Miracle-dz/UniFAR-FTUs huggingface dataset:
Global Genetic Determinants of Mitochondrial DNA Copy Number

Many human diseases including development of cancer is associated with depletion of mitochondrial DNA (mtDNA) content. These diseases are collectively described as mitochondrial DNA depletion syndrome (MDS). High similarity between yeast and human mitochondria allows genomic study of the budding yeast to be used to identify human disease genes. In this study, we systematically screened the pre-existing respiratory-deficient Saccharomyces cerevisiae yeast strains using fluorescent microscopy and identified 102 nuclear genes whose deletions result in a complete mtDNA loss, of which 52 are not reported previously. Strikingly, these genes mainly encode protein products involved in mitochondrial protein biosynthesis process (54.9%). The rest of these genes either encode protein products associated with nucleic acid metabolism (14.7%), oxidative phosphorylation (3.9%), or other protein products (13.7%) responsible for bud-site selection, mitochondrial intermembrane space protein import, assembly of cytochrome-c oxidase, vacuolar protein sorting, protein-nucleus import, calcium-mediated signaling, heme biosynthesis and iron homeostasis. Thirteen (12.7%) of the genes encode proteins of unknown function. We identified human orthologs of these genes, conducted the interaction between the gene products and linked them to human mitochondrial disorders and other pathologies. In addition, we screened for genes whose defects affect the nuclear genome integrity. Our data provide a systematic view of the nuclear genes involved in maintenance of mitochondrial DNA. Together, our studies i) provide a global view of the genes regulating mtDNA content; ii) provide compelling new evidence toward understanding novel mechanism involved in mitochondrial genome maintenance and iii) provide useful clues in understanding human diseases in which mitochondrial defect and in particular depletion of mitochondrial genome plays a critical role.
Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol‐induced apoptosis

Ethanol ingestion during pregnancy elicits damage to the developing brain, some of which appears to result from enhanced apoptotic death of neurons. A consistent characteristic of this phenomenon is a highly differing sensitivity to ethanol within specific neuron populations. One possible explanation for this “selective vulnerability” could be cellular variations in glutathione (GSH) homeostasis. Prior studies have illustrated that ethanol elicits apoptotic death of neurons in the developing brain, that oxidative stress may be an underlying mechanism, and that GSH can be neuroprotective. In the present study, both multiphoton microscopy and flow cytometry demonstrate a striking heterogeneity in GSH content within cortical neuron populations. Ethanol differentially elicits apoptotic death and oxidative stress in these neurons. When neuron GSH content is reduced by treatment with butathione sulfoxamine, the ethanol‐mediated enhancement of reactive oxygen species is exacerbated. Sorting of cells into high‐ and low‐GSH populations further exemplifies ethanol‐mediated oxidative stress whereby apoptotic indices are preferentially elevated in the low‐GSH population. Western blot analysis of the low‐GSH subpopulations shows higher ethanol‐mediated expression of active caspase 3 and 24‐kDa PARP‐1 fragments compared with the high‐GSH subpopulation. In addition, neuronal content of 4‐hydroxynonenal adducts is higher in low‐GSH neurons in response to ethanol. These studies suggest that GSH content is an important predictor of neuronal sensitivity to ethanol‐mediated oxidative stress and subsequent cell death. The data support the proposition that the differences in proapoptotic responses to ethanol within specific neuron populations reflect a heterogeneity of neuron GSH content. © 2007 Wiley‐Liss, Inc.
Functional recovery after facial and sciatic nerve crush injury in the rat.

