Miracle-dz/UniFAR-FTUs huggingface dataset:
Altering attention to split-belt walking increases the generalization of motor memories across walking contexts.

Little is known about the impact of attention during motor adaptation tasks on how movements adapted in one context generalize to another. We investigated this by manipulating subjects' attention to their movements while exposing them to split-belt walking (i.e., legs moving at different speeds), which is known to induce locomotor adaptation. We hypothesized that reducing subjects' attention to their movements by distracting them as participants adapted their walking pattern would facilitate the generalization of recalibrated movements beyond the training environment. We reasoned that awareness of the novel split-belt condition could be used to consciously contextualize movements to that particular situation. To test this hypothesis, young adults adapted their gait on a split-belt treadmill while they observed visual information that either distracted them or made them aware of the belt's speed difference. We assessed adaptation and aftereffects of spatial and temporal gait features known to adapt and generalize differently in different environments. We found that all groups adapted similarly by reaching the same steady state values for all gait parameters at the end of the adaptation period. In contrast, both groups with altered attention to the split-belts environment (distraction and awareness groups) generalized their movements from the treadmill to overground more than controls, who walked without altered attention. This was specifically observed in the generalization of step time (temporal gait feature) which might be less susceptible to online corrections when walking overground. These results suggest that altering attention to one's movements during sensorimotor adaptation facilitates the generalization of movement recalibration.
Development of novel pesticides targeting insect chitinases: A minireview and a perspective.

Chitinase (EC 3.2.1.14) is an enzyme to breakdown β-1,4-glycosidic bonds in chitin and chitooligosaccharides. The loss of chitinase enzymatic activity in insects results in severe exoskeleton defects and lethality at all developmental stages, indicating that insect chitinases can be promising pesticide targets. However, there are no pesticides known to target chitinases. This review will focus on the latest research progress of insect chitinases, paying special attention to crystal structures and chemical biology advances in the field. The physiological importance and unique structural features of insect chitinases may ensure the development of new pesticides through a novel acting mode.
Rethinking of ‘psychosis’ in the era of early intervention in mental health

Since the introduction of the concept of early intervention for psychotic disorders in the 1990s, many early intervention studies and programs for psychosis have been implemented in Western English-speaking countries as well as in Asian countries. This development has expanded the idea of psychosis and of its related earlier stages. There is increasing interest in early intervention programs, and experience-sharing and close collaboration are required to facilitate the development of early intervention for psychosis services, education, and research. This development creates new ideas and terms regarding the description of the earlier stages of the mental state. Terms define the boundaries of the concept and, in medicine, they may change the treatment strategy for cases on said boundaries. These changes may result in a good prognosis. Such change is important not only to deal with the pejorative use of the term, but also to emphasize that there are patients with subthreshold symptoms requiring intervention early in the developmental period. Along with the development of the psychosis concept, new terminology is being used to express a wide range of symptoms within the psychosis continuum. As pointed out by Seiler et al. in this issue, there is currently no consensus on definitions or boundaries among different terminology. Seiler et al. conducted a systematic and narrative review on psychotic terminology to determine definitions and assessment tools for seven terms, specifically: ‘psychotic experiences,’ ‘psychotic-like experiences,’ ‘psychotic-like symptoms,’ ‘attenuated psychotic symptoms,’ ‘prodromal psychotic symptoms,’ ‘psychotic symptomatology,’ and ‘psychotic symptoms. ’ The reviewed information and the model presented are informative, and will help facilitate further discussion and a better understanding of the psychotic dimension. As the first step toward future standardization of terms, they propose a model with two dimensions: (i) psychotic threshold level; and (ii) distress/help-seeking behaviors. The distinctions that Seiler et al. make according to this model among ‘experiences,’ ‘symptoms,’ and ‘signs’ are essential for establishing clear definitions of psychotic terms. This paper is a preliminary report on psychotic terminology, the lack of standardization of these terms, and the need for a consensus statement to clarify them. The authors’ aim is to construct a consensus statement by organizing a working group of experts after this review. It is valuable to discuss terminology from a global view and publish its progress. Translation between languages is difficult but essential for sharing experiences and close collaboration. We hope that Seiler’s initial working group will include members from non-English-speaking countries.
Innate-like CD27+CD45RBhigh γδ T Cells Require TCR Signaling for Homeostasis in Peripheral Lymphoid Organs

