The voltage-gated sodium channel Na v 1.8 is known to function in the transmission of pain signals induced by cold, heat, and mechanical stimuli. Sequence variants of human Na v 1.8 have been linked to altered cardiac conduction. We identified an allele of Scn10a encoding the α-subunit of Na v 1.8 among mice homozygous for N -ethyl- N -nitrosourea-induced mutations. The allele creates a dominant neurobehavioral phenotype termed Possum , characterized by transient whole-body tonic immobility induced by pinching the skin at the back of the neck (“scruffing”). The Possum mutation enhanced Na v 1.8 sodium currents and neuronal excitability and heightened sensitivity of mutants to cold stimuli. Striking electroencephalographic changes were observed concomitant with the scruffing-induced behavioral change. In addition, electrocardiography demonstrated that Possum mice exhibited marked sinus bradycardia and R-R variability upon scruffing, abrogated by infusion of atropine. However, atropine failed to prevent or mitigate the tonic immobility response. Hyperactive sodium conduction via Na v 1.8 thus leads to a complex neurobehavioral phenotype, which resembles catatonia in schizophrenic humans and tonic immobility in other mammals upon application of a discrete stimulus; no other form of mechanosensory stimulus could induce the immobility phenotype. Our data confirm the involvement of Na v 1.8 in transducing pain initiated by cold and additionally implicate Na v 1.8 in previously unknown functions in the central nervous system and heart.

Motivation human microbes play a critical role in an extensive range of complex human diseases and become a new target in precision medicine. In silico methods of identifying microbe–disease associations not only can provide a deep insight into understanding the pathogenic mechanism of complex human diseases but also assist pharmacologists to screen candidate targets for drug development. However, the majority of existing approaches are based on linear models or label propagation, which suffers from limitations in capturing nonlinear associations between microbes and diseases. Besides, it is still a great challenge for most previous methods to make predictions for new diseases (or new microbes) with few or without any observed associations. Results in this work, we construct features for microbes and diseases by fully exploiting multiply sources of biomedical data, and then propose a novel deep learning framework of graph attention networks with inductive matrix completion for human microbe-disease association prediction, named GATMDA. To our knowledge, this is the first attempt to leverage graph attention networks for this important task. In particular, we develop an optimized graph attention network with talking-heads to learn representations for nodes (i.e. microbes and diseases). To focus on more important neighbours and filter out noises, we further design a bi-interaction aggregator to enforce representation aggregation of similar neighbours. In addition, we combine inductive matrix completion to reconstruct microbe-disease associations to capture the complicated associations between diseases and microbes. Comprehensive experiments on two data sets (i.e. HMDAD and Disbiome) demonstrated that our proposed model consistently outperformed baseline methods. Case studies on two diseases, i.e. asthma and inflammatory bowel disease, further confirmed the effectiveness of our proposed model of GATMDA. Availability python codes and data set are available at: https://github.com/yahuilong/GATMDA. Contact luojiawei@hnu.edu.cn.

We report a previously undescribed mechanism for the rugose morphotype in Shewanella oneidensis, a research model for investigating redox transformations of environmental contaminants. Bacteria may form smooth or rugose colonies on agar plates. In general, conversion from the smooth to rugose colony morphotype is attributed to increased production of exopolysaccharide (EPS). In this work, we discovered that aflagellate S. oneidensis mutants grew into rugose colonies, whereas those with nonfunctional flagellar filaments remained smooth. EPS production was not altered in either case, but mutants with the rugose morphotype showed significantly reduced exoprotein secretion. The idea that exoproteins at a reduced level correlate with rugosity gained support from smooth suppressor strains of an aflagellate rugose fliD (encoding the capping protein) mutant, which restored the exoprotein level to the levels of the wild-type and mutant strains with a smooth morphotype. Further analyses revealed that SO1072 (a putative GlcNAc-binding protein) was one of the highly upregulated exoproteins in these suppressor strains. Most intriguingly, this study identified a compensatory mechanism of SO1072 to flagellins possibly mediated by bis-(3=-5=)-cyclic dimeric GMP. Bacteria live in environments abundant with various disturbances. To elevate their ability to persist and survive, bacterial cells often form large assemblages (in multicellularity), which are advantageous in comparison with single cells (1). In the laboratory, the most common multicellular form is colonies resulting from growing populations on top of an agar surface. Depending on the strain and the surrounding conditions, the morphology of colonies (morphotype) varies substantially (2, 3). Colony morphotypes of well-studied bacteria, including Vibrio cholerae, Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium, Escherichia coli, and Bacillus subtilis, are either smooth or rugose (also called wrinkling), in general (4-10). The rugosity promotes persistence under unfavorable conditions, such as conditions of exposure to toxins, UV light, osmotic and oxidative stresses, low pH, low temperatures, and starvation (5,8,(11)(12)(13), and enhances virulence and transmission, such as adherence and invasion of epithelial cells (7,14,15).It is now well acknowledged that in most bacteria the rugosity is due to overproduction of exopolysaccharide (EPS) (2, 4, 9). Diverse genetic screens for genes essential for the rugose phenotype have identified many genes required for EPS synthesis, such as bcsABZC in Acetobacter xylinus, S. enterica serovar Typhimurium, and E. coli (10), pel in P. aeruginosa (16), vps in V. cholerae (17, 18), and eps in B. subtilis, to name a few (19,20). Additionally, extracellular structures such as curli fibers and flagella have been found to be important in determination of colony morphotypes. In S. enterica serovar Typhimurium and E. coli, the rugose morphotype appears only when curli fibers are abundant due to overexpression of CsgD (curli fibe...

The tribological performance of PA6 and carbon fiber reinforced polyamide 6 (CF/PA6) under dry sliding condition was examined. Different contents of carbon fibers were employed as reinforcement. All filled and unfilled polyamide 6 composites were tested against CGr15 ball and representative testing was performed. The effects of carbon fiber content on tribological properties of the composites were investigated. The worn surface morphologies of neat PA6 and its composites were examined by scanning electron microscopy and the wear mechanisms were discussed. Moreover, all filled polyamide 6 have superior tribological characteristics to unfilled polyamides 6. The optimum wear reduction was obtained when the content of carbon fiber is 20 vol%.

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