Effects of combat sports on cerebellar function in adolescents: a resting-state fMRI study

Objectives: To evaluate the effects of combat sports on cerebellar function in adolescents based on resting-state functional MRI (rs-fMRI). Methods: Rs-fMRI data were acquired from the combat sports (CS) group (n = 32, aged 14.2 ± 1.1 years) and non-athlete healthy control (HC) group (n = 29, aged 14.8 ± 0.9 years). The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) within the cerebellum was calculated and then compared between the two groups. Results: None of these participants displayed intracranial lesions on conventional MRI and microhemorrhages on SWI. Compared with the HC group, the CS group showed decreased ALFF and ReHo in the bilateral cerebellum, mainly located in the inferior regions of the cerebellum (Cerebellum_8, Cerebellum_9, Cerebellum_7b, and Cerebellum_Crus2). While increased FC was found within the cerebellar network, mainly located in the superior regions near the midline (bilateral Cerebellum_6, Cerebellum_Crus1_R, and Vermis_6). There is no inter network FC change between the CEN and other networks. Conclusion: This study confirmed extensive effects of combat sports on cerebellar rs-fMRI in adolescents, which could enhance the understanding of cerebellar regulatory mechanism under combat conditions, and provide additional information about cerebellar protective inhibition and compensatory adaptation. Advances in knowledge: Adolescent combat participants are an ideal model to study training-induced brain plasticity and vulnerability. Relative to task-related fMRI, rs-fMRI can bring more information about cerebellar regulation and explain the Central Governor Model more comprehensively.

Preoperative Versus Postoperative Compensation of the Contralateral Normal Kidney in Patients Treated with Radical Nephrectomy for Renal Cell Carcinoma

Background: We sought to identify the factors affecting renal compensatory processes that occur preoperatively as well as postoperatively in patients treated with radical nephrectomy (RNx) for renal cell carcinoma (RCC). Methods: We retrospectively reviewed the records of 906 patients treated with RNx for RCC. We defined the early compensatory process (process 1) as compensatory adaptation of the contralateral normal kidney (CNK) before RNx. We defined the late compensatory process (process 2) as compensatory adaptation of the CNK after RNx. Total compensation was defined as the combination of these two processes. Multivariable logistic regression analyses were used to identify significant factors associated with processes 1, 2, and total compensation. Results: Mean preoperative, 1-week, and 5-year postoperative estimated glomerular filtration rates (eGFR) were 84.5, 57.6, and 63.7 mL/min/1.73 m2, respectively. Female sex (p < 0.001), lower body mass index (BMI) (p < 0.001), absence of hypertension (p = 0.019), lower preoperative eGFR (p < 0.001), larger tumor volume (p < 0.001), and larger CNK volume (p < 0.001) were significantly associated with process 1. Younger age (p = 0.019), higher BMI (p < 0.001), and absence of diabetes mellitus (DM) (p = 0.033) were significantly associated with process 2. Female sex (p < 0.001), younger age (p < 0.001), absence of DM (p = 0.002), lower preoperative eGFR (p < 0.001), and larger tumor (p = 0.001) and CNK volumes (p < 0.001) were significantly associated with total compensation. Conclusions: Different factors affected each compensatory process. Process 1 made a greater contribution to the entire renal compensatory process than process 2.

Exogenous mitochondrial transfer and endogenous mitochondrial fission facilitate AML resistance to OxPhos inhibition

