Vilstrupnance3292

Mole-rats are champions of self-preservation, with increased longevity compared to other rodents their size, strong antioxidant capabilities, and specialized defenses against endogenous oxidative stress. However, how the brains of these subterranean mammals handle acute in vivo hypoxia is poorly understood. This study is the first to examine the molecular response to low oxygen in six different species of hypoxia-tolerant mole-rats from sub-Saharan Africa. Protein carbonylation, a known marker of DNA damage (hydroxy-2'-deoxyguanosine), and antioxidant capacity did not change following hypoxia but HIF-1 protein levels increased significantly in the brains of two species. Nearly 30 miRNAs known to play roles in hypoxia-tolerance were differentially regulated in a species-specific manner. The miRNAs exhibiting the strongest response to low oxygen stress inhibit apoptosis and regulate neuroinflammation, likely providing neuroprotection. A principal component analysis using a subset of the molecular targets assessed herein revealed differences between control and hypoxic groups for two solitary species (Georychus capensis and Bathyergus suillus), which are ecologically adapted to a normoxic environment, suggesting a heightened sensitivity to hypoxia relative to species that may experience hypoxia more regularly in nature. By contrast, all molecular data were included in the PCA to detect a difference between control and hypoxic populations of eusocial Heterocephalus glaber, indicating they may require many lower-fold changes in signaling pathways to adapt to low oxygen settings. Finally, none of the Cryptomys hottentotus subspecies showed a statistical difference between control and hypoxic groups, presumably due to hypoxia-tolerance derived from environmental pressures associated with a subterranean and social lifestyle. © 2020. Published by The Company of Biologists Ltd.Knowledge of the diet of marine mammals is fundamental to understanding their role in marine ecosystems and response to environmental change. Recently, animal-borne video cameras have revealed the diet of marine mammals that make short foraging trips. However, novel approaches that allocate video time to target prey capture events is required to obtain diet information for species that make long foraging trips over great distances. We combined satellite telemetry and depth recorders with newly developed date-/time-, depth- and acceleration-triggered animal-borne video cameras to examine the diet of female northern elephant seals during their foraging migrations across the eastern North Pacific. We obtained 48.2 h of underwater video, from cameras mounted on the head (n=12) and jaw (n=3) of seals. Fish dominated the diet (78% of 697 prey items recorded) across all foraging locations (range 37-55°N, 122-152°W), diving depths (range 238-1167 m) and water temperatures (range 3.2-7.4°C), while squid comprised only 7% of the diet. Identified prey included fish such as myctophids, Merluccius sp. and Icosteus aenigmaticus, and squid such as Histioteuthis sp., Octopoteuthis sp. and Taningia danae Our results corroborate fatty acid analysis, which also found that fish are more important in the diet, and are in contrast to stomach content analyses that found cephalopods to be the most important component of the diet. Our work shows that in situ video observation is a useful method for studying the at-sea diet of long-ranging marine predators. © 2020. Published by The Company of Biologists Ltd.Whether individual results of genetic research studies ought to be disclosed to study participants has been debated in recent decades. Previously, the prevailing expert view discouraged the return of individual research results to participants because of the potential lack of analytic validity, questionable clinical validity and medical actionability, and questions about whether it is the role of research to provide participants with their data. With additional knowledge of participant perspectives and shifting views about the benefits of research and respect for participants, current expert consensus is moving toward support of returning such results. Significant ethical controversies remain, and there are many practical questions left to address, including appropriate procedures for returning results and the potential burden to clinicians when patients seek guidance about the clinical implications of research results. In this review, we describe current views regarding the return of genetic research results, including controversies and practical challenges, and consider the application of these issues to research on apolipoprotein L1 (APOL1), a gene recently associated with health disparities in kidney disease. Although this case is unique, it illustrates the complexities involved in returning results and highlights remaining questions. Copyright © 2020 by the American Society of Nephrology.The Gram-negative pathogen Neisseria gonorrhoeae (Gc) colonizes lysozyme-rich mucosal surfaces. Lysozyme hydrolyzes peptidoglycan, leading to bacterial lysis. Gc expresses two proteins, SliC and NgACP, that bind and inhibit the enzymatic activity of lysozyme. SliC is a surface-exposed lipoprotein, while NgACP is found in the periplasm and also released extracellularly. Purified SliC and NgACP similarly inhibit lysozyme. However, whereas mutation of ngACP increases Gc susceptibility to lysozyme, the sliC mutant is only susceptible to lysozyme when ngACP is inactivated. In this work, we examined how lipidation contributes to SliC expression, cellular localization, and resistance of Gc to killing by lysozyme. To do so, we mutated the conserved cysteine residue (C18) in the N-terminal