Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycation of Plant Proteins: Regulatory Roles and Interplay with Sugar Signalling?

Glycation can be defined as an array of non-enzymatic post-translational modifications of proteins formed by their interaction with reducing carbohydrates and carbonyl products of their degradation. Initial steps of this process rely on reducing sugars and result in the formation of early glycation products—Amadori and Heyns compounds via Schiff base intermediates, whereas their oxidative degradation or reactions of proteins with α-dicarbonyl compounds yield a heterogeneous group of advanced glycation end products (AGEs). These compounds accompany thermal processing of protein-containing foods and are known to impact on ageing, pathogenesis of diabetes mellitus and Alzheimer’s disease in mammals. Surprisingly, despite high tissue carbohydrate contents, glycation of plant proteins was addressed only recently and its physiological role in plants is still not understood. Therefore, here we summarize and critically discuss the first steps done in the field of plant protein glycation during the last decade. We consider the main features of plant glycated proteome and discuss them in the context of characteristic metabolic background. Further, we address the possible role of protein glycation in plants and consider its probable contribution to protein degradation, methylglyoxal and sugar signalling, as well as interplay with antioxidant defense.
Long-range mobile signals mediate seasonal control of shoot growth

Significance In perennial plants such as long-lived trees growing in boreal and temperate forest, transition from summer to winter is associated with induction of growth cessation and bud set at the shoot apex. Where in the plant these seasonal shifts are perceived and how these are communicated to the shoot apex remain unresolved. We identify leaves as a site for perception of seasonal shifts and reveal that components of floral transition such as FLOWERING LOCUS T (FT) and plant hormone GA have been recruited to function as long-range signals to communicate seasonal changes perceived in leaves to the shoot apical meristem to control its activity to synchronize bud set with the change of seasons in perennials. In perennial plants, seasonal shifts provide cues that control adaptive growth patterns of the shoot apex. However, where these seasonal cues are sensed and communicated to the shoot apex remains unknown. We demonstrate that systemic signals from leaves play key roles in seasonal control of shoot growth in model tree hybrid aspen. Grafting experiments reveal that the tree ortholog of Arabidopsis flowering time regulator FLOWERING LOCUS T (FT) and the plant hormone gibberellic acid (GA) systemically convey seasonal cues to the shoot apex. GA (unlike FT) also acts locally in shoot apex, downstream of FT in seasonal growth control. At the shoot apex, antagonistic factors—LAP1, a target of FT and the FT antagonist TERMINAL FLOWER 1 (TFL1)—act locally to promote and suppress seasonal growth, respectively. These data reveal seasonal changes perceived in leaves that are communicated to the shoot apex by systemic signals that, in concert with locally acting components, control adaptive growth patterns.
Pattern Recognition Receptor–Initiated Innate Antiviral Responses in Mouse Epididymal Epithelial Cells

Viral infections of the epididymis may impair male fertility and spread sexually transmitted pathogens. The innate antiviral immune responses in the epididymis have yet to be intensively investigated. This study found that mouse epididymal epithelial cells (EECs) constitutively express several viral sensors, including TLR3, retinoic acid–inducible gene I, and DNA-dependent activator of IFN regulatory factors. Other DNA sensors, including p204 and cGMP-AMP synthase, can be induced by transfection of synthetic HSV genomic DNA (HSV60). TLR3 and retinoic acid–inducible gene I in EECs can be activated by their common agonist, polyinosinic-polycytidylic acid [poly(I:C)]. The signaling pathway of DNA sensors can be initiated by HSV60. Both poly(I:C) and HSV60 induced the expression of type 1 IFNs and various antiviral proteins, including IFN-stimulated gene 15, 2′,5′-oligoadenylate synthetase, and myxovirus resistance 1. Poly(I:C), but not HSV60, also dramatically induced the expression of major proinflammatory cytokines, including TNF-α and MCP-1, in EECs. In vivo assay confirmed that the local injection of poly(I:C) or HSV60 induced the innate antiviral responses in EECs. This study provided novel insights into the mechanisms underlying the innate antiviral responses in the mouse epididymis.
Cutaneous manifestations of pediatric lupus.

