Miracle-dz/UniFAR-FTUs huggingface dataset:
TOR dynamically regulates plant cell–cell transport

Significance Plant cells are connected to each other by plasmodesmata (PD), membrane-bound cytosolic channels that cross the cell wall. Diverse molecules, ranging from metabolites to small RNAs and proteins, can traffic between plant cells via PD. During development, PD transport is regulated to control the redistribution of carbohydrates from mature leaves that photosynthesize excess sugars to young leaves that rapidly consume sugars. Here, we show that the ancient eukaryotic TARGET OF RAPAMYCIN (TOR) metabolic signaling network controls PD transport in plants. TOR is a protein kinase that is activated by nutrients, including sugars, and then coordinates growth with nutrient availability. Our study demonstrates that TOR has evolved new roles in plants by regulating cell–cell connectivity via PD. The coordinated redistribution of sugars from mature “source” leaves to developing “sink” leaves requires tight regulation of sugar transport between cells via plasmodesmata (PD). Although fundamental to plant physiology, the mechanisms that control PD transport and thereby support development of new leaves have remained elusive. From a forward genetic screen for altered PD transport, we discovered that the conserved eukaryotic glucose-TOR (TARGET OF RAPAMYCIN) metabolic signaling network restricts PD transport in leaves. Genetic approaches and chemical or physiological treatments to either promote or disrupt TOR activity demonstrate that glucose-activated TOR decreases PD transport in leaves. We further found that TOR is significantly more active in mature leaves photosynthesizing excess sugars than in young, growing leaves, and that this increase in TOR activity correlates with decreased rates of PD transport. We conclude that leaf cells regulate PD trafficking in response to changing carbohydrate availability monitored by the TOR pathway.
Decrease in Serum HDL-C Level Is Associated with Elevation of Blood Pressure: Correlation Analysis from the Korean National Health and Nutrition Examination Survey 2017

A low-serum, high-density lipoproteins–cholesterol (HDL-C) level and high blood pressure (BP) are independent risk factors for cardiovascular disease and dementia. In the present study, in order to find putative correlation between low HDL-C and hypertension, 4552 subjects (20–80 years old) were selected from the Korean National Health And Nutrition Examination Survey 2017 (KNHANES VII-2, n = 2017 men, n = 2535 women). They were classified into four levels of blood pressure, ranging from BP1 (normal, below 120/80 mmHg for systolic BP (SBP)/diastolic BP (DBP), BP2 (prehypertension, 120/80 to 139/89 mmHg), BP3 (hypertension stage 1, 140/90–159/99 mmHg), and BP4 (hypertension stage 2, higher than 160/100 mmHg). Generally, in the total population, a higher SBP level and age were associated with a lower HDL-C in both genders. However, DBP was not associated with age in men. In the total population, Pearson’s correlation analysis revealed that SBP (r = −0.188, p < 0.001) and DBP (r = −0.198, p < 0.001) showed negative correlations with percentage of HDL-C in total cholesterol (TC), HDL-C/TC (%). In both genders, HDL-C gradually decreased with age and HDL-C/TC (%) was more accurate in expressing a correlation with BP. Women showed a more distinct decrease in HDL-C with an elevation of BP and age than men. Both elevation of DBP and SBP were associated with a decrease in HDL-C, around 2.3–2.4 mg/dL, between normal range and hypertension 2 stage. Additionally, DBP was significantly associated with HDL-C/TC (%) (men: r = −0.136, p < 0.001; women: r = −0.152, p < 0.001), while HDL-C did not show a significant association with a change in DBP. In conclusion, SBP was positively correlated with age, but DBP did not change significantly with age. The correlation of BP and HDL-C depending on age showed that SBP gradually increased and HDL-C decreased with an increase in age. The percentage of HDL-C in TC was more significantly associated with a change in SBP and DBP in both genders.
Bilirubin enhances the activity of ASIC channels to exacerbate neurotoxicity in neonatal hyperbilirubinemia in mice

