Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular analysis of HEM6 (HEM12) in Saccharomyces cerevisiae, the gene for uroporphyrinogen decarboxylase

HEM6 (HEM12) in Saccharomyces cerevisiae encodes uroporphyrinogen decarboxylase, the fifth enzyme in the heme biosynthetic pathway. The HEM6 (HEM12) gene was cloned by complementation of heme auxotrophy of a hem6 mutant. Sequence analysis revealed an open reading frame of 1086 nucleotides. The predicted amino acid sequence of HEM6 (HEM12) shows extensive homology to those reported for uroporphyrinogen decarboxylase from mammalian sources. Expression of HEM6 (HEM12) was investigated and was found to increase two‐fold in a non‐fermentable carbon source. However, HEM6 (HEM12) transcription was unaffected by heme or by intermediates in the heme biosynthetic pathway. In addition, HEM6 (HEM12) expression is not regulated by the transcriptional activator complex HAP2–3–4, as has been shown for some genes encoding heme biosynthetic enzymes.
Income Distribution and Inequality in Indonesia: Study on Middle Class Household

The current positive trend of Indonesia’s economic growth has demonstrated that increasing income per capita is one of the economic prosperity indicators. One pillar of the increase in the income per capita of middle class is its surge to 56.5% in 2010 compared to that of in 2000 which only reached 20%, and it has brought Indonesia to be qualified as a middle-income country. It is believed that, one of the ways to reduce inequality in society is by encouraging economic growth and development of middle-class society. This study aims to analyze the profile of middle class household and its contribution on decreasing inequality in Indonesia using the data of National Survey of Social Economy (Susenas) from 2004 to 2012. By using Keynesian Consumption model and Lorenz Curve, the results showed that middle-class grouping by using the 20th and 80th percentile of income has a higher growth than that of the USD or portion average income approach. However, due to the relatively small contribution of middle class income growth in Indonesia to the economic growth, the changes on Indonesian middle class income is inelastic to the changes on national output.
Blue-on-yellow perimetry can predict the development of glaucomatous visual field loss.

OBJECTIVE The purpose of this investigation was to determine whether blue-on-yellow (B/Y) perimetry is capable of predicting the onset and location of impending glaucomatous visual field loss in patients with ocular hypertension. DESIGN A Humphrey Field Analyzer (Humphrey Instruments, San Leandro, Calif) was modified to perform B/Y perimetry to isolate and measure the sensitivity of short-wavelength-sensitive mechanisms. Participants were tested annually with standard white-on-white (W/W) and B/Y automated perimetry for a period of 5 years. PATIENTS The study population consisted of 38 patients with ocular hypertension and 62 age-matched normal control subjects. RESULTS Initially, all 76 ocular hypertensive eyes had normal W/W automated perimetry results, with 67 eyes having normal and nine eyes having abnormal B/Y test results. Five years later, five of the nine ocular hypertensive eyes with initial B/Y abnormal results developed glaucomatous visual field loss measured by standard W/W automated perimetry, while none of the 67 ocular hypertensive eyes with initially normal B/Y results developed abnormal W/W perimetry results. CONCLUSIONS Blue-on-yellow perimetry deficits are an early indicator of glaucomatous damage and are predictive of impending glaucomatous visual field loss for standard W/W automated perimetry. To our knowledge, this is the first prospective, long-term longitudinal study that demonstrates the ability to predict the onset of glaucomatous visual field loss in patients with ocular hypertension on the basis of psychophysical testing.
Disparate Epitopes Mediating Protective Heterologous Immunity to Unrelated Viruses Share Peptide–MHC Structural Features Recognized by Cross-Reactive T Cells