PURPOSE OF REVIEW To review recent evidence on cutaneous manifestations of lupus, with a focus on evidence for pediatric patients. RECENT FINDINGS Cutaneous manifestations of SLE are common and may precede signs or symptoms of systemic disease. Early recognition and initiation of therapy improves quality of life by reducing cutaneous disease activity. Antimalarials are first line for moderate-to-severe disease. Photo protection is a critical component of therapy and perhaps the only modifiable risk factor for SLE. Recognition of cutaneous vasculopathy may reduce mortality from vascular occlusion. SUMMARY There is a critical need for better understanding of pathogenesis, risk factors and outcomes in cutaneous lupus to determine optimal treatment and surveillance strategies. Correlation of clinical phenotypes with biomarkers may help to stratify patients, optimize targeted interventions, and influence prognosis.
To what extent is bruxism associated with musculoskeletal signs and symptoms? A systematic review.

The aim of the present systematic review was to answer the overall research question: "To what extent is bruxism associated with musculoskeletal signs and symptoms? ". The review was performed in accordance with the PRISMA guidelines. A PubMed search of articles published until 23 November 2017 was conducted. The search string included both MeSH terms and text words. Results were presented in categories according to study design, study population (eg, adults, children), bruxism sub-type (awake, sleep), assessment methods for bruxism and musculoskeletal symptoms (self-report, validated test) and type of outcome (pain, non-painful musculoskeletal symptoms). It could be concluded that bruxism is to some extent associated with musculoskeletal symptoms, even though the evidence is conflicting and seems to be dependent on many factors, such as age, whether the bruxism occurs during sleep or wakefulness, and also the quality of the diagnostic methodology regarding bruxism and musculoskeletal signs and symptoms. The literature does not support a direct linear causal relationship between bruxism and such symptoms, but points more in the direction of a multifaceted relationship dependent on the presence of other risk factors. Pain is by far the most commonly assessed symptom, whereas non-painful musculoskeletal symptoms have generally not been systematically evaluated. In the light of recent findings indicating that non-painful symptoms may precede TMD pain, it is suggested to increase the scientific focus on non-painful musculoskeletal symptoms in future studies. Also, future studies should use validated methods for case definition and outcome assessments.
The association between perceived interpersonal social support and physical and mental health: results from the National Epidemiological Survey on Alcohol and Related Conditions.

BACKGROUND Low social support has been associated with several disorders. We test the relationship between perceived interpersonal social support (ISS) and aspects of mental and physical health. METHODS We used data from National Epidemiological Survey on Alcohol and Related Conditions in which 34,653 individuals aged 20-99 years were interviewed twice (2001-02 and 2004-05), with the second interview including the interpersonal support evaluation list. The association of perceived ISS with lifetime DSM-IV psychopathology and physical health from the past 12 months was investigated. We also tested whether this association changes as a function of number of traumatic events in accordance with the buffering hypothesis. RESULTS Low perceived ISS correlated with increased prevalence of major depressive disorder, generalized anxiety, social phobia and several physical health problems. There was a strong association between excellent self-perceived physical health and high social support. CONCLUSIONS There was evidence for both the main, beneficial effects of high perceived ISS and buffering, whereby increased perceived ISS ameliorated the pathogenic influence of exposure to traumatic life events on psychopathology. Current findings highlight the importance of perceived ISS in individuals' general mental and physical well-being, both in daily life and upon exposure to negative life events.
UV perspective on mixed anomalies at critical points between bosonic symmetry-protected phases

Symmetry-protected phases are gapped phases of matter which are distinguished only in the presence of a global symmetry G. These quantum phases lack any symmetry-breaking or topological order, and have short-range entangled ground states. Based on this short-range entanglement property, we give a general argument for the existence of an emergent unitary or anti-unitary $\mathbb{Z}_2$ symmetry at a critical point separating two different bosonic symmetry-protected phases in any dimension. Often, the emergent symmetry group at criticality has a mixed global anomaly. For those phases classified by group cohomology, we identify a criterion for when such a mixed global anomaly is present, and write down representative cocycles for the corresponding anomaly class. We illustrate our results with a series of examples, and make connections to recent results on (2 + 1)-d beyond-Landau critical points.
Toll-like receptors 2 and 6 mediate apoptosis and inflammation in ischemic skeletal myotubes

