Miracle-dz/UniFAR-FTUs huggingface dataset:
Concomitant Action of Structural Elements and Receptor Phosphorylation Determines Arrestin-3 Interaction with the Free Fatty Acid Receptor FFA4*

Background: FFA4 is a receptor for long chain fatty acids and possible target for diabetes and inflammatory diseases. Results: Sites of phosphorylation and interaction with arrestin-3 were mapped within the C-terminal tail. Conclusion: Both phosphorylation and structural elements are required for interaction with arrestin-3. Significance: Insight gained into arrestin-3 versus G protein signaling and implications for biased ligand development may drive identification of improved therapeutics. In addition to being nutrients, free fatty acids act as signaling molecules by activating a family of G protein-coupled receptors. Among these is FFA4, previously called GPR120, which responds to medium and long chain fatty acids, including health-promoting ω-3 fatty acids, which have been implicated in the regulation of metabolic and inflammatory responses. Here we show, using mass spectrometry, mutagenesis, and phosphospecific antibodies, that agonist-regulated phosphorylation of the human FFA4 receptor occurred primarily at five residues (Thr347, Thr349, Ser350, Ser357, and Ser360) in the C-terminal tail. Mutation of these residues reduced both the efficacy and potency of ligand-mediated arrestin-3 recruitment as well as affecting recruitment kinetics. Combined mutagenesis of all five of these residues was insufficient to fully abrogate interaction with arrestin-3, but further mutagenesis of negatively charged residues revealed additional structural components for the interaction with arrestin-3 within the C-terminal tail of the receptor. These elements consist of the acidic residues Glu341, Asp348, and Asp355 located close to the phosphorylation sites. Receptor phosphorylation thus operates in concert with structural elements within the C-terminal tail of FFA4 to allow for the recruitment of arrestin-3. Importantly, these mechanisms of arrestin-3 recruitment operate independently from Gq/11 coupling, thereby offering the possibility that ligands showing stimulus bias could be developed that exploit these differential coupling mechanisms. Furthermore, this provides a strategy for the design of biased receptors to probe physiologically relevant signaling.
Pronunciation Pedagogy: Second Language Teacher Cognition and Practice

Over the past few decades, increasing research has examined the cognitions (knowledge and beliefs) of second language (L2) teachers. Such efforts have provided insight into what constitutes teachers' beliefs and knowledge about teaching, how these cognitions have developed and how they are reflected in classroom practice (see Borg, 2006). Although numerous studies have been conducted into the curricular areas of L2 grammar and, to a lesser extent, L2 literacy, far fewer have examined L2 teachers' cognitions concerning L2 pronunciation instruction. The purpose of the present study, therefore, was to explore some of the dynamic relationships that exist between L2 teachers’ cognitions and actual pedagogical practices, how these cognitions have developed over time, and what relationships exist between both students’ and teachers’ perceptions. In the study, the cognitions and practices as they relate to the teaching of L2 pronunciation of five experienced teachers in an Intensive English program were investigated. The teachers participated in three types of data collection procedures over one semester three semi-structured interviews, five classroom observations, and two stimulated recall interviews. Also, their students completed questionnaires. Findings revealed that, in terms of the development of teachers' cognitions, a graduate course dedicated to pronunciation pedagogy had the greatest impact of the teachers’ cognitions. In addition, all teachers experienced some degree of insecurity about teaching pronunciation. This was especially true for teachers who had never taken a course in pronunciation pedagogy. Yet even those teacher with specific training in pronunciation pedagogy lacked confidence in certain areas, especially in how to diagnose and address problems with pronunciation. Furthermore, some of the teachers were hesitant to assess students' pronunciation, fearing that negative feedback might be damaging to the learners' identities. However, through viewing the results of the student questionnaires, the participantteachers were surprised to learn that students favored receiving explicit feedback in class in front of their peers over other types of feedback. One final major finding was that the teachers predominantly employed controlled techniques when teaching pronunciation and that, of all the techniques used, guided techniques were used less frequently. INDEX WORDS: Pronunciation teaching, Oral communication, Teacher cognition, Teacher beliefs, Teacher knowledge, English as a second language (ESL), English as a foreign language (EFL), Second language teachers, Classroom research PRONUNCIATION PEDAGOGY: SECOND LANGUAGE TEACHER COGNITION AND PRACTICE
Parental Reports of Preschool Children's Social Behavior: Relations among Peer Play, Language Competence, and Problem Behavior