Key Points Eγ4 is an enhancer element that regulates transcriptions of TCRγ genes. Eγ4−/− mice have fewer CD27+CD45RBhigh Vγ2+ γδ T cells in peripheral organs. Attenuation of TCR signal impairs homeostasis of γδ T cells in peripheral organs. TCR signaling is required for homeostasis of naive αβ T cells. However, whether such a signal is necessary for γδ T cell homeostasis in the periphery remains unknown. In this study, we present evidence that a portion of Vγ2+ γδ T cells, one of the major γδ T cell subsets in the secondary lymphoid organs, requires TCR signaling for homeostasis. To attenuate γδTCR signals, we generated mice lacking Eγ4 (Eγ4−/−), an enhancer located at the 3′-most end of the TCRγ locus. Overall, we found that in thymus, Eγ4 loss altered V-J rearrangement, chromatin accessibility, and transcription of the TCRγ locus in a distance-dependent manner. Vγ2+ γδ T cells in Eγ4−/− mice developed normally both fetal and adult mouse thymi but were relatively reduced in number in spleen and lymph nodes. Although Vγ2 TCR transcription decreased in all subpopulations of Eγ4−/− mice, the number of Vγ2+ γδ T cells decreased and TCR signaling was attenuated only in the innate-like CD27+CD45RBhigh subpopulation in peripheral lymphoid organs. Consistently, CD27+CD45RBhigh Vγ2+ γδ T cells from Eγ4−/− mice transferred into Rag2-deficient mice were not efficiently recovered, suggesting that continuous TCR signaling is required for their homeostasis. Finally, CD27+CD45RBhigh Vγ2+ γδ T cells from Eγ4−/− mice showed impaired TCR-induced activation and antitumor responses. These results suggest that normal homeostasis of innate-like CD27+CD45RBhigh Vγ2+ γδ T cells in peripheral lymphoid organs requires TCR signaling.
Reference Values and Correlations for Multiple Physical Performance Measures: A Cross-Sectional Study among Independently Mobile Older Men in Japan

Purpose: Japan is one of few countries with a male life expectancy over 80 years. The gap between the healthy life span and the total life expectancy is large, highlighting the importance of maintaining physical performance. The present study aims to establish reference values for multiple physical performance measures among high-functioning oldest-old Japanese men and to investigate the correlations among these measurements to understand how these variables are related. Methods: This study was conducted with 120 Japanese males aged 80 years or older who were able to walk independently. Seven measures of physical performance were assessed: handgrip strength, quadriceps strength, static balance ability (one-legged stance), dynamic balance ability (Functional Reach Test; FRT), walking ability (5-m walking time test), combined movement ability (Timed Up & Go test), and bone quality. Cognitive function was also measured (Mini-Mental State Examination; MMSE). Results: Specific reference values are reported for each physical performance measurement explored in this study. Only six participants were classified as cognitively impaired, and 16 had mild cognitive impairment. There were significant correlations of varying levels among all of the measures of physical performance. Age was significantly correlated with all performance measures except FRT, and there was no correlation between age and MMSE. MMSE was weakly correlated with FRT and unrelated to the other performance measures. Conclusions: The reference ranges can be used by older men who have not yet reached 80 years and their health care providers as physical performance targets to facilitate the maintenance of independent mobility in later life.
Barrett-Ösophagus – Update zu klinischem Management und Therapien