Critical limb ischemia (CLI) is associated with skeletal muscle damage. However, the pathophysiology of the muscle damage is poorly understood. Toll-like receptors (TLR) have been attributed to play a role in ischemia-induced tissue damage but their role in skeletal muscle damage in CLI is unknown. TLR2 and TLR6 expression was found to be upregulated in skeletal muscle of patients with CLI. In vitro, ischemia led to upregulation of TLR2 and TLR6 by myotubes, and activation of the downstream TLR signaling pathway. Ischemia-induced activation of the TLR signaling pathway led to secretion of the pro-inflammatory cytokine interleukin-6 and muscle apoptosis, which were abrogated by neutralising TLR2 and TLR6 antibodies. Our study demonstrates that TLR2 and TLR6 are upregulated in ischemic muscle and play a role in ischemia-induced muscle damage. Thus, manipulating the TLR pathway locally may be of potential therapeutic benefit.
Role of nerve block as a diagnostic tool in pudendal nerve entrapment

Pudendal nerve entrapment is a disabling condition which is difficult to diagnose and treat. Nantes criteria include the requirement of positive anaesthetic pudendal nerve block that is widely used to allow identification of patients likely to benefit from the definitive but invasive pudendal nerve release. This study aimed to determine if pudendal nerve blockade under general anaesthesia could diagnose and temporarily treat pudendal nerve entrapment in patients suffering from chronic pelvic/perineal pain and/or organ dysfunction.
An improved scan design for minimization of test power under routing constraint

Scan cell ordering method is widely applied to reduce test power. Such ordering may result in significant routing overhead. In this paper, we propose a new scan design method to minimize test power under routing constraint. We base on the characteristics of scan cell distribution to cluster them prior to the ordering so as to satisfy routing constraint. Flexible scan cells are identified from each cluster to achieve further reduction of test power under routing constraint. Scan cells are finally ordered based on the evaluation of the transitions caused by connected scan cells during test. The experimental results show that the scan designs by our method can always achieve lower test power than those by other existing optimization method while satisfying the routing constraint.
Sound Localization in Real-Time Vocoded Cochlear-Implant Simulations With Normal-Hearing Listeners

Bilateral cochlear-implant (CI) users and single-sided deaf listeners with a CI are less effective at localizing sounds than normal-hearing (NH) listeners. This performance gap is due to the degradation of binaural and monaural sound localization cues, caused by a combination of device-related and patient-related issues. In this study, we targeted the device-related issues by measuring sound localization performance of 11 NH listeners, listening to free-field stimuli processed by a real-time CI vocoder. The use of a real-time vocoder is a new approach, which enables testing in a free-field environment. For the NH listening condition, all listeners accurately and precisely localized sounds according to a linear stimulus–response relationship with an optimal gain and a minimal bias both in the azimuth and in the elevation directions. In contrast, when listening with bilateral real-time vocoders, listeners tended to orient either to the left or to the right in azimuth and were unable to determine sound source elevation. When listening with an NH ear and a unilateral vocoder, localization was impoverished on the vocoder side but improved toward the NH side. Localization performance was also reflected by systematic variations in reaction times across listening conditions. We conclude that perturbation of interaural temporal cues, reduction of interaural level cues, and removal of spectral pinna cues by the vocoder impairs sound localization. Listeners seem to ignore cues that were made unreliable by the vocoder, leading to acute reweighting of available localization cues. We discuss how current CI processors prevent CI users from localizing sounds in everyday environments.
Melatonin as a potential inhibitor of colorectal cancer: Molecular mechanisms