OBJECTIVES To systematically record rat facial nerve recovery following crush injury to the main trunk with respect to ocular and vibrissial function and to compare the rates of facial and sciatic nerve recovery from crush injury in the same animals. This serves as a means of validating the functional parameters of facial nerve recovery against the well-known measure of hind limb function, the Sciatic Function Index. METHODS The main trunk of the facial nerve and the proximal segment of the sciatic nerve were exposed in all animals. Both nerves were subjected to standardized crush injury and subsequent daily functional testing. After a plateau of functional recovery was achieved, the animals were killed, and the distances between the sites of injury and the end musculature were measured, which allowed determination and comparison of recovery rates in both systems. RESULTS All crush injuries resulted in loss of electrical conductivity, as proven by intraoperative proximal nerve stimulation. Recovery of ocular and vibrissial motor function occurred starting at postoperative day (POD) 9 and continuing through POD 20. Hind limb function returned later (POD 14-34); however, when corrected for distance, the sciatic recovery rate (2.26 mm/d) appeared to match that of the facial nerve (1.5-2.4 mm/d). CONCLUSIONS Recovery after facial nerve crush injury follows a predictable time course, and the rate of recovery is consistent with that of sciatic nerve injury. Return of the blink reflex, loss of vibrissial fibrillations, and return of vibrissial sweeping function appear to be internally consistent functional measures of facial recovery. These quantitative measures will be useful for future facial nerve manipulation studies.
Decreased modulation by the risk level on the brain activation during decision making in adolescents with internet gaming disorder

Greater impulse and risk-taking and reduced decision-making ability were reported as the main behavioral impairments in individuals with internet gaming disorder (IGD), which has become a serious mental health issue worldwide. However, it is not clear to date how the risk level modulates brain activity during the decision-making process in IGD individuals. In this study, 23 adolescents with IGD and 24 healthy controls (HCs) without IGD were recruited, and the balloon analog risk task (BART) was used in a functional magnetic resonance imaging experiment to evaluate the modulation of the risk level (the probability of balloon explosion) on brain activity during risky decision making in IGD adolescents. Reduced modulation of the risk level on the activation of the right dorsolateral prefrontal cortex (DLPFC) during the active BART was found in IGD group compared to the HCs. In the IGD group, there was a significant negative correlation between the risk-related DLPFC activation during the active BART and the Barratt impulsivity scale (BIS-11) scores, which were significantly higher in IGD group compared with the HCs. Our study demonstrated that, as a critical decision-making-related brain region, the right DLPFC is less sensitive to risk in IGD adolescents compared with the HCs, which may contribute to the higher impulsivity level in IGD adolescents.
Behaviors The Effects of Visual and Cognitive Distractions on Operational and Tactical Driving

http://hfs.sagepub. com/content/early/2013/07/05/0018720813495279 The online version of this article can be found at: DOI: 10.1177/0018720813495279 2013 published online 8 July Human Factors: The Journal of the Human Factors and Ergonomics Society Yu Zhang, David B. Kaber, Meghan Rogers, Yulan Liang and Shruti Gangakhedkar Behaviors The Effects of Visual and Cognitive Distractions on Operational and Tactical Driving
Improve Effectiveness of Dialogue in Learning Communities

In a learning community, conventional discussion forums are integral to web-based interventions in traditional classrooms as well as on-line learning environments. Despite popular belief that they are a great success in fostering deep and meaningful discussions and support active learning; research has found that there are millions of messages posted by users to express such an opinion, but it is hard to be directly delivered to all users. Finally there are millions of postings in databases across the country stored away and never reused. This paper introduces a PhD student's current in-progress research work. It proposes a distributed intelligent discussion forum system dedicated to supporting both students and teachers. The system is developed with the primary goal of reducing the number of problems associated with conventional discussion forum systems in web-based environments and improving the effectiveness of dialogue between students with each other and with teachers so that it can enhance each individual student's ability to share and learn knowledge.
The V(D)J recombinational and transcriptional activities of the immunoglobulin heavy-chain intronic enhancer can be mediated through distinct protein-binding sites in a transgenic substrate

