Miracle-dz/UniFAR-FTUs huggingface dataset:
Lithium Chloride Dependent Glycogen Synthase Kinase 3 Inactivation Links Oxidative DNA Damage, Hypertrophy and Senescence in Human Articular Chondrocytes and Reproduces Chondrocyte Phenotype of Obese Osteoarthritis Patients

Introduction Recent evidence suggests that GSK3 activity is chondroprotective in osteoarthritis (OA), but at the same time, its inactivation has been proposed as an anti-inflammatory therapeutic option. Here we evaluated the extent of GSK3β inactivation in vivo in OA knee cartilage and the molecular events downstream GSK3β inactivation in vitro to assess their contribution to cell senescence and hypertrophy. Methods In vivo level of phosphorylated GSK3β was analyzed in cartilage and oxidative damage was assessed by 8-oxo-deoxyguanosine staining. The in vitro effects of GSK3β inactivation (using either LiCl or SB216763) were evaluated on proliferating primary human chondrocytes by combined confocal microscopy analysis of Mitotracker staining and reactive oxygen species (ROS) production (2',7'-dichlorofluorescin diacetate staining). Downstream effects on DNA damage and senescence were investigated by western blot (γH2AX, GADD45β and p21), flow cytometric analysis of cell cycle and light scattering properties, quantitative assessment of senescence associated β galactosidase activity, and PAS staining. Results In vivo chondrocytes from obese OA patients showed higher levels of phosphorylated GSK3β, oxidative damage and expression of GADD45β and p21, in comparison with chondrocytes of nonobese OA patients. LiCl mediated GSK3β inactivation in vitro resulted in increased mitochondrial ROS production, responsible for reduced cell proliferation, S phase transient arrest, and increase in cell senescence, size and granularity. Collectively, western blot data supported the occurrence of a DNA damage response leading to cellular senescence with increase in γH2AX, GADD45β and p21. Moreover, LiCl boosted 8-oxo-dG staining, expression of IKKα and MMP-10. Conclusions In articular chondrocytes, GSK3β activity is required for the maintenance of proliferative potential and phenotype. Conversely, GSK3β inactivation, although preserving chondrocyte survival, results in functional impairment via induction of hypertrophy and senescence. Indeed, GSK3β inactivation is responsible for ROS production, triggering oxidative stress and DNA damage response.
Chlamydomonas reinhardtii PsbS Protein Is Functional and Accumulates Rapidly and Transiently under High Light1

Photoprotective proteins PsbS and LhcSR3 accumulate rapidly in the photosynthetic membrane of Chlamydomonas during highlight stress with PsbS activating nonphotochemical quenching. Photosynthetic organisms must respond to excess light in order to avoid photo-oxidative stress. In plants and green algae the fastest response to high light is non-photochemical quenching (NPQ), a process that allows the safe dissipation of the excess energy as heat. This phenomenon is triggered by the low luminal pH generated by photosynthetic electron transport. In vascular plants the main sensor of the low pH is the PsbS protein, while in the green alga Chlamydomonas reinhardtii LhcSR proteins appear to be exclusively responsible for this role. Interestingly, Chlamydomonas also possesses two PsbS genes, but so far the PsbS protein has not been detected and its biological function is unknown. Here, we reinvestigated the kinetics of gene expression and PsbS and LhcSR3 accumulation in Chlamydomonas during high light stress. We found that, unlike LhcSR3, PsbS accumulates very rapidly but only transiently. In order to determine the role of PsbS in NPQ and photoprotection in Chlamydomonas, we generated transplastomic strains expressing the algal or the Arabidopsis psbS gene optimized for plastid expression. Both PsbS proteins showed the ability to increase NPQ in Chlamydomonas wild-type and npq4 (lacking LhcSR3) backgrounds, but no clear photoprotection activity was observed. Quantification of PsbS and LhcSR3 in vivo indicates that PsbS is much less abundant than LhcSR3 during high light stress. Moreover, LhcSR3, unlike PsbS, also accumulates during other stress conditions. The possible role of PsbS in photoprotection is discussed.
Risky Play and Children’s Safety: Balancing Priorities for Optimal Child Development

