Miracle-dz/UniFAR-FTUs huggingface dataset:
A β-Arrestin-dependent Scaffold Is Associated with Prolonged MAPK Activation in Pseudopodia during Protease-activated Receptor-2-induced Chemotaxis*

Cell motility during wound healing and inflammation is often dependent on the ability of the cell to sense a gradient of agonist. The first step in this process is the extension of a pseudopod in the direction of the agonist, and a diverse set of signals mediate pseudopod extension by different receptors. We have reported previously that protease-activated receptor-2 (PAR-2), a proinflammatory receptor that is highly expressed in motile cells such as neutrophils, macrophages, and tumor cells, is one of a growing family of receptors that utilizes a β-arrestin-dependent mechanism for activation of the 42–44-kDa members of the MAPK family (extracellular signal-regulated kinases 1 and 2; ERK1/2). β-Arrestin-bound PAR-2 serves as a scaffold to sequester a pool of activated ERK1/2 in the cytosol; however, a specific role for the sequestered kinase activity has not been established. We now show that PAR-2 activation promotes ERK1/2- and β-arrestin-dependent reorganization of the actin cytoskeleton, polarized pseudopodia extension, and chemotaxis. Using subcellular fractionation, confocal microscopy, and physical isolation of pseudopodial proteins, we demonstrate that the previously identified PAR-2/β-arrestin/ERK1/2 scaffolding complex is enriched in the pseudopodia, where it appears to prolong ERK1/2 activation. These studies suggest that the formation of a β-arrestin/ERK1/2 signaling complex at the leading edge may be involved in localized actin assembly and chemotaxis and provide the first example of a distinct cellular consequence of β-arrestin-sequestered ERK1/2 activity.
Genome-wide identification and expression profile analysis of the Hsp20 gene family in Barley (Hordeum vulgare L.)

In plants, heat shock proteins (Hsps) play important roles in response to diverse stresses. Hsp20 is the major family of Hsps, but their role remains poorly understood in barley (Hordeum vulgare L.). To reveal the mechanisms of barley Hsp20s (HvHsp20s) response to stress conditions, we performed a comprehensive genome-wide analysis of the HvHsp20 gene family using bioinformatics-based methods. In total, 38 putative HvHsp20s were identified in barley and grouped into four subfamilies (C, CP, PX, and MT) based on predicted subcellular localization and their phylogenetic relationships. A sequence analysis indicated that most HvHsp20 genes have no intron or one with a relatively short length. In addition, the same group of HvHsp20 proteins in the phylogenetic tree shared similar gene structure and motifs, indicating that they were highly conserved and might have similar function. Based on RNA-seq data analysis, we showed that the transcript levels of HvHsp20 genes could be induced largely by abiotic and biotic stresses such as heat, salt, and powdery mildew. Three HvHsp20 genes, HORVU7Hr1G036540, HORVU7Hr1G036470, and HORVU3Hr1G007500, were up-regulated under biotic and abiotic stresses, suggesting their potential roles in mediating the response of barley plants to environment stresses. These results provide valuable information for further understanding the complex mechanisms of HvHsp20 gene family in barley.
HIV-1 Subtype C Drug-Resistance Background among ARV-Naive Adults in Botswana

Current HIV-1 antiretroviral (ARV) drug resistance knowledge is limited to HIV-1 subtype B (HIV-1B). We addressed whether unique genetic and phenotypic properties of HIV-1 subtype C (HIV-1C), southern Africa's most prevalent subtype, may foment earlier and/or distinct resistance mutations. Population-level HIV-1C genotypes were evaluated with respect to drug resistance prevalence before Botswana's public ARV treatment programme began. Viruses were genotyped from 11 representative districts of northern and southern Botswana, and consensus sequences from these 71 individuals and 51 previously reported sequences from HIV-positive blood donors were constructed. Phylogenetic analysis classified all 71 sequences but one, which exhibited pol gene mosaicism, as HIV-1C. The protease and reverse transcriptase coding region had no detectable known primary mutations associated with HIV-1B protease inhibitor (PI) drug resistance. Secondary mutations associated with PI drug resistance were found in all sequences. Several HIV-1C—specific polymorphic sites were found across the pol gene. Northern and southern Botswana viral sequences showed no significant differences from each other. Population genotyping shows that, without countrywide ARV treatment, HIV-1C—infected Batswana harbour virtually no primary mutations known to confer resistance to the three major HIV-1B ARV drug classes. Some secondary PI mutations and polymorphic sites in the protease enzyme necessitate continuous population monitoring, particularly after introduction of countrywide ARV treatment in Botswana. Although its PI resistance development rate and kinetics are not known, our data may suggest increased susceptibility and readiness of HIV-1C to develop resistance under drug pressure when the PI class of drugs is used.
Validation of reference genes for ovarian tissue from capuchin monkeys (Cebus apella)

