Miracle-dz/UniFAR-FTUs huggingface dataset:
Postsynaptic Neuroligin-1 Mediates Presynaptic Endocytosis During Neuronal Activity

Fast, high-fidelity neurotransmission and synaptic efficacy requires tightly regulated coordination of pre- and postsynaptic compartments and alignment of presynaptic release sites with postsynaptic receptor nanodomains. Neuroligin-1 (Nlgn-1) is a postsynaptic cell-adhesion protein exclusively localised to excitatory synapses that is crucial for coordinating the transsynaptic alignment of presynaptic release sites with postsynaptic AMPA receptors as well as postsynaptic transmission and plasticity. However, little is understood about whether the postsynaptic machinery can mediate the molecular architecture and activity of the presynaptic nerve terminal, and thus it remains unclear whether there are presynaptic contributions to Nlgn1-dependent control of signalling and plasticity. Here, we employed a presynaptic reporter of neurotransmitter release and synaptic vesicle dynamics, synaptophysin-pHluorin (sypHy), to directly assess the presynaptic impact of loss of Nlgn1. We show that lack of Nlgn1 had no effect on the size of the readily releasable or entire recycling pool of synaptic vesicles, nor did it impact exocytosis. However, we observed significant changes in the retrieval of synaptic vesicles by compensatory endocytosis, specifically during activity. Our data extends growing evidence that synaptic adhesion molecules critical for forming transsynaptic scaffolds are also important for regulating activity-induced endocytosis at the presynapse.
Diffusion- and Susceptibility Weighted Imaging Mismatch Correlates With Collateral Circulation and Prognosis After Middle Cerebral Artery M1-Segment Occlusion

Objective: To explore the relation between diffusion-weighted and susceptibility weighted imaging (DWI-SWI) mismatch and collateral circulation or prognosis in patients with occluded M1 segments of middle cerebral artery (MCA). Methods: We enrolled 59 patients with MCA M1-segment occlusion for a retrospective review of baseline clinical and imaging data. As markers of circulatory collaterals, prominent laterality of posterior (PLPCA) and anterior (PLACA) cerebral arteries on magnetic resonance angiography (MRA) studies and a hyperintense vessel sign (HVS) on T2 fluid-attenuated inversion recovery (FLAIR) images were collectively scored. The extent of acute cerebral infarction was then quantified on DWI, using the Alberta Stroke Program Early CT Score (DWI-ASPECTS). Hypointensity vessel sign prominence (PVS) was also evaluated by SWI and similarly scored (SWI-ASPECT) to calculate DWI-SWI mismatch [(DWI-ASPECTS) – (SWI-ASPECTS)], ranging from −10 to 10 points. Results: DWI-SWI mismatch showed significant associations with PLPCA, PLACA, HVS prominence, and collective collateral scores (all, p < 0.05). National Institutes of Health Stroke Scale (NIHSS), DWI-SWI mismatch, and DWI-ASPECTS also differed significantly according to patient prognosis (good vs. poor) after MCA M1-segment occlusion (p < 0.05). In binary logistic regression analyses, NIHSS and DWI-SWI mismatch emerged as independent prognostic factors (p < 0.05). Conclusions: Collateral circulation may be an important aspect of DWI-SWI mismatch, which in this study correlated with prognostic outcomes of MCA M1-segment occlusion.
Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