Closely related peptide epitopes can be recognized by the same T cells and contribute to the immune response against pathogens encoding those epitopes, but sometimes cross-reactive epitopes share little homology. The degree of structural homology required for such disparate ligands to be recognized by cross-reactive TCRs remains unclear. In this study, we examined the mechanistic basis for cross-reactive T cell responses between epitopes from unrelated and pathogenic viruses, lymphocytic choriomeningitis virus (LCMV) and vaccinia virus. Our results show that the LCMV cross-reactive T cell response toward vaccinia virus is dominated by a shared asparagine residue, together with other shared structural elements conserved in the crystal structures of Kb-VV-A11R and Kb-LCMV-gp34. Based on analysis of the crystal structures and the specificity determinants for the cross-reactive T cell response, we were able to manipulate the degree of cross-reactivity of the T cell response, and to predict and generate a LCMV cross-reactive response toward a variant of a null OVA-derived peptide. These results indicate that protective heterologous immune responses can occur for disparate epitopes from unrelated viruses.
Pharmacist-led intervention study to improve inhalation technique in asthma and COPD patients.

UNLABELLED RATIONAL AND AIMS: Inhaled therapy is the mainstay of treatment in patients with asthma and chronic obstructive pulmonary disease (COPD). For effectiveness of pharmacotherapy, correct use of medication is required. The aims of this study were to survey the quality of inhalation technique in patients and to determine the effect of a single intervention in community pharmacies by means of standardized procedures. METHODS A total of 757 patients with asthma or COPD were randomly selected by 55 community pharmacies. At baseline, patients were interviewed and their inhalation technique was assessed with a 21-items checklist. Any error was recorded and, if necessary, patients were instructed in the proper use of their device. After 4-6 weeks, demonstration of inhalation technique was repeated in the community pharmacies and a pre-post comparison was performed. RESULTS A total of 597 patients (78.9%) made at least one mistake in performing the inhalation technique at baseline. This number dropped to 214 (28.3%) from the first to the second appointment. All patients did benefit from the pharmacists' intervention regardless of their former training experiences. CONCLUSIONS Inhalation technique of asthma and COPD patients is poor. In daily practice, community pharmacy-based pharmacists are well suited to significantly supplement doctor-based education in inhalation technique.
Maternal smoking during pregnancy improves the anatomy of the hip joint in the female neonate

Objective: Because the greater frequency of developmental dysplasia of the hip in the female could have an endocrine etiology, and because maternal smoking in pregnancy causes fetal endocrine disequilibrium, we investigated the anatomy of the hip in neonates of smoking and non-smoking mothers. Methods: Clinical and sonographic examination was performed on 2066 hips of 521 male and 512 female neonates. In 48 male and 53 female neonates, the mothers smoked during pregnancy. Results: The mean ± SD α angle in the male neonates of the non-smoking mothers was 62.3° ± 5.1° and of the smoking mothers 62.1° ± 4.9° (p = 0.7). In the female neonates of the non-smoking and the smoking mothers, it was 60.7° ± 5.3° and 61.9° ± 4.8°, respectively (p = 0.02). The difference between the male and the female neonates of the non-smoking mothers was significant (p < 0.000001), but there was no significant difference between the female neonates of the smoking mothers and the male neonates (p = 0.5). Among the female neonates whose mothers were non-smokers, the number of those with hip type IIa or worse was significantly greater than among the female neonates whose mothers were smokers. The clinical findings were in agreement with the sonographic findings. Conclusions: Maternal smoking during pregnancy reduces the frequency of sonographic and possibly clinically detected hip dysplasia in female but not in male neonates. Nonetheless, because smoking causes numerous adverse effects on the fetus and child, it is contraindicated during pregnancy.
Induction and subcellular localization of high‐mobility group box–1 (HMGB1) in the postischemic rat brain