Immunoglobulin and T-cell receptor gene transcriptional enhancers encompass sequences which stimulate V(D)J recombination of associated variable gene segments. To address the question of whether enhancer-mediated transcriptional activation and recombinational activation depend on the same cis-regulatory sequences, we have produced transgenic mice by using recombination substrates containing various mutations in the immunoglobulin heavy-chain intronic enhancer (E mu). Analysis of substrate rearrangements indicated that specific compound elements including E-box transcriptional motifs are crucial for the recombinational activity of E mu in the developing B and T lymphocytes. In most cases, a faithful correlation between the levels of substrate germ line transcription and recombination was observed. However, some of the E mu mutants which were able to activate transcription of the unrearranged substrate were inefficient in stimulating transgene recombination, implying that the latter function depends on molecular events other than the mere activation of transcription and that both activities can be mediated through distinct regulatory sequences. Together, these results support a model in which lymphoid gene enhancers, in addition to providing docking sites for factors that dictate transcriptional accessibility, must have some specific function(s) for activating V(D)J recombination.
Transportability and Generality in a Natural-Language Interface System

This paper describes the design of a transportable natural language (NL) interface to databases and the constraints that transportability places on each component of such a system. By a transportable NL system, we mean an NL processing system that is constructed so that a domain expert (rather than an AI or linguistics expert) can move the system to a new application domain. After discussing the general problems presented by transportability, this paper describes TEAM (an acronym for Transportable English database Access Medium), a demonstratable prototype of such a system. The discussion of TEAM shows how domain-independent and domain-dependent information can be separated in the different components of a NL interface system, and presents one method of obtaining domain-specific information from a domain expert.
Epigenetic Regulation of Motor Neuron Cell Death through DNA Methylation

DNA methylation is an epigenetic mechanism for gene silencing engaged by DNA methyltransferase (Dnmt)-catalyzed methyl group transfer to cytosine residues in gene-regulatory regions. It is unknown whether aberrant DNA methylation can cause neurodegeneration. We tested the hypothesis that Dnmts can mediate neuronal cell death. Enforced expression of Dnmt3a induced degeneration of cultured NSC34 cells. During apoptosis of NSC34 cells induced by camptothecin, levels of Dnmt1 and Dnmt3a increased fivefold and twofold, respectively, and 5-methylcytosine accumulated in nuclei. Truncation mutation of the Dnmt3a catalytic domain and Dnmt3a RNAi blocked apoptosis of cultured neurons. Inhibition of Dnmt catalytic activity with RG108 and procainamide protected cultured neurons from excessive DNA methylation and apoptosis. In vivo, Dnmt1 and Dnmt3a are expressed differentially during mouse brain and spinal cord maturation and in adulthood when Dnmt3a is abundant in synapses and mitochondria. Dnmt1 and Dnmt3a are expressed in motor neurons of adult mouse spinal cord, and, during their apoptosis induced by sciatic nerve avulsion, nuclear and cytoplasmic 5-methylcytosine immunoreactivity, Dnmt3a protein levels and Dnmt enzyme activity increased preapoptotically. Inhibition of Dnmts with RG108 blocked completely the increase in 5-methycytosine and the apoptosis of motor neurons in mice. In human amyotrophic lateral sclerosis (ALS), motor neurons showed changes in Dnmt1, Dnmt3a, and 5-methylcytosine similar to experimental models. Thus, motor neurons can engage epigenetic mechanisms to drive apoptosis, involving Dnmt upregulation and increased DNA methylation. These cellular mechanisms could be relevant to human ALS pathobiology and disease treatment.
Age-related declines in knee extensor strength and physical performance in healthy Hispanic and Caucasian women.

