Miracle-dz/UniFAR-FTUs huggingface dataset:
LRG1 Promotes Diabetic Kidney Disease Progression by Enhancing TGF-β-Induced Angiogenesis.

BACKGROUND Glomerular endothelial dysfunction and neoangiogenesis have long been implicated in the pathogenesis of diabetic kidney disease (DKD). However, the specific molecular pathways contributing to these processes in the early stages of DKD are not well understood. Our recent transcriptomic profiling of glomerular endothelial cells identified a number of proangiogenic genes that were upregulated in diabetic mice, including leucine-rich α-2-glycoprotein 1 (LRG1). LRG1 was previously shown to promote neovascularization in mouse models of ocular disease by potentiating endothelial TGF-β/activin receptor-like kinase 1 (ALK1) signaling. However, LRG1's role in the kidney, particularly in the setting of DKD, has been unclear. METHODS We analyzed expression of LRG1 mRNA in glomeruli of diabetic kidneys and assessed its localization by RNA in situ hybridization. We examined the effects of genetic ablation of Lrg1 on DKD progression in unilaterally nephrectomized, streptozotocin-induced diabetic mice at 12 and 20 weeks after diabetes induction. We also assessed whether plasma LRG1 was associated with renal outcome in patients with type 2 diabetes. RESULTS LRG1 localized predominantly to glomerular endothelial cells, and its expression was elevated in the diabetic kidneys. LRG1 ablation markedly attenuated diabetes-induced glomerular angiogenesis, podocyte loss, and the development of diabetic glomerulopathy. These improvements were associated with reduced ALK1-Smad1/5/8 activation in glomeruli of diabetic mice. Moreover, increased plasma LRG1 was associated with worse renal outcome in patients with type 2 diabetes. CONCLUSIONS These findings identify LRG1 as a potential novel pathogenic mediator of diabetic glomerular neoangiogenesis and a risk factor in DKD progression.
Intranuclear inclusions in hepatocellular carcinoma contain autophagy‐associated proteins and correlate with prolonged survival

For decades, intranuclear inclusions in many normal and neoplastic cells have been considered to be mere invaginations of cytoplasm into the nucleus without any notable function or influence on disease. We investigated such inclusions in 75 specimens of hepatocellular carcinoma (HCC). In this context we demonstrate that these inclusions are true inclusions, completely closed and delimited by the nuclear membrane, containing degenerate cell organelles and lysosomal proteins. Moreover, their occurrence was positively associated with patient survival but not with tumour grade or stage. In a standardised area a mean of 124 inclusions per specimen was present in the tumorous liver tissue in contrast to 5 inclusions in the non‐tumorous adjacent section and 89% of all scrutinised HCC showed at least one membrane‐bound nuclear inclusion. Ultrastructural characterisation by transmission electron microscopy revealed degenerative materials such as residues of lysosomes, endoplasmic reticulum and Golgi apparatus within the inclusions. Due to the fact that the content of the inclusions appears to be more condensed than cytoplasm and contains fewer intact cell organelles, we assume that they are not mere invaginations of cytoplasm. Three dimensional (3D) reconstruction of isolated and immunofluorescence stained nuclei showed that the inclusions are completely located within the nucleus without any connection to the cytoplasm. The limiting membrane of the inclusions contained lamin B suggesting nuclear membrane origin. The content of the inclusions stained for the autophagy‐associated proteins p62, ubiquitin, LC3B, cathepsin B and cathepsin D. Triple immunofluorescence staining followed by 3D reconstruction revealed co‐localisation of p62, ubiquitin and LC3B in the same inclusion. Our observations uncover that these inclusions are real inclusions completely surrounded by the nucleus. We propose that the presence of autophagy‐associated proteins and proteases within the inclusions contribute to beneficial survival.
Whole Genome Sequencing and Progress Toward Full Inbreeding of the Mouse Collaborative Cross Population

