Miracle-dz/UniFAR-FTUs huggingface dataset:
Unconventional Plasticity of HIV-1 Reverse Transcriptase: How Inhibitors Could Open a Connection "Gate" between Allosteric and Catalytic Sites

Targeted molecular dynamics (TMD) simulations allowed for identifying the chemical/structural features of the nucleotide-competitive HIV-1 inhibitor DAVP-1, which is responsible for the disruption of the T-shape motif between Try183 and Trp229 of the reverse transcriptase (RT). DAVP-1 promoted the opening of a connection "gate" between allosteric and catalytic sites of HIV-1 RT, thus explaining its peculiar mechanism of action and providing useful insights to develop novel nucleotide-competitive RT inhibitors.
Deficit in Response Inhibition in Children with Attention Deficit/Hyperactivity Disorder (ADHD): Impact of Motivation?

To date, neuropsychological and psycho-physiological studies have revealed inconsistent results regarding an executive or motivational deficit explaining the response inhibition deficit in children with attention deficit/hyperactivity disorder (ADHD). Research on differentiating neuropsychological processes in ADHD subtypes is still scarce. Therefore, the motivational impact on response inhibition among boys with ADHD was examined in this study. In the first study, 19 boys with ADHD-combined type (ADHD-C) and 19 age-matched healthy control subjects performed a modified Go/No-Go task with the following experimental conditions: neutral, auditory feedback, reward, response cost, and reward/response cost. Performance and physiological data (heart rate and skin conductance responses) were recorded. In a second study with the modified Go/No-Go task, data for six children with ADHD-C, six with ADHD-inattentive subtype (ADHD-I), and six healthy control subjects were compared. Neither of the two studies revealed group by condition interactions. In study 1, boys with ADHD-C generally made more commissions and omissions compared to the control group. However, feedback significantly improved the response inhibition in all children. The heart rate of all children was increased in the two conditions of reward and reward/response cost. Study 2 revealed that children with ADHD-I responded more slowly and showed increased reaction time variability compared to both other groups. The present study supports an executive rather than a motivational deficit in the response inhibition among children with ADHD-C, though further results also indicate the role of auditory feedback on response inhibition. Additionally, the findings support the differentiation of ADHD-C and ADHD-I, suggesting that ADHD-I children are characterized by a sluggish cognitive tempo.
Characterization of the 2-[(R)-2-hydroxypropylthio]ethanesulfonate dehydrogenase from Xanthobacter strain Py2: product inhibition, pH dependence of kinetic parameters, site-directed mutagenesis, rapid equilibrium inhibition, and chemical modification.

Although the short-chain dehydrogenase/reductase (SDR) superfamily contains a very large number of members defined in annotated databases and by biochemical and structural studies, very few SDR enzymes have been identified that have a homologous partner catalyzing the same reaction but with an opposite stereospecificity. In the present study we have cloned and expressed one of these enzymes, the 2-[(R)-2-hydroxypropylthio]ethanesulfonate (R-HPC) dehydrogenase, that is part of the coenzyme M-dependent pathway of alkene and epoxide metabolism in Xanthobacter strain Py2. Investigation of the kinetic mechanism using product inhibition suggested that a compulsory-ordered ternary complex mechanism was followed. The pH dependence of k(cat)/K(m) indicated the presence of a single ionizable residue of catalytic importance (pK(a) = 6.9) that was proposed to be Y155 of the catalytic triad. Amino acid substitutions of the putative catalytic triad residues produced inactive enzymes (S142C, Y155F, Y155E, and K159A) or enzyme with a greatly decreased activity (S142A). Inhibitors were investigated as probes of the molecular features of R-HPC that contribute to substrate binding. 2-[(S)-2-Hydroxypropylthio]ethanesulfonate (S-HPC) and 2-(2-methyl-2-hydroxypropylthio)ethanesulfonate were found to be competitive inhibitors of R-HPC with K(ic) values close to the K(m) for R-HPC. The arginine-specific modifiers 2,3-butanedione and phenylglyoxal were found to be inactivators, and inactivation could be protected against by the addition of R-HPC. 2,3-Butanedione was found to reduce enzyme activity with R-HPC as a substrate much more dramatically than with substrates that lacked a sulfonate moiety [e.g., 2-propanol, (R)-2-pentanol, and (R)-2-heptanol]. Amino acid analyses of enzyme modified by 2,3-butanedione in the presence and absence of S-HPC suggested protection of a single arginine residue. On the basis of these results, we propose that one or more active site arginines play a key role in substrate binding via an ionic interaction with the sulfonate moiety of R-HPC.
Internal Trade, Productivity and Interconnected Industries: A Quantitative Analysis (Commerce intérieur, productivité et industries interconnectées: une analyse quantitative)