Acute myeloid leukemia (AML) cells are highly dependent on oxidative phosphorylation (OxPhos) for survival and continually adapt to fluctuations in nutrient and oxygen availability in the bone marrow (BM) microenvironment. We investigated how the BM microenvironment affects the response to OxPhos inhibition in AML by using a novel complex I OxPhos inhibitor, IACS-010759. Cellular adhesion, growth, and apoptosis assays, along with measurements of mtDNA expression and mitochondrial reactive oxygen species generation, indicated that direct interactions with BM stromal cells triggered compensatory activation of mitochondrial respiration and resistance to OxPhos inhibition in AML cells. Mechanistically, OxPhos inhibition induced (1) transfer of mesenchymal stem cell (MSC)-derived mitochondria to AML cells via tunneling nanotubes under direct-contact coculture conditions, and (2) mitochondrial fission with an increase in functional mitochondria and mitophagy in AML cells. Mitochondrial fission is known to enhance cell migration, and we observed mitochondrial transport to the leading edge of protrusions of migrating AML cells toward MSCs by electron microscopy analysis. We further demonstrated that cytarabine, a commonly used antileukemia agent, increased OxPhos inhibition-triggered mitochondrial transfer from MSCs to AML cells. Our findings indicate an important role of exogenous mitochondrial trafficking from BM stromal cells to AML cells as well as endogenous mitochondrial fission and mitophagy in the compensatory adaptation of leukemia cells to energetic stress in the BM microenvironment.

Notch-induced endoplasmic reticulum-associated degradation governs mouse thymocyte β- selection

Signals from the pre-T cell receptor and Notch coordinately instruct b-selection of CD4-CD8- double negative (DN) thymocytes to generate ab T cells in the thymus. However, how these signals ensure a high-fidelity proteome and safeguard the clonal diversification of the pre-selection TCR repertoire given the considerable translational activity imposed by b-selection is largely unknown. Here, we identify the endoplasmic reticulum (ER)-associated degradation (ERAD) machinery as a critical proteostasis checkpoint during b-selection. Expression of the SEL1L-HRD1 complex, the most conserved branch of ERAD, is directly regulated by the transcriptional activity of the Notch intracellular domain. Deletion of Sel1l impaired DN3 to DN4 thymocyte transition and severely impaired mouse ab T cell development. Mechanistically, Sel1l deficiency induced unresolved ER stress that triggered thymocyte apoptosis through the PERK pathway. Accordingly, genetically inactivating PERK rescued T cell development from Sel1l-deficient thymocytes. In contrast, IRE1a/XBP1 pathway was induced as a compensatory adaptation to alleviate Sel1l-deficiency induced ER stress. Dual loss of Sel1l and Xbp1 markedly exacerbated the thymic defect. Our study reveals a critical developmental signal controlled proteostasis mechanism that enforces T cell development to ensure a healthy adaptive immunity.

MORPHOLOGICAL AND ANATOMICAL FEATURES OF AGE STATES OF Scutellaria stevenii Juz. (Scutellaria orientalis subsp. orientalis) IN PHYTOCОENOSES OF THE CRIMEA FOOTHILLS

The life cycle implementation features for most plants are species-specific, which is reflected in a change in the morphological, anatomical and physiological spheres of the plant. A study of plant ontogenesis allows a deeper understanding of both the coenotic features of the population and the degree of influence of the environment on the implementation of plant ontomorphogenesis. This work is devoted to the study of the life cycle of one of the taxonomically controversial species for Crimea - Scutellaria stevenii Juz. Ontogenesis study of Scutellaria stevenii was carried out in nature and for seedlings and juvenile individuals in a laboratory. The concept of a discrete description of ontogenesis was used to describe the life cycle of Scutellaria stevenii, under which to revealed a group of anatomical and morphological features characteristic of each onotogenetic state.The study of the anatomical structure of the vegetative organs (root, stem, flower-bearing shoot) was carried out using temporary preparations of a living tissue with standard methods. In this study the life cycle of Scutellaria stevenii contains 4 ontogenetic periods and 10 age states, which are realized in full or partial ontogenesis. In the case of normal development, ontogenesis of genets lasts 10-16 years. In virginal individuals growing on mobile ecotopes, a polyvariant type of development have been found. Polyvariant individuals form the primary bush with xylorizomes of different lengths which carry the function of additional fixation in the soil and the formation of partial bushes that lose their connection with the primary individual by the generative age. The ability of pregenerative individuals to vegetatively established in our study can be considered as compensatory adaptation due to the high death of seedlings in natural phytocоenoses. The anatomical features of the stem and root of various age states to identify morphologically unexpressed incomplete partition. These criteria is an important addition to the morphological identification of age.

