Miracle-dz/UniFAR-FTUs huggingface dataset:
Rab6-dependent retrograde traffic of LAT controls immune synapse formation and T cell activation

The adapter molecule linker for activation of T cells (LAT) orchestrates the formation of signalosomes upon T cell receptor (TCR) stimulation. LAT is present in different intracellular pools and is dynamically recruited to the immune synapse upon stimulation. However, the intracellular traffic of LAT and its function in T lymphocyte activation are ill defined. We show herein that LAT, once internalized, transits through the Golgi–trans-Golgi network (TGN), where it is repolarized to the immune synapse. This retrograde transport of LAT depends on the small GTPase Rab6 and the target soluble N-ethylmaleimide-sensitive factor attachment protein receptor (t-SNARE) Syntaxin-16, two regulators of the endosome-to-Golgi/TGN retrograde transport. We also show in vitro in Syntaxin-16– or Rab6-silenced human cells and in vivo in CD4+ T lymphocytes of the Rab6 knockout mouse that this retrograde traffic controls TCR stimulation. These results establish that the retrograde traffic of LAT from the plasma membrane to the Golgi-TGN controls the polarized delivery of LAT at the immune synapse and T lymphocyte activation.
Cloning, Expression, and Purification of a New Antibacterial Substance Gene From Larvae of Musca domestica (Diptera: Muscidae)

ABSTRACT. Musca domestica L. (Diptera: Muscidae), the housefly, exhibits unique immune defenses and can produce antibacterial substances upon stimulation with bacteria. On the basis of the cDNA library constructed using the suppression subtractive hybridization method, a 1188—bp antibacterial substance gene, which we named AS566, was amplified by rapid amplification of cDNA ends from M. domestica larva stimulated with Salmonella pullorum (Enterobacteriaceae: Salmonella). In this study, the full-length AS566 gene was cloned and inserted into a His-tagged Escherichia coli (Enterobacteriaceae: Escherichia) prokaryotic expression system to enable production of the recombinant protein. The recombinant AS566 protein was purified in denatured form from inclusion bodies and renatured to obtain functionally active AS566 protein. The bacteriostatic activity of the recombinant purified AS566 protein was assessed using the Oxford plate assay system and the results indicated that AS566 had antibacterial activity against six bacteria, including an E. coli clinical isolate, S. pullorum, Streptococcus bovis (Streptococcaceae: Streptococcus), Streptococcus suis, and Staphylococcus aureus (Staphylococcaceae: Staphylococcus) in vitro. The antibacterial activity of AS566 toward Gram— bacteria was two times greater than that against Gram+ bacteria. The sequencing results and BLAST analysis showed that the antibacterial substance gene AS566 was not homologous to any other antibacterial substance genes in GenBank. The antibacterial mechanisms of the newly discovered AS566 protein warrant further study.
Considering interpersonal differences in validating wearable sleep-tracking technologies

This study investigated an important yet usually neglected question in validating consumer sleep tracking devices: does interpersonal difference play a role in the validity of consumer sleep trackers? Most existing validation studies assume that the accuracy of these devices is consistent cross individuals, ignoring the fact that human sleep demonstrates significant interpersonal differences. This study aimed to test this assumption through validating two newest gadgets of home sleep tracking technologies, i.e. Fitbit Charge 2 (wearable wristband) and Neuroon (wearable EEG eye mask), in comparison to a clinical device. Two participants were recruited to track their sleep using a Fitbit, a Neuroon, and a clinical device SLEEP SCOPE simultaneously for approximately 40 nights. Data analysis was conducted for each participant separately. The results showed that the Fitbit measurements completely deviated from the clinical measurements for one participant, but agreed very well for another participant, especially in the dimension of total sleep time. Neuroon measurements agreed well but were uncorrelated to clinical measurements for one participant, and were correlated significantly but agreed poorly for another participant. This study suggested that interpersonal differences should be considered in future validation studies and in designing better consumer sleep-tracking technologies.
Physical Family Violence and Externalizing and Internalizing Behaviors Among Children and Adolescents