Does trade within a country affect welfare and productivity? What are the magnitude and consequences of costs to such trade? To answer these questions, we exploit unique Canadian data to measure internal trade costs in a variety of waysthey are large and vary across sectors and provinces. To quantify their consequences for welfare and productivity, we use a recent multi-sector trade model featuring rich inputoutput relationships. We find interprovincial trade is an important contributor to Canada's GDP and welfare, though there are significant costs to such trade. Reducing interprovincial trade costs by 10% yields aggregate gains of 0.9%; eliminating our preferred estimates of costs, gains average between 3% and 7%equivalent to real GDP gains between $50 billion and $130 billion. Finally, as policy reforms are often sector specific, we liberalize sectors one at a time and find gains are largest in highly interconnected industries.
The relative learning benefits of synchronous and asynchronous text-based discussion

The article examines the two distinct modes of text-based discussion in computer-mediated communication: synchronous (real time) and asynchronous (delayed time). How these two forms impact student cognitive and affective outcomes in a learning environment is considered. The substance of the research concerns an educational psychology course where both synchronous web chat-style discussion and asynchronous web post-style discussion was used. The results of a student survey show that the type of discussion used did not have a demonstrable effect on student test performance.
Language, identity and the achievement gap: comparing experiences of African-American students in a French immersion and a regular education context

The Black/White Achievement gap has been a persistent problem in education. Previous research attributed this gap to students' culture (Jenks & Phillips, 1998; Ogbu, 1995a.b) or teachers' expectancy (Rist, 1970). Post-colonial literature suggests that this research itself is oppressive, and that learning is negotiating the "spaces" between students and teachers (Ellsworth, 1997), creating a hybrid "mestiza" space (Anzaldúa, 1987). The openness of immersion to diversity, and its subsequent educational benefits for African-American students (Caldas & Boudreaux, 1999) conforms to this postcolonial perspective. This mixed-methodology study examined both academic achievement and the experiences of Louisiana fourth grade students/teachers in both the regular education and the French immersion contexts. The quantitative phase compared these students' LEAP test scores. The qualitative phase was a cross-case comparison of four classrooms--an extreme class (90% of the school population in poverty) and a typical class (AfricanAmericans of average academic achievement) in each context. Quantitative findings indicated that while there was a bridging of the achievement gap between the LEAP math scores of African-American immersion students and those of white students in regular education, the gap remained amongst immersion students. In the qualitative phase, the regular education classroom was found to be a more fixed and assimilating context than immersion. Further, immersion students had higher collective self-esteems and a more positive view of schooling. Though Typical Immersion appeared to create a hybrid third space, the regular education context in which immersion programs were situated appeared to negatively influence these programs.
Splicing of Two Internal and Four Carboxyl-terminal Alternative Exons in Nonmuscle Tropomyosin 5 Pre-mRNA Is Independently Regulated during Development*