This investigation examined relations between preschool children's play behavior, language competence, and problem behavior. Parents and teachers provided information on 113 preschool children enrolled in a Head Start program. A subset of these children (n = 34) who participated in a second year of this early intervention preschool program was assessed at 8-month follow-up. Correlational analysis confirmed relations between parent ratings of play performance, parent ratings of problem behavior, and teacher ratings of play performance at time one. Parent ratings of play were also related to assessments of children's language competence at the beginning of the following school year, whereas parent ratings of problem behavior were not related to subsequent language competence. The findings provide additional validity for a parent measure of preschool children's peer play and support the need for greater inclusion of parental assessment of young children's social behavior during early childhood. Implications for the assessment of play behavior, hyperactivity, and attentional difficulties with preschool children are also discussed.
Objective Screening Methods for Prior Refractive Surgery in Donor Tissue

Purpose. Laser refractive surgery presents a growing contamination of the available corneal donor pool. There currently is no objective method for screening donor tissue for previous refractive surgery. We evaluated the usefulness of pachymetry and curvature maps in the screening of donor corneas. Methods. Pachymetry and curvature maps were generated from the Orbscan for 40 normal donor eyes. The average central pachymetry measurement was subtracted from the thinnest average midperipheral pachymetry measurement for each map to generate a normal range of pachymetry measurements. For curvature, the average curvature at the 3-mm zone was subtracted from the average curvature at the 7-mm zone to generate a normal range of corneal curvature. The pachymetry and curvature results from 10 donor eyes that had undergone refractive surgery were then compared with the normal range for each technique. Results. The average difference in pachymetry measurements between the midperipheral and central cornea for normal eyes was 0.040 ± 0.026 mm. Four of 10 corneas that had undergone refractive surgery were outside two standard deviations of this normal range. The average difference in corneal curvature between the 7-mm zone and the 3-mm zone for the healthy eyes was −0.2 ± 1.0 diopters. Four (40%) of 10 corneas that had undergone refractive surgery were identified with this method. When combined, the pachymetry and curvature methods detected seven (70%) of 10 corneas that had undergone refractive surgery. Conclusion. Regional differences in thickness and curvature in donor eyes may provide methods for screening for refractive surgery for myopia. Refinement in mathematical manipulations may further improve the sensitivity of these techniques.
Nutritional anemia.

Nutritional anemia results from deficiency in either iron, vitamin B12 or folic acid, although in most areas of the world, nutritional anemia is synonymous with iron deficiency. Nutritional anemia occurs most commonly at times of heightened physiologic requirements. It is considered a major health problem in developing countries, although it is not a serious concern for the general U.S. population. Iron deficiency without frank anemia, however, does affect some segments of the U.S. population, such as pregnant and menstruating women and children.
In vitro evaluation of cobalt oxide nanoparticle-induced toxicity

Cobalt oxide (Co3O4) nanoparticles have applications in nanomedicine and nanotechnology; therefore, any possible adverse effects require thorough investigation. The present study investigated the effects of Co3O4 nanoparticles on four different cell lines: liver, HepG2 hepatocellular carcinoma cells; lung, A549 lung carcinoma cells; gastrointestinal, Caco-2 colorectal adenocarcinoma cells; and nervous system, SH-SY5Y neuroblastoma cells. A difference was observed in cell sensitivity toward Co3O4 nanoparticles. Co3O4 nanoparticles were taken up by all the cell types. However, no cell death was observed in HepG2, Caco-2, or SH-SY5Y cells; only A549 cells showed cytotoxicity at relatively high exposure concentrations. Co3O4 nanoparticles did not induce DNA damage or apoptosis in the cell lines tested except in A549. Interestingly, Co3O4 nanoparticles induced cellular oxidative damage in all cell types except Caco-2, resulting in increased malondialdehyde and 8-hydroxydeoxyguanosine levels and decreased glutathione levels. According to our results, it could be indicated that high concentrations of Co3O4 nanoparticles affected the pulmonary system but were unlikely to affect the liver, nervous system, or gastrointestinal system. Co3O4 nanoparticles might be safely used for industrial, commercial, and nanomedical applications if dose rates are adjusted depending on the route of exposure. However, further in vivo and in vitro studies are required to confirm the safety of Co3O4 nanoparticles.
Response of Urinary Biomarkers of Systemic Oxidation to Oral Iron Supplementation in Healthy Men