Family violence has been associated with various negative outcomes among children and adolescents. Yet, less is known about how unique forms of physical family violence contribute to externalizing and internalizing behaviors based on a child’s developmental stage. Using data from the Illinois Families Study and administrative Child Protective Services data, we explored the relation between 3 types of physical family violence victimization and externalizing and internalizing behaviors among a sample of 2,402 children and adolescents. After including parent and family level covariates in Poisson regressions, we found that a unique form of family violence victimization was associated with increased externalizing behaviors among children at each age group: exposure to physical intimate partner violence (IPV) among children ages 3–5, exposure to the physical abuse of a sibling among children ages 6–12, and child physical abuse among adolescents ages 13–18. No form of physical family violence was significantly associated with internalizing behaviors for children in any age group. Including exposure to the child maltreatment of a sibling is crucial when attempting to contextualize children’s responses to family violence and providing comprehensive services in an effort to enhance the well-being of all children in a family.
Prediction of Falls and/or Near Falls in People with Mild Parkinson’s Disease

Objective To determine factors associated with future falls and/or near falls in people with mild PD. Methods The study included 141 participants with PD. Mean (SD) age and PD-duration were 68 (9.7) and 4 years (3.9), respectively. Their median (q1–q3) UPDRS III score was 13 (8-18). Those >80 years of age, requiring support in standing or unable to understand instructions were excluded. Self-administered questionnaires targeted freezing of gait, turning hesitations, walking difficulties in daily life, fatigue, fear of falling, independence in activities of daily living, dyskinesia, demographics, falls/near falls history, balance problems while dual tasking and pain. Clinical assessments addressed functional balance performance, retropulsion, comfortable gait speed, motor symptoms and cognition. All falls and near falls were subsequently registered in a diary during a six-month period. Risk factors for prospective falls and/or near falls were determined using logistic regression. Results Sixty-three participants (45%) experienced ≥1 fall and/or near fall. Three factors were independent predictors of falls and/or near falls: fear of falling (OR = 1.032, p<0.001) history of near falls (OR = 3.475, p = 0.009) and retropulsion (OR = 2.813, p = 0.035). The strongest contributing factor was fear of falling, followed by a history of near falls and retropulsion. Conclusions Fear of falling seems to be an important issue to address already in mild PD as well as asking about prior near falls.
Passive Detection of Atrial Fibrillation Using a Commercially Available Smartwatch

Importance Atrial fibrillation (AF) affects 34 million people worldwide and is a leading cause of stroke. A readily accessible means to continuously monitor for AF could prevent large numbers of strokes and death. Objective To develop and validate a deep neural network to detect AF using smartwatch data. Design, Setting, and Participants In this multinational cardiovascular remote cohort study coordinated at the University of California, San Francisco, smartwatches were used to obtain heart rate and step count data for algorithm development. A total of 9750 participants enrolled in the Health eHeart Study and 51 patients undergoing cardioversion at the University of California, San Francisco, were enrolled between February 2016 and March 2017. A deep neural network was trained using a method called heuristic pretraining in which the network approximated representations of the R-R interval (ie, time between heartbeats) without manual labeling of training data. Validation was performed against the reference standard 12-lead electrocardiography (ECG) in a separate cohort of patients undergoing cardioversion. A second exploratory validation was performed using smartwatch data from ambulatory individuals against the reference standard of self-reported history of persistent AF. Data were analyzed from March 2017 to September 2017. Main Outcomes and Measures The sensitivity, specificity, and receiver operating characteristic C statistic for the algorithm to detect AF were generated based on the reference standard of 12-lead ECG–diagnosed AF. Results Of the 9750 participants enrolled in the remote cohort, including 347 participants with AF, 6143 (63.0%) were male, and the mean (SD) age was 42 (12) years. There were more than 139 million heart rate measurements on which the deep neural network was trained. The deep neural network exhibited a C statistic of 0.97 (95% CI, 0.94-1.00; P < .001) to detect AF against the reference standard 12-lead ECG–diagnosed AF in the external validation cohort of 51 patients undergoing cardioversion; sensitivity was 98.0% and specificity was 90.2%. In an exploratory analysis relying on self-report of persistent AF in ambulatory participants, the C statistic was 0.72 (95% CI, 0.64-0.78); sensitivity was 67.7% and specificity was 67.6%. Conclusions and Relevance This proof-of-concept study found that smartwatch photoplethysmography coupled with a deep neural network can passively detect AF but with some loss of sensitivity and specificity against a criterion-standard ECG. Further studies will help identify the optimal role for smartwatch-guided rhythm assessment.
Temperature and Photoperiod Interactions with Phosphorus-Limited Growth and Competition of Two Diatoms