Injury prevention plays a key role in keeping children safe, but emerging research suggests that imposing too many restrictions on children’s outdoor risky play hinders their development. We explore the relationship between child development, play, and conceptions of risk taking with the aim of informing child injury prevention. Generational trends indicate children’s diminishing engagement in outdoor play is influenced by parental and societal concerns. We outline the importance of play as a necessary ingredient for healthy child development and review the evidence for arguments supporting the need for outdoor risky play, including: (1) children have a natural propensity towards risky play; and, (2) keeping children safe involves letting them take and manage risks. Literature from many disciplines supports the notion that safety efforts should be balanced with opportunities for child development through outdoor risky play. New avenues for investigation and action are emerging seeking optimal strategies for keeping children “as safe as necessary,” not “as safe as possible. ” This paradigm shift represents a potential for epistemological growth as well as cross-disciplinary collaboration to foster optimal child development while preserving children’s safety.
A cohort study of patients undergoing distal tibial osteotomy without fibular osteotomy for medial ankle arthritis with mortise widening.

BACKGROUND Although the supramalleolar osteotomy can shift the weight-bearing axis laterally, it cannot reconstruct a widened ankle mortise caused by progression of medial ankle osteoarthritis. The aim of this study was to evaluate radiographic and clinical outcomes of distal tibial osteotomy without fibular osteotomy in patients with medial ankle osteoarthritis and mortise widening. METHODS Distal tibial osteotomy without fibular osteotomy was performed in eighteen patients to treat medial ankle osteoarthritis with mortise widening. Fifteen women and three men with a mean age of fifty-seven years (range, forty-nine to sixty-four years) were followed for a mean of thirty-four months (range, twenty-four to sixty-six months). Mortise widening was diagnosed using valgus stress radiographs and intraoperative examination. The clinical outcome was assessed with the American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analog scale (VAS) score for pain, and the ankle osteoarthritis scale (AOS) score. The translation of the talus within the ankle mortise, talar tilt, medial distal tibial angle, and anterior distal tibial angle were evaluated on weight-bearing radiographs made preoperatively and postoperatively. RESULTS The AOFAS score improved significantly from 78.4 points (95% confidence interval [CI], 74.6 to 80.5 points) to 89 points (95% CI, 86.5 to 90.5 points) (p < 0.001). The VAS score for pain also decreased significantly from 6.7 points (95% CI, 6 to 7.5 points) to 2.7 points (95% CI, 2.3 to 3.3 points) (p < 0.001). The mean AOS score was 29.8 points (95% CI, 22 to 38.2 points) at the latest follow-up. The center of the talus moved laterally within the ankle mortise after the distal tibial osteotomy. The mean medial distal tibial angle changed from 86.6° (95% CI, 85.7° to 87.6°) to 92.9° (95% CI, 91.6° to 94.3°) (p < 0.001), and the mean anterior distal tibial angle changed from 81.1° (95% CI, 78.6° to 83.6°) to 84.3° (95% CI, 81.9° to 86.4°) (p < 0.001). However, talar tilt was not corrected significantly (p = 0.916). CONCLUSIONS Distal tibial osteotomy without fibular osteotomy reduces pain in the short term in patients with ankle arthritis, a widened mortise, and minimal talar tilt.
New insights on transcriptional responses of genes involved in carbon central metabolism, respiration and fermentation to low ATP levels in Escherichia coli