Stress induces divergent gene expression among lateral habenula efferent pathways

The lateral habenula (LHb) integrates critical information regarding aversive stimuli that shapes decision making and behavioral responses. The three major LHb outputs innervate dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and the rostromedial tegmental nucleus (RMTg). LHb neurons that project to these targets are segregated and nonoverlapping, and this led us to consider whether they have distinct molecular phenotypes and adaptations to stress exposure. In order to capture a time-locked profile of gene expression after repeated forced swim stress, we used intersectional expression of RiboTag in rat LHb neurons and next-gen RNA sequencing to interrogate the RNAs actively undergoing translation from each of these pathways. The “translatome” in the neurons comprising these pathways was similar at baseline, but diverged after stress, especially in the neurons projecting to the RMTg. Using weighted gene co-expression network analysis, we found one module comprising genes downregulated after stress in the RMTg-projecting LHb neurons; there was an overrepresentation of genes associated with phosphoinositide 3 kinase (PI3K) signaling in this module. Reduced PI3K signaling in RMTg-projecting LHb neurons may be a compensatory adaptation that alters the functional balance of LHb outputs to GABAergic vs. monoaminergic neurons following repeated stress exposure.

Examining the effectiveness of compensatory adaptation from a consumer's perspective in evaluating products online

PurposeConsumers often encounter issues of perceived ambiguity and performance risk when attempting to evaluate experience goods being offered online. Sellers try to alleviate this knowledge gap often seen in a medium of low naturalness by engaging in effective compensatory adaptation. This research theoretically looks into three primary aspects of compensatory adaption and their potential in securing communication of high-quality information between the online seller and consumer.Design/methodology/approachUtilizing survey data and structural equation modeling, this study tests the effectiveness of different aspects of compensatory adaption to alleviate the knowledge gap in a medium of low naturalness.FindingsDrawing on media naturalness theory and the tripartite model of attitude, this paper identifies three theoretical components that significantly affect the effectiveness of compensatory adaption. They are information retrieval capability from the cognitive/logical aspect, information richness from the affective/audiovisual aspect and interactivity from the behavioral aspect. The effectiveness of compensatory adaptation proves to have a positive impact on perceived information quality.Originality/valueTo the best of our knowledge, this is the first paper in the information systems literature to examine the compensatory adaptation tools for effective transfer of information. This study contributes to the academics by providing three handles to improve effectiveness of compensatory adaptation toward information quality. We focus on three compensatory adaptation tools in cognitive/logical, affective/audiovisual and behavioral aspects, and this compensation perspective leads to three practical factors that affect effective transfer of information between online sellers and consumers. The result of this study complements the nomological network of the enablers and impediments of e-commerce.

Sexual Selection Does Not Increase the Rate of Compensatory Adaptation to a Mutation Influencing a Secondary Sexual Trait in Drosophila melanogaster

Theoretical work predicts that sexual selection can enhance natural selection, increasing the rate of adaptation to new environments and helping purge harmful mutations. While some experiments support these predictions, remarkably little work has addressed the role of sexual selection on compensatory adaptation—populations’ ability to compensate for the costs of deleterious alleles that are already present. We tested whether sexual selection, as well as the degree of standing genetic variation, affect the rate of compensatory evolution via phenotypic suppression in experimental populations of Drosophila melanogaster. These populations were fixed for a spontaneous mutation causing mild abnormalities in the male sex comb, a structure important for mating success. We fine-mapped this mutation to an ∼85 kb region on the X chromosome containing three candidate genes, showed that the mutation is deleterious, and that its phenotypic expression and penetrance vary by genetic background. We then performed experimental evolution, including a treatment where opportunity for mate choice was limited by experimentally enforced monogamy. Although evolved populations did show some phenotypic suppression of the morphological abnormalities in the sex comb, the amount of suppression did not depend on the opportunity for sexual selection. Sexual selection, therefore, may not always enhance natural selection; instead, the interaction between these two forces may depend on additional factors.