Two key features of recombinant inbred panels are well-characterized genomes and reproducibility. Here we report on the sequenced genomes of six additional Collaborative Cross (CC) strains and on inbreeding progress of 72 CC strains. We have previously reported on the sequences of 69 CC strains that were publicly available, bringing the total of CC strains with whole genome sequence up to 75. The sequencing of these six CC strains updates the efforts toward inbreeding undertaken by the UNC Systems Genetics Core. The timing reflects our competing mandates to release to the public as many CC strains as possible while achieving an acceptable level of inbreeding. The new six strains have a higher than average founder contribution from non-domesticus strains than the previously released CC strains. Five of the six strains also have high residual heterozygosity (>14%), which may be related to non-domesticus founder contributions. Finally, we report on updated estimates on residual heterozygosity across the entire CC population using a novel, simple and cost effective genotyping platform on three mice from each strain. We observe a reduction in residual heterozygosity across all previously released CC strains. We discuss the optimal use of different genetic resources available for the CC population.
The metabolomic signatures of alcohol consumption in young adults

Background Metabolomic analysis may help us to understand the association between alcohol consumption and cardio-metabolic health. We aimed to: (i) replicate a previous study of alcohol consumption and metabolic profiles, (ii) examine associations between types of alcoholic beverages and metabolites and (iii) include potential confounders not examined in previous studies. Methods Cross-sectional data of 1785 participants (age 26–36 years, 52% women) from the 2004–2006 Childhood Determinants of Adult Health study were used. Consumption of beer, wine and spirits was assessed by questionnaires. Metabolites were measured by a high-throughput nuclear magnetic resonance platform and multivariable linear regression examined their association with alcohol consumption (combined total and types) adjusted for covariates including socio-demographics, health behaviours and mental health. Results Alcohol consumption was associated with 23 out of 37 lipids, 12 out of 16 fatty acids and six out of 20 low-molecular-weight metabolites independent of confounders with similar associations for combined total alcohol consumption and different types of alcohol. Many metabolites (lipoprotein lipids in high-density lipoprotein (HDL) subclasses, HDL cholesterol, apolipoprotein A-1, phosphotriglycerides, total fatty acids, monounsaturated fatty acids, omega-3 fatty acids) had positive linear associations with alcohol consumption but some showed negative linear (low-density lipoprotein particle size, omega-6 fatty acids ratio to total fatty acids, citrate) or U-shaped (lipoprotein lipids in very-low-density lipoprotein (VLDL) subclasses, VLDL triglycerides) associations. Conclusions Our results were similar to those of the only previous study. Associations with metabolites were similar for total and types of alcohol. Alcohol consumption in young adults is related to a diverse range of metabolomic signatures associated with benefits and harms to health.
Effect of turmeric on glycemic status, lipid profile, hs‐CRP, and total antioxidant capacity in hyperlipidemic type 2 diabetes mellitus patients

Diabetes mellitus is the most common metabolic disorder worldwide. This study examined the effect of turmeric supplementation on glycemic status, lipid profile, hs‐CRP and total antioxidant capacity in hyperlipidemic type 2 diabetic patients. In this double‐blind, randomized clinical trial, 80 hyperlipidemic type 2 diabetic patients were divided into turmeric (2,100 mg powdered rhizome of turmeric daily) and placebo groups for 8 weeks. Body weight, fasting plasma glucose, hemoglobin A1c (HbA1c), serum insulin, triglyceride (TG), total cholesterol, low density lypoprotein cholesterol (LDL‐c), high density lypoprotein cholesterol, apolipoprotein A1, apolipoprotein B, high sensitivity C‐reactive protein (hs‐CRP), and total antioxidant capacity were measured before and after intervention. Statistical analysis was carried out using paired and independent t and chi‐square tests. Seventy five patients completed the study. The turmeric group showed significant decreases in body weight, TG, and LDL‐c compared with baseline (p value < 0.05). Body mass index, TG, and total cholesterol decreased significantly in the turmeric group compared with the placebo group (p value < 0.05). No significant changes were observed in other parameters between the two groups after intervention (p value < 0.05). Turmeric improved some fractions of lipid profile and decreased body weight in hyperlipidemic patients with type 2 diabetes. It had no significant effect on glycemic status, hs‐CRP, and total antioxidant capacity in these patients.
The Effect of Dialectical Behavior Therapy Based Emotion Regulation Program on Decreasing the Emotion Regulation Difficulties of University Students

