Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of Fatty Acid-Related Genes in the Response of H9c2 Cardiac Cells to Palmitate and n-3 Polyunsaturated Fatty Acids

While high levels of saturated fatty acids are associated with impairment of cardiovascular functions, n-3 polyunsaturated fatty acids (PUFAs) have been shown to exert protective effects. However the molecular mechanisms underlying this evidence are not completely understood. In the present study we have used rat H9c2 ventricular cardiomyoblasts as a cellular model of lipotoxicity to highlight the effects of palmitate, a saturated fatty acid, on genetic and epigenetic modulation of fatty acid metabolism and fate, and the ability of PUFAs, eicosapentaenoic acid, and docosahexaenoic acid, to contrast the actions that may contribute to cardiac dysfunction and remodeling. Treatment with a high dose of palmitate provoked mitochondrial depolarization, apoptosis, and hypertrophy of cardiomyoblasts. Palmitate also enhanced the mRNA levels of sterol regulatory element-binding proteins (SREBPs), a family of master transcription factors for lipogenesis, and it favored the expression of genes encoding key enzymes that metabolically activate palmitate and commit it to biosynthetic pathways. Moreover, miR-33a, a highly conserved microRNA embedded in an intronic sequence of the SREBP2 gene, was co-expressed with the SREBP2 messenger, while its target carnitine palmitoyltransferase-1b was down-regulated. Manipulation of the levels of miR-33a and SREBPs allowed us to understand their involvement in cell death and hypertrophy. The simultaneous addition of PUFAs prevented the effects of palmitate and protected H9c2 cells. These results may have implications for the control of cardiac metabolism and dysfunction, particularly in relation to dietary habits and the quality of fatty acid intake.
A pilot study assessing reliability and age‐related differences in corticomuscular and intramuscular coherence in ankle dorsiflexors during walking

Corticomuscular (CMC) and intramuscular (intraMC) coherence represent measures of corticospinal interaction. Both CMC and intraMC can be assessed during human locomotion tasks, for example, while walking. Corticospinal control of gait can deteriorate during the aging process and CMC and intraMC may represent an important monitoring means. However, it is unclear whether such assessments represent a reliable tool when performed during walking in an ecologically valid scenario and whether age‐related differences may occur. Wireless surface electroencephalography and electromyography were employed in a pilot study with young and old adults during overground walking in two separate sessions. CMC and intraMC analyses were performed in the gathered beta and lower gamma frequencies (i.e., 13–40 Hz). Significant log‐transformed coherence area was tested for intersessions test–retest reliability by determining intraclass correlation coefficient (ICC), yielding to low reliability in CMC in both younger and older adults. intraMC exclusively showed low reliability in the older adults, whereas intraMC in the younger adults revealed similar values as previously reported: test–retest reliability [ICC (95% CI): 0.44 (−0.23, 0.87); SEM: 0.46; MDC: 1.28; MDC%: 103; Hedge's g (95% CI): 0.54 (−0.13, 1.57)]. Significant differences between the age groups were observed in intraMC by either comparing the two groups with the first test [Hedge's g (95% CI): 1.55 (0.85, 2.15); p‐value: . 006] or with the retest data [Hedge's g (95% CI): 2.24 (0.73, 3.70); p‐value: . 005]. Notwithstanding the small sample size investigated, intraMC seems a moderately reliable assessment in younger adults. The further development and use of this measure in practical settings to infer corticospinal interaction in human locomotion in clinical practice is warranted and should help to refine the analysis. This necessitates involving larger sample sizes as well as including a wider number of lower limb muscles. Moreover, further research seems warranted by the observed differences in modulation mechanisms of corticospinal control of gait as ascertained by intraMC between the age groups.
Prediction of Metabolizable Energy Concentrations of Herbage in the Qinghai–Tibetan Plateau Using Tibetan Sheep Digestibility Data