Neonatal hyperbilirubinemia aggravates acidosis-dependent long-term brain injury. Targeting acidity in jaundice Neonatal hyperbilirubinemia, also called jaundice, is a pediatric condition caused by high bilirubin levels. When associated with acidosis, jaundice can trigger neurotoxicity and lead to neurological impairments. Now, Lai et al. investigated the link between acidosis and jaundice in human samples and animal models. In samples from children with concomitant acidosis and jaundice, neuronal injury was increased compared with children with jaundice and no acidosis. In mice, bilirubin potentiated the activity of acid-sensing ion channels (ASICs) in neurons, increased firing, and caused cell death. Hyperbilirubinemia and acidosis promoted cognitive impairments in mice that were prevented by ASIC deletion. Targeting ASICs might reduce neurological impairments associated with jaundice. Neonatal hyperbilirubinemia is a common clinical condition that can lead to brain encephalopathy, particularly when concurrent with acidosis due to infection, ischemia, and hypoxia. The prevailing view is that acidosis increases the permeability of the blood-brain barrier to bilirubin and exacerbates its neurotoxicity. In this study, we found that the concentration of the cell death marker, lactate dehydrogenase (LDH) in cerebrospinal fluid (CSF), is elevated in infants with both hyperbilirubinemia and acidosis and showed stronger correlation with the severity of acidosis rather than increased bilirubin concentration. In mouse neonatal neurons, bilirubin exhibits limited toxicity but robustly potentiates the activity of acid-sensing ion channels (ASICs), resulting in increases in intracellular Ca2+ concentration, spike firings, and cell death. Furthermore, neonatal conditioning with concurrent hyperbilirubinemia and hypoxia-induced acidosis promoted long-term impairments in learning and memory and complex sensorimotor functions in vivo, which are largely attenuated in ASIC1a null mice. These findings suggest that targeting acidosis and ASICs may attenuate neonatal hyperbilirubinemia complications.
Effect of Grilled Nux Vomica on Differential RNA Expression Profile of Gastrocnemius Muscle and Toll-Like Receptor 4 (TLR-4)/Nuclear Factor kappa B (NF-κB) Signaling in Experimental Autoimmune Myasthenia Gravis Rats

Background Myasthenia gravis (MG) is a progressive autoimmune disorder caused by the production of antibodies directed against acetylcholine receptors (AChRs), resulting in muscle weakness and fatigue. This study aimed to explore the effect and mechanism of grilled nux vomica (GNV) in experimental autoimmune myasthenia gravis (EAMG) rats. Material/Methods Rat 97–116 peptides were used to mediate disease in the EAMG model in SPF female Lewis rats. The treatment groups received grilled nux vomica (75 mg/kg, 150 mg/kg, and 225 mg/kg). The autoantibody and inflammatory cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). RNA profiling was performed on high-dose and model group rats. Profiling results and TLR-4/NF-κB signaling were validated by q-PCR and Western blot analysis. Results The results showed that GNV could attenuate the symptoms of EAMG rats. There was a decreased level of AChR-ab, IFN-γ, TNF-α, IL-2, IL-4, and IL-17 levels, and an increased level of TGF-β1. In total, 235 differentially expressed genes (DEGs), consisting of 175 upregulated DEGs and 60 downregulated DEGs, were identified. Functional annotation demonstrated that DEGs were largely associated with leukocyte cell–cell adhesion, NF-kappa B signaling pathway, muscle contraction, and cardiac muscle contraction pathway. Rac2, Itgb2, Lcp2, Myl3, and Tnni1 were considered as hub genes with a higher degree value in the protein–protein interaction (PPI) network. The q-PCR and Western blot results of hub genes were consistent with RNA profiles. GNV treatment also significantly reduced the TLR-4 and NF-κB p65 protein expression in EAMG rats. Conclusions These results indicate that grilled nux vomica ameliorates EAMG by depressing the TLR-4/NF-κB signaling pathway, and hub genes may serve as potential targets for MG treatment.
Effect of B-site cation ordering on high temperature thermoelectric behavior of BaxSr2−xTiFeO6 double perovskites