Tinnitus, a phantom auditory perception that can seriously affect quality of life, is generally triggered by cochlear trauma and associated with aberrant activity throughout the auditory pathways, often referred to as hyperactivity. Studies suggest that non-auditory structures, such as prefrontal cortex (PFC), may be involved in tinnitus generation, by affecting sensory gating in auditory thalamus, allowing hyperactivity to reach the cortex and lead to perception. Indeed, human studies have shown that repetitive transcranial magnetic stimulation (rTMS) of PFC can alleviate tinnitus. The current study investigated whether this therapeutic effect is achieved through inhibition of thalamic hyperactivity, comparing effects of two common clinical rTMS protocols with sham treatment, in a guinea pig tinnitus model. Animals underwent acoustic trauma and once tinnitus developed were treated with either intermittent theta burst stimulation (iTBS), 20 Hz rTMS, or sham rTMS (10 days, 10 min/day; weekdays only). Tinnitus was reassessed and extracellular recordings of spontaneous tonic and burst firing rates in auditory thalamus made. To verify effects in PFC, densities of neurons positive for calcium-binding proteins, calbindin and parvalbumin, were investigated using immunohistochemistry. Both rTMS protocols significantly reduced tinnitus compared to sham. However, spontaneous tonic firing decreased following 20 Hz stimulation and increased following iTBS in auditory thalamus. Burst rate was significantly different between 20 Hz and iTBS stimulation, and burst duration was increased only after 20 Hz treatment. Density of calbindin, but not parvalbumin positive neurons, was significantly increased in the most dorsal region of PFC indicating that rTMS directly affected PFC. Our results support the involvement of PFC in tinnitus modulation, and the therapeutic benefit of rTMS on PFC in treating tinnitus, but indicate this is not achieved solely by suppression of thalamic hyperactivity.
Supporting Actionable Science for Environmental Policy: Advice for Funding Agencies From Decision Makers

Successful incorporation of scientific knowledge into environmental policy and decisions is a significant challenge. Although studies on how to bridge the knowledge-action gap have proliferated over the last decade, few have investigated the roles, responsibilities, and opportunities for funding bodies to meet this challenge. In this study we present a set of criteria gleaned from interviews with experts across Canada that can be used by funding bodies to evaluate the potential for proposed research to produce actionable knowledge for environmental policy and practice. We also provide recommendations for how funding bodies can design funding calls and foster the skills required to bridge the knowledge-action gap. We interviewed 84 individuals with extensive experience as knowledge users at the science-policy interface who work for environmentally-focused federal and provincial/territorial government bodies and non-governmental organizations. Respondents were asked to describe elements of research proposals that indicate that the resulting research is likely to be useful in a policy context, and what advice they would give to funding bodies to increase the potential impact of sponsored research. Twenty-five individuals also completed a closed-ended survey that followed up on these questions. Research proposals that demonstrated (1) a team with diverse expertise and experience in co-production, (2) a flexible research plan that aligns timelines and spatial scale with policy needs, (3) a clear and demonstrable link to a policy issue, and (4) a detailed and diverse knowledge exchange plan for reaching relevant stakeholders were seen as more promising for producing actionable knowledge. Suggested changes to funding models to enhance utility of funded research included (1) using diverse expertise to adjudicate awards, (2) supporting co-production and interdisciplinary research through longer grant durations and integrated reward structures, and (3) following-up on and rewarding knowledge exchange by conducting impact evaluation. The set of recommendations presented here can guide both funding agencies and research teams who wish to change how applied environmental science is conducted and improve its connection to policy and practice.
The Different Facets of Heart Rate Variability in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA), a heterogeneous and multifactorial sleep related breathing disorder with high prevalence, is a recognized risk factor for cardiovascular morbidity and mortality. Autonomic dysfunction leads to adverse cardiovascular outcomes in diverse pathways. Heart rate is a complex physiological process involving neurovisceral networks and relative regulatory mechanisms such as thermoregulation, renin-angiotensin-aldosterone mechanisms, and metabolic mechanisms. Heart rate variability (HRV) is considered as a reliable and non-invasive measure of autonomic modulation response and adaptation to endogenous and exogenous stimuli. HRV measures may add a new dimension to help understand the interplay between cardiac and nervous system involvement in OSA. The aim of this review is to introduce the various applications of HRV in different aspects of OSA to examine the impaired neuro-cardiac modulation. More specifically, the topics covered include: HRV time windows, sleep staging, arousal, sleepiness, hypoxia, mental illness, and mortality and morbidity. All of these aspects show pathways in the clinical implementation of HRV to screen, diagnose, classify, and predict patients as a reasonable and more convenient alternative to current measures.
The Muscle Activation Differences in Post-Stroke Upper Limb Flexion Synergy Based on Spinal Cord Segments: A Preliminary Proof-of-Concept Study

