Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Intestinal H+/Peptide Cotransporter

In mammalian small intestine, a H+-coupled peptide transporter is responsible for the absorption of small peptides arising from digestion of dietary proteins. Recently a cDNA clone encoding a H+/peptide cotransporter has been isolated from a rabbit intestinal cDNA library (Fei, Y. J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F. H., Romero, M. F., Singh, S. K., Boron, W. F., and Hediger, M. A.(1994) Nature 368, 563-566). Screening of a human intestinal cDNA library with a probe derived from the rabbit H+/peptide cotransporter cDNA resulted in the identification of a cDNA which when expressed in HeLa cells or in Xenopus laevis oocytes induced H+-dependent peptide transport activity. The predicted protein consists of 708 amino acids with 12 membrane-spanning domains and two putative sites for protein kinase C-dependent phosphorylation. The cDNA-induced transport process accepts dipeptides, tripeptides, and amino β-lactam antibiotics but not free amino acids as substrates. The human H+/peptide cotransporter exhibits a high degree of homology (81% identity and 92% similarity) to the rabbit H+/peptide cotransporter. But surprisingly these transporters show only a weak homology to the H+-coupled peptide transport proteins present in bacteria and yeast. Chromosomal assignment studies with somatic cell hybrid analysis and in situ hybridization have located the gene encoding the cloned human H+/peptide cotransporter to chromosome 13 q33→q34.
What Neural Correlates Underlie Successful Encoding and Retrieval? A Functional Magnetic Resonance Imaging Study Using a Divided Attention Paradigm

If attention is divided during learning, memory suffers. Nevertheless, individuals can learn information with divided attention. This event-related functional magnetic resonance imaging (fMRI) study (n = 17) investigated what neural processes support (1) learning with divided attention and (2) retrieval of information learned with divided attention. Participants encoded words (Is the word abstract or concrete? ) while performing an auditory discrimination task (press a button whenever an auditory pattern changes). The auditory task was easy or hard, depending on the similarity of the patterns. A behavioral study indicated that detailed (“recollective”) information was more likely to be present for words encoded with the easy versus the hard concurrent task. Words encoded with the hard versus the easy concurrent task, in contrast, were more likely to rely on less detailed (“familiarity”-based) information. fMRI revealed encoding-related activation in the left prefrontal cortex (PFC) and left hippocampus that was linked to successful memory formation only for items encoded with the easy task. In contrast, activation in the right PFC and left parahippocampal gyrus was linked to successful memory for all items. Thus, successful encoding with the hard concurrent task was supported by a subset of the regions recruited for successful encoding with the easy task. The neural processes recruited for successful retrieval also depended on the encoding condition: The left PFC was disproportionately recruited for retrieval of items encoded with the easy task, whereas the right PFC was disproportionately recruited for retrieval of items encoded with the hard task. These findings may reflect left-sided specialization for recollective memories and right-sided specialization for familiarity-based traces.
The Pseudomonas aeruginosa N-Acylhomoserine Lactone Quorum Sensing Molecules Target IQGAP1 and Modulate Epithelial Cell Migration

Quorum sensing (QS) signaling allows bacteria to control gene expression once a critical population density is achieved. The Gram-negative human pathogen Pseudomonas aeruginosa uses N-acylhomoserine lactones (AHL) as QS signals, which coordinate the production of virulence factors and biofilms. These bacterial signals can also modulate human cell behavior. Little is known about the mechanisms of the action of AHL on their eukaryotic targets. Here, we found that N-3-oxo-dodecanoyl-L-homoserine lactone 3O-C12-HSL modulates human intestinal epithelial Caco-2 cell migration in a dose- and time-dependent manner. Using new 3O-C12-HSL biotin and fluorescently-tagged probes for LC-MS/MS and confocal imaging, respectively, we demonstrated for the first time that 3O-C12-HSL interacts and co-localizes with the IQ-motif-containing GTPase-activating protein IQGAP1 in Caco-2 cells. The interaction between IQGAP1 and 3O-C12-HSL was further confirmed by pull-down assay using a GST-tagged protein with subsequent Western blot of IQGAP1 and by identifying 3O-C12-HSL with a sensor bioassay. Moreover, 3O-C12-HSL induced changes in the phosphorylation status of Rac1 and Cdc42 and the localization of IQGAP1 as evidenced by confocal and STED microscopy and Western blots. Our findings suggest that the IQGAP1 is a novel partner for P.aeruginosa 3O-C12-HSL and likely the integrator of Rac1 and Cdc42- dependent altered cell migration. We propose that the targeting of IQGAP1 by 3O-C12-HSL can trigger essential changes in the cytoskeleton network and be an essential component in bacterial – human cell communication.
Dopaminergic, serotonergic, and oxytonergic candidate genes associated with infant attachment security and disorganization? In search of main and interaction effects.