Background Urinary biomarkers are used in assessment of severe, clinical oxidative stress. Little is known, however, about their diagnostic value within the normative range. Objective To evaluate the response of urinary thiobarbituric acid reactive substances (TBARS) and 8-hydroxy-2-deoxyguanosine (8-OHdG) as indicators of systemic oxidation in response to short-term oral iron and antioxidant supplementation. Methods Five healthy adult men participated in the pilot study phase and 12 in the definitive intervention trial. For 7 days each, separated by 12-day washouts, the subjects received different treatment regimens, consisting of 120 mg of iron, 120 mg of iron in refined palm oil, and 120 mg of iron in palm oil combined with one of the two doses of Carotino® Tocotrienol Carotene Mixed Concentrate (CTCMC). Creatinine-normalized urinary TBARS and 8-OHdG concentrations were quantified in samples taken from subjects with and without active supplementation. Temporal and correlative associations between TBARS and 8-OHdG were explored. Results Daily intake of supplemental iron failed to produce any increment in urinary excretion of TBARS or 8-OHdG. However, a significant within-individual correlation between the urinary biomarkers was observed (Spearman r = 0.697, p < .0001, n = 466). Both doses of CTCMC significantly lowered urinary excretion of both oxidation indicators. Conclusions Despite the lack of effect of oral iron on the biomarkers of systemic oxidation, they show a strong and significant mutual association within the nonpathological range of oxidative stress in healthy male adults.
Microreview Modelling malaria pathogenesis

Almost 20 years after the development of models of malaria pathogenesis began, we are beyond the ‘proof-of-concept’ phase and these models are no longer abstract mathematical exercises. They have refined our knowledge of within-host processes, and have brought insights that could not easily have been obtained from experimentation alone. There is much potential that remains to be realized, however, both in terms of informing the design of interventions and health policy, and in terms of addressing lingering questions about the basic biology of malaria. Recent research has begun to iterate theory and data in a much more comprehensive way, and the use of statistical techniques for model fitting and comparison offers a promising approach for providing a quantitative understanding of the pathogenesis of such a complex disease.
Deep Stereo Fusion: Combining Multiple Disparity Hypotheses with Deep-Learning

Stereo matching is a popular technique to infer depth from two or more images and wealth of methods have been proposed to deal with this problem. Despite these efforts, finding accurate stereo correspondences is still an open problem. The strengths and weaknesses of existing methods are often complementary and in this paper, motivated by recent trends in this field, we exploit this fact by proposing Deep Stereo Fusion, a Convolutional Neural Network capable of combining the output of multiple stereo algorithms in order to obtain more accurate result with respect to each input disparity map. Deep Stereo Fusion process a 3D features vector, encoding both spatial and cross-algorithm information, in order to select the best disparity hypothesis among those proposed by the single stereo matchers. To the best of our knowledge, our proposal is the first i) to leverage on deep learning and ii) able to predict the optimal disparity assignments by taking only as input cue the disparity maps. This second feature makes our method suitable for deployment even when other cues (e.g., confidence) are not available such as when dealing with disparity maps provided by off-the-shelf 3D sensors. We thoroughly evaluate our proposal on the KITTI stereo benchmark with respect state-of-the-art in this field.
Unified hypothesis for the origin of aplastic anemia and periodic hematopoiesis.

