Neocortical areas communicate through extensive axonal projections, but the logic of information transfer remains poorly understood, because the projections of individual neurons have not been ...systematically characterized. It is not known whether individual neurons send projections only to single cortical areas or distribute signals across multiple targets. Here we determine the projection patterns of 591 individual neurons in the mouse primary visual cortex using whole-brain fluorescence-based axonal tracing and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq). Projections were highly diverse and divergent, collectively targeting at least 18 cortical and subcortical areas. Most neurons targeted multiple cortical areas, often in non-random combinations, suggesting that sub-classes of intracortical projection neurons exist. Our results indicate that the dominant mode of intracortical information transfer is not based on 'one neuron-one target area' mapping. Instead, signals carried by individual cortical neurons are shared across subsets of target areas, and thus concurrently contribute to multiple functional pathways.
Platelets are classically known as essential mediators of hemostasis and thrombosis. However, in recent years, platelets have gained recognition for their inflammatory functions, which modulate the ...immune response during infectious diseases. Platelets contain various immunoreceptors that enable them to act as sentinels to recognize intravascular pathogens. Upon activation, platelets directly limit pathogen growth through the release of AMPs (antimicrobial proteins) and ensure pathogen clearance through activation of immune cells. However, aberrant platelet activation can lead to inflammation and thrombotic events.
•We conduct a choice experiment for conventional- and electric-bike bikeshare in Beijing.•Novel experiment method allows significant mode inertia variable in mode choice model.•E-bikeshare draws ...users from “sheltered” modes more than bikeshare.•E-bikeshare use is less sensitive to longer distances, worse air quality, and bad weather.•E-bikeshare competes with transit, but also draws from automobile modes.
China leads the world in both public bikeshare and private electric bike (e-bike) growth. Current trajectories indicate the viability of deploying large-scale shared e-bike (e-bikeshare) systems in China. We employ a stated preference survey and multinomial logit to model the factors influencing the choice to switch from an existing transportation mode to bikeshare or e-bikeshare in Beijing. Demand is influenced by distinct sets of factors: the bikeshare choice is most sensitive to measures of effort and comfort while the e-bikeshare choice is more sensitive to user heterogeneities. Bikeshare demand is strongly negatively impacted by trip distance, temperature, precipitation, and poor air quality. User demographics however do not factor strongly on the bikeshare choice, indicating the mode will draw users from across the social spectrum. The e-bikeshare choice is much more tolerant of trip distance, high temperatures and poor air quality, though precipitation is also a highly negative factor. User demographics do play a significant role in e-bikeshare demand. Analysis of impact to the existing transportation system finds that both bikeshare and e-bikeshare will tend to draw users away from the “unsheltered modes”, walk, bike, and e-bike. Although it is unclear if shared bikes are an attractive “first-and-last-mile solution”, it is clear that e-bikeshare is attractive as a bus replacement.
Introduction Adverse childhood experiences (ACEs) are associated with early mortality and morbidity. This study evaluated the association among ACEs, high-risk health behaviors, and comorbid ...conditions, as well as the independent effect of ACE components. Methods Data were analyzed on 48,526 U.S. adults from five states in the 2011 Behavioral Risk Factor Surveillance System survey. Exposures included psychological, physical, and sexual forms of abuse as well as household dysfunction such as substance abuse, mental illness, violence, and incarceration. Main outcome measures included risky behaviors and morbidity measures, including binge drinking, heavy drinking, current smoking, high-risk HIV behavior, obesity, diabetes, myocardial infarction, coronary heart disease, stroke, depression, disability caused by poor health, and use of special equipment because of disability. Multiple logistic regression assessed the independent relationship between ACE score categories and risky behaviors/comorbidities in adulthood, and assessed the independent relationship between individual ACE components and risky behaviors/comorbid conditions in adulthood controlling for covariates. Results A total of 55.4% of respondents reported at least one ACE and 13.7% reported four or more ACEs. An ACE score ≥4 was associated with increased odds for binge drinking, heavy drinking, smoking, risky HIV behavior, diabetes, myocardial infarction, coronary heart disease, stroke, depression, disability caused by health, and use of special equipment because of disability. In addition, the individual components had different effects on risky behavior and comorbidities. Conclusions In addition to having a cumulative effect, individual ACE components have differential relationships with risky behaviors, morbidity, and disability in adulthood after controlling for important confounders.
Early Career Researchers Embrace Data Sharing Campbell, Hamish A.; Micheli-Campbell, Mariana A.; Udyawer, Vinay
Trends in ecology & evolution (Amsterdam),
February 2019, 2019-02-00, 20190201, Letnik:
34, Številka:
2
Journal Article
Recenzirano
A request for raw data from the corresponding authors of 771 animal biotelemetry-focused manuscripts, published between 1995 and 2015, highlighted a difference in data sharing practices across ...researcher career levels. Responses were positive in only 11% of requests made to corresponding authors (CAs) that were senior researchers, while 72% of responses were positive when CAs were early career researchers (ECRs), demonstrating that the majority of senior researchers perceived little benefit from the public data archiving of their published research, while they often remain the data custodian.