Here, we have reported the detailed structural analysis in correlation with thermoelectric properties of Ba doped Sr2TiFeO6 (BSTF) double perovskites in the temperature range from 300 K to 1100 K. BSTF compositions exhibit single phase cubic structure with crystal symmetry from room temperature to 523 K and also at temperature beyond 923K. Rietveld refinement of high temperature XRD data suggests the coexistence of two cubic phases with space group having same composition in the intermediate temperature region. Correlation of the phase-fraction with electrical conductivity data posits the possibility of high temperature cubic phase being conductive compared to the insulator-like cubic phase observed at room temperature. The experimental analysis alone seems insufficient to explain the conductivity behavior demonstrating semiconductor to metal like transition. Hence DFT framework has been adopted for computational analysis coupled with the Boltzmann transport equations to understand their thermoelectric properties based on the electronic restructuring occurred due to octahedral arrangements in these double perovskites. It has been shown that clustering of FeO6 octahedra may lead to the formation of a conduction path in the cubic phase of BSTF, which induces metallic behavior in these double perovskites.
Clinic-Based Pediatric Disclosure Intervention Trial Improves Pediatric HIV Status Disclosure in Ghana.

BACKGROUND Disclosing HIV status to HIV-positive children is a major challenge facing families and healthcare providers. Despite recommendations for disclosure, rates remain low. We tested whether a pediatric HIV disclosure intervention delivered as an integral component of routine HIV healthcare in Ghana would improve disclosure to children. METHODS Dyads of HIV-infected children aged 7 to 18 years and their caregivers were enrolled from two HIV clinics in Accra and Kumasi, Ghana. The sites were randomly assigned to one of the two intervention arms to avoid treatment contamination between intervention and control participants. Trained interventionist employed theory-guided therapeutic communication and personalized interaction to promote disclosure. Disclosure outcomes were measured at 12-week intervals. All analyses were completed using a modified intention-to-treat approach. RESULTS We enrolled 446 child-caregiver dyads (N=240 intervention group; N=206 control group); 52% of the children were male, mean age 9.78 (±2.27) years. For disclosure at 1 year, a better overall treatment effect was observed (p<0.001). Children in the treatment group had greater disclosure at each time point (p<0.001) and a higher proportion of them had been disclosed to by 1 year (51.4% vs 16.2%; p<0.001; un-adjusted HR=3.98: 95% CI, 2.63, 6.03) and 3 years (71.3% vs 34.0%; unadjusted HR=4.21: 95% CI, 3.09, 5.72). In the multivariate Cox model, factors associated with disclosure were treatment group (p<0.001), children <11 years of age (p<0.001), HIV-infected caregivers (p=0.015), and caregiver's with greater education (p=0.022). CONCLUSIONS This practical clinic-based disclosure intervention shows excellent promise as a means of improving HIV pediatric disclosure outcomes.
Alterations in pro-nociceptive and anti-nociceptive mechanisms in patients with low back pain: a systematic review with meta-analysis.

Altered pro-nociceptive and anti-nociceptive mechanisms are often implicated in painful conditions and have been increasingly studied over the past decade. For some painful conditions alterations are well-established, but in low back pain (LBP) populations there remains considerable debate whether these mechanisms are altered. The present systematic review aimed to address this issue by identifying studies assessing Conditioned Pain Modulation (CPM) and/or Temporal Summation of Pain (TSP) in LBP patients, comparing to either a healthy control group or using a method with reference data available. Qualitative synthesis and quantitative meta-analysis of group differences were performed. For CPM and TSP, 20 and 29 original articles were eligible, with data for meta-analysis obtainable from 18 (1500 patients, 505 controls) and 27 (1507 patients, 1127 controls) studies, respectively. Most studies were of poor-to-fair quality with significant heterogeneity in study size, population, assessment methodology and outcome. Nonetheless, CPM was impaired in LBP patients compared to controls (standardized mean difference = -0.44 [-0.64, -0.23], P<0.001), and the magnitude of this impairment was related to pain chronicity (acute/recurrent versus chronic, P=0.003), duration (R=-0.62, P=0.006) and severity (R=-0.54, P=0.02). TSP was facilitated in LBP patients compared to controls (standardized mean difference = 0.50 [0.29, 0.72], P<0.001), and the magnitude of this facilitation was weakly related to pain severity (R=0.41, P=0.04) and appeared to be influenced by test modality (P<0.001). Impaired CPM and facilitated TSP was present in LBP patients compared to controls, though the magnitude of differences was small which may direct future research on the clinical utility.
Anomalies in language as a biomarker for schizophrenia.