Simple Summary Robust prediction of herbage nutritive value is critical to improve grazing efficiency and to maintain a sustainable environment in the Qinghai–Tibet Plateau. A range of prediction equations were developed in the present study using sheep digestibility data which can produce an accurate estimation of herbage nutritive value. The adaptation of the present equations is expected to benefit local farmers with higher economical return and to improve the fragile ecological systems the Qinghai–Tibet Plateau. Abstract Due to its extremely harsh environment, including high altitude, hypoxia, long cold season, and strong ultraviolet radiation in the Qinghai–Tibet Plateau (QTP), herbage species and nutritional value of the pasture may differ considerably from elsewhere across the world. The aim of the present study was to develop biologically relevant equations for estimating the metabolizable energy (ME) value of fresh native herbages in the QTP using digestibility variables and chemical concentrations in the herbage offered to Tibetan sheep at the maintenance level. A total of 11 digestibility trials (6 sheep/trial) were performed in different grazing seasons from 2011 to 2016. The herbage was harvested daily in the morning and offered to sheep at the maintenance feeding level. Thirty-seven equations were developed for the prediction of herbage digestible energy (DE) and ME energy values. The mean prediction error for ME was the lowest when using herbage gross energy digestibility as a sole predictor. When using other digestibility variables (e.g., dry matter and organic matter) as primary predictors, addition of herbage nutrient concentration reduced the difference between predicted and actual values. When DE was used as the primary explanatory variable, mean prediction error was reduced with the addition of ash, nitrogen (N), diethyl ether extract (EE), neutral detergent fiber (NDF), and acid detergent fiber (ADF) concentrations. The internal validation of the present equations showed lower prediction errors when compared with those of existing equations for prediction of DE and ME concentrations in the herbage. Equations developed in the current study may thus allow for an improved and accurate prediction of metabolizable energy concentrations of herbage in practice, which is critical for the development of sustainable grazing systems in the QTP.
Differences in stability and calcium sensitivity of the Ig domains in titin's N2A region

Titin is a large filamentous protein that spans half a sarcomere, from Z‐disk to M‐line. The N2A region within the titin molecule exists between the proximal immunoglobulin (Ig) region and the PEVK region and protein–protein interactions involving this region are required for normal muscle function. The N2A region consists of four Ig domains (I80–I83) with a 105 amino acid linker region between I80 and I81 that has a helical nature. Using chemical stability measurements, we show that predicted differences between the adjacent Ig domains (I81–I83) correlate with experimentally determined differences in chemical stability and refolding kinetics. Our work further shows that I83 has the lowest ΔGunfolding, which is increased in the presence of calcium (pCa 4.3), indicating that Ca2+ plays a role in stabilizing this immunoglobulin domain. The characteristics of N2A's three Ig domains provide insight into the stability of the binding sites for proteins that interact with the N2A region. This work also provides insights into how Ca2+ might influence binding events involving N2A.
Psychiatric Disorders in Women Seeking Fertility Treatments: A Clinical Investigation in India

Fertility treatments began in several countries, including India, in the1970s. Despite various advancements in intra uterine insemination (IUI) and in vitro fertilization (IVF), empirical investigations on the psychological endurance and emotional tolerance of Indian women to such treatments are rather scarce. Thus, the aim of this study is to estimate the prevalence of psychiatric disorders in Indian women seeking fertility treatments. It is a cross-sectional study with three hundred women participants undergoing various treatments at the Manipal Assisted Reproductive Centre, Kasturba Medical College, Karnataka, India. Psychiatric disorders were assessed in women using the “ICD- 10 Classification of Mental and Behavioural Disorders” followed by descriptive data analysis. The results show that 78% of women have psychological issues and 45% of them have a diagnosable psychiatric condition. Adjustment Disorders, Anxiety Disorders and Mixed Anxiety and Depression Disorder are established as the top three categories of diagnoses. The findings of this study suggest that women have a high emotional stake in infertility treatments. The data highlights the need for modification of the existing treatment protocol (in Indian clinics) in ways that ensure the emotional wellbeing of patients.
The Drosophila RNA Helicase Belle (DDX3) Non-Autonomously Suppresses Germline Tumorigenesis Via Regulation of a Specific mRNA Set