High‐mobility group box–1 (HMGB1) was originally identified as a ubiquitously expressed, abundant nonhistone DNA‐binding protein. Recently, it was found to act as a cytokine‐like mediator of delayed endotoxin lethality and of acute lung injury. Previously, we reported that HMGB1 is massively released extracellularly and plays a cytokine‐like function in the postischemic brain. In the present study, we examined the expression profile and cellular distribution of HMGB1 in rat brain after transient focal cerebral ischemia. The expression of HMGB1 in infarction areas in the ipsilateral sides gradually declined over 2 days after 1 hr of middle cerebral artery occlusion (MCAO) to below the basal level. However, after 3 days of reperfusion, HMGB1 level increased to above the basal level, especially in infarction cores, and this delayed induction was then maintained for several days. Immunohistochemistry using a polyclonal antibody against HMGB1 revealed its detailed expression pattern and subcellular localization in the postischemic brain. HMGB1 was found to be widely expressed throughout the normal brain and to be localized to the nuclei of almost all neurons and oligodendrocyte‐like cells. After 1 hr of MCAO, HMGB1 immediately translocated from the neuron nuclei to the cytoplasm and subsequently was depleted from neurons during the excitotoxicity‐induced acute damaging process. Moreover, beginning 2 days after reperfusion, HMGB1 was notably induced in activated microglia, astrocytes, and in microvascular structures, and these delayed gradual inductions were sustained for several days. These findings suggest that HMGB1 functions as a cytokine‐like mediator in a paracrine and autocrine manner in the postischemic brain. © 2007 Wiley‐Liss, Inc.
High-throughput Screening Uncovers a Compound That Activates Latent HIV-1 and Acts Cooperatively with a Histone Deacetylase (HDAC) Inhibitor*

Current antiretroviral therapy (ART) provides potent suppression of HIV-1 replication. However, ART does not target latent viral reservoirs, so persistent infection remains a challenge. Small molecules with pharmacological properties that allow them to reach and activate viral reservoirs could potentially be utilized to eliminate the latent arm of the infection when used in combination with ART. Here we describe a cell-based system modeling HIV-1 latency that was utilized in a high-throughput screen to identify small molecule antagonists of HIV-1 latency. A more detailed analysis is provided for one of the hit compounds, antiviral 6 (AV6), which required nuclear factor of activated T cells for early mRNA expression while exhibiting RNA-stabilizing activity. It was found that AV6 reproducibly activated latent provirus from different lymphocyte-based clonal cell lines as well as from latently infected primary resting CD4+ T cells without causing general T cell proliferation or activation. Moreover, AV6 complemented the latency antagonist activity of a previously described histone deacetylase (HDAC) inhibitor. This is a proof of concept showing that a high-throughput screen employing a cell-based model of HIV-1 latency can be utilized to identify new classes of compounds that can be used in concert with other persistent antagonists with the aim of viral clearance.
The influence of adhesive thickness on the microtensile bond strength of three adhesive systems.

PURPOSE To evaluate the effects of multiple adhesive layers of three etch-and-rinse adhesives on both adhesive thickness and microtensile bond strength (microTBS). MATERIALS AND METHODS Midcoronal occlusal dentin of 36 extracted human molars was used. Teeth were randomly assigned to 3 groups (EB, XP, PQ) according to the adhesive system to be used: PQ1 (Ultradent) (PQ), EnaBond (Micerium) (EB), or XP Bond (Dentsply/DeTrey) (XP). Specimens from each group were further divided into three subgroups according to the number of adhesive coatings (1, 2, or 3). In all subgroups, each adhesive layer was light cured before application of each additional layer. After bonding procedures, composite crowns were incrementally built up. Specimens were sectioned perpendicular to the adhesive interface to produce multiple beams, approximately 1 mm2 in area. Beams were tested under tension at a crosshead speed of 0.5 mm/min until failure. Adhesive thicknesses and failure modes were evaluated with SEM. The microTBS data and mean adhesive thickness were analyzed by two-way ANOVA and multiple-comparison Tukey's test (alpha = 0.05). RESULTS The mean bond strength (in MPa (SD)) of group EB gradually increased from 1 to 3 consecutive coatings (27.02 (9.38) to 44.32 (4.93), respectively) (p < 0.05). The highest mean bond strengths for the PQ (46.66 (12.95)) and XP groups (40.55 (5.69)) were obtained applying two adhesive coatings. The mean thickness of the adhesive layer (in microm (SD)) significantly increased with the number of coatings (p < 0.05), ranging from 29.45 (1.42) to 77.64 (1.10) for PQ, from 5.12 (0.68) to 37.75 (0.92) for EB, and from 12.64 (0.68) to 37.92 (0.71) for the XP group. Failure modes for EB specimens were mainly classified as adhesive failure between adhesive and dentin. The XP3 and PQ3 subgroups showed a greater number of total cohesive failure in adhesive. CONCLUSION Multiple adhesive coats significantly affected bond strength to dentin. An excess of adhesive layer thickness can negatively influence the strength and the quality of adhesion.
Language familiarity effects in short-term memory: The role of output delay and long-term knowledge