Four nonmuscle tropomyosin isoforms have been reported to be produced from the rat Tm5 gene by alternative splicing (Beisel, K. W., and Kennedy, J. E. (1994) Gene (Amst.) 145, 251–256). In order to detect additional isoforms that might be expressed from that gene, we used reverse transcriptase-polymerase chain reaction assays and evaluated the presence of all product combinations of two alternative internal exons (6a and 6b) and four carboxyl-terminal exons (9a, 9b, 9c, and 9d) in developing and adult rat brain. We identified five different combinations for exon 9 (9a + 9b, 9a + 9c, 9a + 9d, 9c, and 9d), and the exon combinations 9a + 9c and 9a + 9d were previously unreported. Each of these combinations existed with both exon 6a and exon 6b. Thus, the rat brain generates at least 10 different isoforms from the Tm5 gene. Northern blot hybridization with alternative exon-specific probes revealed that these isoforms were also expressed in a number of different adult rat tissues, although some exons are preferentially expressed in particular tissues. Studies of regulation of the 10 different Tm5 isoform mRNAs during rat brain development indicated that no two isoforms are coordinately accumulated. Furthermore, there is a developmental switch in the use of exon 6a to exon 6b from embryonic to adult isoforms. TM5 protein isoforms show a differential localization in the adult cerebellum.
Government expenditure, economic growth and manpower absorption analysis of regencies and cities in South Sumatra, Indonesia

The economic growth is necessary to increase prosperity and regional economic performance. For major component of economic growth on the demand side is the value of investment and government expenditure. Therefore, investment and government expenditure has a strategic role in improving the performance of regional economy. In line with that matter, this study was aimed to determine the relationship of government expenditure simultaneously with the economic performance of the regencies/cities in South Sumatra province. The data used is secondary data obtained from the Central Statistics Agency (BPS) of regencies/cities in the province of South Sumatra, Bank Indonesia, and the General Director of Fiscal Balance (DJPK) of Indonesia Republic. The analytical method used was multiple regression panel data using simultaneous equations. The results showed: government expenditure, investment and labor altogether significantly affects economic growth; the variables of economic growth, fiscal capacity, general allocation funds and the number of labor altogether affect government expenditure; and the variables of economic growth, government expenditure, wages and the number of investment altogether affect employment. This study has a limitation in a variety of variables that affect government expenditure, because it is for more research needs to re-inventory the variables that affect government expenditure, including variable Special Allocation Fund (DAK).
Baseline serum globulin as a predictor of the recurrence of lone atrial fibrillation after radiofrequency catheter ablation.

OBJECTIVE Inflammation and autoimmune responses play an important role in recurrence of atrial fibrillation (AF). Serum globulin levels are a commonly used clinical index that represents inflammation and autoimmune response. This study aimed to determine the relationship between baseline serum globulin levels and the risk of recurrence after ablation in lone AF patients. METHODS We enrolled 348 lone AF patients undergoing radiofrequency catheter ablation for the first time for whom complete follow-up data were available. Pre-ablation peripheral venous blood samples were obtained for measurement of serum globulin levels. RESULTS During the follow-up period of 22 months (range, 6-62), AF recurred in 129 patients (37.1%). Recurrence was associated with a low level of pre-ablation serum globulins. Multiple Cox proportional hazard regression analysis showed that persistent AF, AF duration, left atrial diameter, no amiodarone after ablation, and the serum globulin level in particular were independent predictors of AF recurrence. According to receiver operating characteristic curve analysis, the best diagnostic cut-off serum globulin level was 25.4 g/L, which showed 74.4% sensitivity, 71.3% specificity, and 73.3% accuracy. CONCLUSION The baseline low serum globulin level is associated with AF recurrence after first-time ablation in lone AF patients. Therefore, it may be used as a predictor of AF recurrence in these patients.
Ascomycete fungal actins differentially support plant spatial cell and organ development