BACKGROUND AND METHODS In two birth cohort studies with genetic, sensitive parenting, and attachment data of more than 1,000 infants in total, we tested main and interaction effects of candidate genes involved in the dopamine, serotonin, and oxytocin systems (DRD4, DRD2, COMT, 5-HTT, OXTR) on attachment security and disorganization. Parenting was assessed using observational rating scales for parental sensitivity (Ainsworth, Bell, & Stayton, 1974), and infant attachment was assessed with the Strange Situation Procedure. RESULTS We found no consistent additive genetic associations for attachment security and attachment disorganization. However, specific tests revealed evidence for a codominant risk model for COMT Val158Met, consistent across both samples. Children with the Val/Met genotype showed higher disorganization scores (combined effect size d = .22, CI = .10-.34, p < .001). Gene-by-environment interaction effects were not replicable across the two samples. CONCLUSIONS This unexpected finding might be explained by a broader range of plasticity in heterozygotes, which may increase susceptibility to environmental influences or to dysregulation of emotional arousal. This study is unique in combining the two largest attachment cohorts with molecular genetic and observed rearing environment data to date.
CYP2D6 and CYP1A1 mutations in the Turkish population

Drugs and carcinogens are substrates of a group of metabolic enzymes including cytochrome p450 enzymes and gluthatione S‐transferases. Many of the genes encoding these enzymes exhibit functional polymorphisms that contribute individual cancer susceptibility and drug response. Molecular studies based on these polymorphic enzymes also explain the aetiology of cancer and therapeutic management in clinics. We analysed the cytochrome p4501A1 (CYP1A1) and 2D6 (CYP2D6) variant genotype and allele frequencies by PCR‐RFLP in Turkish individuals (n = 140). The frequency of the CYP1A1*2A mutant allele was found to be 15.4%, and the CYP2D6*3 and *4 mutant allele (poor metabolizer) frequencies were 2.5% and 13.9%, respectively. This study presents the first results of CYP1A1 and CYP2D6 mutant allele distributions in the Turkish population and these data provide an understanding of epidemiological studies that correlate therapeutic approaches and aetiology of several types of malignancy in Turkish patients. Copyright © 2005 John Wiley & Sons, Ltd.
Determination of Amprenavir Total and Unbound Concentrations in Plasma by High-Performance Liquid Chromatography and Ultrafiltration

Amprenavir is an HIV-1 protease inhibitor with high protein binding (90%) in human plasma. This study was designed to develop an assay to measure the concentration of unbound amprenavir, to study variation with time in patients, and to investigate whether ritonavir and lopinavir, other protease inhibitors that could be combined, interact with amprenavir protein binding in vitro. A reverse-phase high-performance liquid chromatography assay to UV detection was developed and validated to measure total amprenavir in plasma, and this method was adapted to quantitate low concentrations of unbound amprenavir in ultrafiltrate aqueous fluid. Equilibrium dialysis and ultrafiltration were used and compared with separate unbound fraction. The latter method was easier to use and was, therefore, subsequently adopted. In 10 patients who received amprenavir 600 mg bid combined with ritonavir, mean amprenavir free-fraction in plasma was 8.6% (range, 4.4-20%). When added to pooled human plasmas at concentrations close to those found in treated patients, the unbound amprenavir fraction was increased in the presence of lopinavir, but remained unaffected by ritonavir. It remains to be seen whether measurement of unbound concentrations, rather than total concentrations, could improve therapeutic drug monitoring.
Neurocognitive and Clinical Predictors of Long-Term Outcome in Adolescents at Ultra-High Risk for Psychosis: A 6-Year Follow-Up

