Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of Tyrosines 114 and 139 of Subunit NuoB in the Proton Pathway around Cluster N2 in Escherichia coliNADH:Ubiquinone Oxidoreductase*

The proton-pumping NADH:ubiquinone oxidoreductase (complex I) couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane. Electron transfer is accomplished by FMN and a series of iron-sulfur clusters. Its coupling with proton translocation is not yet understood. Here, we report that the redox reaction of the FeS cluster N2 located on subunit NuoB of the Escherichia coli complex I induces a protonation/deprotonation of tyrosine side chains. Electrochemically induced FT-IR difference spectra revealed characteristic tyrosine signals at 1,515 and 1,498 cm−1 for the protonated and deprotonated form, respectively. Mutants of three conserved tyrosines on NuoB were generated by complementing a chromosomal in-frame deletion strain with nuoB on a plasmid. Though the single mutations did not alter the electron transport activity of complex I, the EPR signal of cluster N2 was slightly shifted. The tyrosine signals detected by FT-IR spectroscopy were roughly halved in the mutants Y114C and Y139C while only minor changes were detected in the Y154H mutant. The enzymatic activity of the Y114C/Y139F double mutant was 80% reduced, and FT-IR difference spectra of the double mutant revealed a complete loss the modes characteristic for protonation reactions of tyrosines. Therefore, we propose that tyrosines 114 and 139 on NuoB were protonated upon reduction of cluster N2 and were thus involved in the proton-transfer reaction coupled with its redox reaction.
Recommendation of Tourist Attractions Based on Slope One Algorithm

With the development of domestic tourism, personalized demands for tourist attractions recommendation systems have increased. Since some drawbacks of traditional collaborative filtering include scalability and sensitivity to data sparseness, a new Slope One algorithm with attractions similarity is proposed in this paper. This Slope One algorithm weakens the effect of popular tourist attractions on prediction ratings, integrating attractions rating similarity and attractions attribute similarity calculation. Experimental results show that the proposed Slope One algorithm not only improves the accuracy of prediction effectively, but also optimizes the balanced distribution of recommendation results.
Structured mRNA induces the ribosome into a hyper‐rotated state

During protein synthesis, mRNA and tRNA are moved through the ribosome by the process of translocation. The small diameter of the mRNA entrance tunnel only permits unstructured mRNA to pass through. However, there are structured elements within mRNA that present a barrier for translocation that must be unwound. The ribosome has been shown to unwind RNA in the absence of additional factors, but the mechanism remains unclear. Here, we show using single molecule Förster resonance energy transfer and small angle X‐ray scattering experiments a new global conformational state of the ribosome. In the presence of the frameshift inducing dnaX hairpin, the ribosomal subunits are driven into a hyper‐rotated state and the L1 stalk is predominantly in an open conformation. This previously unobserved conformational state provides structural insight into the helicase activity of the ribosome and may have important implications for understanding the mechanism of reading frame maintenance.
Fragmented QRS on surface electrocardiogram is not a reliable predictor of myocardial scar, angiographic coronary disease or long term adverse outcomes.

PURPOSE Conflicting evidence remains regarding the value of fragmented QRS (fQRS) on surface electrocardiogram (EKG). We present the 5-year outcome of patients with fQRS on EKG and its correlation to SPECT and coronary angiography (CA). METHODS We retrospectively studied EKG's in 248 consecutive patients undergoing SPECT and CA with known or suspected coronary artery disease (CAD). The presence of fQRS or Q waves in two contiguous EKG leads was correlated with major coronary artery distributions on SPECT and cath. Patients with bundle-branch block, paced-rhythm or absence of EKG within one month of SPECT were excluded. The final EKG data for 238 patients were analyzed and compared with myocardial scar on SPECT and the presence of significant (>50%) coronary stenosis on CA. Predictors of MACE (death, MI, heart failure) were evaluated. Freedom from all-cause mortality was assessed by Kaplan-Meier analysis. RESULTS Of 238 patients, no significant difference was noted in the presence of scar on SPECT in fQRS (3/77; 3.8%) versus no fQRS (11/161; 6.8%) (P=0.56); or CA based CAD (55/77; 71% fQRS) and no fQRS (99/161, 61.4%) (P=0.20). EKG Q wave presence was similar in both groups: (12/77; 15.5% fQRS), (17/161; 10.5% no fQRS) (P=0.3). Patients with CA based significant LAD disease were 3.680 times more likely to have fQRS (P=0.04), however, fQRS was not significantly associated with MACE (P=0.92) or all-cause mortality (P=0.93). CONCLUSIONS This study does not support routine assessment of fQRS on surface EKG as a reliable predictor of SPECT myocardial scar, MACE or all-cause mortality over a long period of follow-up.
Eukaryotic translation initiation factor 2B‐beta (eIF2B&bgr;), a new class of plant virus resistance gene

