Defective brain hormonal signaling has been associated with Alzheimer’s disease (AD), a disorder characterized by synapse and memory failure. Irisin is an exercise-induced myokine released upon cleavage of membrane-bound precursor protein FNDC5, also expressed in the hippocampus. Here we show that FNDC5/irisin levels are reduced in AD hippocampi and cerebrospinal fluid, and in experimental AD models. Knockdown of brain FNDC5/irisin impaired long-term potentiation and novel object recognition memory in mice. Conversely, boosting brain levels of FNDC5/irisin rescued synaptic plasticity and memory in AD mouse models. Peripheral overexpression of FNDC5/irisin rescued memory impairment, whereas blockade of either peripheral or brain FNDC5/irisin attenuated the neuroprotective actions of physical exercise on synaptic plasticity and memory in AD mice. By showing that FNDC5/irisin is an important mediator of the beneficial effects of exercise in AD models, our findings place FNDC5/irisin as a novel agent capable of opposing synapse failure and memory impairment in AD.

Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer’s disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAβ initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aβ, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAβ levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAβ to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aβ on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aβ and tau pathology.

Multidrug-resistant (MDR) Salmonella enterica has been deemed a high-priority pathogen by the World Health Organization. Two hundred and sixty-four Salmonella enterica isolates recovered over a 16-year period (2000 to 2016) from the poultry and swine production chains, in Brazil, were investigated by whole-genome sequencing (WGS). Most international lineages belonging to 28 serovars, including, S . enterica serovars S . Schwarzengrund ST96, S . Typhimurium ST19, S . Minnesota ST548, S . Infantis ST32, S . Heidelberg ST15, S . Newport ST45, S . Brandenburg ST65 and S . Kentucky ST198 displayed MDR and virulent genetic backgrounds. In this regard, resistome analysis revealed presence of qnrE1 (identified for the first time in S . Typhimurium from food chain), qnrB19, qnrS1 , bla CTX-M-8 , bla CTX-M-2 and bla CMY-2 genes, as well as gyrA mutations; whereas ColpVC, IncHI2A, IncHI2, IncFIA, Incl1, IncA/C2, IncR, IncX1 and po111 plasmids were detected. In addition, phylogenetic analysis revealed multiple independent lineages such as S . enterica serovars S . Infantis, S . Schwarzengrund, S . Minnesota, S . Kentucky and S . Brandenburg. In brief, ocurrence and persistence of international lineages of S . enterica serovars in food production chain is supported by conserved genomes and wide virulome and resistome.

Background Ctenocephalides felis, the cat flea, is the most common ectoparasite of cats and dogs worldwide. As a cause of flea allergy dermatitis and a vector for two genera of zoonotic pathogens (Bartonella and Rickettsia spp.), the effect of the C. felis microbiome on pathogen transmission and vector survival is of substantial medical importance to both human and veterinary medicine. The aim of this study was to assay the pathogenic and commensal eubacterial microbial communities of individual C. felis from multiple geographic locations and analyze these findings by location, qPCR pathogen prevalence, and flea genetic diversity. Methods 16S Next Generation Sequencing (NGS) was utilized to sequence the microbiome of fleas collected from free-roaming cats, and the cox1 gene was used for flea phylogenetic analysis. NGS data were analyzed for 168 individual fleas from seven locations within the US and UK. Given inconsistency in the genera historically reported to constitute the C. felis microbiome, we utilized the decontam prevalence method followed by literature review to separate contaminants from true microbiome members. Results NGS identified a single dominant and cosmopolitan amplicon sequence variant (ASV) from Rickettsia and Wolbachia while identifying one dominant Bartonella clarridgeiae and one dominant Bartonella henselae/Bartonella koehlerae ASV. Multiple less common ASVs from these genera were detected within restricted geographical ranges. Co-detection of two or more genera (Bartonella, Rickettsia, and/or Wolbachia) or multiple ASVs from a single genus in a single flea was common. Achromobacter, Peptoniphilus, and Rhodococcus were identified as additional candidate members of the C. felis microbiome on the basis of decontam analysis and literature review. Ctenocephalides felis phylogenetic diversity as assessed by the cox1 gene fell within currently characterized clades while identifying seven novel haplotypes. NGS sensitivity and specificity for Bartonella and Rickettsia spp. DNA detection were compared to targeted qPCR. Conclusions Our findings confirm the widespread coinfection of fleas with multiple bacterial genera and strains, proposing three additional microbiome members. The presence of minor Bartonella, Rickettsia, and Wolbachia ASVs was found to vary by location and flea haplotype. These findings have important implications for flea-borne pathogen transmission and control. Graphical Abstract

