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Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis.

Background Habitual high-intensity endurance exercise is associated with increased atrial fibrillation (AF) risk and impaired cardiac conduction. It is unknown whether these observations extend to prior strength-type sports exposure. The primary aim of this study was to compare AF prevalence in former National Football League (NFL) athletes to population-based controls. The secondary aim was to characterize other conduction system parameters. Methods and Results This cross-sectional study compared former NFL athletes (n=460, age 56±12 years, black 47%) with population-based controls of similar age and racial composition from the cardiovascular cohort Dallas Heart Study-2 (n=925, age 54±9 years, black 53%). AF was present in 28 individuals (n=23 [5%] in the NFL group; n=5 [0.5%] in the control group). After controlling for other cardiovascular risk factors in multivariable regression analysis, former NFL participation remained associated with a 5.7 (95% CI: 2.1-15.9, P

Phagocytosis is required for a broad range of physiological functions, from pathogen defense to tissue homeostasis, but the mechanisms required for phagocytosis of diverse substrates remain incompletely understood. Here, we developed a rapid magnet-based phenotypic screening strategy, and performed eight genome-wide CRISPR screens in human cells to identify genes regulating phagocytosis of distinct substrates. After validating select hits in focused miniscreens, orthogonal assays and primary human macrophages, we show that (1) the previously uncharacterized gene NHLRC2 is a central player in phagocytosis, regulating RhoA-Rac1 signaling cascades that control actin polymerization and filopodia formation, (2) very-long-chain fatty acids are essential for efficient phagocytosis of certain substrates and (3) the previously uncharacterized Alzheimer's disease-associated gene TM2D3 can preferentially influence uptake of amyloid-β aggregates. These findings illuminate new regulators and core principles of phagocytosis, and more generally establish an efficient method for unbiased identification of cellular uptake mechanisms across diverse physiological and pathological contexts.

We explored the association between liver metastases, tumor CD8+ T-cell count, and response in patients with melanoma or lung cancer treated with the anti-PD-1 antibody, pembrolizumab. The melanoma discovery cohort was drawn from the phase I Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote 002, 006, and EAP trials and the non-small cell lung cancer (NSCLC) cohort from Keynote 001. Liver metastasis was associated with reduced response and shortened progression-free survival [PFS; objective response rate (ORR), 30.6%; median PFS, 5.1 months] compared with patients without liver metastasis (ORR, 56.3%; median PFS, 20.1 months) P ≤ 0.0001, and confirmed in the validation cohort (P = 0.0006). The presence of liver metastasis significantly increased the likelihood of progression (OR, 1.852; P < 0.0001). In a subset of biopsied patients (n = 62), liver metastasis was associated with reduced CD8+ T-cell density at the invasive tumor margin (liver metastasis+ group, n = 547 ± 164.8; liver metastasis- group, n = 1,441 ± 250.7; P < 0.016). A reduced response rate and shortened PFS was also observed in NSCLC patients with liver metastasis [median PFS, 1.8 months; 95% confidence interval (CI), 1.4-2.0], compared with those without liver metastasis (n = 119, median PFS, 4.0 months; 95% CI, 2.1-5.1), P = 0.0094. Thus, liver metastatic patients with melanoma or NSCLC that had been treated with pembrolizumab were associated with reduced responses and PFS, and liver metastases were associated with reduced marginal CD8+ T-cell infiltration, providing a potential mechanism for this outcome. Cancer Immunol Res; 5(5); 417-24. ©2017 AACR.

Health has become a key focus for scholarship within the geographies of gender and sexualities. This progress report offers a schematic overview of the multiple ways in which the study of health (and especially disease and the lack of good health) has been studied in relation to such geographies. It explores the multiple ways in which an understanding of place has been operationalised, considers the potential importance still for large-scale quantitative studies, and highlights the importance of studies of health for broader debates and interests within the discipline. This progress report then concludes with some questions for future scholarship. [ABSTRACT FROM AUTHOR]

The specific function of microglia, the tissue resident macrophages of the brain and spinal cord, has been difficult to ascertain because of a lack of tools to distinguish microglia from other immune cells, thereby limiting specific immunostaining, purification, and manipulation. Because of their unique developmental origins and predicted functions, the distinction of microglia from other myeloid cells is critically important for understanding brain development and disease; better tools would greatly facilitate studies of microglia function in the developing, adult, and injured CNS. Here, we identify transmembrane protein 119 (Tmem119), a cell-surface protein of unknown function, as a highly expressed microglia-specific marker in both mouse and human. We developed monoclonal antibodies to its intracellular and extracellular domains that enable the immunostaining of microglia in histological sections in healthy and diseased brains, as well as isolation of pure nonactivated microglia by FACS. Using our antibodies, we provide, to our knowledge, the first RNAseq profiles of highly pure mouse microglia during development and after an immune challenge. We used these to demonstrate that mouse microglia mature by the second postnatal week and to predict novel microglial functions. Together, we anticipate these resources will be valuable for the future study and understanding of microglia in health and disease.