The clinical and laboratory data related to periodic hematopoiesis (PH) are briefly reviewed, and it is concluded that the dynamics of PH probably originate in the hematopoietic pluripotential stem cell (PPSC) population. A model for the PPSC population is developed and analyzed. Based on the model, the simplest hypothesis for the origin of aplastic anemia (AA) and PH is that they are both due to the irreversible loss of proliferative stem cells. In addition to offering estimates for normal PPSC parameters in man and dogs, the model offers an explanation for the rarity of PH and its observed dynamics. The hypothesis predicts that for subjects without proliferative PPSC loss and with a normal differentiation flux M* out of the PPSc, the effect of cell loss from proliferation will be hypocellularity and pancytopenia. However, in both man and dogs withanM* significantly less than normal, loss of proliferating PPSC at a low rate gives mild pancytopenia, loss at a higher rate gives PH, and at an even higher rate severe pancytopenia appears. The threshold M for the appearance of PH in man is predicted to be about 3.7 x iO cells/ kg/day at a minimal period of 17 days. For mongrel dogs, the M* at which PH ensues is 6.6 x iO cells/kg/day and the period is about 9 days. Finally, the hypothesis predicts that the PPSC in subjects with AA and PH will have an increased proliferating fraction, and that stem cells should display an increased doubling time during periods of exponential growth.
Distribution of the F374 Allele of the SLC45A2 (MATP) Gene and Founder‐Haplotype Analysis

The membrane‐associated transporter protein (MATP) plays an important role in melanin synthesis. The L374F mutation in the SLC45A2 gene encoding MATP has been suggested to be associated with skin colour in major human populations. In this study more detailed distribution of the F374 allele was investigated in 1649 unrelated subjects from 13 Eurasian populations and one African population. The highest allele frequency was observed in Germans (0.965); French and Italians showed somewhat lower frequencies; and Turks had an intermediate value (0.615). Indians and Bangladeshis from South Asia were characterized by low frequencies (0.147 and 0.059, respectively). We also found the F374 allele in some East and Southeast Asian populations, and explained this by admixture. Haplotype analysis revealed that the haplotype diversity was much lower in Germans than in Japanese, and suggest that the L374F mutation occurred only once in the ancestry of Caucasians. The large differences in distribution of the F374 allele and its haplotypes suggest that this allele may be an important factor in hypopigmentation in Caucasian populations.
Dialysate calcium individualisation: a pending issue.

UNLABELLED Calcium is one of the key elements to consider in patients on dialysis due to its relationship with cardiovascular risk. The introduction of non-calcium-based phosphate binders and calcimimetics has changed the setting for pre-dialysis serum calcium in recent years from 9.5-10.5mg/dl to 8.5-9.5mg/dl. To assess more accurately the changes in calcium (Ca) during haemodialysis sessions and to individualise prescriptions, the aim of this study was to assess the intradialytic changes of two different dialysate Ca concentrations before and after hemodialysis and their implications in controlling calcium-phosphate metabolism. PATIENTS AND METHOD We analysed 98 patients with a mean age of 59.3 ± 15 years, 68 of which were men and 30 women. Each patient received two HD sessions with two different dialysate Ca concentrations: 2.5 mEq/l (Ca25 group) or 3.0 mEq/l (Ca30 group). Pre- and post-dialysis Ca, phosphorus (P) and PTH were determined, and associated medications were recorded. For a more individualised analysis, patients were divided into four subgroups of Ca<8.5mg/dl, 8.5-9.0mg/dl, 9.0-9.5mg/dl, and >9.5mg/dl, according to pre-dialysis serum calcium levels. RESULTS There were no differences in pre-dialysis values of Ca: 8.81 ± 0.65 (CA25) and 8.88 ± 0.61 (CA30), P: 4.01 ± 1.3 (CA25) and 4.19 ± 1.2 (CA30), or PTH: 352 ± 288 (CA25) and 369 ± 310 (CA30). Post-dialysis Ca and PTH did not change significantly with CA25 dialysate, although there was a significant post-dialysis Ca increase to 10.2 ± 0.6 (P<.001) accompanied by a decrease in post-dialysis PTH (181 ± 227, P<.001) with CA30. However, with CA25 dialysate, when different subgroups of pre-dialysis Ca were analysed: <8.5mg/dl (30.6%), 8.5-9.0mg/dl (31.6%), 9.1-9.5mg/dl (23.5%) and >9.5mg/dl (14.3%) we observed a Ca increase during the session in the <8.5 (P<.001) and 8.5-9.0 (P<.01) subgroups. Ca was unchanged in the 9.1-9.5 group and Ca decreased when the initial Ca values were >9.5mg/dL (P<.01). A Ca increase (P<.001) and a decrease in PTH (P<.01) were observed in all subgroups with CA30 dialysate. A total of 42% of patients were taking calcimimetics, 47% paricalcitol, and 32% calcium-based phosphate binders, although these drugs were not linked with pre- or post-dialysis Ca levels in or dialysate treatment. CONCLUSION We concluded that the prescription of Ca dialysate needs to be individualised based on pre- and post-dialysis Ca values and the need for an increase, decrease, or no changes in post-dialysis calcium in relation to the clinical condition of the patient's phosphorous-calcium metabolism.
MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior.