Objective: This study examined the activation difference of muscles innervated by cervical cord 5-6 (C5-C6) and cervical cord 8- thoracic cord 1 (C8-T1) in upper limb flexion synergy after stroke. Methods: Surface electromyography (sEMG) signals were collected during elbow flexion in stroke patients and healthy controls. The study compared normalized activation of two pairs of muscles that could cause similar joint movement but which dominated different spinal cord segments (clavicular part of the pectoralis major, PC vs. Sternocostal part of the pectoralis major, PS; Flexor carpi radialis, FCR vs. Flexor carpi ulnaris, FCU). In each muscle pair, one muscle was innervated by the same spinal cord segment (C5-C6), dominating the elbow flexion and the other was not. The comparison of the activation of the same muscle between patients and healthy controls was undertaken after standardization based on the activation of the biceps brachii in elbow flexion. Results: There was no difference between the PC and PS's normalized activation in healthy controls while the PC's normalized activation was higher than PS in stroke patients during elbow flexion. Similarly, there was no significant difference in normalized activation between FCR and FCU in healthy controls, and the same is true for stroke patients. However, the standardized activation of both FCR and FCU in stroke patients was significantly lower than that in healthy controls. Conclusion: After stroke, the activation of the distal muscles of the upper limb decreased significantly regardless of the difference of spinal cord segments; while the activation of the proximal muscles innervated by the same spinal cord segment (C5-C6) dominating the elbow flexion showed higher activation during flexion synergy. The difference in muscle activation based on spinal cord segments may be the reason for the stereotyped joint movement of upper limb flexion synergy.
Sex Differences are Reflected in Microstructural White Matter Alterations of Musical Sophistication: A Diffusion MRI Study

Background: The human-specified ability to engage with different kinds of music in sophisticated ways is named “Musical Sophistication. ” Herein, we investigated specific white matter (WM) tracts that are associated with musical sophistication and musicality in both genders, separately, using Diffusion MRI connectometry approach. We specifically aimed to explore potential sex differences regarding WM alterations correlated with musical sophistication. Methods: 123 healthy participants [70 (56.9%) were male, mean age = 36.80 ± 18.86 year], who were evaluated for musical sophistication using Goldsmiths Musical Sophistication Index (Gold-MSI) self-assessment instrument from the LEMON database, were recruited in this study. The WM correlates of two Gold-MSI subscales (active engagement and music training) were analyzed. Images were prepared and analyzed with diffusion connectometry to construct the local connectome. Multiple regression models were then fitted to address the correlation of local connectomes with Gold-MSI components with the covariates of age and handedness. Results: a significant positive correlation between WM integrity in the corpus callosum (CC), right corticospinal tract (CST), cingulum, middle cerebellar peduncle (MCP), bilateral parieto-pontine tract, bilateral cerebellum, and left arcuate fasciculus (AF) and both active engagement [false discovery rate (FDR) = 0.008] and music training (FDR = 0.057) was detected in males. However, WM integrity in the body of CC, MCP, and cerebellum in females showed an inverse association with active engagement (FDR = 0.046) and music training (FDR = 0.032). Conclusion: WM microstructures with functional connection with motor and somatosensory areas (CST, cortico-pontine tracts, CC, cerebellum, cingulum, and MCP) and language processing area (AF) have significant correlation with music engagement and training. Our findings show that these associations are different between males and females, which could potentially account for distinctive mechanisms related to musical perception and musical abilities across genders.
Epigenetics of Male Infertility: The Role of DNA Methylation

