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Simple Summary: Farmed Atlantic salmon are routinely exposed to bacterial pathogens, e.g., Piscirickettsia salmonis. Infection by Piscirickettsia sp. leads to a complex array of skin ulcers that can be difficult to treat and increases susceptibility to opportunistic infections. Evidence indicates that bacterial networks residing on salmon skin protect against developing ulcers by excluding pathogen colonization. A collapse of these beneficial interactions is thought to promote susceptibility to pathogen colonization during early stages of infection. We characterized the types and abundances of bacterial constituents on the skin of healthy Atlantic salmon compared with fish suffering from P. salmonis infection to test this hypothesis. The knowledge we gained can be used to optimize methods for early detection and prevention of skin ulcers by disrupting cooperative interactions between pathogenic bacteria. Maintaining the high overall health of farmed animals is a central tenant of their well-being and care. Intense animal crowding in aquaculture promotes animal morbidity especially in the absence of straightforward methods for monitoring their health. Here, we used bacterial 16S ribosomal RNA gene sequencing to measure bacterial population dynamics during P. salmonis infection. We observed a complex bacterial community consisting of a previously undescribed core pathobiome. Notably, we detected Aliivibrio wodanis and Tenacibaculum dicentrarchi on the skin ulcers of salmon infected with P. salmonis, while Vibrio spp. were enriched on infected gills. The prevalence of these co-occurring networks indicated that coinfection with other pathogens may enhance P. salmonis pathogenicity. [ABSTRACT FROM AUTHOR]

The pancreatic islets of Langerhans, mainly formed by glucagon‐producing α‐cells and insulin‐producing β‐cells, are critical for glucose homeostasis. Insulin and glucagon oppositely modulate blood glucose levels in health, but a combined decline in insulin secretion together with increased glucagon secretion contribute to hyperglycemia in diabetes. Despite this bi‐hormonal dysregulation, most studies have focused on insulin secretion and much less is known about glucagon secretion. Therefore, a deeper understanding of α‐cell metabolism and glucagon secretion is of great interest. Here, we show that phosphoenolpyruvate carboxykinase (PCK1), an essential cataplerotic enzyme involved in metabolism and long considered to be absent from the pancreatic islet, is expressed in pancreatic α‐cells of both murine and human. Furthermore, PCK1 transcription is induced by fasting and diabetes in rat pancreas, which indicates that the PCK1 activity is required for α‐cell adaptation to different metabolic states. To our knowledge, this is the first evidence implicating PCK1 expression in α‐cell metabolism. [ABSTRACT FROM AUTHOR]

We describe general methods to detect and quantify small numbers of specific molecules. We redirected self-splicing protein inteins to create 'tadpoles', chimeric molecules comprised of a protein head covalently coupled to an oligonucleotide tail. We made different classes of tadpoles that bind specific targets, including Bacillus anthracis protective antigen and the enzyme cofactor biotin. We measured the amount of bound target by quantifying DNA tails by T7 RNA polymerase runoff transcription and real-time polymerase chain reaction (PCR) evaluated by rigorous statistical methods. These assays had a dynamic range of detection of more than 11 orders of magnitude and distinguished numbers of molecules that differed by as little as 10%. At their low limit, these assays were used to detect as few as 6,400 protective antigen molecules, 600 biotin molecules and 150 biotinylated protein molecules. In crudely fractionated human serum, the assays were used to detect as few as 32,000 protective antigen molecules. Tadpoles thus enable sensitive detection and precise quantification of molecules other than DNA and RNA. [ABSTRACT FROM AUTHOR]

Patients present a wide range of clinical severities in response severe acute respiratory syndrome coronavirus 2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein-protein interaction analysis indicated that early-responding cytotoxic natural killer cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine-cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue., Competing Interests: MM, FF, CQ, FA, RR, MR, SB, YP, MC, IB, CK, RA, JG, MB No competing interests declared, (© 2024, Medina et al.)