DOI: 10.14812/cufej.2015. 010 Bu araştırma, Diyalektik Davranış Terapisi (DDT) temelli bir duygu düzenleme programının, üniversite öğrencilerinin duygu düzenleme güçlüklerini azaltmadaki etkisini değerlendirmek amacıyla hazırlanmıştır. 8 oturumluk program, DDT’nin danışanlara kazandırmayı hedeflediği Farkındalık, Duygu Düzenleme, Sıkıntıya Dayanma ve Kişiler Arası Etkililik becerilerine odaklanmaktadır. Mersin Üniversitesi Eğitim Fakültesi Psikolojik Danışma ve Anabilim Dalı’nda öğrenim gören 128 öğrenciye Rugancı ve Gençöz (2010) tarafından Türkçe’ye uyarlanan ‘Duygu Düzenlemede Güçlükler Ölçeği’ (DDGÖ) uygulanarak duygu düzenleme becerileri yetersiz olduğu tespit edilen 18 öğrenci (9 deney, 9 kontrol) çalışma grubuna alınmıştır. Araştırma, öntest-sontest modelli deneysel bir çalışmadır. Bulgular, kontrol grubu ile karşılaştırıldığında, 8 oturum süren programın ardından deney grubu öğrencilerinin DDGÖ puanlarının anlamlı derecede düştüğünü göstermektedir. Bu sonuç, DDT Temelli Duygu Düzenleme Programının üniversite öğrencilerinin duygu düzenleme güçlüklerini azaltmada etkili olduğunu ortaya koymaktadır. Makale Geçmişi: Geliş Düzeltme Kabul 03 Aralık 2014 10 Ağustos 2015 17 Eylül 2015
Multisensory Neurons in the Primate Amygdala

Animals identify, interpret, and respond to complex, natural signals that are often multisensory. The ability to integrate signals across sensory modalities depends on the convergence of sensory inputs at the level of single neurons. Neurons in the amygdala are expected to be multisensory because they respond to complex, natural stimuli, and the amygdala receives inputs from multiple sensory areas. We recorded activity from the amygdala of 2 male monkeys (Macaca mulatta) in response to visual, tactile, and auditory stimuli. Although the stimuli were devoid of inherent emotional or social significance and were not paired with rewards or punishments, the majority of neurons that responded to these stimuli were multisensory. Selectivity for sensory modality was stronger and emerged earlier than selectivity for individual items within a sensory modality. Modality and item selectivity were expressed via three main spike-train metrics: (1) response magnitude, (2) response polarity, and (3) response duration. None of these metrics were unique to a particular sensory modality; rather, each neuron responded with distinct combinations of spike-train metrics to discriminate sensory modalities and items within a modality. The relative proportion of multisensory neurons was similar across the nuclei of the amygdala. The convergence of inputs of multiple sensory modalities at the level of single neurons in the amygdala rests at the foundation for multisensory integration. The integration of visual, auditory, and tactile inputs in the amygdala may serve social communication by binding together social signals carried by facial expressions, vocalizations, and social grooming. SIGNIFICANCE STATEMENT Our brain continuously decodes information detected by multiple sensory systems. The emotional and social significance of the incoming signals is likely extracted by the amygdala, which receives input from all sensory domains. Here we show that a large portion of neurons in the amygdala respond to stimuli from two or more sensory modalities. The convergence of visual, tactile, and auditory signals at the level of individual neurons in the amygdala establishes a foundation for multisensory integration within this structure. The ability to integrate signals across sensory modalities is critical for social communication and other high-level cognitive functions.
Formal and Informal Institutions and Going Public in China

