Miracle-dz/UniFAR-FTUs huggingface dataset:
G Protein Activation Stimulates Phospholipase D Signaling in Plants.

We provide direct evidence for phospholipase D (PLD) signaling in plants by showing that this enzyme is stimulated by the G protein activators mastoparan, ethanol, and cholera toxin. An in vivo assay for PLD activity in plant cells was developed based on the use of a "reporter alcohol" rather than water as a transphosphatidylation substrate. The product was a phosphatidyl alcohol, which, in contrast to the normal product phosphatidic acid, is a specific measure of PLD activity. When 32P-labeled cells were treated with 0.1% n-butanol, 32P-phosphatidyl butanol (32P-PtdBut) was formed in a time-dependent manner. In cells treated with any of the three G protein activators, the production of 32P-PtdBut was increased in a dose-dependent manner. The G protein involved was pertussis toxin insensitive. Ethanol could activate PLD but was itself consumed by PLD as transphosphatidylation substrate. In contrast, secondary alcohols (e.g., sec-butyl alcohol) activated PLD but did not function as substrate, whereas tertiary alcohols did neither. Although most of the experiments were performed with the green alga Chlamydomonas eugametos, the relevance for higher plants was demonstrated by showing that PLD in carnation petals could also be activated by mastoparan. The results indicate that PLD activation must be considered as a potential signal transduction mechanism in plants, just as in animals.
A Novel TNF Receptor-Associated Factor 6 Binding Domain Mediates NF-κB Signaling by the Common Cytokine Receptor β Subunit

GM-CSF, IL-3, and IL-5 are proinflammatory cytokines that control the production and function of myeloid and lymphoid cells. Their receptors are composed of a ligand-specific α subunit and a shared common signal-transducing β subunit (β common receptor or GM-CSFR β [βc]). The pleiotropic nature of biologic outcomes mediated by βc and the presence of large, uncharacterized regions of its cytoplasmic domain suggest that much remains to be learned about its downstream signaling pathways. Although some previous work has attempted to link βc with NF-κB activation, a definitive mechanism that mediates this pathway has not been described and, to date, it has not been clear whether the receptor can directly activate NF-κB. We demonstrate that NF-κB activation by βc is dependent on TNFR-associated factor 6 (TRAF6) and that association of TRAF6 with βc requires a consensus-binding motif found in other molecules known to interact with TRAF6. Furthermore, point mutation of this motif abrogated the ability of βc to mediate NF-κB activation and reduced the viability of an IL-3–dependent hematopoietic cell line. Because this receptor plays a key role in hematopoiesis and the βc cytoplasmic domain identified in this work mediates hematopoietic cell viability, this new pathway is likely to contribute to immune cell biology. This work is significant because it is the first description of a TRAF6-dependent signaling pathway associated with a type I cytokine receptor. It also suggests that TRAF6, a mediator of TNFR and TLR signaling, may be a common signaling intermediate in diverse cytokine receptor systems.
A program to interest medical students in Changhua, Taiwan in the incorporation of visual arts in medicine.

INTRODUCTION Visual arts have been used to facilitate the teaching of the United States Accreditation Council for Graduate Medical Education (ACGME) competencies used in some countries. Some medical students may not appreciate the usefulness of incorporating arts in medical education. Therefore, arts programs that can interest medical students are necessary. We initiated and evaluated a visual arts program at the Changhua Christian Hospital in Changhua, Taiwan, with an aim to give the students a short review of visual arts and to interest them in the incorporation of arts in medicine. METHODS A total of 110 students in clerkship or internship participated in a visual arts program with emphasis on medicine-related visual arts. Content analysis of the data from the notes made by the instructor from direct observation of students; descriptions during discussions and the written feedback from students at the end of the program was used to evaluate the effect of the program. Anonymous questionnaires were also used for self-assessment of students. RESULTS Qualitative analysis of the data revealed that the course was interesting to students. Themes emerged including its helpfulness to students in interpreting paintings, enhanced empathy, increased cultural awareness, enhanced observational skills, better team work, listening and communication skills and reduced stress. Ratings on the questionnaire showed similar results. Moreover, students had an increase in their confidence and desire to interpret paintings. CONCLUSION The structured visual arts program, with emphasis on medicine-related visual arts and other humanities subjects, was able to attract the attention of medical students. It might be helpful to improve the required skills of ACGME competencies, but further studies are needed to support these conclusions.
Genetic polymorphisms in the amino acid transporters LAT1 and LAT2 in relation to the pharmacokinetics and side effects of melphalan

