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Aims/hypothesis Intramyocellular lipids, including diacylglycerol (DAG) and ceramides, have been linked to insulin resistance. This randomised repeated-measures study examined the effects of diet-induced weight loss (DIWL) and aerobic exercise (EX) on insulin sensitivity and intramyocellular triacylglycerol (IMTG), DAG and ceramide. Methods Sixteen overweight to obese adults (BMI 30.6 ± 0.8; 67.2 ± 4.0 years of age) with either impaired fasting glucose, or impaired glucose tolerance completed one of two lifestyle interventions: DIWL ( n  = 8) or EX ( n  = 8). Insulin sensitivity was determined using hyperinsulinaemic–euglycaemic clamps. Intramyocellular lipids were measured in muscle biopsies using histochemistry and tandem mass spectrometry. Results Insulin sensitivity was improved with DIWL (20.6 ± 4.7%) and EX (19.2 ± 12.9%). Body weight and body fat were decreased by both interventions, with greater decreases in DIWL compared with EX. Muscle glycogen, IMTG content and oxidative capacity were all significantly ( p  < 0.05) decreased with DIWL and increased with EX. There were decreases in DAG with DIWL (−12.4 ± 14.6%) and EX (−40.9 ± 12.0%). Ceramide decreased with EX (−33.7 ± 11.2%), but not with DIWL. Dihydroceramide was decreased with both interventions. Sphingosine was decreased only with EX. Changes in total DAG, total ceramides and other sphingolipids did not correlate with changes in glucose disposal. Stearoyl-coenzyme A desaturase 1 (SCD1) content was decreased with DIWL (−19.5 ± 8.5%, p  < 0.05), but increased with EX (19.6 ± 7.4%, p  < 0.05). Diacylglycerol acyltransferase 1 (DGAT1) was unchanged with the interventions. Conclusions/interpretation Diet-induced weight loss and exercise training both improved insulin resistance and decreased DAG, while only exercise decreased ceramides, despite the interventions having different effects on IMTG. These alterations may be mediated through differential changes in skeletal muscle capacity for oxidation and triacylglycerol synthesis. Trial registration: ClinicalTrials.gov NCT00766298 Funding: ADA Clinical Research Award (B. H. Goodpaster), NIH R01 AG20128 (B. H. Goodpaster), Obesity and Nutrition Research (1P30DK46204) and Clinical and Translational Research Centers (UL1 RR024153)

Frogs are immediately associated to their conspicuous vocalizations emitted during the breeding season. Therefore, many scientists were inspired to study their acoustic communication. Nowadays, many types of calls are described and we felt the need of reviewing the terminology currently and historically applied. As a result, we proposed the classification of anuran vocalization into three major categories: reproductive, aggressive, and defensive calls. These categories are subdivided according to the social context of emission mostly reflecting also acoustic differences among call types. Some call types are here proposed to be synonymies of the mostly used and inclusive terms. We also suggest terminologies for basic bioacoustical analyses, mostly applied in call descriptions. Furthermore, we present cases of complex calls, including call gradation. Finally, based on novel data (such as an unusual case of juvenile vocalizations), we discuss situations in which it is difficult to classify call types, reflecting the need of experimental studies.

Hybridization of parasites can generate new genotypes with high virulence. The fungal amphibian parasite Batrachochytrium dendrobatidis ( Bd ) hybridizes in Brazil’s Atlantic Forest, a biodiversity hotspot where amphibian declines have been linked to Bd , but the virulence of hybrid genotypes in native hosts has never been tested. We compared the virulence (measured as host mortality and infection burden) of hybrid Bd genotypes to the parental lineages, the putatively hypovirulent lineage Bd -Brazil and the hypervirulent Global Pandemic Lineage ( Bd -GPL), in a panel of native Brazilian hosts. In Brachycephalus ephippium , the hybrid exceeded the virulence (host mortality) of both parents, suggesting that novelty arising from hybridization of Bd is a conservation concern. In Ischnocnema parva , host mortality in the hybrid treatment was intermediate between the parent treatments, suggesting that this species is more vulnerable to the aggressive phenotypes associated with Bd -GPL. Dendropsophus minutus showed low overall mortality, but infection burdens were higher in frogs treated with hybrid and Bd -GPL genotypes than with Bd -Brazil genotypes. Our experiment suggests that Bd hybrids have the potential to increase disease risk in native hosts. Continued surveillance is needed to track potential spread of hybrid genotypes and detect future genomic shifts in this dynamic disease system.