Summary There is no tradition in studies reporting the effect of exposure to cryoprotectants or simply hypoxia and hypothermia on gene expression in the ovarian tissue and there has been only one study on reference or target genes quantification, and comparisons of normoxic with hypoxic, hypothermic and toxic conditions. Our aim in the present study was to investigate the stability of three reference genes in the ovarian tissue of capuchin monkeys (Cebus apella). To this end, fresh and cryoprotectant-exposed ovarian biopsies were used. Both fresh and exposed ovarian tissues were subjected to total RNA extraction and synthesis of cDNA. cDNA was amplified by real-time polymerase chain reaction (PCR), and GeNorm, BestKeeper and NormFinder software were used to evaluate the stability of glyceraldehyde-2-phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and TATA-binding protein (TBP). Results demonstrated that, in the ovarian tissue from capuchin monkeys, HPRT1 and TBP were the most suitable reference genes and thus could be used as parameters to normalize data in future studies. In contrast, GAPDH appeared as the least stable gene among the tested reference genes. In conclusion, HPRT1 and TBP were the most stable reference genes in fresh and cryoprotectant-exposed ovarian tissue from capuchin monkeys.
Risk Premia and Knightian Uncertainty in an Experimental Market Featuring a Long-Lived Asset

Objectives: I examine risk premia and the influence of Knightian uncertainty in a laboratory market featuring a long-lived asset. Methods: I employ an experimental asset market, utilizing features which are designed to forestall bubbles and crashes. I alter the riskiness of the asset from market to market along two dimensionsâ€” expected variance and upside/downside potential. Furthermore, I include a treatment which introduces uncertainty with respect to the expected value of the asset. Results: Bubbles and crashes are absent. Positive, statistically significant risk premia emerge. The risk premia are not sensitive to expected variance, but do vary positively with the magnitude of potential loss. The introduction of Knightian uncertainty does not appear to influence market prices, however it does increase trading volume. Conclusions: When speculative activity is tempered, risk aversion is manifest in market prices. Subjects appear to view risk in the context of potential loss rather than volatility. Return premia for uncertainty are absent, suggesting a lack of uncertainty aversion. Increased trading activity in the presence of uncertainty may be due to differing opinions with regards to the value of the asset or to divergent levels of uncertainty aversion.
Financial inclusion and its determinants: the case of Argentina

This paper analyses the three dimensions determining financial inclusion in the case of Argentina, from a micro-economic perspective. On the supply side, formal financial services are accessed through traditional channels: branches and ATMs, with an as-yet incipient regulation for financial inclusion, unlike the situation in neighbouring countries. In terms of use, a personâ€™s level of education, income and age are all important variables which determine whether they have financial products such as accounts, credit and debit cards, formal credit and electronic payments. Finally, the factors affecting the perception of different barriers of involuntary exclusion are: income and age.
Programmatic Effects of a Large-Scale Multiple-Micronutrient Supplementation Trial in Indonesia: Using Community Facilitators as Intermediaries for Behavior Change