Hispanic women may undergo greater age-related reductions in physical functional capacity compared with Caucasian women. If so, a greater rate of decline in muscle strength with age could contribute. We tested this hypothesis in 82 healthy sedentary Caucasian (n = 37) and Hispanic (n = 45) adult women aged 21-78 years of similar socioeconomic status. Absolute one-repetition maximum (1-RM) strength of the knee extensors (KE) declined with advancing age in the Caucasian (r = -.55, p < .01) and Hispanic (r = -.45, p < .01) women; the rates of decline were similar in the two groups (-7% to 8% x decade(-1), p = . 60). KE strength normalized for thigh fat-free mass (FFM) also declined with age in the Caucasian (r = .52, p < .01) and Hispanic (r = -.41, p < .01) women, the rates of decline being similar (-6% to 7% x decade(-1), p = . 66). For all functional performance tasks (10-m walk, stair ascent, stair descent, and chair stand), performance time increased with advancing age (mean of four tasks vs age: Caucasian, r = .64, p < .01; Hispanic, r = .56, p < .01). Absolute and normalized KE 1-RM were inversely related to the mean time for the four performance tasks (r = -.34 to -.58, all p < .01). Normalized KE 1-RM was the best independent predictor of the age-related decline in task performance in both groups. These cross-sectional findings do not support the hypothesis that Hispanic ethnicity per se is associated with a greater decline in KE strength and performance tasks associated with KE strength in healthy women.
Sows’ parity and coconut oil postnatal supplement on piglets performance

Objective. The study aimed to evaluate the effect of sows' of different parities and the supplement of coconut oil for piglets, on the development of litter. Materials and methods. A total of 51 sows of different parities and their 642 piglets were used in the trial. Each piglet was weighed and identified at birth in a sequential order. They were randomly distributed in two treatments (CG=control group and TG=test group). TG piglets had the first access to a dosage of 3.0 ml of coconut oil 12 hours after birth, and the second at 36 h after the first. Piglets were weighed at 21 days. In order to analyze the effect of the coconut oil supplement as a function of the weight at birth, piglets were grouped according to their weight (0.600 to 0.900 kg; 1.000 to 1.499kg; 1.500 to 1.999 kg; and 2.000 to 2.499 kg). Results. Sows parity affected the number and weight of born piglets. Sows in 4th, 5th and 7th parity had a larger litter than those from the 2nd parity. Sows from 2nd and 3rd parity had a lower number of piglets but heavier litter. No effect of the coconut oil supplement on neonatal piglets' performance was found. Conclusions. The coconut meal was neither beneficial to neonatal piglets nor to those with low weight at birth, which usually present low body energy.
Multispecies Analysis of Expression Pattern Diversification in the Recently Expanded Insect Ly6 Gene Family

Gene families often consist of members with diverse expression domains reflecting their functions in a wide variety of tissues. However, how the expression of individual members, and thus their tissue-specific functions, diversified during the course of gene family expansion is not well understood. In this study, we approached this question through the analysis of the duplication history and transcriptional evolution of a rapidly expanding subfamily of insect Ly6 genes. We analyzed different insect genomes and identified seven Ly6 genes that have originated from a single ancestor through sequential duplication within the higher Diptera. We then determined how the original embryonic expression pattern of the founding gene diversified by characterizing its tissue-specific expression in the beetle Tribolium castaneum, the butterfly Bicyclus anynana, and the mosquito Anopheles stephensi and those of its duplicates in three higher dipteran species, representing various stages of the duplication history (Megaselia abdita, Ceratitis capitata, and Drosophila melanogaster). Our results revealed that frequent neofunctionalization episodes contributed to the increased expression breadth of this subfamily and that these events occurred after duplication and speciation events at comparable frequencies. In addition, at each duplication node, we consistently found asymmetric expression divergence. One paralog inherited most of the tissue-specificities of the founder gene, whereas the other paralog evolved drastically reduced expression domains. Our approach attests to the power of combining a well-established duplication history with a comprehensive coverage of representative species in acquiring unequivocal information about the dynamics of gene expression evolution in gene families.
mRNA Expression levels of genes involved in antitumor immunity: Identification of a 3-gene signature associated with prognosis of muscle-invasive bladder cancer