A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism 1 , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings 2 , 3 . Although technology can satisfy the first two of these requirements 4 – 7 , the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human ‘free will’ could be used rigorously to ensure unpredictability in Bell tests 8 . Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology 9 . The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons 5 , 6 , single atoms 7 , atomic ensembles 10 and superconducting devices 11 . Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bipartite and tripartite 12 scenarios. Project outcomes include closing the ‘freedom-of-choice loophole’ (the possibility that the setting choices are influenced by ‘hidden variables’ to correlate with the particle properties 13 ), the utilization of video-game methods 14 for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science. The BIG Bell Test, which used an online video game with 100,000 participants worldwide to provide random bits to 13 quantum physics experiments, contradicts the Einstein–Podolsky–Rosen worldview of local realism.

The fungal pathogen Batrachochytrium dendrobatidis (Bd) is the causative agent of chytridiomycosis and has been a key driver in the catastrophic decline of amphibians globally. While many strategies have been proposed to mitigate Bd outbreaks, few have been successful. In recent years, the use of probiotic formulations that protect an amphibian host by killing or inhibiting Bd have shown promise as an effective chytridiomycosis control strategy. The North American bullfrog (Lithobates catesbeianus) is a common carrier of Bd and harbours a diverse skin microbiota that includes lactic acid bacteria (LAB), a microbial group containing species classified as safe and conferring host benefits. We investigated beneficial/probiotic properties: anti-Bd activity, and adhesion and colonisation characteristics (hydrophobicity, biofilm formation and exopolysaccharide-EPS production) in two confirmed LAB (cLAB-Enterococcus gallinarum CRL 1826, Lactococcus garvieae CRL 1828) and 60 presumptive LAB (pLAB) [together named as LABs] isolated from bullfrog skin.We challenged LABs against eight genetically diverse Bd isolates and found that 32% of the LABs inhibited at least one Bd isolate with varying rates of inhibition. Thus, we established a score of sensitivity from highest (BdGPL AVS7) to lowest (BdGPL C2A) for the studied Bd isolates. We further reveal key factors underlying host adhesion and colonisation of LABs. Specifically, 90.3% of LABs exhibited hydrophilic properties that may promote adhesion to the cutaneous mucus, with the remaining isolates (9.7%) being hydrophobic in nature with a surface polarity compatible with colonisation of acidic, basic or both substrate types. We also found that 59.7% of LABs showed EPS synthesis and 66.1% produced biofilm at different levels: 21% weak, 29% moderate, and 16.1% strong. Together all these properties enhance colonisation of the host surface (mucus or epithelial cells) and may confer protective benefits against Bd through competitive exclusion. Correspondence analysis indicated that biofilm synthesis was LABs specific with high aggregating bacteria correlating with strong biofilm producers, and EPS producers being correlated to negative biofilm producing LABs. We performed Random Amplified Polymorphic DNA (RAPD)-PCR analysis and demonstrated a higher degree of genetic diversity among rod-shaped pLAB than cocci. Based on the LAB genetic analysis and specific probiotic selection criteria that involve beneficial properties, we sequenced 16 pLAB which were identified as Pediococcus pentosaceus, Enterococcus thailandicus, Lactobacillus pentosus/L. plantarum, L. brevis, and L. curvatus. Compatibility assays performed with cLAB and the 16 species described above indicate that all tested LAB can be included in a mixed probiotic formula. Based on our analyses, we suggest that E. gallinarum CRL 1826, L. garvieae CRL 1828, and P. pentosaceus 15 and 18B represent optimal probiotic candidates for Bd control and mitigation.