Background Clinical trials can serve as an opportunity gateway for enhanced health benefits to the target population, above and beyond the specific intervention being tested. Objective The Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a randomized, controlled clinical trial in Lombok, Indonesia, found that supplementation during pregnancy with multiple micronutrients reduced 90-day infant mortality by nearly 20% as compared with iron–folic acid. This trial was designed as both a program and research trial and used community facilitators to serve as liaisons between the study and the pregnant women. This analysis documents the programmatic impacts of SUMMIT on health-seeking and early infant mortality resulting from community facilitators' field activities. Methods Data on compliance, human resource practices, health-seeking, and health outcomes from the 31,290 SUMMIT enrollees were analyzed. Results Overall compliance with either iron–folic acid or multiple micronutrients was high in the program, at 85.0%. Early prenatal care visits increased significantly. Sixty-three percent of primiparous women used a skilled birth attendant (SBA); among multiparous women, the rate of use of a SBA rose from 35% for the last birth to 53%. Use of a SBA resulted in a 30% reduction in early infant mortality (RR, 0.70; 95% CI, 0.59 to 0.83; p < .0001), independently of any reductions due to multiple micronutrients. The community facilitators played a central role in improving health-seeking; however, the quality of the community facilitators' performance was associated with the impact of the micronutrient supplement on infant health. In a subsample of community facilitators, better-performing facilitators were found to markedly improve the overall impact of the multiple micronutrients on early infant mortality (RR, 0.67; 95% CI, 0.49 to 0.92; p = .0117). In contrast, infants of women with poorly performing community facilitators were found to derive no additional benefit from the multiple micronutrients (RR, 1.04; 95% CI, 0.64 to 1.72; p = .8568). Conclusions Systematic enhancements to the quality of implementation of SUMMIT led to significant increases in use of SBAs at delivery, resulting in a 30% reduction in early infant mortality independent of the impact of micronutrient supplementation. Therefore, if women were to consume multiple micronutrients on a regular basis and were to use a SBA at delivery, the risk of early infant mortality could be reduced by nearly 50%. The impacts of community facilitators in effecting changes in women's health behaviors are notable and are applicable to other health programs. Enhancements to program implementation should be driven by evidence, be accountable to the communities the program serves, and be evaluated on the basis of measurable gains in health for women and children.
Bone healing in critical-size defects treated with either bone graft, membrane, or a combination of both materials: a histological and histometric study in rat tibiae.

OBJECTIVES The aim of the present investigation was to histologically analyze the effect of using lyophilized bovine bone (GenOx® organic matrix) with (or without) guided tissue regeneration (using a decalcified cortical osseous membrane [GenDerm®]) on bone healing in surgically created critical-size defects created in rat tibia. MATERIAL AND METHODS Surgical critical-size bone defects were created in 64 animals that were randomly divided into four groups: group I (control); group II (defect filled with GenOx®); group III (defect covered by GenDerm®); group IV (defect filled with GenOx® and covered by GenDerm®). Animals were killed at 30 or 90 days post-surgery. The specimens were embedded in paraffin, serially cut, and stained with hematoxylin and eosin for analysis under light microscopy. The formation of new bone in the cortical area of the defect was histomorphometrically evaluated. RESULTS All experimental groups demonstrated superior bone healing compared with the control group. However, group IV samples showed evidence of more advanced healing at both 30 and 90 days post-surgery as compared with the other experimental groups. CONCLUSIONS The bovine organic bone graft GenOx® associated with GenDerm® this produced the best treatment results in the case of critical-size defects in rat tibia.
The Transmission of Education across Generations: Evidence from Australia

Abstract This study analyzes changes in the transmission of education across generations in Australia for the birth cohorts 1942 through 1991 using a range of measures: the estimated effect of parental education on that of the child, schooling correlations between parents and children and a series of mobility indices. Our results suggest that while the overall level of education and intergenerational education mobility has increased over time, there are considerable regional and gender differences. Daughters’ education attainment is still relatively highly correlated with their parents compared to sons and the extent of absolute upward mobility was modest while immobility and downward mobility have remained relatively steady during the last five decades. During this period, relative education opportunities have increased over time at lower education levels, while the trend has been comparatively stable at higher levels.
Mortality of tuberculosis patients in Chennai, India.