In recent years, a number of studies focused on the role of epigenetics, including DNA methylation, in spermatogenesis and male infertility. We aimed to provide an overview of the knowledge concerning the gene and genome methylation and its regulation during spermatogenesis, specifically in the context of male infertility etiopathogenesis. Overall, the findings support the hypothesis that sperm DNA methylation is associated with sperm alterations and infertility. Several genes have been found to be differentially methylated in relation to impaired spermatogenesis and/or reproductive dysfunction. Particularly, DNA methylation defects of MEST and H19 within imprinted genes and MTHFR within non-imprinted genes have been repeatedly linked with male infertility. A deep knowledge of sperm DNA methylation status in association with reduced reproductive potential could improve the development of novel diagnostic tools for this disease. Further studies are needed to better elucidate the mechanisms affecting methylation in sperm and their impact on male infertility.
An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-Dependent

Adult hematopoietic stem and progenitor cells (HSPCs) respond to bacterial infections by expansion to myeloid cells. Sepsis impairs this process by suppressing differentiation of stem cells subsequently contributing to an ineffective immune response. Whether the magnitude of HSPCs impairment in sepsis is severity-dependent remains unknown. This study investigated dynamics of the HSPC immune-inflammatory response in the bone marrow, splenic, and blood compartments in moribund and surviving septic mice. The 12-week-old outbred CD-1 female mice (n=65) were subjected to a cecal ligation and puncture (CLP) sepsis, treated with antibiotics and fluid resuscitation, and stratified into predicted-to-die (P-DIE) and predicted-to-survive (P-SUR) cohorts for analysis. CLP strongly reduced the common myeloid and multipotent progenitors, short- and long-term hematopoietic stem cell (HSC) counts in the bone marrow; lineage−ckit+Sca-1+ and short-term HSC suppression was greater in P-DIE versus P-SUR mice. A profound depletion of the common myeloid progenitors occurred in the blood (by 75%) and spleen (by 77%) of P-DIE. In P-SUR, most common circulating HSPCs subpopulations recovered to baseline by 72 h post-CLP. Analysis of activated caspase-1/-3/-7 revealed an increased apoptotic (by 30%) but not pyroptotic signaling in the bone marrow HSCs of P-DIE mice. The bone marrow from P-DIE mice revealed spikes of IL-6 (by 5-fold), CXCL1/KC (15-fold), CCL3/MIP-1α (1.7-fold), and CCL2/MCP-1 (2.8-fold) versus P-SUR and control (TNF, IFN-γ, IL-1β, -5, -10 remained unaltered). Summarizing, our findings demonstrate that an early sepsis-induced impairment of myelopoiesis is strongly outcome-dependent but varies among compartments. It is suggestive that the HSCPC loss is at least partly due to an increased apoptosis but not pyroptosis.
Proactive Personality Measurement Using Item Response Theory and Social Media Text Mining

This prospective study was designed to propose a novel method of assessing proactive personality by combining text mining technology and Item Response Theory (IRT) to measure proactive personality more efficiently. We got freely expressed texts (essay question text dataset and social media text dataset) and item response data on the topic of proactive personality from 901 college students. To enhance validity and reliability, three different approaches were employed in the study. In Method 1, we used item response data to develop a proactive personality evaluation model based on IRT. In Method 2, we used freely expressed texts to develop a proactive personality evaluation model based on text mining. In Method 3, we utilized the text mining results as the prior information for the IRT estimation and built a proactive personality evaluation model combining text mining and IRT. Finally, we evaluated those three approaches via the confusion matrix indicators. The major result revealed that (1) the combined method based on essay question text, micro-blog text with pre-estimated IRT parameters performed the highest accuracy of 0.849; (2) the combined method using essay question text and pre-estimated IRT parameters performed the highest sensitivity of 0.821; (3) the text classification method based on essay question text had the best performance on the specificity of 0.959; and (4) if the models were considered comprehensively, the combined method using essay question text, micro-blog text, and pre-estimated IRT parameters achieved the best performance. Thus, we concluded that the novel combined method was significantly better than the other two traditional methods based on IRT and text mining.
Lifelong Bilingualism Functions as an Alternative Intervention for Cognitive Reserve Against Alzheimer's Disease