This article examines the similarities and differences between the COVID-19 and AIDS pandemics, cautioning against oversimplification and emphasizing the role of social factors in understanding disease. It discusses the concept of "scientific hubris" and how it can overshadow the social aspects of pandemics. The article also explores the idea of societal attitudes shaping neglect and the value placed on certain lives. The authors stress the importance of considering social relations when studying pandemics and their impact on different groups. The report by Andrew Tucker and Gerry Kearns analyzes the impact of globalization on local communities, acknowledging both the economic benefits and cultural losses associated with it. It calls for policymakers to consider the social and cultural consequences of globalization and proposes strategies to mitigate negative effects. Overall, the report provides a balanced perspective on the complex nature of globalization and its implications for local communities. [Extracted from the article]

Documentary filmmakers are gradually embracing immersive media to create novel Virtual Reality Nonfiction (VRNF) content. Over the past twenty years initial experimentation in this new medium has brought forward numerous linearly structured 360° documentaries that maintain a close link to traditional documentary modes. More recently, we have observed a shift from the relatively passive 360° cinema towards more open-world, non-linear, game-like interactive experiences that challenge traditional definitions of the documentary genre. Volumetric world-building techniques provide nonfiction creators with additional tools that afford 'viewer-users' spatial and interactive agency, leading to a heightened autopoietic realisation of the storyworld. VRNF creators have the potential to allow their viewer-users enhanced control over framing, temporal ordering of the plot and spatial unfolding of the diegetic world, thus inviting them to become actual co-creators of a deeply personal and personalized experience. This article addresses how VRNF may go beyond the mere 'documentation' of people, places or past events that existed in a pre-filmic reality and provide viewer-users through augmented agency a unique present-tense autopoietic experience that pushes the boundaries of traditional 2D documentary. [ABSTRACT FROM AUTHOR]

War and asymmetrical conflicts are becoming increasingly prevalent in the modern world. Due to improvements in conflict medicine, survivable injuries are now more severe than they once were. Therefore, it is now more important than ever that there exist scientific and engineering methods for replicating wartime injuries in the context of the laboratory. We have developed one such method: a shock tube platform for testing ex vivo samples of the porcine respiratory system. Using this platform, we can, to some extent, simulate the pathophysiological consequences of blast lung. This is a condition commonly present in victims of explosive blasts, both those due to typical armaments and Improvised Explosive Devices (IEDs). Presented here are the results of experiments conducted using porcine bronchiole tissue as ex vivo organ cultures. Data presented show epithelial damage, consistent with known trauma-induced cell injury that can lead to acute respiratory distress syndrome (ARDS).

Our understanding of land‐based cool season temperature variability over the past millennium is limited by the relative lack of annually resolved temperature proxies, especially in the Southern Hemisphere. Here, we develop the first earlywood (EW) and latewood (LW) width chronologies from Australia based on the Tasmanian endemic conifer Athrotaxis selaginoides in the far southeast of Australia. We also develop total ring width (RW), EW and LW chronologies from a new site in the far south. We compare the climate responses of RW, EW and adjusted LW chronologies of three A. selagnoides sites near the southern extent of the species with three sites of the species near the northern extent of the species. RW and EW at the southern sites are strongly and positively related to cool season temperature (July–October), but in the north, RW and EW are more strongly and positively related with summer (December–February) temperatures. Once adjusted for the influence of the same growing season EW, LW in the north is very strongly negatively correlated with January–February temperatures across southeastern Australia. The new southern RW and EW chronologies can be used to extend one of only two annually resolved regional cool season temperature reconstructions in the Southern Hemisphere back a further 180 years. [ABSTRACT FROM AUTHOR]

Geographers working on sexuality - and specifically of relevance to this report, scholars working on non-heternormative sexualities - have come to understand the need to engage with the urban South, culminating in acknowledgement of the benefits of engagements with Southern urbanism literature. I summarise how very recent sexualities scholarship is starting to signal direct connections with some of the broader interests of Southern urbanism. Such scholarship, I argue, has more in common with some of the empirical and theoretical interests of Southern urbanism than existing interests of the geographies of sexualities literature. I also consider how such emergent scholarship can potentially enrich interests of the geographies of sexualities literature in new and exciting ways. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to examine the impact of break duration between consecutive shifts, time of break onset, and prior shift duration on total sleep time (TST) between shifts in heavy vehicle drivers (HVDs), and to assess the interaction between break duration and time of break onset. The sleep (actigraphy and sleep diaries) and work shifts (work diaries) of 27 HVDs were monitored during their usual work schedule for up to 9 weeks. Differences in TST between consecutive shifts and days off were assessed. Linear mixed models (followed by pairwise comparisons) assessed whether break duration, prior shift duration, time of break onset, and the interaction between break duration and break onset were related to TST between shifts. Investigators found TST between consecutive shifts (mean [SD] 6.38 [1.38] h) was significantly less than on days off (mean [SD] 7.63 [1.93] h; p < 0.001). Breaks starting between 12:01 and 8:00 a.m. led to shorter sleep (p < 0.05) compared to breaks starting between 4:01 and 8:00 p.m. Break durations up to 7, 9, and 11 h (Australian and European minimum break durations) resulted in a mean (SD) of 4.76 (1.06), 5.66 (0.77), and 6.41 (1.06) h of sleep, respectively. The impact of shift duration prior to the break and the interaction between break duration and time of break were not significant. HVDs' sleep between workdays is influenced independently by break duration and time of break onset. This naturalistic study provides evidence that current break regulations prevent sufficient sleep duration in this industry. Work regulations should evaluate appropriate break durations and break onset times to allow longer sleep opportunities for HVDs. [ABSTRACT FROM AUTHOR]