Recessive resistances to plant viruses in the Potyvirus genus have been found to be based on mutations in the plant eukaryotic translation initiation factors, eIF4E and eIF4G or their isoforms. Here we report that natural, monogenic recessive resistance to the Potyvirus Turnip mosaic virus (TuMV) has been found in a number of mustard (Brassica juncea) accessions. Bulked segregant analysis and sequencing of resistant and susceptible plant lines indicated the resistance is controlled by a single recessive gene, recessive TuMV resistance 03 (retr03), an allele of the eukaryotic translation initiation factor 2B-beta (eIF2Bβ). Silencing of eIF2Bβ in a TuMV-susceptible mustard plant line and expression of eIF2Bβ from a TuMV-susceptible line in a TuMV-resistant mustard plant line confirmed the new resistance mechanism. A functional copy of a specific allele of eIF2Bβ is required for efficient TuMV infection. eIF2Bβ represents a new class of virus resistance gene conferring resistance to any pathogen. eIF2B acts as a guanine nucleotide exchange factor (GEF) for its GTP-binding protein partner eIF2 via interaction with eIF2·GTP at an early step in translation initiation. Further genotyping indicated that a single non-synonymous substitution (A120G) in the N-terminal region of eIF2Bβ was responsible for the TuMV resistance. A reproducible marker has been developed, facilitating marker-assisted selection for TuMV resistance in B. juncea. Our findings provide a new target for seeking natural resistance to potyviruses and new opportunities for the control of potyviruses using genome editing techniques targeted on eIF2Bβ.
Studying the effect of paralleling settings on the functioning of a barcode recognition app

The paper proposes a parallel video stream processing method for a linear barcode recognition. The researchers have simulated the system for various memory usage modes. A number of experiments have been carried out to identify the weaknesses and peculiarities of the system. Based on these data, improvements were made to solve the problem of a more efficient identifying of the objects in a video stream. Theoretical studies were carried out on the basis of the parallel computing theory, vector algebra and the pattern recognition theory. The approach enables a more efficient usage of processor capabilities.
PRMT7 regulates RNA-binding capacity and protein stability in Leishmania parasites

Abstract RNA binding proteins (RBPs) are the primary gene regulators in kinetoplastids as transcriptional control is nearly absent, making Leishmania an exceptional model for investigating methylation of non-histone substrates. Arginine methylation is an evolutionarily conserved protein modification catalyzed by Protein aRginine Methyl Transferases (PRMTs). The chromatin modifier PRMT7 is the only Type III PRMT found in higher eukaryotes and a restricted number of unicellular eukaryotes. In Leishmania major, PRMT7 is a cytoplasmic protein implicit in pathogenesis with unknown substrates. Using comparative methyl-SILAC proteomics for the first time in protozoa, we identified 40 putative targets, including 17 RBPs hypomethylated upon PRMT7 knockout. PRMT7 can modify Alba3 and RBP16 trans-regulators (mammalian RPP25 and YBX2 homologs, respectively) as direct substrates in vitro. The absence of PRMT7 levels in vivo selectively reduces Alba3 mRNA-binding capacity to specific target transcripts and can impact the relative stability of RBP16 in the cytoplasm. RNA immunoprecipitation analyses demonstrate PRMT7-dependent methylation promotes Alba3 association with select target transcripts and thus indirectly stabilizes mRNA of a known virulence factor, δ-amastin surface antigen. These results highlight a novel role for PRMT7-mediated arginine methylation of RBP substrates, suggesting a regulatory pathway controlling gene expression and virulence in Leishmania. This work introduces Leishmania PRMTs as epigenetic regulators of mRNA metabolism with mechanistic insight into the functional manipulation of RBPs by methylation.
Effector Immediate-Early Gene Arc in the Amygdala Plays a Critical Role in Alcoholism

The immediate early gene, activity-regulated cytoskeleton-associated protein (Arc), has been implicated in synaptic plasticity. However, the role of Arc in alcoholism is unknown. Here, we report that the anxiolytic effects of acute ethanol were associated with increased brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (trkB) expression, increased phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), Elk-1, and cAMP responsive element-binding protein (CREB), increased Arc expression, and increased dendritic spine density (DSD) in both the central amygdala (CeA) and medial amygdala (MeA) but not in the basolateral amygdala (BLA) of rats. Conversely, the anxiogenic effects of withdrawal after long-term ethanol exposure were associated with decreased BDNF and trkB expression, decreased phosphorylation of Erk1/2, Elk-1, and CREB, decreased Arc expression, and decreased DSD in both the CeA and MeA but not in the BLA of rats. We also showed that BDNF infusion into the CeA normalized phosphorylation of Erk1/2, Elk-1, and CREB, and normalized Arc expression, thereby protecting against the onset of ethanol withdrawal-related anxiety. We further demonstrated that arresting Arc expression in the CeA decreased DSD, thereby increasing anxiety-like and alcohol-drinking behaviors in control rats. These results revealed that BDNF–Arc signaling and the associated DSD in the CeA, and possibly in the MeA, may be involved in the molecular processes of alcohol dependence and comorbidity of anxiety and alcohol-drinking behaviors.
Impaired executive functioning in young adults born very preterm

Individuals born very preterm (VPT) are at increased risk of perinatal brain injury and long-term cognitive and behavioral problems. Executive functioning, in particular, has been shown to be impaired in VPT children and adolescents. This study prospectively assessed executive function in young adults who were born VPT (<33 weeks of gestation) [n = 61; mean age, 22.25 (±1.07) years; range, 20.62–24.78 years] and controls [n = 64; mean age, 23.20 (±1.48) years; range, 19.97–25.46 years]. Tests used comprised the Wechsler Abbreviated Scale of Intelligence (WASI), the Hayling Sentence Completion Test (HSCT), the Controlled Oral Word Association Test (COWAT), the Animal and Object test, the Trail-Making Test (TMT), and the Test of Attentional Performance (TAP). VPT participants showed specific executive function impairments in tasks involving response inhibition and mental flexibility, even when adjusting for IQ, gender, and age. No significant associations were observed between executive function test scores and perinatal variables or neonatal ultrasound classification. The results suggest that, although free from major physical disability, VPT young adults perform worse than controls on tasks involving selective aspects of executive processing, such as mental flexibility and response inhibition. (JINS, 2007, 13, 571–581.)
Patch tests to metals in childhood

Patch tests were performed in 100 consecutive children, 45 boys and 55 girls, whose ages ranged from 8 months to 11 years (Table 1). They were selected at random from paediatric and dermatologic outpatients. Some patients' healthy brothers were included. Most patients had trivial conditions, e.g. naevi, papillomas, verrucae, alopecia. Atopic dermatitis, asthma or rhinitis were present in a few cases. Personal and familial history of atopy or sensitivity to metals was recorded in all cases. Parents gave informed consent. Al-test® patches were used fixed on the back with tape. The patches were removed after 48 hand read at 60 min and at 48 and 96 h. The test substances were nickel sulfate 2.5 %, cobalt chloride 1%, potassium dichromate 0.5%, mercury 0.5% in white soft paraffin.
The scope for biased recall of risk-factor exposure in case-control studies: Evidence from a cohort study of Scottish men

Aims: Case-control studies are prone to recall bias, a participant's case-control status influencing their recall of exposure to risk factors. We aimed to demonstrate empirically the scope for this bias. Methods: Two thousand five hundred and fifty men without coronary heart disease at enrolment to a prospective cohort study underwent two health assessments, about 5 years apart. The association between the development of coronary heart disease in the intervening period and changes in reported stress and cigarette smoking were investigated. Results: Men admitted to hospital with coronary heart disease reported a greater increase in psychological stress (p=0.032) and greater cessation of smoking (22% vs. 10%; p=0.007) than men not admitted. Consequently, when exposure data are collected at the end rather than at the start of the follow-up period, coronary heart disease is observed to be more strongly associated with psychological stress, and more weakly associated with smoking. Conclusions: At the time when a case-control study is conducted, levels of exposure to risk factors will have been influenced by disease development. When participants are asked about their level of exposure for a previous time period, recall is likely to be influenced by present outcome and exposure status, especially when psychological states are being investigated.
Effect of intercistronic length on internal ribosome entry site (IRES) efficiency in bicistronic mRNA.

Specific structures found in the mRNA of picornavirus are known to allow a cap-independent translation. These structures, named internal ribosome entry sites (IRES), are also able to favor translation of the second cistron in bicistronic mRNAs. Their mechanism of action is not well understood. In the present study, two IRESs have been used: the IRES from poliovirus and a newly discovered IRES (SUR) composed of the 5' P untranslated sequence from SV40 early genes, the R structure, and a small part of the U5 region from the human leukemia virus-1 (HTLV-1). The bicistronic constructs containing the firefly luciferase gene as the first cistron and the chloramphenicol acetyltransferase (CAT) as the second cistron were driven by the Rous sarcoma virus (RSV) promoter and contained the early gene SV40 terminator. All the resulting plasmids were tested by transfection in HeLa and CHO cells. In the bicistronic mRNAs without IRES, the expression of the CAT gene was dependent on the distance between the two cistrons. The maximum efficiency in the expression of the second cistron was obtained when the intercalating RNA was composed of 30 to 90 nucleotides. This expression was deeply reduced when the intercalating fragment contained 8 or 300 nucleotides and was undetectable with 500 nucleotides. Unexpectedly, the luciferase mRNA was almost not expressed when the intercalating RNA was of 8 or 30 nucleotides. Expression of the luciferase gene occurred when the intercistronic RNA fragment was of 80 nucleotides and it became lower at 300 and 500 nucleotides. The same observations were done when the poliovirus or the SUR IRESs were added after the intercistronic spacers. However, expression of the CAT gene was amplified by both IRESs. When the CAT cistron preceded by the poliovirus or SUR IRES was introduced within luciferase cistron, 316 nucleotides before its termination codon, the IRESs were able to initiate translation of the following CAT gene irrespectively of the mRNA luciferase reading frame. Moreover, with all these constructs the highest expression level of the CAT cistron did not exceed 10% of that obtained with the same vector carrying only the CAT cistron. To identify a possible relation between the IRESs and the cap site, the CAT cistron preceded or not with an IRES was introduced 210 nucleotides downstream of the AUG codon of the luciferase gene (i.e., 258 nucleotides from the cap site) and 100 nucleotides after an added UAG termination codon. Expression of the CAT gene was not modified by the addition of the poliovirus IRES but it was strongly stimulated by the SUR IRES (the level of expression corresponded to 65% of that obtained with the same vector carrying only the CAT cistron). These results suggest that there is a cooperation between the cap and the SUR IRES and not the poliovirus IRES to stimulate translation. These data indicate that IRESs must be introduced in precise position to allow an efficient expression of the second cistron in bicistronic mRNAs.
Re‐evaluation of nestin as a marker of oligodendrocyte lineage cells

Maturation of oligodendrocyte progenitors (O2A) is characterized by morphological changes and the sequential expression of specific antigens leading to the formation of myelin membrane. Monoclonal antibodies A2B5, A007, anti‐vimentin, and anti‐galactocerebroside, recognize oligodendroglia at different stages of development. The neuroepithelial precursor marker nestin is also expressed by the oligodendroglial lineage; we have used enriched populations of progenitors isolated from neonatal rat brain cultures to further examine the cellular distribution of this intermediate filament protein. The phenotypic distribution of nestin positive cells among the oligodendrocyte lineage showed that 65% reacted with A2B5, whereas only 5% were A007+, and 4% galactocerebroside+. The remaining 25% of the cells were not labeled and had small cellular bodies devoid of processes, characteristic of the pre‐O2A progenitor. Further analysis of the nestin+ population showed that the majority of the cells were also vimentin+. Antibody‐dependent complement mediated cytolysis of A2B5+ (O2A cells) and galactocerebroside+ (mature oligodendrocytes) cells left a population of nestin+ cells that were induced to proliferate in the presence of growth factors and to differentiate into A2B5+ and galactocerebroside+ cells. Proliferating cells maintained in the presence of platelet‐derived growth factor or basic fibroblast growth factor retained nestin expression along with A2B5. By contrast, in serum‐free medium nestin expression decreased while postmitotic cells acquired A007 and galactocerebroside. Our results suggest that nestin expression is a marker of pre‐O2A cells that is maintained in proliferating glial progenitors, but is quickly down‐regulated in postmitotic oligodendrocytes (A007+/galacto‐cerebroside+) along with A2B5 and vimentin. However, other glial cells including type 2 astrocytes and some amoeboid microglia also share nestin expression. Microsc. Res. Tech. 52:753–765, 2001. © 2001 Wiley‐Liss, Inc.
Gut Microbiota‐Dependent Trimethylamine N‐oxide and Cardiovascular Outcomes in Patients With Prior Myocardial Infarction: A Nested Case Control Study From the PEGASUS‐TIMI 54 Trial