OBJECTIVE We aimed to measure the mortality rate and excess general mortality as well as identify groups at high risk for mortality among a cohort of tuberculosis patients treated in Chennai Corporation clinics in south India. METHODS In this retrospective cohort study we followed up 2674 patients (1800 males and 874 females) who were registered and treated under the DOTS strategy in Chennai Corporation clinics in 2000. The follow-up period from the date of start of treatment to either the date of interview, or death was 600 days. FINDINGS The mortality rate among this cohort of tuberculosis patients was 60/1000 person-years. The excess general mortality expressed as standardized mortality ratio (SMR) was 6.1 (95% confidence interval (CI)=5.4-6.9). Younger patients, men, patients with Category II disease, patients who defaulted on, or failed courses of treatment, and male smokers who were alcoholics, all had higher mortality ratios when compared to the rest of the cohort. CONCLUSION The excess mortality in this cohort was six times more than that in the general population. Young age, male sex, smear-positivity, treatment default, treatment failure and the combination of smoking and alcoholism were identified as risk factors for tuberculosis mortality. We suggest that mortality rate and excess mortality be routinely used as a monitoring tool for evaluating the efficiency of the national control programme.
Assessment of disease activity in acromegaly by means of a single blood sample: comparison of the 120th minute postglucose value with spontaneous GH secretion and with the IGF system

objective It has been suggested that the threshold of 1 µg/l of GH nadir after glucose load for definition of controlled acromegalic disease proposed in the 2000 consensus statement should be lowered to 0·30. We evaluated these two cut‐off values in comparison with IGF‐I, ALS and IGFBP‐3 in a group of acromegalic patients. With the aim of simplifying the follow‐up protocol in these patients we also tested if one single sample taken after glucose load could replace the nadir value.
Comparison of Contractile Responses Relative to Protein between Isolated Diabetic and Non-diabetic Rat Aortae to KCl and a-Adrenoceptor Agonists in Different Extracellular Calcium Concentrations

Summary The influence of extracellular Ca2+ concentration on contractile responses of aortae isolated from diabetic rats to KCl and α-adrenoceptor agonists was compared with that of non-diabetic rat aortae. Diabetic rats 6 weeks after administration of streptozotocin showed significantly lower body weight and higher plasma glucose concentration, but the protein content per each aortic ring preparation was not significantly different from that of non-diabetic preparation. Both diabetic and non-diabetic aortae showed concentration-dependent contractile responses to norepinephrine, which were concentration-dependently inhibited by prazosin. On the other hand, Clonidine induced small contractions in both aortae, which tended to be more inhibited by prazosin than yohimbine. In non-diabetic aortae, the contractile responses to KCl, norepinephrine, methoxamine and Clonidine were significantly greater with 2.5 mmol/l of extracellular Ca2+ than 1.25 mmol/l. In diabetic aortae, however, the contractile responses were not significantly influenced by changes in extracellular Ca2+ concentration. Additionally, the contractile responses to each agonist were markedly greater in non-diabetic aortae than diabetic ones. The present results indicate that the contractions of diabetic vasculature do not respond to changes in extracellular Ca2+ concentration, suggesting that there may be some impairment of Ca2+ related mechanisms.
Silencing of survivin gene by small interfering RNAs produces supra-additive growth suppression in combination with 17-allylamino-17-demethoxygeldanamycin in human prostate cancer cells