In lakes, trophic change and climate change shift the relationship between nutrients and physical factors, like temperature and photoperiod, and interactions between these factors should affect the growth of phytoplankton species differently. We therefore determined the relationship between P-limited specific growth rates and P-quota (biovolume basis) of Stephanodiscus minutulus and Nitzschia acicularis (diatoms) at or near light saturation in axenic, semi-continuous culture at 10, 15 and 20 °C and at 6, 9 and 12 h d−1 photoperiod. Photoperiod treatments were performed at constant daily light exposure to allow comparison. Under these conditions, we also performed competition experiments and estimated relative P-uptake rates of the species. Temperature strongly affected P-limited growth rates and relative P uptake rates, whereas photoperiod only affected maximum growth rates. S. minutulus used internal P more efficiently than N. acicularis. N. acicularis was the superior competitor for P due to a higher relative uptake rate and its superiority increased with increasing temperature and photoperiod. S. minutulus conformed to the Droop relationship but N. acicularis did not. A model with a temperature-dependent normalised half-saturation coefficient adequately described the factor interactions of both species. The temperature dependence of the quota model reflected each species’ specific adaptation to its ecological niche. The results demonstrate that increases in temperature or photoperiod can partially compensate for a decrease in P-quota under moderately limiting conditions, like during spring in temperate lakes. Thus warming may counteract de-eutrophication to some degree and a relative shift in growth factors can influence the phytoplankton species composition.
Acceleration of Ileal Pacemaker Activity in Mice Lacking Interleukin 10

Background: Epidemiological studies indicate the genetic association between irritable bowel syndrome and inflammatory bowel disease, including genetic mutations related with interleukin 10 (IL-10), serotonin, and so on. On the other hand, it becomes clearer that interstitial cells of Cajal (ICC) play a major role in gut motility by coordinating the electric activity of cellular members and generating pacemaker potentials. Methods: Ileal musculatures containing the myenteric plexus and ICC were isolated from wild-type (WT) and IL-10–deficient mice. A microelectrode array system was used to simultaneously measure 8 × 8 field potentials over a ∼1 mm2 area. Nifedipine and tetrodotoxin were applied to predominantly evaluate ICC electric activity. Histological changes were also assessed by immunohistochemistry. Results: Potential mapping revealed that spontaneous electric activity was synchronized throughout the recording area in ileal musculature preparations of both WT and IL-10–deficient mice, but rapid propagation was observed in the latter. The spectral power in the frequency range of 9.4 to 30.0 cpm (Pw9.4–30.0) did not differ between these preparations, but the oscillation frequency estimated using autocorrelation analysis was significantly higher in IL-10–deficient mice than in WT mice (22.16 ± 4.10 versus 15.72 ± 1.61 cpm). In immunohistochemistry, no significant changes were observed in ICC, macrophages, and enteric neurons in the ileum of WT and IL-10–deficient mice. Conclusions: This study provides evidence for accelerated pacemaker activity in the ileum of IL-10–deficient mice, not accompanied by any significant histological changes. This could be accounted, as an example, by a genetic cross-link between inflammatory bowel disease and irritable bowel syndrome.
Five tools for manual sexological examination: Efficient treatment of genital and pelvic pains and sexual dysfunctions without side effects