DDX3 subfamily DEAD-box RNA helicases are essential developmental regulators of RNA metabolism in eukaryotes. belle, the single DDX3 ortholog in Drosophila, is required for fly viability, fertility, and germline stem cell maintenance. Belle is involved both in translational activation and repression of target mRNAs in different tissues; however, direct targets of Belle in the testes are essentially unknown. Here we showed that belle RNAi knockdown in testis cyst cells caused a disruption of adhesion between germ and cyst cells and generation of tumor-like clusters of stem-like germ cells. Ectopic expression of β-integrin in cyst cells rescued early stages of spermatogenesis in belle knockdown testes, indicating that integrin adhesion complexes are required for the interaction between somatic and germ cells in a cyst. To address Belle functions in spermatogenesis in detail we performed cross-linking immunoprecipitation and sequencing (CLIP-seq) analysis and identified multiple mRNAs that interacted with Belle in the testes. The set of Belle targets includes transcripts of proteins that are essential for preventing the tumor-like clusters of germ cells and for sustaining spermatogenesis. By our hypothesis, failures in the translation of a number of mRNA targets additively contribute to developmental defects observed in the testes with belle knockdowns both in cyst cells and in the germline.
Sclerenchyma cell thickening through enhanced lignification induced by OsMYB30 prevents fungal penetration of rice leaves.

Broad-spectrum resistance is highly preferred in crop breeding programs. Previously, we reported the identification of the broad-spectrum resistance-Digu 1 (bsr-d1) allele from rice Digu. The bsr-d1 allele prevents activation of Bsr-d1 expression by Magnaporthe oryzae infection and degradation of H2 O2 by peroxidases, leading to resistance to M. oryzae. However, it remains unknown whether defense pathways other than H2 O2 burst and peroxidases contribute to the bsr-d1-mediated immunity. Blast resistance was determined in rice leaves by spray and punch inoculations. Target genes of OsMYB30 was identified by one-hybrid assays in yeast and electrophoretic mobility shift assay. Lignin contents were measured by phloroglucinol-HCl staining, and acetyl bromide and thioacidolysis methods. Here, we report the involvement of the OsMYB30 gene in the bsr-d1-mediated blast resistance. Expression of OsMYB30 is induced during M. oryzae infection or when Bsr-d1 is knocked out or downregulated, as occurs in bsr-d1 plants upon infection. We further find that OsMYB30 binds to and activates the promoters of 4-coumarate:coenzyme A ligase genes (Os4CL3 and Os4CL5) resulting in accumulation of lignin subunits G and S. This action leads to obvious thickening of sclerenchyma cells near the epidermis, inhibiting M. oryzae penetration at the early stage of infection. Our study reveals novel components required for bsr-d1-mediated resistance and penetration-dependent immunity, and advances our understanding of broad-spectrum disease resistance.
Estimating Respirable Dust Exposure from Inhalable Dust Exposure

Abstract In the sector of occupational safety and health only a limited amount of studies are concerned with the conversion of inhalable to respirable dust. This conversion is of high importance for retrospective evaluations of exposure levels or of occupational diseases. For this reason a possibility to convert inhalable into respirable dust is discussed in this study. To determine conversion functions from inhalable to respirable dust fractions, 15 120 parallel measurements in the exposure database MEGA (maintained at the Institute for Occupational Safety and Health of the German Social Accident Insurance) are investigated by regression analysis. For this purpose, the whole data set is split into the influencing factors working activity and material. Inhalable dust is the most important predictor variable and shows an adjusted coefficient of determination of 0.585 (R2 adjusted to sample size). Further improvement of the model is gained, when the data set is split into six working activities and three material groups (e.g. high temperature processing, adj. R2 = 0.668). The combination of these two variables leads to a group of data concerned with high temperature processing with metal, which gives rise to a better description than the whole data set (adj. R2 = 0.706). Although it is not possible to refine these groups further systematically, seven improved groups are formed by trial and error, with adj. R2 between 0.733 and 0.835: soldering, casting (metalworking), welding, high temperature cutting, blasting, chiseling/embossing, and wire drawing. The conversion functions for the seven groups are appropriate candidates for data reconstruction and retrospective exposure assessment. However, this is restricted to a careful analysis of the working conditions. All conversion functions are power functions with exponents between 0.454 and 0.946. Thus, the present data do not support the assumption that respirable and inhalable dust are linearly correlated in general.
Daily Activities and Breathing Parameters for Use in Respiratory Tract Dosimetry