We report a series of 1,3-diphenylureido hydroxamate HDAC inhibitors evaluated against sensitive and drug-resistant P. falciparum strains. Compounds 8a–d show potent antiplasmodial activity, indicating that a phenyl spacer allows improved potency relative to cinnamyl and di-hydrocinnamyl linkers. In vitro , mechanistic studies demonstrated target activity for Pf HDAC1 on a recombinant level, which agreed with cell quantification of the acetylated histone levels. Compounds 6c , 7c , and 8c , identified as the most active in phenotypic assays and Pf HDAC1 enzymatic inhibition. Compound 8c stands out as a remarkable inhibitor, displaying an impressive 85% inhibition of Pf HDAC1, with an IC 50 value of 0.74 µM in the phenotypic screening on Pf 3D7 and 0.8 µM against multidrug-resistant Pf Dd2 parasites. Despite its potent inhibition of Pf HDAC1, 8c remains the least active on human HDAC1, displaying remarkable selectivity. In silico studies suggest that the phenyl linker has an ideal length in the series for permitting effective interactions of the hydroxamate with Pf HDAC1 and that this compound series could bind as well as in Hs HDAC1. Taken together, these results highlight the potential of diphenylurea hydroxamates as a privileged scaffold for the generation of potent antimalarial HDAC inhibitors with improved selectivity over human HDACs.

Some centers utilize ventriculopleural shunt (VPLS) for treating hydrocephalus when conventional approaches are not feasible. Nonetheless, the literature regarding this approach is scarce. Evaluate the outcomes of VPLS through a single-arm meta-analysis. Following PRISMA guidelines, the authors systematically searched for articles utilizing the VPLS in a cohort with more than four patients. Outcomes included: mortality, pleural effusion, number of patients who underwent revisions, obstructions, shunt migration, emphysema, and subdural hematoma. A total of 404 articles were reviewed, resulting in the inclusion of 13 retrospective studies encompassing 543 patients, with the majority being children (62.6 %). The median average follow-up period was 35.4 months (10–64.1). After analysis, results yielded a revision rate of 54 % (95 % CI: 44 %-64 %; I2=73 %). The most common complication observed was pleural effusion, with a post-analysis incidence of 16 % (95 % CI: 11 %-21 %; I2=63 %), followed by infections at 7 % (95 % CI: 4 %-10 %; I2=33 %). Shunt obstruction occurred in 13 % (95 % CI: 4 %-21 %; I2=84 %) of cases after analysis, while migrations, overdrainage, subdural hematoma, and cutaneous emphysema had minimal occurrence rates (0 %, 95 % CI: 0 %-1 %; I2=0 %). Notably, there were no reported cases of shunt-related mortality. VPLS can be considered when there are no other suitable options for placing the distal catheter. However, the notable rates of shunt revisions, pleural effusion, infections, and the inherent heterogeneity of outcomes currently limit the widespread adoption of VPLS. In this scenario, other alternatives should be given priority. •Ventriculopleural shunt is an option when the atrium and the peritoneum are not available as distal sites for shunting.•Pleural effusion emerges as the primary complication following ventriculopleural shunt placement.•The literature on ventriculopleural shunts exhibits a lower level of robustness when compared to literature of other shunts.

Supplementation of dairy calves with essential oils in the liquid diet can reduce the incidence and severity of infectious diseases and promote better performance. Our objective was to evaluate an essential oil blend containing peppermint, eucalyptus, and menthol crystals and its effect on performance and health during the pre and postweaning period of dairy calves. At birth, 40 dairy calves (34 males and 6 females) were blocked according to sex and birth weight, randomly assigned to one of two treatments–commercial milk replacer diluted at 14% (MR) and the same liquid diet plus essential oil blend (MREO) at a dose of 4 mL per calf per day, divided into two meals during the first 28 days of life. Calves were individually housed and fed 6 L/d of the liquid diet, divided into two meals, and received starter concentrate and water ad libitum. Weaning was gradually reduced by 1L per day at d 51 until complete weaning at 56 days. After weaning, calves were evaluated until 70 days of age, when the experimental period ended. Intake, fecal, and health scores were evaluated daily, weight and body measures were recorded weekly, and blood parameters were evaluated at weeks 1, 2, 3, 4, and 8. Calves fed MREO tended to have higher total dry matter intake during the preweaning period. Furthermore, MREO calves had lower health scores and fewer days with a health score ≥ 4 (suggestive of bronchopneumonia), tended to lower coughing days and fewer veterinary interventions preweaning, and tended to lower health scores postweaning. The supplementation with a blend of essential oils containing peppermint, eucalyptus, and menthol crystals can reduce respiratory problems. Further studies are needed to investigate the dose and the supplementation period.