This paper empirically investigates the role of formal institutions and social trust in the initial public offerings and their long-term performance in China. We find that the state-owned and bigger IPOs experience higher underpricing and stronger demand when they are incorporated in regions with stronger formal legal institutions (court enforcement and contract holding), while the privately owned and smaller IPOs experience higher underpricing and stronger demand when they are incorporated in regions with more political pluralism and more social trust. Such distinctive role of formal and informal institutions maintains for the long-term performance except we find that both the state-owned and privately owned IPOs of firms perform better in regions with more political pluralism. In addition, our evidence shows that stronger social trust substitute the quality of court enforcement but strengthens the role of contract holding. These results are robust after controlling for alternative definitions of ownership, outliers, nonlinear effects of institutions, and potential endogeneity of institutions in the model.
The Influence of Continuous Exercising on Chronotropic Incompetence in Multi-Episode Schizophrenia

People with schizophrenia die on average 15–20 years earlier than age and gender matched controls in the general population. An essential part of this excess mortality in people with schizophrenia is caused by physical illnesses. Among the physical illnesses, cardiovascular disease (CVD) has been identified as the most common natural cause of death in up to 40–45% of the cases. Chronotropic incompetence (CI) is defined as the inability of the heart to increase its beating frequency in proportion to increased physical activity or higher metabolic demand. It is an established independent cardiovascular risk factor for major cardiac events and overall mortality and might explain adaptation intolerance of the cardiovascular system to even minor exercise courses. CI needs objective exercise testing for definitive diagnosis and therefore represents a biological marker indicating the integrity of the cardiovascular system. It was recently described in patients with schizophrenia and might help explain the reduced physical fitness in these patients and the inability of a subgroup of patients to benefit from exercise interventions. In this study, we tried to replicate the occurrence of CI in an independent sample of patients with schizophrenia and evaluated whether CI can be influenced by a continuous endurance training of 12 weeks. Therefore, we re-analyzed the fitness testing data of 43 patients with schizophrenia and 22 aged and gender matched healthy controls. Parameters of aerobic fitness and chronotropic response to exercise were calculated. Patients with schizophrenia were less physically fit than the healthy controls and displayed a significantly higher heart rate at rest. 10 of 43 patients with schizophrenia and no healthy control subject were classified as chronotropically incompetent. Chronotropic response to exercise did not change significantly after 12 weeks of continuous aerobic exercise training. No differences were observed for baseline heart rate and peak heart rate in both subgroups of schizophrenia patients. Aerobic fitness did not improve significantly in the patients with schizophrenia classified as chronotropically incompetent. Our results confirm the occurrence of CI in patients with multi-episode schizophrenia. This should be taken into account when planning an exercise or lifestyle intervention studies in this population. Schizophrenia patients with CI do not seem to benefit as well as schizophrenia patients without CI from aerobic exercise training interventions. Larger, prospective randomized controlled clinical trials with different training interventions are urgently needed to address the topic of schizophrenia patients not responding to exercise and the relationship to the illness itself.
Household water sharing: A review of water gifts, exchanges, and transfers across cultures

Water sharing offers insight into the everyday and, at times, invisible ties that bind people and households with water and to one another. Water sharing can take many forms, including so‐called “pure gifts,” balanced exchanges, and negative reciprocity. In this study, we examine water sharing between households as a culturally embedded practice that may be both need‐based and symbolically meaningful. Drawing on a wide‐ranging review of diverse literatures, we describe how households practice water sharing cross‐culturally in the context of four livelihood strategies (hunter‐gatherer, pastoralist, agricultural, and urban). We then explore how cross‐cutting material conditions (risks and costs/benefits, infrastructure and technologies), socioeconomic processes (social and political power, water entitlements, ethnicity and gender, territorial sovereignty), and cultural norms (moral economies of water, water ontologies, and religious beliefs) shape water sharing practices. Finally, we identify five new directions for future research on water sharing: conceptualization of water sharing; exploitation and status accumulation through water sharing, biocultural approaches to the health risks and benefits of water sharing, cultural meanings and socioeconomic values of waters shared; and water sharing as a way to enact resistance and build alternative economies.
Deformed Wing Virus Infection in Honey Bees (Apis mellifera L.)