Adenosine‐5‐triphosphate (ATP) plays a fundamental role in many cellular processes such as transport, central carbon metabolism, biosynthetic reactions, macromolecular synthesis, signal transduction and cellular division. In addition, the intracellular [ATP]/[ADP] ratio in Escherichia coli plays an important role in controlling the specific rates of growth (µ), glucose consumption (qGlc) and oxygen uptake (qO2), as well as the transcriptome pattern in the cell, as was recently reported. In the current study, the energetic level (expressed as [ATP]/[ADP] ratio) was substantially reduced in E. coli strains by either over‐expressing the F1‐ATPase activity (JMAGD+) or inactivating ATP synthase (JMat−). The physiological characterization of the wild‐type JM101 strain and its derivative JMAGD+ and JMatp− strains was conducted in bioreactors containing minimal medium with glucose. The inactivation of the atp operon and F1‐ATPase overexpression significantly diminished the energetic level and cAMP concentration in derivative strains. Relative transcription levels of 105 genes involved in glucose transport, glycolysis, tricarboxylic acid (TCA) cycle, fermentation, respiration, transcriptional regulators, transcription and genes involved in stress were determined by using qPCR. Interestingly, in the JMAGD+ and JMatp− strains, having a reduced energetic level, many transcripts of glycolysis, TCA cycle and respiratory genes were down‐regulated when compared to wild type JM101. The transcriptional responses, detected in the strains with reduced energetic level show down‐regulation of genes involved in central carbon metabolism and respiration, these results are apposite to the observed trends of increased metabolic fluxes in glucose consumption, glycolysis, acetate synthesis, TCA cycle and respiration. Regulation mediated by CRP‐cAMP complex may explain some observed transcriptional responses of TCA cycle genes, since cAMP concentration and crp transcript level were significant reduced in the JMatp− mutant. Therefore, the substantial reduction of [ATP]/[ADP] ratio had a relevant effect on the CRP‐cAMP regulatory system (among other global regulators), which may trigger an extensive transcriptional response.
Excretion of sodium, potassium, chloride and carbon dioxide in human parotid saliva.

H EIDENHAIN (I) first demonstrated that the concentration of inorganic salts in the submaxillary saliva of dogs varies in proportion to the secretory rate. Gregersen and Ingalls (2) showed that the concentration of sodium increases with increasing rates of secretion, whereas the concentration of potassium is independent of salivary flow. This finding has been confirmed by later investigators working on submaxillary saliva of various animals (3-5) and on human mixed saliva (6). In the present experiments the concentrations of sodium, potassium, bicarbonate, and chloride were measured simultaneously in human parotid saliva following stimulation of the secretion by the subcutaneous injection of beta-methyl-acetylcholine hydrochloride. The results obtained on the relative rates of excretion of potassium and sodium by the parotid gland are compatible with the hypothesis that both cations are brought into a precursor solution at a rate which varies in direct proportion to the rate of salivary flow, and that sodium is withdrawn from this precursor solution by a process of reabsorption which is limited by a maximal capacity.
Immigrants’ Satisfaction With Regional Employment: A Human Agency Perspective

Attracting and retaining immigrant workers is a challenge in Canadian regions, where many employers face labor shortages. Based on an agency framework, this study explores immigrants’ satisfaction with settling in a region and how they have engaged, are engaging, or plan to engage in strategies to improve their work and life satisfaction. The results of focus group discussions and interviews with 41 immigrants enable us to classify them in a two-by-two table: satisfied, unsatisfied, work-oriented, and community-oriented. As agents, immigrants develop two broad strategies that impact their satisfaction: cognitive and behavioral. Our results put forward several benefits for employees, employers, communities, and society.
A Genomic Approach to Suberin Biosynthesis and Cork Differentiation1[C][W][OA]

Cork (phellem) is a multilayered dead tissue protecting plant mature stems and roots and plant healing tissues from water loss and injuries. Cork cells are made impervious by the deposition of suberin onto cell walls. Although suberin deposition and cork formation are essential for survival of land plants, molecular studies have rarely been conducted on this tissue. Here, we address this question by combining suppression subtractive hybridization together with cDNA microarrays, using as a model the external bark of the cork tree (Quercus suber), from which bottle cork is obtained. A suppression subtractive hybridization library from cork tree bark was prepared containing 236 independent sequences; 69% showed significant homology to database sequences and they corresponded to 135 unique genes. Out of these genes, 43.5% were classified as the main pathways needed for cork biosynthesis. Furthermore, 19% could be related to regulatory functions. To identify genes more specifically required for suberin biosynthesis, cork expressed sequence tags were printed on a microarray and subsequently used to compare cork (phellem) to a non-suberin-producing tissue such as wood (xylem). Based on the results, a list of candidate genes relevant for cork was obtained. This list includes genes for the synthesis, transport, and polymerization of suberin monomers such as components of the fatty acid elongase complexes, ATP-binding cassette transporters, and acyltransferases, among others. Moreover, a number of regulatory genes induced in cork have been identified, including MYB, No-Apical-Meristem, and WRKY transcription factors with putative functions in meristem identity and cork differentiation.
The Effects of Family and School Interpersonal Relationships on Depression in Chinese Elementary School Children: The Mediating Role of Academic Stress and the Moderating Role of Self-Esteem