Objectives Melphalan is widely used in the treatment of multiple myeloma. Pharmacokinetics of this alkylating drug shows high inter-individual variability. As melphalan is a phenylalanine derivative, the pharmacokinetic variability may be determined by genetic polymorphisms in the L-type amino acid transporters LAT1 (SLC7A5) and LAT2 (SLC7A8). Methods Pharmacokinetics were analysed in 64 patients after first administration of intravenous melphalan. Severity of side effects was documented according to WHO criteria. Genomic DNA was analysed for polymorphisms in LAT1 and LAT2 by sequencing of the entire coding region, intron-exon boundaries and 2 kb upstream promoter region. Selected polymorphisms in the common heavy chain of both transporters, the protein 4F2hc (SLC3A2), were analysed by single nucleotide primer extension. Results Melphalan pharmacokinetics was highly variable with up to 6.2-fold differences in total clearance. A total of 44 polymorphisms were identified in LAT1 and 21 polymorphisms in LAT2. From all variants, only five were in the coding region and only one heterozygous non-synonymous polymorphism (Ala94Thr) was found in LAT2. Numerous polymorphisms were found in the LAT1 and LAT2 5′-flanking regions but did not correlate with expression of the respective genes. No significant correlations could be observed between the polymorphisms in 4F2hc, LAT1, and LAT2 with melphalan pharmacokinetics or with melphalan side effects. Conclusions The study confirmed that these transporter genes are highly conserved, particularly in the coding sequences. Genetic variation in 4F2hc, LAT1, and LAT2 does not appear to be a major cause of inter-individual variability in pharmacokinetics and of adverse reactions to melphalan.
Closely Spaced Pregnancies Are Associated With Increased Odds of Autism in California Sibling Births

OBJECTIVE: To determine whether the interpregnancy interval (IPI) is associated with the risk of autism in subsequent births. METHODS: Pairs of first- and second-born singleton full siblings were identified from all California births that occurred from 1992 to 2002 using birth records, and autism diagnoses were identified by using linked records of the California Department of Developmental Services. IPI was calculated as the time interval between birth dates minus the gestational age of the second sibling. In the primary analysis, logistic regression models were used to determine whether odds of autism in second-born children varied according to IPI. To address potential confounding by unmeasured family-level factors, a case-sibling control analysis determined whether affected sibling (first versus second) varied with IPI. RESULTS: An inverse association between IPI and odds of autism among 662 730 second-born children was observed. In particular, IPIs of <12, 12 to 23, and 24 to 35 months were associated with odds ratios (95% confidence intervals) for autism of 3.39 (3.00–3.82), 1.86 (1.65–2.10), and 1.26 (1.10–1.45) relative to IPIs of ≥36 months. The association was not mediated by preterm birth or low birth weight and persisted across categories of sociodemographic characteristics, with some attenuation in the oldest and youngest parents. Second-born children were at increased risk of autism relative to their firstborn siblings only in pairs with short IPIs. CONCLUSIONS: These results suggest that children born after shorter intervals between pregnancies are at increased risk of developing autism; the highest risk was associated with pregnancies spaced <1 year apart.
p16INK4a deficiency promotes DNA hyper‐replication and genetic instability in melanocytes

Activated oncogenes restrict cell proliferation and transformation by triggering a DNA damage‐dependent senescence checkpoint in response to DNA hyper‐replication. Here, we show that loss of the p16INK4a cyclin‐dependent kinase inhibitor and melanoma tumour suppressor facilitates a DNA damage response after a hyper‐replicative phase in human melanocytes. Unlike cells expressing activated oncogenes, however, melanocytes depleted for p16INK4a display enhanced proliferation and an extended replicative lifespan in the presence of replication‐associated DNA damage. Analysis of human benign naevi confirmed that DNA damage and loss of p16INK4a expression co‐segregate closely. Thus, we propose that loss of p16INK4a facilitates tumourigenesis by promoting the proliferation of genetically unstable cells.
Production of HIV-1 vif mRNA Is Modulated by Natural Nucleotide Variations and SLSA1 RNA Structure in SA1D2prox Genomic Region

Genomic RNA of HIV-1 contains localized structures critical for viral replication. Its structural analysis has demonstrated a stem-loop structure, SLSA1, in a nearby region of HIV-1 genomic splicing acceptor 1 (SA1). We have previously shown that the expression level of vif mRNA is considerably altered by some natural single-nucleotide variations (nSNVs) clustering in SLSA1 structure. In this study, besides eleven nSNVs previously identified by us, we totally found nine new nSNVs in the SLSA1-containing sequence from SA1, splicing donor 2, and through to the start codon of Vif that significantly affect the vif mRNA level, and designated the sequence SA1D2prox (142 nucleotides for HIV-1 NL4-3). We then examined by extensive variant and mutagenesis analyses how SA1D2prox sequence and SLSA1 secondary structure are related to vif mRNA level. While the secondary structure and stability of SLSA1 was largely changed by nSNVs and artificial mutations introduced to restore the original NL4-3 form from altered ones by nSNVs, no clear association of the two SLSA1 properties with vif mRNA level was observed. In contrast, when naturally occurring SA1D2prox sequences that contain multiple nSNVs were examined, we attained significant inverse correlation between the vif level and SLSA1 stability. These results may suggest that SA1D2prox sequence adapts over time, and also that the altered SA1D2prox sequence, SLSA1 stability, and vif level are mutually related. In total, we show here that the entire SA1D2prox sequence and SLSA1 stability critically contribute to the modulation of vif mRNA level.
Ultrastructure and chromogranin A immunogold labelling of ECL cell carcinoids