Colorectal cancer (CRC) is a prevalent disease and a major cause of mortality in the world. Several factors including population aging, poor dietary habits, obesity, insufficient physical activity, and smoking can explain its increased prevalence. CRC is a heterogeneous disease both histopathologically and in term of its molecular and genetic aspects. Melatonin a derivative of tryptophan, is synthesized and released from pineal gland but it is also found in numerous extrapineal tissues including retina, testes, lymphocytes, Harderian gland, gastrointestinal tract, etc. This molecule has several tasks which enhance physiological functions such as antioxidant, antiaging, immunomodulatory, and tumor inhibition. Multiple immunocytochemical studies reported melatonin in the intestinal mucosa where its concentration is greater than in the blood. These findings suggest that melatonin may have a potential inhibitory role in CRC progression. The purpose of this review is to examine the effects of melatonin in molecular pathogenesis and signaling pathways of CRC.
A real-time virtual integration environment for the design and development of neural prosthetic systems

We have developed a virtual integration environment (VIE) for the development of neural prosthetic systems. The VIE is a software environment that modularizes the core functions of a neural prosthetic system — receiving signals, decoding signals and controlling a real or simulated device. Complete prosthetic systems can be quickly assembled by linking pre-existing modules together through standard interfaces. Systems can be simulated in real-time, and simulated components can be swapped out for real hardware. This paper is the first of two companion papers that describe the VIE and its use. In this paper, we first describe the architecture of the VIE and review implemented modules. We then describe the use of the VIE for the real-time validation of neural decode algorithms from pre-recorded data, the use of the VIE in closed loop primate experiments and the use of the VIE in the clinic.
TRACKING OF CARDIORESPIRATORY FITNESS FROM CHILDHOOD TO EARLY ADOLESCENCE: MODERATION EFFECT OF SOMATIC MATURATION

ABSTRACT Objective: To evaluate cardiorespiratory fitness’ tracking from childhood to adolescence, as well as to test the moderation role of somatic maturation. Methods: Our sample was composed by 375 children (197 boys), with a baseline age between 7 and 10 years old. The children were followed-up over three years. Body mass and stature were measured as anthropometric indicators and were used to estimate maturity status through Moore’s method. Cardiorespiratory fitness was evaluated through 9-minute running test. Body adiposity was estimated through the subcutaneous skinfold method, with measures of triceps and subscapular skinfolds and used as a covariate. Sample was categorized into tertiles. Thereafter, the Kappa (k) coefficient and Lin’s concordance correlation coefficient (LCCC) tests were adopted to verify stability. Dummy variable in regression was used to test moderation effects. All analyses were conducted in Stata 14.0, adopting p<0.05. Results: Cardiorespiratory fitness presented a moderate to low tracking from childhood to adolescence (k=0.294; LCCC=0.458). Moreover, maturity status significantly moderated the association between cardiorespiratory fitness at childhood and adolescence (regardless of cohort and body adiposity) among boys (β=0.644; p=0.003) and role sample (β=0.184; p=0.020), but not girls (-0.217; p=0.413). Conclusions: Tracking of cardiorespiratory fitness from childhood to adolescence is moderate to low in both sexes. Moreover, maturity status moderated the relationship between cardiorespiratory fitness at baseline and in adolescence. A lower age at peak height velocity was associated to a greater cardiorespiratory fitness.
Renal function in normal and disordered pregnancy

Purpose of review Renal dysfunction during pregnancy is a common and serious complication. Understanding normal physiology during pregnancy provides a context to further describe changes in pregnancy that lead to renal dysfunction and may provide clues to better management. Recent findings Hormonal changes during pregnancy allow for increased blood flow to the kidneys and altered autoregulation such that glomerular filtration rate (GFR) increases significantly through reductions in net glomerular oncotic pressure and increased renal size. The mechanisms for maintenance of increased GFR change through the trimesters of pregnancy, continuing into the postpartum period. Important causes of pregnancy-specific renal dysfunction have been further studied, but much needs to be learned. Pre-eclampsia is due to abnormal placentation, with shifts in angiogenic proteins and the renin–angiotensin–aldosterone system leading to endothelial injury and clinical manifestations of hypertension and organ dysfunction. Other thrombotic microangiopathies occurring during pregnancy have been better defined as well, with new work focusing on the contribution of the complement system to these disorders. Summary Advances have been made in understanding the physiology of the kidney in normal pregnancy. Diseases that affect the kidney during pregnancy alter this physiology in various ways that inform clinicians on pathogenesis and may lead to improved therapeutic approaches and better outcomes of pregnancy.
Highlights from the 2018 North American cystic fibrosis conference