This study explores the relative contributions and psychological mechanisms of the effects of family (father–child and mother–child) and school (teacher–student and student–student) interpersonal relationships on depression in elementary school children. The participants (n = 20,629) were elementary school children (48.19% male) aged nine to 13 years from Southwest China during the COVID-19 pandemic. They voluntarily completed questionnaires regarding parent–child, teacher–student, and student–student relationships, as well as academic stress and self-esteem. The results indicate that the effect of family interpersonal relationships on children’s depression was stronger than that of school interpersonal relationships. The predictive effects of father–child and mother–child relationships on children’s depression did not significantly differ; however, the effect of student–student relationships was significantly stronger than that of teacher–student relationships. Academic stress partially mediated the effect of interpersonal relationships on depression in elementary school children. The effects of family interpersonal relationships and academic stress on depression were moderated by self-esteem. These findings underscore the disparities and mechanisms pertaining to the impacts of diverse interpersonal associations on children’s depression, thus signifying significant implications for the advancement of research and intervention strategies aimed at addressing this issue.
SEASONAL DIFFERENCES IN IMMUNOLOGICAL CONDITION OF THREE SPECIES OF THRUSHES

Abstract Migratory birds are exposed to a diverse pathogen fauna by virtue of their long-distance travels. Although the immune system is an organism's primary defense against pathogenic microorganisms, few studies have investigated avian immune function during migration, much less shown seasonal differences in immune function. We describe the immunological condition of three intercontinental migratory species, Swainson's Thrush (Catharus ustulatus), Veery (C. fuscescens), and Wood Thrush (Hylocichla mustelina) during spring migration. In addition, we compare their immunological condition with conspecifics captured during fall migration and during the breeding season to provide a frame of reference for the spring immunological data. Measures of immunological condition presented include total leukocyte count, heterophil:lymphocyte (H:L) ratio, heterophil and lymphocyte counts, hematocrit, and IgG titers. In addition, we assessed each bird's energetic condition by measuring body mass and calculating a size-corrected condition index. Migrating birds had lower leukocyte and lymphocyte counts, lower hematocrit, reduced fat stores, and higher H:L ratios relative to nonmigrating individuals sampled during the breeding season. We also found that birds sampled during spring migration had lower lymphocyte counts and reduced fat stores, and higher heterophil counts and H:L ratios than fall migrants. Our results suggest that migrating birds are immunocompromised compared with conspecifics during the breeding season. Furthermore, compared with conspecifics sampled after a shorter overland flight, migrants sampled after crossing the Gulf of Mexico exhibited higher H:L ratios, which is indicative of heightened energetic stress.
Long-term climate commitments projected with climate-carbon cycle models

Eight earth system models of intermediate complexity (EMICs) are used to project climate change commitments for the recent Intergovernmental Panel on Climate Change’s (IPCC’s) Fourth Assessment Report (AR4). Simulations are run until the year 3000 A.D. and extend substantially farther into the future than conceptually similar simulations with atmosphere–ocean general circulation models (AOGCMs) coupled to carbon cycle models. In this paper the following are investigated: 1) the climate change commitment in response to stabilized greenhouse gases and stabilized total radiative forcing, 2) the climate change commitment in response to earlier CO2 emissions, and 3) emission trajectories for profiles leading to the stabilization of atmospheric CO2 and their uncertainties due to carbon cycle processes. Results over the twenty-first century compare reasonably well with results from AOGCMs, and the suite of EMICs proves well suited to complement more complex models. Substantial climate change commitments for sea level rise and global mean surface temperature increase after a stabilization of atmospheric greenhouse gases and radiative forcing in the year 2100 are identified. The additional warming by the year 3000 is 0.6–1.6 K for the low-CO2 IPCC Special Report on Emissions Scenarios (SRES) B1 scenario and 1.3–2.2 K for the high-CO2 SRES A2 scenario. Correspondingly, the post-2100 thermal expansion commitment is 0.3–1.1 m for SRES B1 and 0.5–2.2 m for SRES A2. Sea level continues to rise due to thermal expansion for several centuries after CO2 stabilization. In contrast, surface temperature changes slow down after a century. The meridional overturning circulation is weakened in all EMICs, but recovers to nearly initial values in all but one of the models after centuries for the scenarios considered. Emissions during the twenty-first century continue to impact atmospheric CO2 and climate even at year 3000. All models find that most of the anthropogenic carbon emissions are eventually taken up by the ocean (49%–62%) in year 3000, and that a substantial fraction (15%–28%) is still airborne even 900 yr after carbon emissions have ceased. Future stabilization of atmospheric CO2 and climate change requires a substantial reduction of CO2 emissions below present levels in all EMICs. This reduction needs to be substantially larger if carbon cycle–climate feedbacks are accounted for or if terrestrial CO2 fertilization is not operating. Large differences among EMICs are identified in both the response to increasing atmospheric CO2 and the response to climate change. This highlights the need for improved representations of carbon cycle processes in these models apart from the sensitivity to climate change. Sensitivity simulations with one single EMIC indicate that both carbon cycle and climate sensitivity related uncertainties on projected allowable emissions are substantial.
Safe anesthesia for endoscopic laryngeal laser surgery