Background Most studies aiming to predict transition to psychosis for individuals at ultra-high risk (UHR) have focused on either neurocognitive or clinical variables and have made little effort to combine the two. Furthermore, most have focused on a dichotomous measure of transition to psychosis rather than a continuous measure of functional outcome. We aimed to investigate the relative value of neurocognitive and clinical variables for predicting both transition to psychosis and functional outcome. Methods Forty-three UHR individuals and 47 controls completed an extensive clinical and neurocognitive assessment at baseline and participated in long-term follow-up approximately six years later. UHR adolescents who had converted to psychosis (UHR-P; n = 10) were compared to individuals who had not (UHR-NP; n = 33) and controls on clinical and neurocognitive variables. Regression analyses were performed to determine which baseline measures best predicted transition to psychosis and long-term functional outcome for UHR individuals. Results Low IQ was the single neurocognitive parameter that discriminated UHR-P individuals from UHR-NP individuals and controls. The severity of attenuated positive symptoms was the only significant predictor of a transition to psychosis and disorganized symptoms were highly predictive of functional outcome. Conclusions Clinical measures are currently the most important vulnerability markers for long-term outcome in adolescents at imminent risk of psychosis.
Hardiness training facilitates performance in college

In 25 years of research and practice, hardiness has emerged as a pattern of attitudes and skills that is a pathway to resilience under stressful circumstances. As such, it is important to determine whether hardiness can be trained, and if such training improves performance and health. The few relevant studies available thus far have suggested this training effectiveness among working adults and students. Furthering this theme, the present study involves a large sample of undergraduate students, comparing those who experienced hardiness training as a regular credit course, with those who went through other courses taught by the same teachers. At the beginning of the courses, these two groups did not differ in demographics, hardiness levels, or grade-point-average (GPA). At the end of the courses, the Hardiness Training Group showed higher levels of hardiness, and GPA than did the Comparison Group. This improvement in GPA for the Hardiness Training Group persisted over the following 2-year period, even controlling for GPA and hardiness level prior to the training, and the grade received in the training. These results suggest the importance of hardiness training in facilitating a major indicator of excellent performance in college life.
Helping Coworkers and Helping the Organization: The Role of Support Perceptions, Exchange Ideology, and Conscientiousness1

This study examined 2 types of organizational citizenship behaviors: those that benefit the organization, and those that benefit one's coworkers. Parallel hypotheses were developed that predicted that support perceptions (both organizational and individual) would predict their respective type of citizenship behavior, and that exchange ideology (also both organizational and individual) would moderate this relation. The contributions of conscientiousness and empathy were also explored for their potential incremental value. Existing measures of perceived organizational support and exchange ideology were used to develop two new measures to assess perceived coworker support and individual exchange ideology. Results from a diverse sample support the importance of support perceptions as well as the moderating role of organizational exchange ideology. With respect to the 2 personality variables, conscientiousness played a significant role, but empathy did not. Implications for citizenship research and practice are discussed.
Social cognition and moral cognition in bullying: What's wrong?

Two different models have been proposed that describe the bully alternatively as a child lacking in social skills [Crick and Dodge, 1994], or as a cold manipulative individual, who leads gangs to achieve personal goals [Sutton et al., 1999a]. The present study examined the performance of 204 8–11-year-olds in a set of stories that assessed understanding of cognitions and emotions, in relation to their Participant Role in bullying. Moreover, children's understanding of moral emotions and proneness to moral disengagement was assessed. Victims showed some difficulties in the social cognition task, whereas bullies did not. Aggressive children, instead, were found to be more ready to show moral disengagement mechanisms, whereas defenders showed higher levels of moral sensibility. Results are discussed in relation to the two models, and the need for further research into empathy and moral cognition of children involved in bullying episodes is highlighted. Aggr. Behav. 32:528–539, 2006. © 2006 Wiley-Liss, Inc.
Specific Neurological Phenotypes in Autism Spectrum Disorders Are Associated with Sex Representation