Survivin is an antiapoptotic gene, which is overexpressed in most human tumors and involved in mitotic checkpoint control. Recent evidence points to an essential role for heat shock protein 90 (Hsp90) in survivin function regulation. Although the survivin-Hsp90 association may promote tumor cell proliferation, it may also suggest new opportunities for the design of novel anticancer approaches. We evaluated the effect of small interfering RNA (siRNA)–mediated inhibition of survivin on the proliferative potential of prostate cancer cells and their sensitivity to the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). Human androgen-independent prostate cancer cell lines (DU145 and PC-3) were transfected with four 21-mer double-stranded siRNAs (100 nmol/L) directed against different portions of survivin mRNA. After transfection, cells were collected and analyzed for survivin mRNA and protein expression, cell proliferation rate, ability to undergo apoptosis, and sensitivity to 17-AAG. Transfection of prostate cancer cells with siRNAs induced a variable extent of inhibition of survivin mRNA expression (39–60% compared with controls), which was paralleled by a 38% to 75% reduction in survivin protein abundance. The three siRNAs able to induce the greatest inhibition of survivin expression also significantly reduced cell proliferation and enhanced the rate of apoptosis, with a concomitant increase in caspase-9 activity. Sequential treatment with siRNA and 17-AAG induced supra-additive antiproliferative effects in all cell lines, with an enhanced caspase-9-dependent apoptotic response. These findings suggest that combined strategies aimed at interfering with the survivin-Hsp90 connection may provide novel approaches for treatment of androgen-independent prostate cancer. [Mol Cancer Ther 2006;5(1):179–86]
An Incentive-Compatible Experiment on Probabilistic Insurance and Implications for an Insurer's Solvency Level

This paper is the first to conduct an incentive-compatible experiment using real monetary payoffs to test the hypothesis of probabilistic insurance which states that willingness to pay for insurance decreases sharply in the presence of even small default probabilities as compared to a risk-free insurance contract. In our experiment, 181 participants state their willingness to pay for insurance contracts with different levels of default risk. We find that the willingness to pay sharply decreases with increasing default risk. Our results hence strongly support the hypothesis of probabilistic insurance. Furthermore, we study the impact of customer reaction to default risk on an insurer’s optimal solvency level using our experimentally obtained data on insurance demand. We show that an insurer should choose to be default-free rather than having even a very small default probability. This risk strategy is also optimal when assuming substantial transaction costs for risk management activities undertaken to achieve the maximum solvency level.
Intraoperative cholangiography in combination with laparoscopic ultrasonography for the detection of occult choledocholithiasis.

BACKGROUND There is still a debate about the utility of intraoperative cholangiography (IOC) or laparoscopic ultrasonography (LUS) for detection of occult choledocholithiasis during laparoscopic cholecystectomy (LC). The aim of this study was to assess the value of IOC combined with LUS for detection of occult common bile duct (CBD) stones at LC. MATERIAL/METHODS From Dec 2002 to Aug 2006, 103 patients with moderate risk of CBD stones underwent IOC and LUS simultaneously during LC. The physician teams for the two different procedures were blinded by each other. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were calculated by several contingency tables that cross-tabulated the results of each technique with those of the gold standard. RESULTS The success rate of IOC and LUS were 91.3% and 100% respectively and the time required for LUS was significantly shorter (P<0.01). The visualization of intrapancreatic part of CBD by IOC (97.3%) was significantly higher than LUS (73.8%). The sensitivities, specificities, accuracies, positive and negative predictive values, positive and negative likelihood rations identifying occult CBD stones were 75.0%, 98.7%, 92.2%, 95.5%, 91.4%, 57.7 and 0.253 by IOC, and 82.1%, 98.7%, 94.2%, 95.8%, 93.7%, 63.2 and 0.181 by IUS respectively. The McNemar test showed no significant difference between two methods. The sensitivity of IOC combined with LUS was 92.9%, which was greater than that of IOC and LUS taken separately. CONCLUSIONS LUS is usually performed in case where IOC has failed or is contraindicated. The combination of both methods maximizes intraoperative detection of occult CBD stones and should at least be recommended as two complementary methods.
Effects of a Three-Set Tennis Match on Knee Kinematics and Leg Muscle Activation during the Tennis Serve

The purpose of this study was to determine the effect of a three-set tennis match on knee kinematics and leg muscle activation during the tennis serve in a real-time environment. Motion capture data and wireless electromyography of hamstrings and quadriceps muscles were collected from the back leg during the serve. A reduction of maximum knee flexion angle and a decrease of electromyography amplitudes in leg muscles were observed during the match. However, the knee angular velocity and the electromyography frequency of leg muscles remain unchanged throughout the match. The intermuscular compensation strategy to counteract fatigue might explain that the knee angular velocity was maintained despite reductions in knee flexion angle and electromyography activity of leg muscles.