Bilingualism has been reported to significantly delay the onset of dementia and plays an important role in the management of Alzheimer's disease (AD), a condition inducing impairment in the brain network and cognitive decline. Cognitive reserve is associated with the adaptive maintenance of neural functions by protecting against neuropathology. Bilingualism acts as a beneficial environmental factor contributing to cognitive reserve, although some potential confounding variables still need further elucidation. In this article, the relationship between bilingualism and cognitive reserve is discussed, interpreting the advantage of bilingualism in protecting against cognitive decline. In addition, the possible brain and biochemical mechanisms, supporting the advantageous effects of bilingualism in delaying the onset of dementia, involved in bilingualism are reviewed. Effectively, bilingualism can be considered as a pharmacological intervention with no side effects. However, the investigation of the pharmacological parameters of bilingualism is still at an early stage.
Psychological Capital and Career Commitment Among Chinese Urban Preschool Teachers: The Mediating and Moderating Effects of Subjective Well-being

This study explored the effects of psychological capital (PsyCap) on career commitment among preschool teachers in China, with a particular focus on the mediating effects of subjective well-being (SWB). A total of 759 teachers were subjected to the PsyCap Questionnaire and Career Commitment Scale. The data were analyzed and used for structural modeling with Mplus Version 7.4. Results indicated that PsyCap positively influenced career commitment, with SWB significantly mediating and moderating this causal association. Thus, the influence of PsyCap on career commitment is improved through enhanced SWB. These findings highlight avenues for improving both PsyCap and career commitment in the Chinese context among urban preschool teachers.
Myogenic Tone in Peripheral Resistance Arteries and Arterioles: The Pressure Is On!

Resistance arteries and downstream arterioles in the peripheral microcirculation contribute substantially to peripheral vascular resistance, control of blood pressure, the distribution of blood flow to and within tissues, capillary pressure, and microvascular fluid exchange. A hall-mark feature of these vessels is myogenic tone. This pressure-induced, steady-state level of vascular smooth muscle activity maintains arteriolar and resistance artery internal diameter at 50–80% of their maximum passive diameter providing these vessels with the ability to dilate, reducing vascular resistance, and increasing blood flow, or constrict to produce the opposite effect. Despite the central importance of resistance artery and arteriolar myogenic tone in cardiovascular physiology and pathophysiology, our understanding of signaling pathways underlying this key microvascular property remains incomplete. This brief review will present our current understanding of the multiple mechanisms that appear to underlie myogenic tone, including the roles played by G-protein-coupled receptors, a variety of ion channels, and several kinases that have been linked to pressure-induced, steady-state activity of vascular smooth muscle cells (VSMCs) in the wall of resistance arteries and arterioles. Emphasis will be placed on the portions of the signaling pathways underlying myogenic tone for which there is lack of consensus in the literature and areas where our understanding is clearly incomplete.
Respiratory Viral and Bacterial Factors That Influence Early Childhood Asthma

Asthma is a chronic respiratory condition characterised by episodes of shortness of breath due to reduced airway flow. The disease is triggered by a hyperreactive immune response to innocuous allergens, leading to hyper inflammation, mucus production, changes in structural cells lining the airways, and airway hyperresponsiveness. Asthma, although present in adults, is considered as a childhood condition, with a total of about 6.2 million children aged 18 and below affected globally. There has been progress in understanding asthma heterogeneity in adults, which has led to better patient stratification and characterisation of multiple asthma endotypes with distinct, but overlapping inflammatory features. The asthma inflammatory profile in children is not well-defined and heterogeneity of the disease is less described. Although many factors such as genetics, food allergies, antibiotic usage, type of birth, and cigarette smoke exposure can influence asthma development particularly in children, respiratory infections are thought to be the major contributing factor in poor lung function and onset of the disease. In this review, we focus on viral and bacterial respiratory infections in the first 10 years of life that could influence development of asthma in children. We also review literature on inflammatory immune heterogeneity in asthmatic children and how this overlaps with early lung development, poor lung function and respiratory infections. Finally, we review animal studies that model early development of asthma and how these studies could inform future therapies and better understanding of this complex disease.