Four experiments examined the origins of language familiarity effects in bilingual short-term recall. In Experiments 1A and 1B, bilingual adults were tested on serial recall and probed serial recall of words and nonwords in their first and second languages. A first-language advantage was obtained on both measures, indicating that the beneficial effects of language familiarity are not exclusively attributable to lesser output delay during overt recall. In Experiments 2A and 2B, the same group of bilinguals was tested on serial recall and serial recognition of word lists in both languages. Although a sizeable first-language advantage was obtained on the serial recall measure, recognition performance was comparable in the two languages. On the basis of these results it is suggested that language differences in bilingual immediate memory arise in large part as a consequence of the differential availability of language-specific long-term knowledge with which to support retrieval processes in serial recall.
Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication.

Individuals with the recessive condition trimethylaminuria exhibit variation in metabolic detoxication of xenobiotics by hepatic flavin-containing monooxygenases. We show here that mutations in the human flavin-containing monooxygenase isoform 3 gene ( FMO3 ) impair N -oxygenation of xenobiotics and are responsible for the trimethylaminuria phenotype. Three disease-causing mutations in nine Australian-born probands have been identified which share a particular polymorphic haplotype. Nonsense and missense mutations are associated with a severe phenotype and are also implicated in impaired metabolism of other nitrogen- and sulfur-containing substrates including biogenic amines, both clinically and when mutated proteins expressed from cDNA are studied in vitro . These findings illustrate the critical role played by human FMO3 in the metabolism of xenobiotic substrates and endogenous amines.
The Neolithic Agricultural Revolution and the Origins of Private Property

Familiar explanations of why hunter-gatherers first took up farming—superior labor productivity, population pressure, or adverse climate—receive little support from recent evidence. Farming would be an unlikely choice without possession-based private property, which appears to have existed among rare groups of sedentary hunter-gatherers who became the first farmers. Our model shows that among them, farming could have benefited first adopters because private possession was more readily established and defended for cultivated crops and domesticated animals than for the diffuse wild resources on which hunter-gatherers relied, thus explaining how farming could have been introduced even without a productivity advantage.
Number Needed to Benefit From Information (NNBI): Proposal From a Mixed Methods Research Study With Practicing Family Physicians

PURPOSE We wanted to describe family physicians’ use of information from an electronic knowledge resource for answering clinical questions, and their perception of subsequent patient health outcomes; and to estimate the number needed to benefit from information (NNBI), defined as the number of patients for whom clinical information was retrieved for 1 to benefit. METHODS We undertook a mixed methods research study, combining quantitative longitudinal and qualitative research studies. Participants were 41 family physicians from primary care clinics across Canada. Physicians were given access to 1 electronic knowledge resource on handheld computer in 2008–2009. For the outcome assessment, participants rated their searches using a validated method. Rated searches were examined during interviews guided by log reports that included ratings. Cases were defined as clearly described searches where clinical information was used for a specific patient. For each case, interviewees described information-related patient health outcomes. For the mixed methods data analysis, quantitative and qualitative data were merged into clinical vignettes (each vignette describing a case). We then estimated the NNBI. RESULTS In 715 of 1,193 searches for information conducted during an average of 86 days, the search objective was directly linked to a patient. Of those searches, 188 were considered to be cases. In 53 cases, participants associated the use of information with at least 1 patient health benefit. This finding suggested an NNBI of 14 (715/53). CONCLUSION The NNBI may be used in further experimental research to compare electronic knowledge resources. A low NNBI can encourage clinicians to search for information more frequently. If all searches had benefits, the NNBI would be 1. In addition to patient benefits, learning and knowledge reinforcement outcomes are frequently reported.
Indirect Pathways of Self-Interest and the TPP