Autism spectrum disorder (ASD) is a heritable disorder occurring predominantly in males. The aim of this study was to compare sex differences in the prevalence of specific neurological phenotypes commonly described in ASD. The study included 663 participants, aged 18 months to 15 years, diagnosed with ASD. Neurological and behavioral assessments were performed using standardized tests, and obtaining medical, developmental, and familial histories from the parents. Phenotypes under investigation were macro‐ and microcephaly, developmental regression, minor neurological and musculoskeletal deficits (MNMD), and seizures. Male : female ratio in the ASD group was 6.7:1. No sex differences in autism severity, cognitive ability, and adaptive functioning were noted. Mean head circumference percentile for males (50.1 ± 25.6) was significantly larger than females (43.4 ± 30.2). Micro‐ and macrocephaly were more frequent in ASD than expected (5.9%; 18.1%, respectively). Microcephaly in females (15.1%) was significantly more prevalent than in males (4.5%). The prevalence of macrocephaly in both sexes did not differ significantly. Regression was noted in 30.2% of the females with ASD, significantly higher than in males (18.9%). MNMD was documented in 73.8% of the females, significantly higher than in males (57.1%). M:F ratio decreased in a group with two or more phenotypes (3.6:1), while male predominance was more significant in the group without phenotypes (13.6:1). Neurological phenotypes associated with ASD are more prevalent in females than in males, resulting in more complex clinical and neurological manifestations in females. Therefore, involvement of different etiologies is suggested in ASD in females. Autism Res 2013, 6: 596–604. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Endoscope-Guided Interstitial Intensity-Modulated Brachytherapy and Intracavitary Brachytherapy as Boost Radiation for Primary Early T Stage Nasopharyngeal Carcinoma

Background Intracavitary brachytherapy (ICBT) is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC) after primary extern-beam radiptherapy (ERT). Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT) boost radiation for deep-seated residual NPC. Methodology/Principal Findings Two hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005–2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium) were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium). We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P<0.001) and stage II (90.5% VS 61.4%, P = 0.001) than that of ICBT boost subgroup. The dosage of external-beam radiotherapy in the nasopharyngeal (63.0±3.8 VS 62.6±4.3 Gray (Gy), P = 0.67) and regional lymph nodes (55.8±5.0 VS 57.5±5.7 Gy, P = 0.11) was comparable in both groups. For brachytherapy, IMBT subgroup had a lower boost radiation dosage than ICBT subgroup (11.0±2.9 VS 14.8±3.2 Gy, P<0.01). Though the IMBT group had deeper residual tumors and received lower boost radiation dosages, both subgroups had the similar 5-year actuarial overall survival rate (IMBT VS ICBT group: 96.8% VS 93.6%, P = 0.87), progression-free survival rate (92.4% VS 86.5%, P = 0.41) and distant metastasis-free survival rate (94.9% VS 92.7%, P = 0.64). Moreover, IMBT boost radiation subgroup had a similar local (97.4% VS 94.4%, P = 0.57) and regional (95.0% VS 97.2%, P = 0.34) control to ICBT subgroup. The acute and late toxicities rates were comparable between the both subgroups. Conclusions/Significance IMBT boost radiation may be a promising therapeutic selection for deep-seated residual NPC.
Biological characterization of gene response in Rpe65‐/‐ mouse model of Leber's congenital amaurosis during progression of the disease