Actin interacts with a wide variety of cytoplasmic and nuclear proteins to support spatial development in nearly all eukaryotes. Null mutations in plant vegetative actins produce dramatically altered cell, tissue, and organ morphologies. Animal cytoplasmic actins (e.g., human HsACTB, HsACTG1) and some ancestral protist actins fully suppress these mutant phenotypes suggesting that some animal, plant, and protist actins share functional competence for spatial development. Considering that fungi have a phylogenetic origin closer to animals than plants, we were interested to explore whether the fungal actins may have this same capacity to function in plants and support development. We ectopically expressed actins from four highly divergent ascomycete fungi in two different Arabidopsis double vegetative actin null mutants. We found that expression of actin from the earliest diverging ascomycete subphyla, the archiascomycete Schizosaccharomyces pombe, qualitatively and quantitatively suppressed the root cell polarity and root organ developmental defects of act8/act7 mutants and the root‐hairless cell elongation phenotype of act2/act8 mutants. Interestingly, the actin from the pyrenomycete Neurospora crassa was modestly effective in the suppression of vegetative actin mutant phenotypes. In contrast, actins from the saccharomycetes Saccharomyces cerevisiae and Candida albicans were unable to support any aspect of plant development, and moreover induced severe dwarfism and sterility. These data imply that basal fungi inherited an actin with full competence for spatial development from their protist ancestor and maintained it via non‐progressive sequence evolution, while the later more derived fungal species lost these activities. © 2014 Wiley Periodicals, Inc.
Enhanced Electron Flux and Reduced Calmodulin Dissociation May Explain “Calcium-independent” eNOS Activation by Phosphorylation*

Bovine endothelial nitric oxide synthase (eNOS) is phosphorylated directly by the protein kinase Akt at serine 1179. Mutation of this residue to the negatively charged aspartate (S1179D eNOS) increases nitric oxide (NO) production constitutively, in the absence of agonist challenge. Here, we examine the potential mechanism of how aspartate at 1179 increases eNOS activity using purified proteins. Examination of NO production and cytochrome creduction resulted in no substantial changes in theK m /EC50 for l-arginine, calmodulin, and calcium, whereas there was a 2-fold increase in the rate of NO production for S1179D and a 2–4-fold increase in reductase activity (based on cytochrome c reduction). The observed increase in activity for both assays of NOS function indicates that a faster rate of electron flux through the reductase domain is likely the rate-limiting step in NO formation from eNOS. In addition, S1179D eNOS did show an increased resistance to inactivation by EGTA compared with wild type eNOS. These results suggest that a negative charge imposed at serine 1179, either by phosphorylation or by replacement with aspartate, increases eNOS catalytic activity by increasing electron flux at the reductase domain and by reducing calmodulin dissociation from activated eNOS when calcium levels are low.
Functional changes in the retina during and after acute intraocular pressure elevation in mice.

PURPOSE To examine retinal function using the full-field electroretinogram (ERG) during and after acute intraocular pressure (IOP) elevation in wild-type mice. METHODS IOP was elevated by anterior chamber cannulation in wild-type C57/BL6 mice. The pressure-function relationship was determined by IOP elevation in steps from baseline to 80 mm Hg. The rate of functional recovery was assessed for 60 minutes after an IOP spike of 50 mm Hg for 30 minutes. During and immediately after IOP elevation, scotopic ERG signals were recorded in response to dim and bright flashes (-4.54, -2.23, and 0.34 log cd x s x m(-2)) and analyzed for photoreceptoral (a-wave), ON-bipolar (b-wave), oscillatory potentials (OPs), and scotopic threshold responses (positive [p]STR/negative [n] STR). A full ERG protocol was collected 2 days before and 7 days after the single 50-mm Hg IOP spike. RESULTS The pSTR was most sensitive to IOP elevation with 50% amplitude loss (mu) at 41 mm Hg (mu, 95% confidence limits (CL): 37.7, 45.6) followed by nSTR at 45 mm Hg (95% CL: 41.0, 49.1). pSTR was significantly more sensitive than the b-wave (95% CL: 41.4, 49.1), a-wave (95% CL: 47.6, 55.3), and OPs (95% CL: 49.6, 59.2). pSTR showed slower recovery immediately after the 50 mm Hg spike compared with the b-wave (P = 0.02). One week after the 50-mm Hg spike, pSTR (-30% +/- 6%, P < 0.001) and OP (-27% +/- 2%, P < 0.001) amplitudes were reduced, whereas other components were unaffected. CONCLUSIONS The STR in mice is more sensitive to acute IOP elevation and recovers slower than other ERG components. Reduction in pSTR and OP amplitude at 1 week suggests persistent impairment of inner retinal function can occur after a single IOP spike.
Resourcefulness in African American and Caucasian American Caregivers of Persons With Dementia: Associations With Perceived Burden, Depression, Anxiety, Positive Cognitions, and Psychological Well-Being.

