits a high diversity of spiking network dynamics depending on the values of only three network parameters. The LFP generated by the network was computed using a hybrid scheme where spikes computed from the point-neuron network were replayed on biophysically detailed multicompartmental neurons. We assessed how accurately the three model parameters could be estimated from power spectra of stationary 'background' LFP signals by application of convolutional neural nets (CNNs). All network parameters could be very accurately estimated, suggesting that LFPs indeed can be used for network model validation.The Hybrid Automata Library (HAL) is a Java Library developed for use in mathematical oncology modeling. It is made of simple, efficient, generic components that can be used to model complex spatial systems. HAL's components can broadly be classified into on- and off-lattice agent containers, finite difference diffusion fields, a GUI building system, and additional tools and utilities for computation and data collection. These components are designed to operate independently and are standardized to make them easy to interface with one another. As a demonstration of how modeling can be simplified using our approach, we have included a complete example of a hybrid model (a spatial model with interacting agent-based and PDE components). HAL is a useful asset for researchers who wish to build performant 1D, 2D and 3D hybrid models in Java, while not starting entirely from scratch. It is available on GitHub at https//github.com/MathOnco/HAL under the MIT License. HAL requires the Java JDK version 1.8 or later to compile and run the source code.BACKGROUND Osteosarcoma (OS) is the most prevalent malignant primary bone tumor, resulting from severe transformation of primitive mesenchymal cells, which induces osteogenesis. Long non-coding RNA (lncRNA) MSC-AS1 triggers osteogenic differentiation by sponging microRNA (miR)-140-5p. The present study assessed the mechanism of lncRNA MSC-AS1 in OS biological features and sensitivity to cisplatin (DDP) by binding to miR-142. MATERIAL AND METHODS Firstly, lncRNA MSC-AS1 expression in OS tissues and cells was analyzed. OS cells were transfected with silenced MSC-AS1 to determine its role in OS biological behaviors, and we also assessed the effect of MSC-AS1 on OS sensitivity to DDP. Then, website prediction and dual-luciferase reporter gene assay were utilized for verification of the binding site between MSC-AS1 and miR-142. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were performed to determine the effect of MSC-AS1 on expression of miR-142, cyclin-dependent kinase 6 (CDK6), and the PI3K/AKT signaling pathway. Xenograft transplantation was also applied to confirm the in vitro experiments. RESULTS Overexpressed MSC-AS1 was associated with poor prognosis of OS patients. OS cell proliferation, invasion, and migration were reduced after silencing MSC-AS1, while cell apoptosis was enhanced. Moreover, silencing MSC-AS1 made OS cells more sensitive to DDP. Interestingly, MSC-AS1 knockdown induced miR-142 expression and reduced CDK6 levels, thereby decreasing the protein expression of p-PI3K/t-PI3K and p-AKT/t-AKT. Silencing MSC-AS1 repressed OS progression in vivo. CONCLUSIONS Our study demonstrated that silencing MSC-AS1 inhibited OS biological behaviors by enhancing miR-142 to decrease CDK6 and inactivating the PI3K/AKT axis. Our results may provide new insights for OS treatment.Worldwide, cigarette smoking is a major cause of premature mortality and diseases that can be prevented. Given that people continue smoking despite the health risks, delivering nicotine without combustion should be considered a valuable and much less harmful way to reduce public health burden caused by smoking. E-cigarettes could play such a role if they are proved to be less harmful than combustible cigarettes. Although the number of clinical trials and human studies assessing safety of e-cigarettes is limited, numerous in vitro and in vivo studies reported the potential harmful effects of aerosol generated from e-cigarettes. This article reviews results of major clinical trials and laboratory studies with regard to cancer, cardiovascular and respiratory risk of e-cigarettes. Additionally, it also discusses the potential application of e-cigarettes as smoking cessation tools. Most studies so far indicated that e-cigarettes are less harmful, but this applies only to smokers who completely switched to e-cigarettes.
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