Was ist neu? Pathogenese Adenokarzinome des Ösophagus sind denen des Magens sehr ähnlich und entstehen mit hoher Wahrscheinlichkeit im Bereich der Kardia im Magen, von wo aus proliferierende Zellen in den Ösophagus expandieren und dort zunächst benigne „Barrett-Schleimhautinseln“ bilden. Eine hinzukommende genomische Instabilität führt zur klonalen Evolution bestimmter Zellen, die zur Entwicklung eines Adenokarzinoms führen kann. Risikofaktoren Eine klare Definition von Faktoren ist zur besseren Risikostratifizierung und Etablierung präventiver Strategien dringend notwendig. Aktuelle Prädiktionsmodelle, die unter anderem Übergewicht, Ernährungsweise oder Tabakkonsum erfassen, haben sich in der klinischen Anwendung noch nicht durchsetzen können. Diagnostik und Überwachung Zur Diagnostik und Überwachung existieren aktuelle Leitlinien. Die Diagnose eines Barrett-Ösophagus erfolgt histopathologisch aus 4-Quadranten-Biopsien. Darüber hinaus sollten makroskopisch auffällige Areale der Barrett-Schleimhaut gezielt biopsiert werden. Die Detektion neoplastischer Areale kann durch Einsatz der Chromoendoskopie in Kombination mit Vergrößerungsendoskopie und Färbetechniken (Methylenblau oder Essigsäure) verbessert werden. Therapie Die kurativ intendierte endoskopische Resektion ist die Standardtherapie der dysplastischen Barrett-Metaplasie, des mukosalen (T1a-m) und des oberflächlich submukosal (T1a-sm1) wachsenden Adenokarzinoms. Hier stellen die Kappen- und Ligatur-Resektion sowie zunehmend die endoskopische Submukosa-Dissektion die empfohlenen Resektionstechniken und in Kombination mit der Radiofrequenzablation die leitliniengerechte Therapie dar.
Extremely Sensitive Microwave Sensor for Evaluation of Dielectric Characteristics of Low-Permittivity Materials

In this paper, an extremely sensitive microwave sensor is designed based on a complementary symmetric S shaped resonator (CSSSR) to evaluate dielectric characteristics of low-permittivity material. CSSSR is an artificial structure with strong and enhanced electromagnetic fields, which provides high sensitivity and a new degree of freedom in sensing. Electromagnetic simulation elucidates the effect of real relative permittivity, real relative permeability, dielectric and magnetic loss tangents of the material under test (MUT) on the resonance frequency and notch depth of the sensor. Experiments are performed at room temperature using low-permittivity materials to verify the concept. The proposed design provides differential sensitivity between 102% to 95% as the relative permittivity of MUT varies from 2.1 to 3. The percentage error between simulated and measured results is less than 0.5%. The transcendental equation has been established by measuring the change in the resonance frequency of the fabricated sensor due to interaction with the MUT.
Effects of Dietary Supplementation of Lauric Acid on Lactation Function, Mammary Gland Development, and Serum Lipid Metabolites in Lactating Mice

Simple Summary Milk secreted from mammary glands is an important nutrition source for offspring after parturition. Mammary gland development and lactation ability have important effects on the growth and health of the offspring. Many studies have demonstrated that external factors, including the environment and nutrition influence the development of mammary glands. Lauric acid is a fatty acid that has many nutritional and physiological properties. In this study, we investigated the effects of dietary supplementation of lauric acid on lactation function and mammary gland development in lactating mice. We found that dietary supplementation of lauric acid during lactation might enhance the mammary development to promote the lactation function of mice. Through the study of mice, we hoped that the results could be applied to animal feed development and animal breeding production. Abstract Our previous studies demonstrated that lauric acid (LA) stimulated mammary gland development during puberty. However, the roles of LA on lactation in mice remain indeterminate. Thus, the aim of this study was to investigate the effects of dietary LA supplementation on lactation functioning and to study the potential mechanisms during lactation. in vivo, there was no effect of 1% LA dietary supplementation during lactation on the feed intake or body weight of breast-feeding mice. However, maternal LA supplementation significantly expanded the number of mammary gland alveoli of mice during lactation and the average body weight of the offspring, suggesting that LA supplementation enhanced the development and lactation function of the mammary glands. in vitro, 100 μM of LA significantly increased the content of triglycerides (TG) in the cell supernatant of induced HC11 cells, however, with no effect on the expression of the genes associated with fatty acid synthesis. LA also activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. LA dietary supplementation significantly expanded the serum levels of lipid metabolites, including sphingomyelin and other metabolites with the sn-2 position of C12 and sn-1 position of C18 in the TG of the lactating mice. Taken together, dietary supplementation of LA during lactation could promote the lactation function of mice, which might be related to increasing the development of the mammary glands and alternation of serum lipid metabolites. These findings provided more theoretical and experimental basis for the application of lauric acid in the development of mammary glands and lactation function of lactating animals.
Refractory epilepsy in PSEN 1 mutation (I83T)