Dosimetry of inhaled substances is based on the air volumes breathed every day by people under exposure to gases and aerosols. In order to assess modern standards for average inspired air volumes, according to age and gender, information was recorded on daily activities and breathing rates both indoors and outdoors, of specific categories of the population.
In vivo FRET analyses reveal a role of ATP hydrolysis–associated conformational changes in human P-glycoprotein

P-glycoprotein (P-gp; also known as MDR1 or ABCB1) is an ATP-driven multidrug transporter that extrudes various hydrophobic toxic compounds to the extracellular space. P-gp consists of two transmembrane domains (TMDs) that form the substrate translocation pathway and two nucleotide-binding domains (NBDs) that bind and hydrolyze ATP. At least two P-gp states are required for transport. In the inward-facing (pre-drug transport) conformation, the two NBDs are separated, and the two TMDs are open to the intracellular side; in the outward-facing (post-drug transport) conformation, the NBDs are dimerized, and the TMDs are slightly open to the extracellular side. ATP binding and hydrolysis cause conformational changes between the inward-facing and the outward-facing conformations, and these changes help translocate substrates across the membrane. However, how ATP hydrolysis is coupled to these conformational changes remains unclear. In this study, we used a new FRET sensor that detects conformational changes in P-gp to investigate the role of ATP binding and hydrolysis during the conformational changes of human P-gp in living HEK293 cells. We show that ATP binding causes the conformational change to the outward-facing state and that ATP hydrolysis and subsequent release of γ-phosphate from both NBDs allow the outward-facing state to return to the original inward-facing state. The findings of our study underscore the utility of using FRET analysis in living cells to elucidate the function of membrane proteins such as multidrug transporters.
Viruses go modular

The WW domain is a modular protein structure that recognizes the proline-rich Pro-Pro-x-Tyr (PPxY) motif contained in specific target proteins. The compact modular nature of the WW domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the Hippo pathway). As a result, WW domains play key roles in a plethora of both normal and disease processes. Intriguingly, RNA and DNA viruses have evolved strategies to hijack cellular WW domain–containing proteins and thereby exploit the modular functions of these host proteins for various steps of the virus life cycle, including entry, replication, and egress. In this review, we summarize key findings in this rapidly expanding field, in which new virus-host interactions continue to be identified. Further unraveling of the molecular aspects of these crucial virus-host interactions will continue to enhance our fundamental understanding of the biology and pathogenesis of these viruses. We anticipate that additional insights into these interactions will help support strategies to develop a new class of small-molecule inhibitors of viral PPxY-host WW-domain interactions that could be used as antiviral therapeutics.
Going Beyond Conventional Mammographic Density to Discover Novel Mammogram-Based Predictors of Breast Cancer Risk

This commentary is about predicting a woman’s breast cancer risk from her mammogram, building on the work of Wolfe, Boyd and Yaffe on mammographic density. We summarise our efforts at finding new mammogram-based risk predictors, and how they combine with the conventional mammographic density, in predicting risk for interval cancers and screen-detected breast cancers across different ages at diagnosis and for both Caucasian and Asian women. Using the OPERA (odds ratio per adjusted standard deviation) concept, in which the risk gradient is measured on an appropriate scale that takes into account other factors adjusted for by design or analysis, we show that our new mammogram-based measures are the strongest of all currently known breast cancer risk factors in terms of risk discrimination on a population-basis. We summarise our findings graphically using a path diagram in which conventional mammographic density predicts interval cancer due to its role in masking, while the new mammogram-based risk measures could have a causal effect on both interval and screen-detected breast cancer. We discuss attempts by others to pursue this line of investigation, the measurement challenge that allows different measures to be compared in an open and transparent manner on the same datasets, as well as the biological and public health consequences.
Using the CNI Model to Investigate Individual Differences in Moral Dilemma Judgments