The 32nd annual North American Cystic Fibrosis Conference was held in Denver, CO on Oct. 18 to 20, 2018. This review highlights presentations in several topic areas, including the pathophysiology and basic science of cystic fibrosis lung disease, clinical trials, clinical care, and quality improvement. Citations from the conference are by first author and abstract or symposium number, as designated in the previously published supplement.
SGK1/Nedd4–2 signaling pathway regulates the activity of human organic anion transporters 3

Human organic anion transporter 3 (hOAT3) is localized at the basolateral membrane of renal proximal tubule cells and facilitates the renal secretion of numerous clinical drugs, including anti‐HIV therapeutics, anti‐tumor drugs, antibiotics, antihypertension drugs and anti‐inflammatories. The present study explored the role of serum and glucocorticoid‐inducible kinase 1 (sgk1) in the regulation of hOAT3. It was shown that over‐expression of sgk1 in hOAT3‐expressing cells stimulated hOAT3 transport activity by enhancing the transporter expression at the plasma membrane, kinetically reflected as an increased maximal transport velocity Vmax without substantial change in the substrate‐binding affinity Km. In contrast, treatment of cells with the sgk‐specific inhibitor GSK650394 resulted in a dose‐dependent inhibition of hOAT3 transport activity. Evidence was further provided that sgk1 regulation of hOAT3 activity was mediated by ubiquitin ligase Nedd4–2, an enzyme previously shown to have an inhibitory effect on hOAT3. It was shown that sgk1 phosphorylated Nedd4–2, weakened the association between Nedd4–2 and hOAT3, and decreased hOAT3 ubiquitination. Functionally, the sgk1‐stimulated hOAT3 transport activity was attenuated in the presence of a ligase‐dead mutant of Nedd4–2. In summary, the investigation established for the first time that sgk1 stimulates hOAT3 transport activity by interfering with the inhibitory effect of Nedd4–2 on the transporter.
Multiplexing Angiogenic Receptor Quantification via Quantum Dots.

Clinical and biomedical research seeks single-cell quantification to better understand their roles in a complex, multicell environment. Recently, quantification of vascular endothelial growth factor receptors (VEGFRs) provided important insights into endothelial cell characteristics and response in tumor microenvironments. However, existing technologies for quantifying plasma membrane receptor tyrosine kinases (RTKs) lack multiplexing capabilities, limiting detailed characterization. Here, we use the unique spectral properties of quantum dots (Qdots) to optimize and dually quantify VEGFR1 and VEGFR2 on human umbilical vein endothelial cells (HUVECs). To enable this quantification, we reduce nonspecific binding between Qdot-conjugated antibodies and cells via buffer optimization. Second, we identify optimal labeling conditions by examining Qdot-conjugated antibody binding to five receptors: VEGFRs (VEGFR1 and VEGFR2), their coreceptor neuropilin1 (NRP1), and platelet-derived growth factor receptor (PDGFRα and PDGFRβ). We establish that 800-20 000 is the dynamic range where accurate Qdot-enabled quantification can be achieved. Through these optimizations, we demonstrate measurement of 1 100 VEGFR1 and 6 900 VEGFR2 per HUVEC. We induce ∼90% upregulation of VEGFR1 and ∼30% downregulation of VEGFR2 concentration via 24 h VEGF-A165 treatment. We observe no change in VEGFR1 or VEGFR2 concentration with 24 h VEGF-B167 treatment. We further apply Qdots to analyze HUVEC heterogeneity and observe that 24 h VEGF-A165 treatment induces a ∼15% decrease in VEGFR2 heterogeneity, but little to no change in VEGFR1 heterogeneity. We observe that VEGF-B167 induces little to no change in either VEGFR1 or VEGFR2 heterogeneity. Overall, we demonstrate experimental and analytical strategies for quantifying two or more RTKs at single-level using Qdots, which will help provide new insights into biological systems.