Sex-inducing effects toward planarians widely present among parasitic flatworms

Summary Various parasitic flatworms infect vertebrates for sexual reproduction, often causing devastating diseases in their hosts. Consequently, flatworms are of great socioeconomic and biomedical importance. Although the cessation of parasitic flatworm sexual reproduction is a major target of anti-parasitic drug design, little is known regarding bioactive compounds controlling flatworm sexual maturation. Using the planarian Dugesia ryukyuensis, we observed that sex-inducing substances found in planarians are also widespread in parasitic flatworms, such as monogeneans and flukes (but not in tapeworms). Reverse-phase HPLC analysis revealed the sex-inducing substance(s) eluting around the tryptophan retention time in the fluke Calicophoron calicophorum, consistent with previous studies on the planarian Bipalium nobile, suggesting that the substance(s) is likely conserved among flatworms. Moreover, six of the 18 ovary-inducing substances identified via transcriptome and metabolome analyses are involved in purine metabolism. Our findings provide a basis for understanding and modifying the life cycles of various parasitic flatworms.journal articl

Measuring the Interpretability and Explainability of Model Decisions of Five Large Language Models

This study conducts a comprehensive analysis of the interpretability and explainability of five leading Large Language Models (LLMs): TripoSR by Stability AI, Gemma-7b by Google, Mistral 7B by Mistral AI, Llama-2-7b by Meta, and GemMoE-Beta-1 by CrystalCare AI. Through a methodical evaluation encompassing both qualitative and quantitative benchmarks, we assess these models' capacity to make their decision-making processes understandable to humans. Our findings reveal significant variability in the models' ability to provide transparent reasoning and accurate, contextually relevant explanations across different contexts. Notably, TripoSR and GemMoE-Beta-1 demonstrated superior transparency, while Gemma-7b and Llama-2-7b excelled in the accuracy of their explanations. However, challenges in maintaining consistent interpretability and explainability across varying inputs and the need for enhanced adaptability to feedback highlight areas for future improvement. This research underscores the importance of interpretability and explainability in fostering trust and reliability in LLM applications, advocating for continued advancement in these areas to achieve more transparent, accountable, and user-centric AI systems. Directions for future research include the development of standardized evaluation methodologies and interdisciplinary approaches to enhance model transparency and user understanding

Hair cortisol concentration is associated with executive function in female college football players

Chronic stress in athletes can diminish brain functions and mental health which can potentially affect health and sports performance. However, its influences on mental health and executive function remain unknown. This study examined the effects of chronic stress change on mental health and executive function in college female football players by analyzing hair cortisol concentration (HCC) as a chronic stress indicator. Measurements were taken in August and December, just before the Japan college national tournament. The results indicated a positive correlation trend between HCC and self-reported training load, suggesting a potential HCC decrease in athletes with reduced training load before the December competition. A significant negative correlation existed between changes in HCC and spatial Stroop task reaction time, indicating that as HCC decreased, executive function also decreased. These findings suggest that an excessively reduced training load may decrease executive function during fatigue recovery before competitions. This study implies that HCC could serve as a physiological training plan evaluation index

Behavior and possible function of Arabidopsis BES1/BZR1 homolog 2 in brassinosteroid signaling

Two key transcription factors (TFs) in brassinosteroid (BR) signaling BRASSINOSTEROID INSENSITIVE 1-EMS-SUPPRESSOR 1 (BES1) and BRASSINAZOLE RESISTANT 1 (BZR1), belong to a small family with four BES1/BZR1 homologs (BEH1–4). To date, in contrast to the wealth of knowledge regarding BES1 and BZR1, little is known about BEH1–4. Here, we show that BEH2 was expressed preferentially in the roots and leaf margins including serrations, which was quite different from another member BEH4, and that BRs downregulated BEH2 through a module containing GSK3-like kinases and BES1/BZR1 TFs, among which BES1, rather than BZR1, contributed to this process. In addition, BEH2 consistently existed in the nucleus, suggesting that its subcellular localization is not under BR-dependent nuclear-cytoplasmic shuttling control. Furthermore, gene ontology analysis on RNA-seq data indicated that BEH2 may be implicated in stress response and photosynthesis. These findings might assist in the future elucidation of the molecular mechanisms underlying BR signaling

Design and Synthesis of Two-Photon Responsive Chromophores for Near-Infrared Light-Induced Uncaging Reactions

C.K. acknowledges the HPC resources of CINES and IDRIS under the allocations 2016- [x2016080649] made by GENCI.International audienceNear-infrared two-photon (TP)-induced photorelease (uncaging) of bioactive molecules such as drugs has attracted considerable attention because of its ability to elucidate mechanistic aspects of biological processes. This short review summarizes recent developments in the design and synthesis of TP-responsive chromophores

Sex-inducing effects toward planarians widely present among parasitic flatworms

Summary: Various parasitic flatworms infect vertebrates for sexual reproduction, often causing devastating diseases in their hosts. Consequently, flatworms are of great socioeconomic and biomedical importance. Although the cessation of parasitic flatworm sexual reproduction is a major target of anti-parasitic drug design, little is known regarding bioactive compounds controlling flatworm sexual maturation. Using the planarian Dugesia ryukyuensis, we observed that sex-inducing substances found in planarians are also widespread in parasitic flatworms, such as monogeneans and flukes (but not in tapeworms). Reverse-phase HPLC analysis revealed the sex-inducing substance(s) eluting around the tryptophan retention time in the fluke Calicophoron calicophorum, consistent with previous studies on the planarian Bipalium nobile, suggesting that the substance(s) is likely conserved among flatworms. Moreover, six of the 18 ovary-inducing substances identified via transcriptome and metabolome analyses are involved in purine metabolism. Our findings provide a basis for understanding and modifying the life cycles of various parasitic flatworms

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo