Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Immunodeficiency Virus Reverse Transcriptase Displays Dramatically Higher Fidelity under Physiological Magnesium Conditions In Vitro

ABSTRACT The fidelity of human immunodeficiency virus (HIV) reverse transcriptase (RT) has been a subject of intensive investigation. The mutation frequencies for the purified enzyme in vitro vary widely but are typically in the 10−4 range (per nucleotide addition), making the enzyme severalfold less accurate than most polymerases, including other RTs. This has often been cited as a factor in HIV's accelerated generation of genetic diversity. However, cellular experiments suggest that HIV does not have significantly lower fidelity than other retroviruses and shows a mutation frequency in the 10−5 range. In this report, we reconcile, at least in part, these discrepancies by showing that HIV RT fidelity in vitro is in the same range as cellular results from experiments conducted with physiological (for lymphocytes) concentrations of free Mg2+ (∼0.25 mM) and is comparable to Moloney murine leukemia virus (MuLV) RT fidelity. The physiological conditions produced mutation rates that were 5 to 10 times lower than those obtained under typically employed in vitro conditions optimized for RT activity (5 to 10 mM Mg2+). These results were consistent in both commonly used lacZα complementation and steady-state fidelity assays. Interestingly, although HIV RT showed severalfold-lower fidelity under high-Mg2+ (6 mM) conditions, MuLV RT fidelity was insensitive to Mg2+. Overall, the results indicate that the fidelity of HIV replication in cells is compatible with findings of experiments carried out in vitro with purified HIV RT, providing more physiological conditions are used. IMPORTANCE Human immunodeficiency virus rapidly evolves through the generation and subsequent selection of mutants that can circumvent the immune response and escape drug therapy. This process is fueled, in part, by the presumably highly error-prone HIV polymerase reverse transcriptase (RT). Paradoxically, results of studies examining HIV replication in cells indicate an error frequency that is ∼10 times lower than the rate for RT in the test tube, which invokes the possibility of factors that make RT more accurate in cells. This study brings the cellular and test tube results in closer agreement by showing that HIV RT is not more error prone than other RTs and, when assayed under physiological magnesium conditions, has a much lower error rate than in typical assays conducted using conditions optimized for enzyme activity.
Phenolic compounds and antioxidant properties of arabinoxylan hydrolysates from defatted rice bran.

BACKGROUND The water unextractable arabinoxylans (WUAX) contain beneficial phenolic compounds that can be used for food rather than for animal feed. The antioxidant activities of defatted rice bran obtained by xylanase-aided extraction is reported herein. The chemical and molecular characteristics of extracted fractions were investigated. RESULTS The WUAX hydrolysate precipitated by 0-60% ethanol (F60), 60-90% ethanol (F6090), and more than 90% ethanol (F90) had decreased molar masses with increasing ethanol concentration. The fractions of interest, F60 and F6090, contained 75% arabinoxylans with ferulic acid as the major bound phenolic acid, followed by p-coumaric acid. According to chemical-based antioxidant assays F60 and F6090 exhibited higher diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric iron reducing ability than F90 which contained minor contents of small sugars and free phenolic acids. In cell-based antioxidant assays, using the fluorescent 2',7'-dichlorofluorescein diacetate probe, all three fractions were potent intracellular scavengers. CONCLUSION The high molar mass of WUAX hydrolysates with high amount of bound phenolics contributes to the chemical-based antioxidant activity. All fractions of WUAX hydrolysates showed high potent intracellular scavenging activity regardless of molar mass, content and the component of bound phenolics. © 2017 Society of Chemical Industry.
Yap and Taz regulate retinal pigment epithelial cell fate

The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Tead-responsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant alleles such that, when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap-dependent RPE cell type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosage-dependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson's chorioretinal atrophy and congenital retinal coloboma. Summary: In zebrafish, the transcriptional regulators Yap/Taz and Tead are necessary and sufficient for optic vesicle progenitors to adopt retinal pigmented epithelium identity.
Comprehensive Phenotype/Genotype Analyses of the Norepinephrine Transporter Gene (SLC6A2) in ADHD: Relation to Maternal Smoking during Pregnancy

Objective Despite strong pharmacological evidence implicating the norepinephrine transporter in ADHD, genetic studies have yielded largely insignificant results. We tested the association between 30 tag SNPs within the SLC6A2 gene and ADHD, with stratification based on maternal smoking during pregnancy, an environmental factor strongly associated with ADHD. Methods Children (6–12 years old) diagnosed with ADHD according to DSM-IV criteria were comprehensively evaluated with regard to several behavioral and cognitive dimensions of ADHD as well as response to a fixed dose of methylphenidate (MPH) using a double-blind placebo controlled crossover trial. Family-based association tests (FBAT), including categorical and quantitative trait analyses, were conducted in 377 nuclear families. Results A highly significant association was observed with rs36021 (and linked SNPs) in the group where mothers smoked during pregnancy. Association was noted with categorical DSM-IV ADHD diagnosis (Z = 3.74, P = 0.0002), behavioral assessments by parents (CBCL, P = 0.00008), as well as restless-impulsive subscale scores on Conners’-teachers (P = 0.006) and parents (P = 0.006). In this subgroup, significant association was also observed with cognitive deficits, more specifically sustained attention, spatial working memory, planning, and response inhibition. The risk allele was associated with significant improvement of behavior as measured by research staff (Z = 3.28, P = 0.001), parents (Z = 2.62, P = 0.009), as well as evaluation in the simulated academic environment (Z = 3.58, P = 0.0003). Conclusions By using maternal smoking during pregnancy to index a putatively more homogeneous group of ADHD, highly significant associations were observed between tag SNPs within SLC6A2 and ADHD diagnosis, behavioral and cognitive measures relevant to ADHD and response to MPH. This comprehensive phenotype/genotype analysis may help to further understand this complex disorder and improve its treatment. Clinical trial registration information – Clinical and Pharmacogenetic Study of Attention Deficit with Hyperactivity Disorder (ADHD); www.clinicaltrials. gov; NCT00483106.
DNA-Binding Proteins Essential for Protein-Primed Bacteriophage Φ29 DNA Replication

Bacillus subtilis phage Φ29 has a linear, double-stranded DNA 19 kb long with an inverted terminal repeat of 6 nucleotides and a protein covalently linked to the 5′ ends of the DNA. This protein, called terminal protein (TP), is the primer for the initiation of replication, a reaction catalyzed by the viral DNA polymerase at the two DNA ends. The DNA polymerase further elongates the nascent DNA chain in a processive manner, coupling strand displacement with elongation. The viral protein p5 is a single-stranded DNA binding protein (SSB) that binds to the single strands generated by strand displacement during the elongation process. Viral protein p6 is a double-stranded DNA binding protein (DBP) that preferentially binds to the origins of replication at the Φ29 DNA ends and is required for the initiation of replication. Both SSB and DBP are essential for Φ29 DNA amplification. This review focuses on the role of these phage DNA-binding proteins in Φ29 DNA replication both in vitro and in vivo, as well as on the implication of several B. subtilis DNA-binding proteins in different processes of the viral cycle. We will revise the enzymatic activities of the Φ29 DNA polymerase: TP-deoxynucleotidylation, processive DNA polymerization coupled to strand displacement, 3′–5′ exonucleolysis and pyrophosphorolysis. The resolution of the Φ29 DNA polymerase structure has shed light on the translocation mechanism and the determinants responsible for processivity and strand displacement. These two properties have made Φ29 DNA polymerase one of the main enzymes used in the current DNA amplification technologies. The determination of the structure of Φ29 TP revealed the existence of three domains: the priming domain, where the primer residue Ser232, as well as Phe230, involved in the determination of the initiating nucleotide, are located, the intermediate domain, involved in DNA polymerase binding, and the N-terminal domain, responsible for DNA binding and localization of the TP at the bacterial nucleoid, where viral DNA replication takes place. The biochemical properties of the Φ29 DBP and SSB and their function in the initiation and elongation of Φ29 DNA replication, respectively, will be described.
Ezetimibe Combined With Simvastatin Compared With Simvastatin Alone Results in a Greater Suppression of Oxidative Stress and Enhanced Fibrinolysis in Patients After Acute Coronary Events

We compared the effect of simvastatin versus simvastatin combined with ezetimibe on hemostasis and inflammation after acute coronary events [acute coronary syndromes (ACS)]. In an investigator-initiated, double-blind, placebo-controlled, randomized study, patients with ACS were assigned to 40 mg/d of simvastatin + 10 mg/d of ezetimibe (n = 26) or 40 mg/d of simvastatin + placebo (n = 28) administered for 2 months. Markers of coagulation (prothrombin fragments 1.2, thrombin-antithrombin complexes, free tissue factor pathway inhibitor), fibrinolysis [plasminogen activator inhibitor-1, clot lysis time (CLT)], platelet activation (soluble CD40 ligand, β-thromboglobulin, thromboxane B2), oxidative stress [8-iso-prostaglandin F2α (8-iso-PGF2α)], and inflammation (interleukin-6, interleukin-18, and interleukin-1β) were measured within the first 12 hours of ACS and at 1 and 2 months of therapy. A final analysis comprised 20 patients in the simvastatin + ezetimibe group and 26 patients in the simvastatin + placebo group. Both groups were similar with regard to demographics, risk factors, medications, and routine laboratory results. Inflammatory, coagulation, and platelet markers did not differ between both treatment groups at all time points. Reductions in low-density lipoprotein cholesterol, CLT, plasminogen activator inhibitor-1, and 8-iso-PGF2α were significantly greater (by 10%, 8.7%, 17.5%, and 22.4%) in the simvastatin + ezetimibe group after 1 month, with further decreases in CLT and 8-iso-PGF2α at 2 months (all P < 0.05). These changes were not associated with lipid and inflammatory parameters. In conclusion, compared with simvastatin alone, simvastatin + ezetimibe results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients with ACS, indicating that ezetimibe might exert cholesterol-independent actions in humans (NCT00725829).
Design and Analysis of a Reflectarray Using Slot Antenna Elements for Ka-band SatCom

This paper presents a folded reflectarray designed for Ka-band satellite communication applications. The array element is a dual-polarized slot antenna with multilayered PCB structure and is designed to operate at 29.5-30.8 GHz band for both transmitting and receiving with single linear polarization. Vias are employed to suppress the surface wave propagation and reduce the mutual coupling between adjacent array elements, for achieving a reflectarray with a wide scan angle range. An equivalent circuit model for the array element is developed and it agrees well with the EM simulation results. Several passive demonstrators consisting of 116 elements spaced by 0. 5λ30GHz were fabricated and measured. The experimental results show that the presented reflectarray is capable of steering the beam up to ±60° in both Eand H-planes with low cross-polarization level.
Arid and humid phases in southern Spain during the last 4000 years: the Zoñar Lake record, Córdoba

A multiproxy study of sediment cores from Zoñar Lake (37°29′00″N, 4°41′22″W, 300 m a.s.l.) supported by 11 14C AMS dates provides the first high-resolution centennial-scale reconstruction of past humidity changes in southern Spain during the last 4000 years. Arid periods occurred prior to 2.9 cal. kyr BP and during 1.3—0.6 cal. kyr BP (`Mediaeval Climate Anomaly'). The most humid period occurred during 2.6—1.6 cal. kyr BP encompassing the late Iron Age—Iberian and Roman epochs. Two humid periods of lower intensity occurred between 0.8 and 0.6 cal. kyr BP (AD 1200—1400) and about 400 cal. yr BP (around AD 1600) coinciding with the onset of the `Little Ice Age'. Humid conditions are synchronous with a decline in solar output and seem to correspond to atmospheric patterns similar to negative NAO phases. Arid conditions show better correlation with northern Africa climate evolution, suggesting a possible link to subtropical dynamics. The geographic location of Zoñar Lake and the robust chronology provides an opportunity to improve our understanding of the climate evolution in mid latitudes during the late Holocene and to evaluate subtropical and high latitude factors in Mediterranean climate evolution.
Reactivation of Motor Brain Areas during Explicit Memory for Actions

Recent functional brain imaging studies have shown that sensory-specific brain regions that are activated during perception/encoding of sensory-specific information are reactivated during memory retrieval of the same information. Here we used PET to examine whether verbal retrieval of action phrases is associated with reactivation of motor brain regions if the actions were overtly or covertly performed during encoding. Compared to a verbal condition, encoding by means of overt as well as covert activity was associated with differential activity in regions in contralateral somatosensory and motor cortex. Several of these regions were reactivated during retrieval. Common to both the overt and covert conditions was reactivation of regions in left ventral motor cortex and left inferior parietal cortex. A direct comparison of the overt and covert activity conditions showed that activation and reactivation of left dorsal parietal cortex and right cerebellum was specific to the overt condition. These results support the reactivation hypothesis by showing that verbal-explicit memory of actions involves areas that are engaged during overt and covert motor activity.
Using Social Sensing to Understand the Links between Sleep, Mood, and Sociability

In recent years, reality mining experiments have provided several novel insights into human social behavior that would not have been possible without the novel use of smart phone sensing. In this work, we leverage the latest reality mining experiment to study social behavior from a public health perspective. In particular, we focus on sleep and mood as they have a considerable public health impact with serious societal and significant financial effects. We endeavor to explore and uncover the associations between sleep, mood and sociability by studying a population of healthy young adults going about their everyday life. We find significant associations between sleep and mood, reiterating observations in the literature. More importantly, we find that individuals with lower overall sociability tend to report poor mood more often, a statistically significant observation. In addition, we also uncover associations between daily sociability and sleep, a previously unreported observation. These results demonstrate the potential of reality mining studies for studying the sociological aspects of significant public health problems. Further, we hope that our work will provide the impetus for larger studies validating some of these observations and ultimately result in behavioral interventions that can improve public health through better social interaction.
Acute Drug-Induced Hepatitis during Aripiprazole Monotherapy: A CaseReport

Only a few case studies have been reported about antipsychotic-induced hepatitis for second generation antipsychotics. A 52-year old patient with recurrent schizoaffective psychosis was switched over from clozapine to aripiprazole monotherapy. Six weeks afterwards the otherwise asymptomatic patient presented herself with skin and scleral jaundice. Hepatic laboratory parameters and liver histological evaluation were initiated. Blood tests performed in outpatient clinic revealed significantly pathological hepatic laboratory parameters (total bilirubin 17.9 mg/dl, direct bilirubin 9.0 mg/dl, GOT 1613 U/l, GPT 2585 U/l). The liver histological evaluation shows a portal inflammatory cellular reaction with eosinophilia. After immediate discontinuation of aripiprazole medication, the elevated laboratory parameters normalised. We assume that the patient had suffered drug-induced hepatitis with predominant cytolysis. This is the first case of aripiprazole-induced hepatitis described in the literature.
Exosomes Mediate the Intercellular Communication after Myocardial Infarction

The mechanisms of cardiac repair after myocardial infarction (MI) are complicated and not well-understood currently. It is known that exosomes are released from most cells, recognized as new candidates with important roles in intercellular and tissue-level communication. Cells can package proteins and RNA messages into exosome and secret to recipient cells, which regulate gene expression in recipient cells. The research on exosomes in cardiovascular disease is just emerging. It is well-known that exosomes from cardiomyocyte can transfect endothelial cells, stem cells, fibroblasts and smooth muscle cells to induce cellular changes. After myocardial infarction (MI), the exosomes play important roles in local and distant microcommunication. Nowadays, exosomal microRNAs transportation has been found to deliver signals to mediate cardiac repair after MI. However, the exosomes quality and quantities are variable under different pathological conditions. Therefore, we speculate that the monitoring of the quality and quantity of exosomes may serve as diagnosis and prognosis biomarkers of MI, and the study of exosomes will provide insights for the new therapeutics to cardiac remodeling after MI.
Antioxidant enzymes in paraquat and cadmium resistant cell lines of horseradish MA

Effect of paraquat (PQ) and cadmium on the activity and isoenzymatic pattern of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (POX) and ascorbate peroxidase (APX), was investigated in non-stressed and PQor Cd-tolerant cells of horseradish (Armoracia rusticana Gaertn.). The activities of these enzymes were used as biochemical markers of the stress resistance capacity of the selected cells able to grow in suspension culture in the presence of 1 μM, 5 μM and 15 μM PQ or 50 μM, 100 μM and 200 μM Cd ions. Native polyacrylamide gel electrophoresis, followed by appropriate staining, showed that in herbicide-tolerant cells the most active enzyme was catalase, whereas in metal-tolerant cells the most important role was played by POX and APX. We regenerated plants from control cells and cells tolerant to 1 μM PQ. At 5 μM PQ, only early stages of plant formation from callus were observed. There were no signs of regeneration in callus derived from Cd-treated cells. In plants regenerated from cells tolerant to 1 μM PQ, the activity of POX was slightly higher than in control plants but the SOD activity remained unaffected.
Age dependence of cerebrovascular response mechanisms in domestic pigs.

Hypercapnia-induced cerebral vasodilation in the newborn pig is a prostanoid-associated response. In some adult models, hypercapnic cerebral vasodilation is associated with the generation of nitric oxide (NO). Acetylcholine (ACh) produces a NO-dependent cerebral vasodilation in many adult models, but topical ACh is a prostanoid-associated cerebral vasoconstrictor in the newborn pig. We hypothesized that mediators influencing cerebral response can be age dependent. Juvenile domestic pigs were compared with newborn pigs, and pial arteriolar diameters were measured by use of a closed cranial window during hypercapnia and topical ACh (10(-5) M). Four different conditions were explored: control, topical N omega-nitro-L-arginine (L-NNA, 10(-3) M), indomethacin (5 mg/kg i.v.), and both L-NNA and indomethacin. All animals were anesthetized with alpha-chloralose. As opposed to the complete block in the newborn, indomethacin only partially attenuated the hypercapnic cerebral vasodilation in the juvenile pig.L-NNA, which had no effect on the response of the newborn, produced a partial attenuation of the hypercapnic response of the juvenile. The combination of indomethacin and L-NNA blocked the response in both age groups. Topical ACh in both age groups initially produced cerebral vasoconstriction, but, in the juvenile, this was followed by a sustained cerebral vasodilation. Indomethacin blocked the early vasoconstriction in both age groups. L-NNA, which had no effect in the response of the newborn to ACh, blocked the vasodilation seen in the juvenile. The combination of both inhibitors blocked all response to ACh in the juvenile. These data indicate that although the cerebral vascular responses to ACh and hypercapnia are prostanoid associated and NO independent in the newborn pig, NO assumes an increasing role in dilatory responses with development.