Manual sexology is clinical, holistic medicine focu sed on sexual healing. Sexual healing occurs when the pati ent understands and assumes responsibility for the dist urbances in her psychosexual development. The tools can be categorized as small and large tools of manual sexo logy, with comparison to the pelvic examination. This pap er reviews five tools for examination and the simultan eous treatment of the patient (i.e. clinical medicine): 1) “Acceptance through touch” is therapeutic touch in sexology, where the therapist gives the acceptance to the patient on a sexual and bodily level that she needs but did not get from her parents, 2) Vaginal acupressure (Hippocratic pelvic massage) is massage of the orga ns of the pelvis through the vagina, which helps the pati ent to get present in the lower parts of her body and integrat e repressed negative feelings and emotions often rela ted to sexual traumas. Hippocrates and his students used t his method 2,300 years ago for the treatment of hysteri a, 3) The pelvic examination is itself highly therapeutic but only if the physician or gynecologist addresses the emot ions it provokes, 4) The holistic pelvic examination is the pelvic examination done in an empathic and therapeutic way, 5) The sexological examination, often called the “educ ational, gynecological, sexological examination” is a yet mo re complicated and time consuming and also more therapeutic procedure that involves the exploration of the pati ents sexual energies, character, sexual problems, sexual history and also use the large therapeutic tool of direct s exual stimulation of the patients clitoris and vagina. Th is tool can often bring a chronic, an-orgasmic patient all the way back to orgasmic potency in short-term therapy. It has b een used for sexological research, but has so strong curativ e qualities that it potentially could help many patients, who a re not sufficiently helped with the smaller sexological to ols. The ethical and legal aspects of the manual sexological tools are discussed.
Evaluation of the association between the number of natural teeth and anemia among Korean adults using nationally representative data

BACKGROUND Anemia as a chronic disease is defined as anemia occurring in chronic infections with inflammatory conditions. The purpose of this study is to assess the association between the number of natural teeth and anemia using nationally representative data. METHODS This study involved a cross-sectional analysis using data from the Korean National Health and Nutrition Examination Survey from 2010 to 2012. A total of 16,875 respondents aged > 19 years without missing values were included in this study. The association between the number of natural teeth and anemia was evaluated by multivariable logistic regression analyses after adjusting for age, sex, body mass index, smoking habits, drinking habits, exercise levels, income levels, education levels, vitamin D levels, diabetes, toothbrushing frequency, energy intake, and percentage of fat in total energy intake among Korean adults. RESULTS There was a significant decrease in prevalence of anemia and a significant increase in hemoglobin levels in participants with more natural teeth (P < 0.05). Adjusted odds ratios and their 95% confidence intervals for anemia in participants with numbers of natural teeth of < 15, 15 to 19, 20 to 24, or 24 to 28 were 1 (reference), 0.856(0.591 to 1.24), 0.659(0.5 to 0.868), and 0.607(0.463 to 0.797), respectively, with adjustment for confounding factors (P < 0.05). CONCLUSION The number of natural teeth is negatively associated with anemia in Korean adults, and the number of natural teeth may be considered an independent risk indicator of anemia.
Attentional Modulation and Selection – An Integrated Approach

Various models of the neural mechanisms of attentional modulation in the visual cortex have been proposed. In general, these models assume that an ‘attention’ parameter is provided separately. Its value as well as the selection of neuron(s) to which it applies are assumed, but its source and the selection mechanism are unspecified. Here we show how the Selective Tuning model of visual attention can account for the modulation of the firing rate at the single neuron level, and for the temporal pattern of attentional modulations in the visual cortex, in a self-contained formulation that simultaneously determines the stimulus elements to be attended while modulating the relevant neural processes.
University of Southern Denmark Determinants of evidence use in Public Health Policy making Results from a Study across Six EU Countries