The inclusion of forage sources in calf diets is often discussed, and the main point debated is whether the inclusion level, particle size, source, and how forage is offered may impact gut fill and reduce body weight gain, as well as impact gastrointestinal tract development. This study aimed to determine the effects of feeding forage sources with different qualities on rumen fermentation, gut fill, and development of the gastrointestinal tract of dairy calves. Forty-eight Holstein dairy calves were blocked according to sex and body weight (BW) at 28 days of life and randomly assigned to 1 of 4 dietary treatments. Treatments consisted of a no-forage coarsely ground starter (CON) or total mixed rations containing 7.5% on DM basis of Tifton hay of either medium quality (MH) or low quality (LH) or 10% on DM basis of corn silage (CS). The nutritional content, including crude protein, NDF, lignin, and in vitro digestibility, was used as forage quality criteria. During the first 28 days of life, all calves received 3 L of whole milk twice daily, a commercial pelleted starter ad libitum, and no forage. After that, the solid diet was changed to the respective dietary treatments. Rumen samples were taken to determine rumen pH and volatile fatty acid (VFA) proportions. Calves were gradually weaned from 52 to 56 d of age, and 20 calves, 5 per treatment, were harvested two weeks after weaning. The anatomical parts of the gastrointestinal tract were weighed with and without contents, and histological analysis of rumen epithelium was conducted. The CON diet increased total VFA concentration compared to forage diets. The forage diets increased rumen pH, fecal pH, and gut fill. However, regardless of the source, the forage provision did not affect empty body weight. In addition, the forage provision increased the number of papillae in the rumen, but diets did not influence the length and width of papillae. The results suggest that 7.5% of Tifton hay, regardless of the quality, and 10% of corn silage in high-starch mixed diets benefit rumen health and promote greater gut fill without negative effects on final body weight.

Fifty Holstein calves were allocated in randomized blocks and distributed in a 2 × 2 factorial arrangement; (A) two sources of Ig: (1) Control: bovine colostrum (25% Brix); (2) Enriched colostrum: mid-quality bovine colostrum (20% Brix) enriched with colostrum replacer to 25% Brix; and (B) two transition feeding diets: (1) Whole milk (WM): supply of 4 L/day of whole milk for 3 days after the colostrum feeding; and (2) Formulated transition milk (FTM): supply 4 L/day of whole milk enriched with 70 g/L of colostrum replacer for 3 days after the colostrum feeding. Blood samples were collected at 0, 24, 48, and 72 h of age to determine total serum protein (TSP), glucose, non-esterified fatty acids (NEFA), erythrocyte and leukocyte concentrations. IgG was measured at 48 h. During the preweaning period, calves received 6 L/day of whole milk. Blood samples were collected weekly to determine TSP, glucose, and lactate. The colostrum protocols were equally efficient for transfer of passive immunity with IgG concentration at 48 h ≥ 49.6 g/L. Colostrum or transition feeding program did not influence the erythrocyte and leukocyte concentrations. The TSP concentration measured until 72 h was higher for calves fed maternal colostrum. Calves fed milk in the transition period had higher glucose concentrations. Calves receiving bovine colostrum and FTM had higher glucose concentrations in the preweaning period, while the enriched colostrum decreased plasma lactate concentrations. In summary, enrichment of mid-quality colostrum is an alternative in situations of a shortage of high-quality colostrum; however, feeding 4 L/day of FTM only for 3 days after colostrum feeding does not show additional benefits.