PURPOSE We investigated the global microRNA expression patterns in normal pancreas, pancreatic endocrine tumors and acinar carcinomas to evaluate their involvement in transformation and malignant progression of these tumor types. MicroRNAs are small noncoding RNAs that regulate gene expression by targeting specific mRNAs for degradation or translation inhibition. Recent evidence indicates that microRNAs can contribute to tumor development and progression and may have diagnostic and prognostic value in several human malignancies. MATERIALS AND METHODS Using a custom microarray, we studied the global microRNA expression in 12 nontumor pancreas and 44 pancreatic primary tumors, including 12 insulinomas, 28 nonfunctioning endocrine tumors, and four acinar carcinomas. RESULTS Our data showed that a common pattern of microRNA expression distinguishes any tumor type from normal pancreas, suggesting that this set of microRNAs might be involved in pancreatic tumorigenesis; the expression of miR-103 and miR-107, associated with lack of expression of miR-155, discriminates tumors from normal; a set of 10 microRNAs distinguishes endocrine from acinar tumors and is possibly associated with either normal endocrine differentiation or endocrine tumorigenesis; miR-204 is primarily expressed in insulinomas and correlates with immunohistochemical expression of insulin; and the overexpression of miR-21 is strongly associated with both a high Ki67 proliferation index and presence of liver metastasis. CONCLUSION These results suggest that alteration in microRNA expression is related to endocrine and acinar neoplastic transformation and progression of malignancy, and might prove useful in distinguishing tumors with different clinical behavior.
Life and Death of Proteins: A Case Study of Glucose-starved Staphylococcus aureus*

The cellular amount of proteins not only depends on synthesis but also on degradation. Here, we expand the understanding of differential protein levels by complementing synthesis data with a proteome-wide, mass spectrometry-based stable isotope labeling with amino acids in cell culture analysis of protein degradation in the human pathogen Staphylococcus aureus during glucose starvation. Monitoring protein stability profiles in a wild type and an isogenic clpP protease mutant revealed that 1) proteolysis mainly affected proteins with vegetative functions, anabolic and selected catabolic enzymes, whereas the expression of TCA cycle and gluconeogenesis enzymes increased; 2) most proteins were prone to aggregation in the clpP mutant; 3) the absence of ClpP correlated with protein denaturation and oxidative stress responses, deregulation of virulence factors and a CodY repression. We suggest that degradation of redundant, inactive proteins disintegrated from functional complexes and thereby amenable to proteolytic attack is a fundamental cellular process in all organisms to regain nutrients and guarantee protein homeostasis.
Abortion in young women and subsequent mental health.

BACKGROUND The extent to which abortion has harmful consequences for mental health remains controversial. We aimed to examine the linkages between having an abortion and mental health outcomes over the interval from age 15-25 years. METHODS Data were gathered as part of the Christchurch Health and Development Study, a 25-year longitudinal study of a birth cohort of New Zealand children. Information was obtained on: a) the history of pregnancy/abortion for female participants over the interval from 15-25 years; b) measures of DSM-IV mental disorders and suicidal behaviour over the intervals 15-18, 18-21 and 21-25 years; and c) childhood, family and related confounding factors. RESULTS Forty-one percent of women had become pregnant on at least one occasion prior to age 25, with 14.6% having an abortion. Those having an abortion had elevated rates of subsequent mental health problems including depression, anxiety, suicidal behaviours and substance use disorders. This association persisted after adjustment for confounding factors. CONCLUSIONS The findings suggest that abortion in young women may be associated with increased risks of mental health problems.