Anesthesia safety for endoscopic laryngeal laser surgery has been a major limiting factor for laser applications in the larynx and the hypopharynx. Several anesthesia techniques have been proposed and each technique appears to have its own limitations. This paper will deal with the distinct advantages offered by the malleable copper tube which is used for delivery of the open Venturi system anesthesia for endoscopic laser surgery. A retrospective study of 100 patients who have undergone this modality of anesthesia at our institution will be presented. Our conclusion from this study shows clearly the superiority of the copper tube over the conventional aluminium‐foil‐wrapped endotracheal tube in safety and the exposure of the larynx during surgery.
Epidemiology of respiratory distress and the illness severity in late preterm or term infants: a prospective multi-center study.

BACKGROUND The severity of respiratory distress was associated with neonatal prognosis. This study aimed to explore the clinical characteristics, therapeutic interventions and short-term outcomes of late preterm or term infants who required respiratory support, and compare the usage of different illness severity assessment tools. METHODS Seven neonatal intensive care units in tertiary hospitals were recruited. From November 2008 to October 2009, neonates born at ≥ 34 weeks' gestational age, admitted at < 72 hours of age, requiring continuous positive airway pressure (CPAP) or mechanical ventilation for respiratory support were enrolled. Clinical data including demographic variables, underlying disease, complications, therapeutic interventions and short-term outcomes were collected. All infants were divided into three groups by Acute care of at-risk newborns (ACoRN) Respiratory Score < 5, 5 - 8, and > 8. RESULTS During the study period, 503 newborn late preterm or term infants required respiratory support. The mean gestational age was (36.8 ± 2.2) weeks, mean birth weight was (2734.5 ± 603.5) g. The majority of the neonates were male (69.4%), late preterm (63.3%), delivered by cesarean section (74.8%), admitted in the first day of life (89.3%) and outborn (born at other hospitals, 76.9%). Of the cesarean section, 51.1% were performed electively. Infants in the severe group were more mature, had the highest rate of elective cesarean section, Apgar score < 7 at 5 minutes and resuscitated with intubation, the in-hospital mortality increased significantly. In total, 58.1% of the patients were supported with mechanical ventilation and 17.3% received high frequency oscillation. Adjunctive therapies were commonly needed. Higher rate of infants in severe group needed mechanical ventilation or high frequency oscillation, volume expansion, bicarbonate infusion or vasopressors therapy (P < 0.05). The incidence of complications was also increased significantly in severe group (P < 0.05). The in-hospital mortality in the severe group was significantly higher than other two groups (P < 0.05). ACoRN Respiratory Score was correlated with Score for Neonatal Acute Physiology-Version II (SNAP-II) (P < 0.01). High gestational age, high SNAP-II score and oxygenation index (OI), and Apgar score at 5 minutes < 5 were independent risks for death. CONCLUSIONS Neonatal respiratory distress is still a common cause of hospitalization in China. Illness severity assessment is important for the management. ACoRN Respiratory Score which correlated with SNAP-II score is easy to use and may be helpful in facilitating the caregivers in local hospital to identify the early signs and make the transfer decision promptly.