The knowledge-practice gap in public health is widely known. The importance of using different types of evidence for the development of effective health promotion has also been emphasized. Nevertheless, in practice, intervention decisions are often based on perceived short-term opportunities, lacking the most effective approaches, thus limiting the impact of health promotion strategies. This article focuses on facilitators and barriers in the use of evidence in developing health enhancing physical activity policies. Data was collected in 2012 by interviewing 86 key stakeholders from six EU countries (FI, DK, UK, NL, IT, RO) using a common topic guide. Content analysis and concept mapping was used to construct a map of facilitators and barriers. Barriers and facilitators experienced by most stakeholders and policy context in each country are analysed. A lack of locally useful and concrete evidence, evidence on costs, and a lack of joint understanding were specific hindrances. Also users’ characteristics and the role media play were identified as factors of influence. Attention for individual and social factors within the policy context might provide the key to enhance more sustainable evidence use. Developing and evaluating tailored approaches impacting on networking, personal relationships, collaboration and evidence coproduction is recommended. © 2017 The Author(s under the CC BY-NC-N ∗ Corresponding author at: Tilburg University, Tilburg School of Social and Be he Netherlands. E-mail addresses: L.vandegoor@uvt.nl (I. van de Goor), Riitta-maija.hama athrine.juel. lau@regionh.dk (C. Juel Lau), Petru.sandu@publichealth.ro (P. Sandu arlsson), Diana.dulf@publichealth.ro (D. Dulf), Adriana.valente@cnr.it (A. Valent 1 The authors would like to thank all members of the REPOPA consortium ( ontributed to doing interviews and processing data. http://dx.doi.org/10.1016/j.healthpol.2017.01.003 168-8510/© 2017 The Author(s). Published by Elsevier Ireland Ltd. This is an ope rg/licenses/by-nc-nd/4.0/). ). Published by Elsevier Ireland Ltd. This is an open access article D license (http://creativecommons.org/licenses/by-nc-nd/4.0/). havioral Sciences, Department Tranzo, P.O. Box 90153, 5000 LE Tilburg, lainen@thl.fi (R.-M. Hämäläinen), Ahmed.sy3d@gmail.com (A. Syed), ), H.p.e.m. spitters@uvt.nl (H. Spitters), Leklund@health.sdu. dk (L. Eklund e), T.castellani@irpps.it (T. Castellani), Araro@health.sdu. dk (A.R. Aro). http://www.repopa. eu/content/consortium), especially those who have n access article under the CC BY-NC-ND license (http://creativecommons. alth Poli 274 I. van de Goor et al. / He
LSD1 mediates metabolic reprogramming by glucocorticoids during myogenic differentiation

Abstract The metabolic properties of cells are formed under the influence of environmental factors such as nutrients and hormones. Although such a metabolic program is likely initiated through epigenetic mechanisms, the direct links between metabolic cues and activities of chromatin modifiers remain largely unknown. In this study, we show that lysine-specific demethylase-1 (LSD1) controls the metabolic program in myogenic differentiation, under the action of catabolic hormone, glucocorticoids. By using transcriptomic and epigenomic approaches, we revealed that LSD1 bound to oxidative metabolism and slow-twitch myosin genes, and repressed their expression. Consistent with this, loss of LSD1 activity during differentiation enhanced the oxidative capacity of myotubes. By testing the effects of various hormones, we found that LSD1 levels were decreased by treatment with the glucocorticoid dexamethasone (Dex) in cultured myoblasts and in skeletal muscle from mice. Mechanistically, glucocorticoid signaling induced expression of a ubiquitin E3 ligase, JADE-2, which was responsible for proteasomal degradation of LSD1. Consequently, in differentiating myoblasts, chemical inhibition of LSD1, in combination with Dex treatment, synergistically de-repressed oxidative metabolism genes, concomitant with increased histone H3 lysine 4 methylation at these loci. These findings demonstrated that LSD1 serves as an epigenetic regulator linking glucocorticoid action to metabolic programming during myogenic differentiation.
Transfusion of murine red blood cells expressing the human KEL glycoprotein induces clinically significant alloantibodies

Red blood cell (RBC) alloantibodies to nonself antigens may develop after transfusion or pregnancy, leading to morbidity and mortality in the form of hemolytic transfusion reactions or hemolytic disease of the newborn. A better understanding of the mechanisms of RBC alloantibody induction, or strategies to mitigate the consequences of such antibodies, may ultimately improve transfusion safety. However, such studies are inherently difficult in humans.