There are currently no disease-modifying therapies for the treatment of tauopathies, a group of progressive neurodegenerative disorders that are pathologically defined by the presence of tau protein ...aggregates in the brain. Current challenges for the treatment of tauopathies include the inability to diagnose early and to confidently discriminate between distinct tauopathies in patients, alongside an incomplete understanding of the cellular mechanisms involved in pathogenic tau-induced neuronal death and dysfunction. In this review, we describe current diagnostic and therapeutic strategies, known drivers of pathogenic tau formation, recent contributions to our current mechanistic understanding of how pathogenic tau induces neuronal death, and potential diagnostic and therapeutic approaches.
Injury induces retinal Müller glia of certain cold-blooded vertebrates, but not those of mammals, to regenerate neurons. To identify gene regulatory networks that reprogram Müller glia into ...progenitor cells, we profiled changes in gene expression and chromatin accessibility in Müller glia from zebrafish, chick, and mice in response to different stimuli. We identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, reactivity, and neurogenesis. In zebrafish and chick, the transition from quiescence to reactivity is essential for retinal regeneration, whereas in mice, a dedicated network suppresses neurogenic competence and restores quiescence. Disruption of nuclear factor I transcription factors, which maintain and restore quiescence, induces Müller glia to proliferate and generate neurons in adult mice after injury. These findings may aid in designing therapies to restore retinal neurons lost to degenerative diseases.
RNA viruses can exchange genetic material during coinfection, an interaction that creates novel strains with implications for viral evolution and public health. Influenza A viral genetic exchange can ...occur when genome segments from distinct strains reassort in coinfected cells. Predicting potential genomic reassortment between influenza strains has been a long-standing goal. Experimental coinfection studies have shed light on factors that limit or promote reassortment. However, determining the reassortment potential between diverse Influenza A strains has remained elusive. To address this challenge, we developed a high throughput genotyping approach to quantify reassortment among a diverse panel of human influenza virus strains encompassing two pandemics (swine and avian origin), three specific epidemics, and both circulating human subtypes A/H1N1 and A/H3N2. We found that reassortment frequency (the proportion of reassortants generated) is an emergent property of specific pairs of strains where strain identity is a predictor of reassortment frequency. We detect little evidence that antigenic subtype drives reassortment as intersubtype (H1N1xH3N2) and intrasubtype reassortment frequencies were, on average, similar. Instead, our data suggest that certain strains bias the reassortment frequency up or down, independently of the coinfecting partner. We observe that viral productivity is also an emergent property of coinfections, but uncorrelated to reassortment frequency; thus viral productivity is a separate factor affecting the total number of reassortants produced. Assortment of individual segments among progeny and pairwise segment combinations within progeny generally favored homologous combinations. These outcomes were not related to strain similarity or shared subtype but reassortment frequency was closely correlated to the proportion of both unique genotypes and of progeny with heterologous pairwise segment combinations. We provide experimental evidence that viral genetic exchange is potentially an individual social trait subject to natural selection, which implies the propensity for reassortment is not evenly shared among strains. This study highlights the need for research incorporating diverse strains to discover the traits that shift the reassortment potential to realize the goal of predicting influenza virus evolution resulting from segment exchange.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Autism spectrum disorder (ASD) is defined by hallmark behaviors involving reduced communication and social interaction as well as repetitive activities and restricted interests. ASD represents a ...broad spectrum, from minimally affected individuals to those requiring intense support, with additional manifestations often including anxiety, irritability/aggression and altered sensory processing. Gastrointestinal (GI) issues are also common in ASD, and studies have identified changes in the gut microbiome of individuals with ASD compared to control populations, complementing recent findings of differences in gut-derived metabolites in feces and circulation. However, a role for the GI tract or microbiome in ASD remains controversial. Here we report that an oral GI-restricted adsorbent (AB-2004) that has affinity for small aromatic or phenolic molecules relieves anxiety-like behaviors that are driven by a gut microbial metabolite in mice. Accordingly, a pilot human study was designed and completed to evaluate the safety of AB-2004 in an open-label, single-cohort, multiple-ascending-dose clinical trial that enrolled 30 adolescents with ASD and GI symptoms in New Zealand and Australia. AB-2004 was shown to have good safety and tolerability across all dose levels, and no drug-related serious adverse events were identified. Significant reductions in specific urinary and plasma levels of gut bacterial metabolites were observed between baseline and end of AB-2004 treatment, demonstrating likely target engagement. Furthermore, we observed improvements in multiple exploratory behavioral endpoints, most significantly in post hoc analysis of anxiety and irritability, as well as GI health, after 8 weeks of treatment. These results from an open-label study (trial registration no. ACTRN12618001956291) suggest that targeting gut-derived metabolites with an oral adsorbent is a safe and well-tolerated approach to improving symptoms associated with ASD, thereby emboldening larger placebo-controlled trials.
Light-sheet microscopy is an ideal technique for imaging large cleared samples; however, the community is still lacking instruments capable of producing volumetric images of centimeter-sized cleared ...samples with near-isotropic resolution within minutes. Here, we introduce the mesoscale selective plane-illumination microscopy initiative, an open-hardware project for building and operating a light-sheet microscope that addresses these challenges and is compatible with any type of cleared or expanded sample ( www.mesospim.org ).
PDF