Background: Behavioral economic approaches have revealed several characteristics of alcohol demand (e.g., intensity, elasticity, and essential value) in university students; however, these approaches have not yet examined alcohol demand among students outside of the United States. The current study examined alcohol demand among student samples in the United States and France using a hypothetical alcohol purchase task (APT) and a novel APT Choice task, in which nonalcoholic beverages were concurrently available at a fixed low price.Methods: Participants at each site (United States, n = 132; France, n = 132) were asked to complete an Internet-based survey including the APT, APT Choice, Alcohol Use Disorders Identification Test, Daily Drinking Questionnaire, and Drinking Motives Questionnaire-Revised Short Form. Group demand functions were produced for each of the 2 samples in both country-specific and standardized drink units, and the exponential demand equation was fitted to each of the APT and APT Choice demand curves. Slope analyses were performed on the Non-Alcoholic Cross-Price demand to assess substitutability.Results: APT data revealed that in both samples, alcohol price and consumption were inversely related and demand measures were significantly associated with other alcohol measures. In addition, the availability of a nonalcoholic alternative reduced alcohol demand in both samples, with evidence of substitutability revealed by increases in cross-price consumption.Conclusions: Low-cost alcohol is associated with increased alcohol consumption in both French and U.S. university students, and concurrent availability of a nonalcoholic beverage within the APT both reduces alcohol demand and demonstrates behavioral economic substitutability. These findings will inform future studies investigating behavioral and environmental factors underlying transcultural differences and specific prevention efforts.

Behavioral economic principles have been useful for addressing strategies to reduce alcohol consumption among college students. For example, academic variables (such as class schedule or academic rigor) have been found to affect alcohol demand assessed with a hypothetical alcohol purchase task (APT). The present studies used the APT to address the effects of 2 academic variables: next-day course level (no class, introductory level or upper level) and class size (no class, 30-student or 12-student). In each of 2 experiments, undergraduate participants read a description of a drinking context (either a no-class control version or 1 of the academic constraint conditions) and were asked to indicate how many drinks they would purchase at a variety of prices. Hursh and Silberberg's (2008) exponential demand equation was used to determine intensity and elasticity of demand, and Hursh and Roma's (2015) essential value (EV) parameter was calculated to assess essential value. In both experiments, a next-day class reduced alcohol demand, and alcohol consumption decreased as drink price increased. The presence of a smaller next-day class reduced alcohol demand compared with a larger next-day class; however, course level did not differentially affect alcohol demand. These results suggest that smaller next-day classes may reduce alcohol demand among college students and also provide initial evidence for the reliability of EV across studies. (PsycINFO Database Record

Community-wide high-throughput sequencing has transformed the study of the vaginal microbiome, and clinical applications are on the horizon. Here we outline the three main community sequencing methods: (1) amplicon sequencing, (2) shotgun metagenomic sequencing, and (3) metatranscriptomic sequencing. We discuss the advantages and limitations of community sequencing generally, and the unique strengths and weaknesses of each method. We briefly review the contributions of community sequencing to vaginal microbiome research and practice. We develop suggestions for critically interpreting research results and potential clinical applications based on community sequencing of the vaginal microbiome.

Salmonella enterica subsp. enterica serovar Heidelberg has been associated with a broad host range, such as poultry, dairy calves, swine, wild birds, environment, and humans. The continuous evolution of S. Heidelberg raises a public health concern since there is a global dispersal of lineages harboring a wide resistome and virulome on a global scale. Here, we characterized the resistome, phylogenetic structure and clustered regularly interspaced short palindromic repeats (CRISPR) array composition of 81 S. Heidelberg strains isolated from broiler farms (n = 16), transport and lairage (n = 5), slaughterhouse (n = 22), and retail market (n = 38) of the poultry production chain in Brazil, between 2015 and 2016 using high-resolution approaches including whole-genome sequencing (WGS) and WGS-derived CRISPR genotyping. More than 91% of the S. Heidelberg strains were multidrug-resistant. The total antimicrobial resistance (AMR) gene abundances did not vary significantly across regions and sources suggesting the widespread distribution of antibiotic-resistant strains from farm to market. The highest AMR gene abundance was observed for fosA7, aac(6′)-Iaa, sul2, tet(A), gyrA, and parC for 100% of the isolates, followed by 88.8% for blaCMY–2. The β-lactam resistance was essentially driven by the presence of the plasmid-mediated AmpC (pAmpC) blaCMY–2 gene, given the isolates which did not carry this gene were susceptible to cefoxitin (FOX). Most S. Heidelberg strains were classified within international lineages, which were phylogenetically nested with Salmonella strains from European countries; while CRISPR genotyping analysis revealed that the spacer content was overall highly conserved, but distributed into 13 distinct groups. In summary, our findings underscore the potential role of S. Heidelberg as a key pathogen disseminated from farm to fork in Brazil and reinforce the importance of CRISPR-based genotyping for salmonellae. Hence, we emphasized the need for continuous mitigation programs to monitor the dissemination of this high-priority pathogen.