ABSTRACT Mutations in the presenilin-1 gene (PSEN1) on chromosome 14 are the most common cause of autosomal dominant Alzheimer's disease (ADAD), which has a broad clinical phenotype, encompassing not only dementia but a variety of other neurological features. We report the case of a 32 years old man with a family history of early onset AD associated with a PSEN1 mutation in the exon 4 (I83T). The proband’s, carrying the mutation, present a refractory epilepsy predating cognitive decline. We discuss the physiopathological mechanisms of epilepsy during AD associated with PSEN 1 mutation, the possibility of linking this epilepsy to the mutation?
The Arabidopsis thaliana trehalose-6-phosphate phosphatase gene AtTPPI enhances drought tolerance by regulating stomatal apertures.

Transpiration occurs through stomata. The alteration of stomatal apertures in response to drought stress is an important process associated with water use efficiency (WUE). Trehalose-6-phosphate phosphatase (TPP) family genes have been reported to participate in stomatal aperture adjustment. However, there have been no reports of the trehalose metabolism pathway genes improving WUE, and the upstream signalling pathway modulating these genes is not clear. Here, we demonstrated that a member of the TPP gene family, AtTPPI, confers drought resistance and improves WUE by decreasing stomatal apertures and improving root architecture. The reduced expression of AtTPPI caused a drought-sensitive phenotype, while its overexpression significantly increased drought tolerance. Abscisic acid (ABA)-induced stomatal closure experiments confirmed that AtTPPI mutation increased the stomatal aperture compared to that of wild-type (WT) plants; in contrast, overexpression plants had smaller stomatal apertures than those of WT plants. Moreover, AtTPPI mutation also caused stunted primary root length and compromised auxin transport, while overexpression plants had longer primary root lengths. Yeast one-hybrid assays showed that ABA-responsive element-binding factor1 (ABF1), ABF2 and ABF4 directly regulated AtTPPI expression. In summary, the way AtTPPI responds to drought stress suggests that AtTPPI-mediated stomatal regulation is an important mechanism to cope with drought stress and improve WUE.
Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists

Low intrinsic efficacy can explain the reduced side effects of apparently biased μ-opioid receptor agonists. Opioids: Efficacy versus bias Because of its antinociceptive effects, the μ-opioid receptor (MOR) is an important target for pain management, but serious side effects limit the use of drugs that target this GPCR. Because the MOR stimulates intracellular signaling through both G proteins and β-arrestins, G protein–biased agonists have been developed to promote pain relief without causing β-arrestin–associated side effects. Gillis et al. compared the biochemical, signaling, and physiological properties of some G protein–biased MOR agonists with those of unbiased opioids. The observed reductions in side effects could be explained by the low intrinsic efficacy of the biased agonists rather than by their signaling bias per se. These findings suggest possible strategies for developing new MOR agonists that relieve pain with fewer unwanted side effects. Biased agonism at G protein–coupled receptors describes the phenomenon whereby some drugs can activate some downstream signaling activities to the relative exclusion of others. Descriptions of biased agonism focusing on the differential engagement of G proteins versus β-arrestins are commonly limited by the small response windows obtained in pathways that are not amplified or are less effectively coupled to receptor engagement, such as β-arrestin recruitment. At the μ-opioid receptor (MOR), G protein–biased ligands have been proposed to induce less constipation and respiratory depressant side effects than opioids commonly used to treat pain. However, it is unclear whether these improved safety profiles are due to a reduction in β-arrestin–mediated signaling or, alternatively, to their low intrinsic efficacy in all signaling pathways. Here, we systematically evaluated the most recent and promising MOR-biased ligands and assessed their pharmacological profile against existing opioid analgesics in assays not confounded by limited signal windows. We found that oliceridine, PZM21, and SR-17018 had low intrinsic efficacy. We also demonstrated a strong correlation between measures of efficacy for receptor activation, G protein coupling, and β-arrestin recruitment for all tested ligands. By measuring the antinociceptive and respiratory depressant effects of these ligands, we showed that the low intrinsic efficacy of opioid ligands can explain an improved side effect profile. Our results suggest a possible alternative mechanism underlying the improved therapeutic windows described for new opioid ligands, which should be taken into account for future descriptions of ligand action at this important therapeutic target.
Selection of Features with Consistent Profiles Improves Relative Protein Quantification in Mass Spectrometry Experiments*