Typical moral dilemmas pitting the consequences of a given action against the action’s consistency with moral norms confound several determinants of moral judgments. Dissociating these determinants, the CNI model allows researchers to quantify sensitivity to consequences, sensitivity to norms, and general preference for inaction over action regardless of consequences and norms. However, with the currently available set of dilemmas for research using the CNI model, the model is not suitable for studies with individual-difference designs. To overcome this limitation, the current research investigated the suitability of an extended dilemma battery to make the CNI model amenable for individual-difference research, examining relations of its parameters with psychopathy, empathic concern, need for cognition, self-reported utilitarianism, behavioral activation/inhibition, moral identity, and religiosity. The results support the suitability of the CNI model for individual-difference research with the extended dilemma battery, providing more nuanced insights into the underpinnings of individual differences in moral dilemma judgments.
Therapeutic Effects of Idebenone on Leber Hereditary Optic Neuropathy

ABSTRACT Purpose: To characterize the potential therapeutic effects of idebenone on Leber hereditary optic neuropathy (LHON) in terms of visual acuity (VA), visual field (VF) defects, visual evoked potential (VEP) and retinal nerve fibre layer (RNFL) thickness using optical coherence tomography (OCT) measurements. Methods: This was a retrospective case-controlled study of the effect of idebenone (900 mg/d) on 30 patients with LHON due to m.3460 G > A, m.11778 G > A and m.14484 T > C mutations. The primary end-point was the recovery in VA after 3 and 6 mon. The main secondary end-point was the change in VF, VEP and RNFL thickness. The other secondary end-point was the correlation between visual changes after 6 mon and the VF, VEP and RNFL thickness at baseline of the groups. Results: Idebenone was shown to be safe and well tolerated. The primary end-point reached statistical significance. The VA in the idebenone group improved in both the best eye and worst eye. The mean defect of VF decreased and amplitude of VEP increased. There was no significant difference in latency and RNFL thickness between the groups. The treatment, together with the VA and amplitude at baseline, had a significant effect on the improvement in VA at 6 mon. Conclusion: This case-controlled study of LHON provides evidence that idebenone treatment may be beneficial in cases of LHON and that the influential factors governing outcomes are the VA and amplitude of the VEP at baseline.
Longterm Survival After Liver Transplantation for Autoimmune Hepatitis: Results From the European Liver Transplant Registry

The aim of this study was to analyze longterm patient and graft survival after liver transplantation for autoimmune hepatitis (AIH‐LT) from the prospective multicenter European Liver Transplant Registry. Patient and liver graft survival between 1998 and 2017 were analyzed. Patients after AIH‐LT (n = 2515) were compared with patients receiving LT for primary biliary cholangitis (PBC‐LT; n = 3733), primary sclerosing cholangitis (PSC‐LT; n = 5155), and alcohol‐related cirrhosis (AC‐LT; n = 19,567). After AIH‐LT, patient survival was 79.4%, 70.8%, and 60.3% and graft survival was 73.2%, 63.4%, and 50.9% after 5, 10, and 15 years of follow‐up. Overall patient survival was similar to patients after AC‐LT (P = 0.44), but worse than after PBC‐LT (hazard ratio [HR], 1.48; P < 0.001) and PSC‐LT (HR, 1.19; P = 0.002). AIH‐LT patients were at increased risk for death (HR, 1.37‐1.84; P < 0.001) and graft loss (HR, 1.35‐1.80; P < 0.001) from infections compared with all other groups and had a particularly increased risk for lethal fungal infections (HR, 3.38‐4.20; P ≤ 0.004). Excluding patients who died within 90 days after LT, risk of death after AIH‐LT was superior compared with AC‐LT (HR, 0.84; P = 0.004), worse compared with PBC‐LT (HR, 1.38; P < 0.001) and similar compared with PSC‐LT (P = 0.93). Autoimmune hepatitis (AIH) patients with living donor liver transplantation (LDLT) showed reduced survival compared with patients receiving donation after brain death (HR, 1.96; P < 0.001). In AIH‐LT patients, overall survival is inferior to PBC‐LT and PSC‐LT. The high risk of death after AIH‐LT is caused mainly by early fatal infections, including fungal infections. Patients with LDLT for AIH show reduced survival.