PURPOSE OF REVIEW After more than a century of neuroscience research, reproducible, clinically relevant biomarkers for schizophrenia have not yet been established. This article reviews current advances in evaluating the use of language as a diagnostic or prognostic tool in schizophrenia. RECENT FINDINGS The development of computational linguistic tools to quantify language disturbances is rapidly gaining ground in the field of schizophrenia research. Current applications are the use of semantic space models and acoustic analyses focused on phonetic markers. These features are used in machine learning models to distinguish patients with schizophrenia from healthy controls or to predict conversion to psychosis in high-risk groups, reaching accuracy scores (generally ranging from 80 to 90%) that exceed clinical raters. Other potential applications for a language biomarker in schizophrenia are monitoring of side effects, differential diagnostics and relapse prevention. SUMMARY Language disturbances are a key feature of schizophrenia. Although in its early stages, the emerging field of research focused on computational linguistics suggests an important role for language analyses in the diagnosis and prognosis of schizophrenia. Spoken language as a biomarker for schizophrenia has important advantages because it can be objectively and reproducibly quantified. Furthermore, language analyses are low-cost, time efficient and noninvasive in nature.
Nuclear export of replication protein A in the nonreplicative infective forms of Trypanosoma cruzi

Replication protein A (RPA), a heterotrimeric complex, is the major single‐stranded DNA binding protein in eukaryotes. Recently, we characterized RPA from Trypanosoma cruzi, showing that it is involved in DNA replication and DNA damage response in this organism. Better efficiency in differentiation from epimastigote to metacyclic trypomastigote forms was observed in TcRPA‐2 subunit heterozygous knockout cells, suggesting that RPA is involved in this process. Here, we show that RPA cellular localization changes during the T. cruzi life cycle, with RPA being detected only in the cytoplasm of the metacyclic and bloodstream trypomastigotes. We also identify a nuclear export signal (NES) in the trypanosomatid RPA‐2 subunit. Mutations in the negatively charged residues of RPA‐2 NES impair the differentiation process, suggesting that RPA exportation affects parasite differentiation into infective forms.
Psychological Correlates of Ghosting and Breadcrumbing Experiences: A Preliminary Study among Adults

The present study aimed to examine differences in three psychological constructs (satisfaction with life, loneliness, and helplessness) among adults experiencing ghosting and breadcrumbing. A sample of 626 adults (303 males and 323 females), aged from 18 to 40 years, completed an online survey asking to indicate whether someone they considered a dating partner had ghosted or breadcrumbed them in the last year and to complete three different scales regarding satisfaction with life, loneliness, and helplessness. The results showed than those participants who had indicated experiencing breadcrumbing or the combined forms (both breadcrumbing and ghosting) reported less satisfaction with life, and more helplessness and self-perceived loneliness. The results from the regression models showed that suffering breadcrumbing would significantly increase the likelihood of experiencing less satisfaction with life, and of having more feelings of loneliness and helplessness. However, no significant relation was found between ghosting and any of the examined psychological correlates.
An Overview on Conventional and Non-Conventional Therapeutic Approaches for the Treatment of Candidiasis and Underlying Resistance Mechanisms in Clinical Strains

Fungal infections and, in particular, those caused by species of the Candida genus, are growing at an alarming rate and have high associated rates of mortality and morbidity. These infections, generally referred as candidiasis, range from common superficial rushes caused by an overgrowth of the yeasts in mucosal surfaces to life-threatening disseminated mycoses. The success of currently used antifungal drugs to treat candidiasis is being endangered by the continuous emergence of resistant strains, specially among non-albicans Candida species. In this review article, the mechanisms of action of currently used antifungals, with emphasis on the mechanisms of resistance reported in clinical isolates, are reviewed. Novel approaches being taken to successfully inhibit growth of pathogenic Candida species, in particular those based on the exploration of natural or synthetic chemicals or on the activity of live probiotics, are also reviewed. It is expected that these novel approaches, either used alone or in combination with traditional antifungals, may contribute to foster the identification of novel anti-Candida therapies.
Alpine grassland plants grow earlier and faster but biomass remains unchanged over 35 years of climate change