Summaries of protein abundance are undermined by mass spectrometric features inconsistent with the overall protein profile. We develop an automated statistical approach that detects such inconsistent features. These features can be separately investigated, curated, or removed. Accounting for such inconsistent features improves the estimation and the detection of differential protein abundance between conditions. The approach is implemented as an option in the open-source R-based software MSstats. Graphical Abstract Highlights Automated statistical approach for detecting uninformative features and outliers. Improved performance on relative protein quantification. An option in the open-source R-based software MSstats. In bottom-up mass spectrometry-based proteomics, relative protein quantification is often achieved with data-dependent acquisition (DDA), data-independent acquisition (DIA), or selected reaction monitoring (SRM). These workflows quantify proteins by summarizing the abundances of all the spectral features of the protein (e.g. precursor ions, transitions or fragments) in a single value per protein per run. When abundances of some features are inconsistent with the overall protein profile (for technological reasons such as interferences, or for biological reasons such as post-translational modifications), the protein-level summaries and the downstream conclusions are undermined. We propose a statistical approach that automatically detects spectral features with such inconsistent patterns. The detected features can be separately investigated, and if necessary, removed from the data set. We evaluated the proposed approach on a series of benchmark-controlled mixtures and biological investigations with DDA, DIA and SRM data acquisitions. The results demonstrated that it could facilitate and complement manual curation of the data. Moreover, it can improve the estimation accuracy, sensitivity and specificity of detecting differentially abundant proteins, and reproducibility of conclusions across different data processing tools. The approach is implemented as an option in the open-source R-based software MSstats.
Strontium-substituted calcium sulfate hemihydrate/hydroxyapatite scaffold enhances bone regeneration by recruiting bone mesenchymal stromal cells

Fabrication of osteoconductive scaffold with osteoinductive capability and appropriate resorption rate is of great significance for treating bone defects. To achieve this aim, strontium-substituted calcium sulfate hemihydrate (Sr-CSH) and hydroxyapatite (HA) were mixed to develop a novel composite. Sr-CSH containing 5% and 10% strontium was mixed with HA at the weight ratio of 6:4, respectively. Female Sprague-Dawley rats underwent bone defect surgery in left tibia were randomly assigned to three different treatment groups filled with CSH/HA, 5% and 10% Sr-CSH/HA. Micro-CT analysis showed increased new bone formation in 10% Sr-CSH/HA group compared to CSH/HA group. In addition, histological analysis showed large amounts of chondrocytes and osteoblasts within the pores of Sr-CSH/HA composites as a result of the CSH resorption. Further, CFU-F assay demonstrated the increased amount of bone marrow mesenchymal stromal cells (BMSCs) colonies in 10% Sr-CSH/HA group. In primary BMSCs, extraction from Sr-CSH/HA composite significantly increased the migration of cells, up-regulated the expression of osteoblastic marker genes, and increased the area of mineralized nodules. Together, Sr-CSH/HA may promote bone formation by recruiting and stimulating osteogenic differentiation of BMSCs. Therefore, this composite may be proposed as an ideal substitute to repair bone defects.