ABSTRACT Immunotherapy for bladder cancer has given promising results. Here we aimed to evaluate the possible involvement and prognostic value of 33 genes involved in the immune response during bladder carcinogenesis. Expression levels were assessed by quantitative real-time RT-PCR in normal and tumor human bladder samples. Immunohistochemistry was performed to evaluate the protein expression of 2 genes and relation of the mRNA and protein levels was analyzed. Tumors were obtained from 154 patients (83 with muscle-invasive bladder cancer [MIBC] and 71 non-MIBC [NMIBC]) who underwent transurethral bladder resection or radical cystectomy between 2002 and 2006. All patients signed an informed consent. Results of molecular analyses were coupled with survival analyses. Overall, 25 genes (75.8%) were significantly overexpressed in MIBC and 15 (45.5%) were deregulated in NMIBC as compared with normal tissue. On multivariate analysis, risk of NMIBC recurrence was increased with high FOXP3/CD8 ratio and overexpression of OX40L (p = 0.016 and p = 0.0039, respectively). In MIBC, a molecular signature of 3 genes (OX40L, CD8 and TIGIT) was significantly associated with prognosis in terms of recurrence-free and overall survival (p = 0.0007 and p = 0.007). RT-PCR findings were confirmed by immunohistochemistry for CD8 and FOXP3, with high association between mRNA and protein levels. Finally, risk of recurrence of non–muscle-invasive bladder cancer was increased with high FOXP3/CD8 ratio and OX40L overexpression. We identified a 3 gene molecular signature associated with prognosis of muscle-invasive bladder cancer. These results confirm the useful role of immune checkpoints in bladder carcinogenesis and suggest targets for therapy.
Mosaik: A framework for modular simulation of active components in Smart Grids

This paper presents the requirements and a concept for a modular Smart Grid simulation framework based on an automatic composition of existing, heterogeneous simulation models. The composition problem is broken down into different layers, for each of which first concepts for solving the problem are presented. A prototype showing the feasibility of the presented concept has been developed. First simulation results of a Smart Grid scenario including electric vehicles as well as renewable energy sources are presented. Finally, the limitations of the prototype and possible improvements are discussed.
Breathing exercises for asthma: a randomised controlled trial

Background: The effect of breathing modification techniques on asthma symptoms and objective disease control is uncertain. Methods: A prospective, parallel group, single-blind, randomised controlled trial comparing breathing training with asthma education (to control for non-specific effects of clinician attention) was performed. Subjects with asthma with impaired health status managed in primary care were randomised to receive three sessions of either physiotherapist-supervised breathing training (n = 94) or asthma nurse-delivered asthma education (n = 89). The main outcome was Asthma Quality of Life Questionnaire (AQLQ) score, with secondary outcomes including spirometry, bronchial hyper-responsiveness, exhaled nitric oxide, induced sputum eosinophil count and Asthma Control Questionnaire (ACQ), Hospital Anxiety and Depression (HAD) and hyperventilation (Nijmegen) questionnaire scores. Results: One month after the intervention there were similar improvements in AQLQ scores from baseline in both groups but at 6 months there was a significant between-group difference favouring breathing training (0.38 units, 95% CI 0.08 to 0.68). At the 6-month assessment there were significant between-group differences favouring breathing training in HAD anxiety (1.1, 95% CI 0.2 to 1.9), HAD depression (0.8, 95% CI 0.1 to 1.4) and Nijmegen (3.2, 95% CI 1.0 to 5.4) scores, with trends to improved ACQ (0.2, 95% CI 0.0 to 0.4). No significant between-group differences were seen at 1 month. Breathing training was not associated with significant changes in airways physiology, inflammation or hyper-responsiveness. Conclusion: Breathing training resulted in improvements in asthma-specific health status and other patient-centred measures but not in asthma pathophysiology. Such exercises may help patients whose quality of life is impaired by asthma, but they are unlikely to reduce the need for anti-inflammatory medication.