Abstract Satellite data indicate significant advancement in alpine spring phenology over decades of climate warming, but corresponding field evidence is scarce. It is also unknown whether this advancement results from an earlier shift of phenological events, or enhancement of plant growth under unchanged phenological pattern. By analyzing a 35‐year dataset of seasonal biomass dynamics of a Tibetan alpine grassland, we show that climate change promoted both earlier phenology and faster growth, without changing annual biomass production. Biomass production increased in spring due to a warming‐induced earlier onset of plant growth, but decreased in autumn due mainly to increased water stress. Plants grew faster but the fast‐growing period shortened during the mid‐growing season. These findings provide the first in situ evidence of long‐term changes in growth patterns in alpine grassland plant communities, and suggest that earlier phenology and faster growth will jointly contribute to plant growth in a warming climate.
Association Between the Use of Antidepressants and the Risk of Type 2 Diabetes: A Large, Population-Based Cohort Study in Japan

OBJECTIVE This study aimed to reveal the associations between the risk of new-onset type 2 diabetes and the duration of antidepressant use and the antidepressant dose, and between antidepressant use after diabetes onset and clinical outcomes. RESEARCH DESIGN AND METHODS In this large-scale retrospective cohort study in Japan, new users of antidepressants (exposure group) and nonusers (nonexposure group), aged 20–79 years, were included between 1 April 2006 and 31 May 2015. Patients with a history of diabetes or receipt of antidiabetes treatment were excluded. Covariates were adjusted by using propensity score matching; the associations were analyzed between risk of new-onset type 2 diabetes and the duration of antidepressant use/dose of antidepressant in the exposure and nonexposure groups by using Cox proportional hazards models. Changes in glycated hemoglobin (HbA1c) level were examined in groups with continuous use, discontinuation, or a reduction in the dose of antidepressants. RESULTS Of 90,530 subjects, 45,265 were in both the exposure and the nonexposure group after propensity score matching; 5,225 patients (5.8%) developed diabetes. Antidepressant use was associated with the risk of diabetes onset in a time- and dose-dependent manner. The adjusted hazard ratio was 1.27 (95% CI 1.16–1.39) for short-term low-dose and 3.95 (95% CI 3.31–4.72) for long-term high-dose antidepressant use. HbA1c levels were lower in patients who discontinued or reduced the dose of antidepressants (F[2,49] = 8.17; P < 0.001). CONCLUSIONS Long-term antidepressant use increased the risk of type 2 diabetes onset in a time- and dose-dependent manner. Glucose tolerance improved when antidepressants were discontinued or the dose was reduced after diabetes onset.
A Location Privacy Attack Based on the Location Sharing Mechanism with Erroneous Distance in Geosocial Networks

Geographical social networks (GSN) is an emerging research area. For example, Foursquare, Yelp, and WeChat are all well-known service providers in this field. These applications are also known as location-based services (LBS). Previous studies have suggested that these location-based services may expose user location information. In order to ensure the privacy of the user’s location data, the service provider may provide corresponding protection mechanisms for its applications, including spatial cloaking, fuzzy location information, etc., so that the user’s real location cannot be easily cracked. It has been shown that if the positioning data provided by the user is not accurate enough, it is still difficult for an attacker to obtain the user’s true location. Taking this factor into consideration, our attack method is divided into two stages for the entire attack process: (1) Search stage: cover the area where the targeted user is located with unit discs, and then calculate the minimum dominating set. Use the triangle positioning method to find the minimum precision disc. (2) Inference phase: Considering the existence of errors, an Error-Adjusted Space Partition Attack Algorithm (EASPAA) was proposed during the inference phase. Improved the need for accurate distance information to be able to derive the user’s true location. In this study, we focus on the Location Sharing Mechanism with Maximal Coverage Limit to implement the whole attack. Experimental results show that the proposed method still can accurately infer the user’s real location even when there is an error in the user’s location information.