Deformed wing virus (DWV) is a single-stranded RNA virus of honey bees (Apis mellifera L.) transmitted by the parasitic mite Varroa destructor. Although DWV represents a major threat to honey bee health worldwide, the pathological basis of DWV infection is not well documented. The objective of this study was to investigate clinicopathological and histological aspects of natural DWV infection in honey bee workers. Emergence of worker honey bees was observed in 5 colonies that were clinically affected with DWV and the newly emerged bees were collected for histopathology. DWV-affected bees were 2 times slower to emerge and had 30% higher mortality compared to clinically normal bees. Hypopharyngeal glands in bees with DWV were hypoplastic, with fewer intracytoplasmic secretory vesicles; cells affected by apoptosis were observed more frequently. Mandibular glands were hypoplastic and were lined by cuboidal epithelium in severely affected bees compared to tall columnar epithelium in nonaffected bees. The DWV load was on average 1.7 × 106 times higher (P < .001) in the severely affected workers compared to aged-matched sister honey bee workers that were not affected by deformed wing disease based on gross examination. Thus, DWV infection is associated with prolonged emergence, increased mortality during emergence, and hypoplasia of hypopharyngeal and mandibular glands in newly emerged worker honey bees in addition to previously reported deformed wing abnormalities.
Milk Urea Concentration in Dairy Sheep: Accounting for Dietary Energy Concentration

Simple Summary In this paper, we show that milk urea concentration (MUC) of dairy ewes is markedly affected not only by dietary protein concentration, as evidenced by previous research, but also by dietary energy concentration. Thus, to avoid misleading interpretations, the utilization of MUC as indicator of the protein status of ewes should account for the dietary energy concentration. Minimal, optimal, and maximal MUC values for different combinations of dietary energy and protein are proposed. Because frequent bulk tank MUC analysis is easy to perform and cost-effective, the reference values proposed here can be used for optimizing sheep milk and reproductive performances while curbing N release from excreta. Abstract In dairy sheep milk urea concentration (MUC) is highly and positively correlated with dietary crude protein (CP) content and, to a lesser extent, with protein intake. However, the effect of dietary energy and carbohydrate sources on MUC of lactating ewes is not clear. Thus, the objective of this study was to assess the effects of diets differing in energy concentration and carbohydrate sources on MUC values in lactating dairy ewes. Two experiments were conducted (experiment 1, E1, and experiment 2, E2) on Sarda ewes in mid and late lactation kept in metabolic cages for 23 d. In both experiments, homogeneous groups of five ewes were submitted to four (in E1) or three (in E2) dietary treatments, consisting of pelleted diets ranging from low energy (high-fiber diets: 1.2–1.4 Mcal of net energy for lactation (NEL)) to high energy (high-starch diets: 1.7–1.9 Mcal of NEL) contents, but with a similar CP concentration (18.4% dry matter (DM), on average). Each diet had a different main ingredient as follows: corn flakes, barley meal, beet pulp, or corn cobs in E1 and corn meal, dehydrated alfalfa, or soybean hulls in E2. Regression analysis using treatment means from both experiments showed that the best predictor of MUC (mg/100 mL) was the dietary NEL (Mcal/kg DM, MUC = 127.6 − 51.2 × NEL, R2 = 0.85, root of the mean squared error (rmse) = 4.36, p < 0.001) followed by the ratio CP/NEL (g/Mcal, MUC = −14.9 + 0.5 × CP/ NEL, R2 = 0.83, rmse = 4.63, p < 0.001). A meta-regression of an extended database on stall-fed dairy ewes, including the E1 and E2 experimental data (n = 44), confirmed the predictive value of the CP/ NEL ratio, which resulted as the best single predictor of MUC (MUC = −13.7 + 0.5 × CP/NEL, R2 = 0.93, rmse = 3.30, p < 0.001), followed by dietary CP concentration (MUC = −20.7 + 3.7 × CP, R2 = 0.82, rmse = 4.89, p < 0.001). This research highlights that dietary energy content plays a pivotal role in modulating the relationship between MUC and dietary CP concentration in dairy sheep.