Environmental DNA (eDNA) is useful for delimiting species ranges in aquatic systems, whereby water samples are screened for the presence of DNA from a single species. However, DNA from many species is collected in every sample, and high-throughput sequencing approaches allow for more passive surveillance where a community of species is identified. In this study, we use active (targeted) and passive molecular surveillance approaches to detect species in the Muskingum River Watershed in Ohio, USA. The presence of bighead carp (Hypophthalmichthys nobilis) eDNA in the Muskingum River Watershed was confirmed with active surveillance using digital droplet polymerase chain reaction (ddPCR). The passive surveillance method detected the presence of eDNA from northern snakehead (Channa argus), which was further confirmed with active ddPCR. Whereas active surveillance may be more sensitive to detecting rare DNA, passive surveillance has the capability of detecting unexpected invasive species. Deploying both active and passive surveillance approaches with the same eDNA samples is beneficial for invasive species management. L'ADN environnemental (ADNe) est utile pour delimiter les aires de repartition d'especes dans des systemes aquatiques en analysant des echantillons d'eau pour verifier la presence d'ADN d'especes precises. De l'ADN de nombreuses especes est toutefois preleve dans chaque echantillon et des approches de sequencage a haut debit permettent une plus grande surveillance passive dans les cas ou une communaute d'especes est identifiee. Nous utilisons des approches de surveillance moleculaire active (ciblee) et passive pour determiner si des especes sont presentes dans le bassin versant de la riviere Muskingum (Ohio, Etats-Unis). La presence d'ADNe de carpe a grosse tete (Hypophthalmichthys nobilis) dans ce bassin versant a ete confirmee par la surveillance active reposant sur la RCP numerique a gouttelettes (<< ddPCR >>). La methode de surveillance passive a permis de deceler la presence d'ADNe de poisson a tete de serpent du Nord (Channa argus), ce qui a ete corrobore par la methode active de ddPCR. Si la surveillance active peut s'averer plus sensible pour detecter des ADN rares, la surveillance passive peut quant a elle permettre de deceler la presence d'especes envahissantes non attendues. L'utilisation d'approches de surveillance active et passive pour les memes echantillons d'ADNe est une approche utile pour la gestion des especes envahissantes. [Traduit par la Redaction], Introduction Environmental DNA (eDNA) surveillance is a valuable tool used to screen for rare species, particularly in aquatic environments (Ficetola et al. 2008; Rees et al. 2014). It offers many [...]

Introduction: Nicotine dependence is one of the main causes of preventable diseases in the United States. Nicotine-seeking and avoidance behavioral assays in larval zebrafish could be used for identifying potential new pharmacotherapeutics in an early phase of drug discovery and could facilitate the identification of genes and genomic variations associated with nicotine-seeking and avoidance behavior. Methods: A new three-choice behavioral assay has been developed for the identification of nicotine-seeking and avoiding larval zebrafish. The three choices are represented by three compartments of a gradient maze. Video-recording and subsequent quantitative analysis of the swimming track was carried out using EthovisionXT (Noldus). Results: Three behavioral phenotypes could be identified. Nicotine-seeking larval zebrafish occupied nicotine compartments for longer periods and entered the nicotine-containing compartments most frequently. Nicotine-avoiders spent most of the cumulative time in the water compartment or entered the water compartment most frequently. Non-seekers remained in the center compartment for most of the time. In the gradient maze, about 20-30% of larval zebrafish had a preference for low nicotine concentrations whereas nicotine avoidance was stronger at higher nicotine concentrations. Lower concentrations of nicotine (0.63 µM, 6.3 µM) resulted in higher percentages of nicotine seekers whereas high nicotine concentrations (63 µM, 630 µM) resulted in higher percentages of nicotine avoiders. Pre-treatment of larval zebrafish with nicotine slightly increased the percentage of nicotine avoiders at lower nicotine concentrations. Treatment with varenicline strongly increased the percentage of nicotine avoiders at lower nicotine concentrations. Conclusion: The results show that larval zebrafish have individual preferences for nicotine that could change with drug treatment. The three-choice gradient maze assay for larval zebrafish provides a new testing paradigm for studying the molecular and cellular mechanisms of nicotine action and the discovery of potential new pharmacotherapeutics for the treatment of smoking cessation. [ABSTRACT FROM AUTHOR]