Abstract Do consumer and producer considerations influence support for future trade agreements and, if so, how? Prior research has pitted self-interest-based explanations of trade preferences against perception-based explanations, finding limited empirical support for the self-interest hypothesis. Instead of treating perceptions and self-interest as competing explanations, we construct a theoretical model with perceptions of trade as a mediating factor linking self-interest and support for prospective free trade agreements (FTAs). Using new survey data collected by the Asia Pacific Foundation of Canada, we examine how two distinct forms of self-interest (consumer and producer considerations) can indirectly shape attitudes toward the Trans-Pacific Partnership (TPP). We find that the impact of respondents' income level (proxying producer considerations) and their recognition of the price-lowering effect of international trade (proxying consumer considerations) on support for the TPP are largely mediated by perceptions of trade. Together the findings suggest a middle ground between the two sides of the self-interest debate. Résumé Les considérations des consommateurs et des producteurs exercent-elles une influence sur l'appui aux futurs accords commerciaux et, dans l'affirmative, de quelle façon ? La recherche a mis en opposition les explications des préférences commerciales fondées sur l'intérêt personnel et les explications fondées sur les attitudes perceptives, trouvant un appui empirique limité pour l'hypothèse de l'intérêt personnel. Au lieu de traiter les perceptions et l'intérêt personnel comme des explications concurrentes, nous construisons un modèle théorique dans lequel les perceptions du commerce constituent un facteur de médiation reliant l'intérêt personnel et le soutien aux futurs ALE. À l'aide de nouvelles données recueillies par la Fondation Asie Pacifique du Canada, nous examinons comment deux formes distinctes d'intérêt personnel (considérations des consommateurs et des producteurs) peuvent indirectement façonner les attitudes à l'égard du Partenariat transpacifique (PTP). Nous constatons que l'incidence du niveau de revenu des répondants (remplaçant les considérations des producteurs) et leur reconnaissance de l'effet de baisse des prix du commerce international (remplaçant les considérations des consommateurs) sur le soutien au PTP est largement médiée par les perceptions du commerce. Ensemble, les conclusions suggèrent un juste milieu entre les deux côtés du débat autour de l'intérêt personnel.
Mutations in the gene coding for the pre-mRNA splicing factor, PRPF31, in patients with autosomal dominant retinitis pigmentosa.

PURPOSE Retinitis pigmentosa is a clinically and genetically heterogeneous disorder. It is characterized by progressive degeneration of the peripheral retina, leading to night blindness and loss of the peripheral visual field. PRPF31 is one of four pre-mRNA splicing factors identified as causing autosomal dominant retinitis pigmentosa, with incomplete penetrance being the unique feature associated with mutations in this gene. The purpose of this study was to identify PRPF31 mutations in a cohort of 118 cases of autosomal dominant retinitis pigmentosa and determine the genotype-phenotype correlation emerging from the spectrum of mutations in this gene. METHODS Probands with autosomal dominant retinitis pigmentosa underwent ophthalmic evaluation. Blood samples were obtained, genomic DNA was isolated, and PRPF31 exons along with adjacent splice junctions were amplified by PCR and screened by direct sequencing. RESULTS In the 118 individuals with autosomal dominant retinitis pigmentosa, six mutations were identified, of which four were novel. One previously known splice site mutation was identified in two other apparently unrelated families. CONCLUSIONS Mutations in PRPF31 causing adRP were present in nearly 5% of a mixed U.K. population. The age of onset and the severity of the disease varied with different mutations. In addition, individuals carrying the same mutation showed a range of phenotypic variation, suggesting the involvement of other modifying genes.