Poorly differentiated neuroendocrine cells can be difficult to recognise. Sensitive methods are needed to label cells that have lost their ultrastructural features and have reduced concentrations of neuroendocrine markers. In gastric neoplasms, enterochromaffin‐like cells might dedifferentiate and lose their characteristic granules and secretory vesicles, making detection of such cells increasingly difficult. However, chromogranin A (CgA) immunogold labelling could provide sensitive and specific detection of gastric neuroendocrine cells. We present ultrastructural findings, CgA immunogold labelling as well as conventional immunohistochemical findings of two human enterochromaffin‐like cell carcinoids. Electron‐dense granules of poorly differentiated cells were less intensely labelled than granules in well‐differentiated cells. Granules with atypical shape as well as punctuate granules previously found in neuroendocrine neoplasms were also CgA labelled. The CgA labelling efficacy after antigen retrieval in an alkaline solution was higher after heating in an autoclave at 135 °C compared to a microwave at 100 °C for both granules and secretory vesicles without significant deterioration of the ultrastructure. In conclusion, the use of CgA immunogold labelling could ensure a specific classification of cells with neuroendocrine granules and be a supplement to immunohistochemical examination of poorly differentiated tumours.
A complex association between DNA methylation and gene expression in human placenta at first and third trimesters

The human placenta is a maternal-fetal organ essential for normal fetal development and maternal health. During pregnancy, the placenta undergoes many structural and functional changes in response to fetal needs and environmental exposures. Previous studies have demonstrated widespread epigenetic and gene expression changes from early to late pregnancy. However, on the global level, how DNA methylation changes impact on gene expression in human placenta is not yet well understood. We performed DNA methylome analysis by reduced representation bisulfite sequencing (RRBS) and gene expression analysis by RNA-Seq for both first and third trimester human placenta tissues. From first to third trimester, 199 promoters (corresponding to 189 genes) and 2,297 gene bodies were differentially methylated, with a clear dominance of hypermethylation (96.8% and 93.0% for promoters and gene bodies, respectively). A total of 2,447 genes were differentially expressed, of which 77.2% were down-regulated. Gene ontology analysis using differentially expressed genes were enriched for cell cycle and immune response functions. The correlation between DNA methylation and gene expression was non-linear and complex, depending on the genomic context (promoter or gene body) and gene expression levels. A wide range of DNA methylation and gene expression changes were observed at different gestational ages. The non-linear association between DNA methylation and gene expression indicates that epigenetic regulation of placenta development is more complex than previously envisioned.
On Delay-Dependent Approach for Robust Stability and Stabilization of T–S Fuzzy Systems With Constant Delay and Uncertainties

This paper investigates robust stability analysis and stabilization of delay and uncertain systems approximated by a Takagi-Sugeno (T-S) fuzzy model. An innovative approach is proposed to develop delay-dependent stability criteria of the systems, which makes use of less-redundant information to construct Lyapunov function, employs an integral equation method to handle the cross-product terms, and alleviates the requirements of the bounding technique and model transformations that have been popularly adopted in many existing references. This leads to significant improvement in the stability performance with far fewer unknown variables in the stability computation. From the derived stability criteria, a new memoryless state-feedback control is further developed. The controller gain and the maximum allowable delay bound of the closed-loop control system can be obtained simultaneously by solving an optimization problem. Numerical examples are also given to demonstrate the theoretical results.
Complete Nucleotide Sequence of Polyomavirus SA12