PURPOSE Providing care to persons with dementia can have negative effects on caregivers' physical and psychological well-being. This secondary analysis explored relationships among perceived burden, depression, anxiety, resourcefulness, and psychological well-being in 28 African American (AA) and 45 Caucasian American (CA) caregivers of persons with dementia. DESIGN AND METHODS Descriptive, cross-sectional design was used to examine the hypothesized relationships in a sample of 73 caregivers. FINDINGS CAs reported greater burden (t=-3.68, p<.001), more anxiety (t=-2.66, p<.01), depression (t=-2.21, p<.05), and hostility (t=-2.30, p<.05) than AAs. AAs reported higher scores than CAs on resourcefulness, positive cognitions, and psychological well-being. PRACTICE IMPLICATIONS The study findings provided directions for the development of resourcefulness interventions to enhance the psychological well-being among dementia caregivers.
Experimental epididymitis due to Chlamydia trachomatis in rats

A new animal model of epididymitis due to Chlamydia trachomatis was developed. Adult male Wistar rats were inoculated in the vas deferens with C. trachomatis biovar mouse pneumonitis. After infection, C. trachomatis was recovered from the epididymides for up to 90 days. At day 30, organisms were also reisolated from the testes. Clinical findings included enlargement of infected epididymides and concurrent atrophy of the ipsilateral testes. Histological lesions in the epididymides consisted of pyogranulomatous inflammation, abscesses, and spermatic granulomas. Infection of the testis by C. trachomatis was associated with pyogranulomatous changes. In addition, testicular degeneration, characterized by moderate to severe loss of the germinal epithelium, was noted. Chlamydial antigen was detected within epithelial cells, intratubular macrophages, and macrophages in the stroma of the epididymis by immunoperoxidase staining. This rat model of chlamydial epididymitis appears to clinically and histopathologically mimic the human disease. This model offers the opportunity for further studies on the pathogenesis and sequelae of chlamydial epididymitis.
Related trends in locomotor and respiratory muscle oxygenation during exercise.

PURPOSE We investigated the potential effect of respiratory muscle work on leg muscle oxygenation without artificial intervention in non-endurance-trained young subjects and searched for the range of intensity when this effect could occur. METHODS We simultaneously monitored accessory respiratory and leg muscle oxygenation patterns with near-infrared spectroscopy (NIRS) in 15 healthy young men performing maximal incremental exercise on a cycle ergometer. Pulmonary gas exchange was measured. The respiratory compensation point (RCP) was determined. Oxygenation (RMO2) and blood volume (RMBV) of the serratus anterior (accessory respiratory muscle) and of the vastus lateralis (LegO2 and LegBV) were monitored with NIRS. The breakdown point of accessory respiratory muscle oxygenation (BPRMO2) and the accelerated (BP1LegO2) and attenuated fall (BP2LegO2) in leg muscle oxygenation were detected. RESULTS BPRMO2 occurred at approximately 85% . VO2max and was related to RCP (r = 0.88, P < 0.001). BP2LegO2 appeared at approximately 83% . VO2max and was related to RCP (r = 0.57, P < 0.05) and with BPRMO2 (r = 0.64, P = 0.01). From BP2LegO2 to maximal exercise, LegBV was significantly reduced (P < 0.05). CONCLUSION In active subjects exercising at heavy exercise intensities, we observed that the appearance of the accelerated drop in accessory respiratory muscle oxygenation-associated with high ventilatory level-was related with the attenuated fall in leg muscle oxygenation detected with near-infrared spectroscopy. This suggests that the high oxygen requirement of respiratory muscle leads to limited oxygen use by locomotor muscles as demonstrated in endurance-trained subjects. The phenomenon observed was associated with reduced leg blood volume, supporting the occurrence of leg vasoconstriction. These events appeared not only at maximal exercise but onward above the respiratory compensation point.