Background Trimethylamine N‐oxide (TMAO) may have prothrombotic properties. We examined the association of TMAO quartiles with major adverse cardiovascular events (MACE) and the effect of TMAO on the efficacy of ticagrelor. Methods and Results PEGASUS‐TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin ‐ Thrombolysis in Myocardial Infarction 54) randomized patients with prior myocardial infarction to ticagrelor or placebo (median follow‐up 33 months). Baseline plasma concentrations of TMAO were measured in a nested case‐control study of 597 cases with cardiovascular death, myocardial infarction, or stroke (MACE) and 1206 controls matched for age, sex, and estimated glomerular filtration rate [eGFR]. Odds ratios (OR) were used for the association between TMAO quartiles and MACE, adjusting for baseline clinical characteristics (age, sex, eGFR, region, body mass index, hypertension, hypercholesterolemia, diabetes mellitus, smoking, peripheral artery disease, index event, aspirin dosage and treatment arm), and cardiovascular biomarkers (hs‐TnT [high‐sensitivity troponin T], hs‐CRP [high‐sensitivity C‐reactive protein], NT‐proBNP [N‐terminal‐pro‐B‐type natriuretic peptide]). Higher TMAO quartiles were associated with risk of MACE (OR for quartile 4 versus quartile 1, 1.43, 95% CI, 1.06–1.93, P trend=0.015). The association was driven by cardiovascular death (OR 2.25, 95% CI, 1.28–3.96, P trend=0.003) and stroke (OR 2.68, 95% CI, 1.39–5.17, P trend<0.001). After adjustment for clinical factors, the association persisted for cardiovascular death (OR adj 1.89, 95% CI, 1.03–3.45, P trend=0.027) and stroke (OR adj 2.01, 95% CI, 1.01–4.01, P trend=0.022), but was slightly attenuated after adjustment for cardiovascular biomarkers (cardiovascular death: OR adj 1.74, 95% CI, 0.88–3.45, P trend=0.079; and stroke: OR adj 1.82, 95% CI, 0.88–3.78, P trend=0.056). The reduction in MACE with ticagrelor was consistent across TMAO quartiles (P interaction=0.92). Conclusions Among patients with prior myocardial infarction, higher TMAO levels were associated with cardiovascular death and stroke but not with recurrent myocardial infarction. The efficacy of ticagrelor was consistent regardless of TMAO levels. Registration URL: https://www.clinicaltrials. gov; Unique identifiers: PEGASUS‐TIMI 54, NCT01225562.
Structure-Activity-Relationship and Mechanistic Insights for Anti-HIV Natural Products

Acquired Immunodeficiency Syndrome (AIDS), which chiefly originatesfroma retrovirus named Human Immunodeficiency Virus (HIV), has impacted about 70 million people worldwide. Even though several advances have been made in the field of antiretroviral combination therapy, HIV is still responsible for a considerable number of deaths in Africa. The current antiretroviral therapies have achieved success in providing instant HIV suppression but with countless undesirable adverse effects. Presently, the biodiversity of the plant kingdom is being explored by several researchers for the discovery of potent anti-HIV drugs with different mechanisms of action. The primary challenge is to afford a treatment that is free from any sort of risk of drug resistance and serious side effects. Hence, there is a strong demand to evaluate drugs derived from plants as well as their derivatives. Several plants, such as Andrographis paniculata, Dioscorea bulbifera, Aegle marmelos, Wistaria floribunda, Lindera chunii, Xanthoceras sorbifolia and others have displayed significant anti-HIV activity. Here, weattempt to summarize the main results, which focus on the structures of most potent plant-based natural products having anti-HIV activity along with their mechanisms of action and IC50 values, structure-activity-relationships and important key findings.