lipobox motif of SliC, the site for lipid anchor attachment, to alanine. SliC (C18A) localized to soluble rather than membrane fractions in Gc and was not displayed on the bacterial surface. Less SliC (C18A) was detected in Gc lysatipidation was required for surface exposure of SliC, yet was dispensable for protecting the gonococcus from killing by lysozyme. To our knowledge, this is the first time the role of lipid anchoring of a lysozyme inhibitor has been investigated. These results help us understand how different lysozyme inhibitors are localized in bacteria and how this impacts resistance to lysozyme. Copyright © 2020 American Society for Microbiology.For high frequency transfer of pCF10 between E. faecalis cells, induced expression of the pCF10 genes encoding conjugative machinery from the prgQ operon is required. This process is initiated by the C inducer peptide produced by potential recipient cells. The expression timing of prgB, an "early" gene just downstream of the inducible promoter, has been studied extensively in single cells. However, several previous studies suggest that only 1-10% of donors induced for early prgQ gene expression actually transfer plasmids to recipients, even at very high recipient population density. One possible explanation for this is that only a minority of pheromone-induced donors actually transcribe the entire prgQ operon. Such cells would not be able to functionally conjugate but might play another role in the group behavior of donors. Here, we sought to (1) simultaneously assess the presence of RNAs produced from the proximal (early Q L ) and distal (late QL ) portions of the prgQ operon in individual cells; (2) investifer the plasmid. We examined whether induced cells might not be able to functionally conjugate due to premature induced transcript termination. read more Single cell analysis showed that most induced cells do, in fact, express all of the genes required for conjugation, suggesting that premature transcription termination within the prgQ operon does not account for failure of induced donor cell gene transfer. Copyright © 2020 American Society for Microbiology.We reported that the absence of a guanine oxidized (GO) system or the AP-endonucleases Nfo, ExoA and Nth promoted stress-associated mutagenesis (SAM) in B. subtilis YB955 (hisC952, metB5, leuc427). Moreover, MutY-promoted SAM was Mfd-dependent suggesting that transcriptional transactions over non-bulky DNA lesions promoted error-prone repair. Here, we inquired whether Mfd and GreA, which control transcription-coupled repair and transcription fidelity, influence the mutagenic events occurring in nutritionally stressed B. subtilis YB955 cells deficient for the guanine oxidized (GO) or the AP-endonuclease repair proteins. To this end, mfd and greA were disabled in genetic backgrounds defective in the GO and the AP-endonuclease repair proteins and tested for growth-associated and SAM. Results revealed that disruption of mfd or greA abrogated the production of SA amino acid revertants in the GO and nfo exoA nth strains, respectively. These results suggest that in nutritionally stressed B. subtilis cells, accumulatntain genome fidelity, under starving conditions, both factors promote error-prone repair to produce genetic diversity allowing B. subtilis to escape from growth-limiting conditions. Copyright © 2020 American Society for Microbiology.Salmonella enterica serovar Typhimurium colonizes and invades host intestinal epithelial cells using the Type Three Secretion System (T3SS) encoded on Salmonella Pathogenicity Island 1 (SPI1). The level of SPI1 T3SS gene expression is controlled by the transcriptional activator HilA, encoded on SPI1. Expression of hilA is positively regulated by three homologous transcriptional regulators, HilD, HilC and RtsA, belonging to the AraC/XylS family. These regulators also activate the hilD, hilC and rtsA genes by binding to the same DNA sequences upstream of these promoters, forming a complex feed-forward loop to control SPI1 expression. Despite the apparent redundancy in function, HilD has a unique role in SPI1 regulation because the majority of external regulatory inputs act exclusively through HilD. To better understand SPI1 regulation, the nature of interaction between HilD, HilC, and RtsA has been characterized using biochemical and genetic techniques. Our results showed that HilD, HilC, and RtsA can form hetet pathogen as well as general signal integration to control gene expression. Copyright © 2020 American Society for Microbiology.Chlamydiae lack the conserved central coordinator protein of cell division FtsZ, a tubulin-like homolog. Current evidence indicates Chlamydia uses the actin-like homolog, MreB, to substitute for the role of FtsZ in a polarized division mechanism. Interestingly, we observed MreB as a ring at the septum in dividing cells of Chlamydia We hypothesize that MreB, to substitute for FtsZ in Chlamydia, must possess unique properties compared to canonical MreB orthologs. Sequence differences between chlamydial MreB and orthologs in other bacteria revealed that chlamydial MreB possesses an extended N-terminal region, encoding predicted amphipathicity, as well as the conserved amphipathic helix found in other bacterial MreBs. The conserved amphipathic helix directed GFP to label the membrane uniformly in E. coli but the extended N-terminal region did not. However, the extended N-terminal region together with the conserved amphipathic region directed GFP to restrict the membrane label to the cell poles. In Chlamydia, the extended N-terminal region was sufficient to direct GFP to the membrane, and this localization was independent of an association with endogenous MreB.