Vibrio parahaemolyticus is the leading cause of seafood-borne diarrheal diseases. Experimental overproduction of a type 3 secretion system (T3SS1) in this pathogen leads to decreased intestinal colonization, which suggests that T3SS1 repression is required for maximal virulence. However, the mechanisms by which T3SS1 is repressed in vivo are unclear. Here, we show that host-derived nitrite modifies the activity of a bacterial histidine kinase and mediates T3SS1 repression. More specifically, nitrite activates histidine kinase sensor VbrK through S-nitrosylation on cysteine 86, which results in downregulation of the entire T3SS1 operon through repression of its positive regulator exsC. Replacement of cysteine 86 with a serine (VbrK C86S mutant) leads to increased expression of inflammatory cytokines in infected Caco-2 cells. In an infant rabbit model of infection, the VbrK C86S mutant induces a stronger inflammatory response at the early stage of infection, and displays reduced intestinal colonization and virulence at the later stage of infection, in comparison with the parent strain. Our results indicate that the pathogen V. parahaemolyticus perceives nitrite as a host-derived signal and responds by downregulating a proinflammatory factor (T3SS1), thus enhancing intestinal colonization and virulence.Nuclear export complexes composed of rev response element (RRE) ribonucleic acid (RNA) and multiple molecules of rev protein are promising targets for the development of therapeutic strategies against human immunodeficiency virus type 1 (HIV-1), but their assembly remains poorly understood. Using native mass spectrometry, we show here that rev initially binds to the upper stem of RRE IIB, from where it is relayed to binding sites that allow for rev dimerization. The newly discovered binding region implies initial rev recognition by nucleotides that are not part of the internal loop of RRE stem IIB RNA, which was previously identified as the preferred binding region. Our study highlights the unique capability of native mass spectrometry to separately study the binding interfaces of RNA/protein complexes of different stoichiometry, and provides a detailed understanding of the mechanism of RRE/rev association with implications for the rational design of potential drugs against HIV-1 infection.Fluvial erosion is usually assumed to be absent on Venus, precluded by a high surface temperature of ~450 °C and supported by extensive uneroded volcanic flows. However, recent global circulation models suggest the possibility of Earth-like climatic conditions on Venus for much of its earlier history, prior to catastrophic runaway greenhouse warming. We observe that the stratigraphically oldest, geologically most complex units, tesserae, exhibit valley patterns morphologically similar to the patterns resulting from fluvial erosion on Earth. Given poor topographic resolution, we use an indirect technique to recognize valleys, based on the pattern of lava flooding of tesserae margins by adjacent plains volcanism. These observed valley patterns are attributed to primary geology, tectonic deformation, followed by fluvial erosion (and lesser wind erosion). This proposed fluvial erosion in tesserae provides support for climate models for a cool, wet climate on early Venus and could be an attractive research theme for future Venus missions.The inhibition of the PD1/PDL1 pathway has led to remarkable clinical success for cancer treatment in some patients. Many, however, exhibit little to no response to this treatment. To increase the efficacy of PD1 inhibition, additional checkpoint inhibitors are being explored as combination therapy options.  https://www.selleckchem.com/products/deg-35.html  TSR-042 and TSR-033 are novel antibodies for the inhibition of the PD1 and LAG3 pathways, respectively, and are intended for combination therapy. Here, we explore the effect on cellular interactions of TSR-042 and TSR-033 alone and in combination at the single-cell level. Utilizing our droplet microfluidic platform, we use time-lapse microscopy to observe the effects of these antibodies on calcium flux in CD8+ T cells upon antigen presentation, as well as their effect on the cytotoxic potential of CD8+ T cells on human breast cancer cells. This platform allowed us to investigate the interactions between these treatments and their impacts on T-cell activity in greater detail than previously applied in vitro tests. The novel parameters we were able to observe included effects on the exact time to target cell killing, contact times, and potential for serial-killing by CD8+ T cells. We found that inhibition of LAG3 with TSR-033 resulted in a significant increase in calcium fluctuations of CD8+ T cells in contact with dendritic cells. We also found that the combination of TSR-042 and TSR-033 appears to synergistically increase tumor cell killing and the single-cell level. This study provides a novel single-cell-based assessment of the impact these checkpoint inhibitors have on cellular interactions with CD8+ T cells.An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  Cross-sectional survey.
 
  Persons with disabilities are disproportionately impacted by extreme weather disasters and climate change. Individuals with spinal cord injury (SCI) are especially at risk due to inability to control their body temperature and mobility concerns. We surveyed rehabilitation professionals in the field of SCI to determine their experiences, concerns and educational needs regarding natural disasters, climate change and sustainability and the effects on their clientele.
 
  Online survey available to an international cohort.
 
  The survey was developed by the authors and conducted in 2019. It was distributed amongst various international health care organizations whose members care for persons with SCI. Descriptive statistics and chi-square test for association were performed using Microsoft Excel 2016.
 
  Of 125 respondents, 50% were from Europe, 18% from North America, and 18% from Asia; 74% were physicians and 13% physical therapists. In total 57.6% believed climate change had impacted their client's health and well-being.