RPE65 is the retinal isomerase essential for conversion of all‐trans‐retinyl ester to 11‐cis‐retinolin the visual cycle. Leber's congenital amaurosis (LCA),an autosomal recessive form of RP resulting in blindness, is commonly caused by mutations in the Rpe65gene. Whereas the molecular mechanisms by which these mutations contribute to retinal disease remain largely unresolved, affected patients show marked RPE damage and photoreceptor degeneration. We evaluated gene expression in Rpe65‐/‐ mouse model of LCA before and at the onset of photoreceptor cell death in 2, 4, and 6 month old animals. Microarray analysis demonstrates altered expression of genes involved in phototransduction, apoptosis regulation, cytoskeleton organization, and extracellular matrix (ECM) constituents. Cone‐specific phototransduction genes arestrongly decreased, reflecting early loss of cones. In addition, remaining rods show modified expression of genes encoding components of the cytoskeleton and ECM. This may affect rod physiology and interaction with the adjacent RPE and lead to loss of survival signals, as reflected by the alteration of apoptosisrelated genes Together, these results suggest that RPE65 defect triggers an overall remodeling of the neurosensitive retina that may, in turn, disrupt photoreceptor homeostasis and induce apoptosis signaling cascade toward retinal cell death. —Cottet, S. , Michaut, L. , Boisset, G. , Schlecht, U. , Gehring, W. , Schorderet, D. F. Biological characterization of gene response in Rpe65‐/‐ mouse model of Leber's congenital amaurosis during progression of the disease. FASEB J. 20,2036–2049 (2006)
Anxiety levels of pregnant women during ultrasound examination: coping styles, amount of feedback and learned resourcefulness

Anxiety levels were measured before and after ultrasound examination in 183 women who underwent the procedure as part of their routine prenatal care. Women were classified according to their preferred mode of information gathering, their amount of available cognitive resources and predetermined feedback conditions. The results indicated significant reductions in state or situational anxiety levels for all subjects while trait anxiety was unaffected. In addition, the results suggested a correspondence between learned resourcefulness and informational coping styles. Women who had higher levels of cognitive resources and actively sought out information showed significantly greater decreases in state anxiety levels. This finding was also true for women who had lower levels of cognitive resources and tended to block out information. The impact of the scan was more profoundly affected by personality repertoires and informational coping styles than by either of the feedback conditions. Copyright © 1995 International Society of Ultrasound in Obstetrics and Gynecology
Physiological Role of Calcium-Activated Potassium Currents in the Rat Lateral Amygdala

Principal neurons in the lateral nucleus of the amygdala (LA) exhibit a continuum of firing properties in response to prolonged current injections ranging from those that accommodate fully to those that fire repetitively. In most cells, trains of action potentials are followed by a slow afterhyperpolarization (AHP) lasting several seconds. Reducing calcium influx either by lowering concentrations of extracellular calcium or by applying nickel abolished the AHP, confirming it is mediated by calcium influx. Blockade of large conductance calcium-activated potassium channel (BK) channels with paxilline, iberiotoxin, or TEA revealed that BK channels are involved in action potential repolarization but only make a small contribution to the fast AHP that follows action potentials. The fast AHP was, however, markedly reduced by low concentrations of 4-aminopyridine and α-dendrotoxin, indicating the involvement of voltage-gated potassium channels in the fast AHP. The medium AHP was blocked by apamin and UCL1848, indicating it was mediated by small conductance calcium-activated potassium channel (SK) channels. Blockade of these channels had no effect on instantaneous firing. However, enhancement of the SK-mediated current by 1-ethyl-2-benzimidazolinone or paxilline increased the early interspike interval, showing that under physiological conditions activation of SK channels is insufficient to control firing frequency. The slow AHP, mediated by non-SK BK channels, was apamin-insensitive but was modulated by carbachol and noradrenaline. Tetanic stimulation of cholinergic afferents to the LA depressed the slow AHP and led to an increase in firing. These results show that BK, SK, and non-BK SK-mediated calcium-activated potassium currents are present in principal LA neurons and play distinct physiological roles.
Evaluating coherence in open domain conversational systems

We propose a method for evaluating coherence between user utterances and those generated from open domain conversational systems. Our aim is to make it possible for such systems to ascertain whether utterances generated from them are appropriate to the context before generation so that possible breakdown in conversation arising from inappropriate utterances can be avoided. In our method, we train a classiﬁer that distinguishes a pair of a user utterance and that generated from a system as coherent or incoherent by using various pieces of information related to dialogue exchange, such as dialogue acts, question types, and predicate-argument structures. Experimental results show that our method signiﬁcantly outperforms the baseline, conﬁrming its effectiveness.