ABSTRACT The Polyomaviridae have small icosahedral virions that contain a genome of approximately 5,000 bp of circular double-stranded DNA. Polyomaviruses infect hosts ranging from humans to birds, and some members of this family induce tumors in test animals or in their natural hosts. We report the complete nucleotide sequence of simian agent 12 (SA12), whose natural host is thought to be Papio ursinus, the chacma baboon. The 5,230-bp genome has a genetic organization typical of polyomaviruses. Sequences encoding large T antigen, small t antigen, agnoprotein, and the viral capsid proteins VP1, VP2, and VP3 are present in the expected locations. We show that, like its close relative simian virus 40 (SV40), SA12 expresses microRNAs that are encoded by the late DNA strand overlapping the 3′ end of large T antigen coding sequences. Based on sequence comparisons, SA12 is most closely related to BK virus (BKV), a human polyomavirus. We have developed a real-time PCR test that distinguishes SA12 from BKV and the other closely related polyomaviruses JC virus and SV40. The close relationship between SA12 and BKV raises the possibility that these viruses circulate between human and baboon hosts.
AppTwins: A new approach to identify app package in network traffic

The smartphone applications have taken place of the web browser and became the user's primary internet entrance. One application's popularity can be measured by its downloading times, and it is valuable for commercial advertising. Identifying app installation packages from network traffic is one of the most feasible approaches to collect these data. But asymmetric routing, incomplete capture and so on make it challenging to determine app's name at large scale in network traffic. With these constraints, we proposed AppTwins, an efficient, robust and automatical approach which has the ability to determine corrupted package's name. The identification consists of three distinct steps. Step 1, identify app packages with a stream fuzzy hash fingerprint database in live network traffic. Step 2, the unprecedented ones were captured and decompiled to acquire new app's name, a fingerprint was also calculated. Step3, update the database with new app's name and fingerprint. AppTwins achieves up a recall rate of 97.63% and a precision rate of 96.44% when app packages are almost complete. Furthermore, It can also identify incomplete app packages in the real traffic where there are no name or URL.
Age and Prospective Memory

This paper reports an investigation into the effects of age, intelligence, and retrospective memory on performance in a prospective memory task in which subjects aged between 52 and 95 were required to telephone once a day either between two times or at an exact time. The most important influence on performance was how subjects chose to remember to make the telephone calls. The best performance was from subjects who telephoned either in conjunction with another routine event or engaged in some form of advanced planning of the daily schedule. The worst performance was from those who relied on internal cues from their own memory. Performance was intermediate from those who used external cues such as notes or diary entries. Subjects in the between condition were less likely to choose internal cues than those in the exact condition, possibly because the task appeared more difficult, and this resulted in their showing superior performance. The effect of age was influenced by the cue used. For subjects using internal cues, those who forgot were older than those who remembered, whereas for subjects using the other cues, those who forgot were younger than those who remembered. Regardless of cue, self-ratings of cognitive failures were related to performance such that those who reported more minor everyday mistakes were indeed more likely to forget to telephone. While there was some indirect effect of general intelligence on performance in the task, there was no relationship between retrospective memory scores and whether or not subjects remembered to telephone.
Obstetrical and neonatal outcomes of pregnancies complicated by endometriosis

Abstract Objective: Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, associated with pelvic pain and subfertility, affecting 0.6–10% of the general female population. The association between endometriosis and obstetrical outcomes is not well established. We aimed to evaluate whether endometriosis is associated with a higher incidence of obstetrical and neonatal complications. Study design: A retrospective cohort study of all deliveries in a university-affiliated tertiary hospital (2007–2014). Eligibility was limited to women with previously diagnosed endometriosis and singleton pregnancies. Fetuses or neonates diagnosed with structural or chromosomal anomalies were excluded. We compared labor and delivery outcomes and immediate neonatal outcomes among women with endometriosis compared with women without endometriosis. Results: Overall, 61,535 deliveries were eligible for analysis, of which 135 (0.002%) had endometriosis. Women with in the endometriosis group were characterized by higher maternal age, lower parity and higher nulliparity rate, and an earlier gestational age at delivery. Women with endometriosis had higher rate of failure of induction of labor (aOR 5.2, 95%CI 1.8–14.9), cesarean delivery (aOR 5.0, 95%CI 3.3–7.4), postpartum hemorrhage (aOR 3.7, 95%CI 1.6–8.5), placenta accreta (aOR 6.24, 95%CI 2.20–17.67), postpartum hemoglobin <10 mg/dL (aOR 2.03, 95%CI 1.31–3.14), and packed cell transfusion (aOR 3.66, 95%CI 1.94–6.91). No significant differences in neonatal outcomes were observed. Conclusions: Endometriosis is associated with higher risk of cesarean delivery and postpartum hemorrhage. Our findings suggest appropriate preparations for delivery, such as uterotonic agents and blood products, should be considered in these women.
From consensus to conflict in the regional policy mix for broadband deployment: examining the role of informal coordination

This paper examines the policy mix for broadband infrastructure deployment, and asks what role is there for coordination agents. While research has begun to examine coordination of policy, analysis has largely focused on organization and structures. This paper seeks to develop this further by examining the informal role that coordination actors play in managing synergies and tensions in the policy mix. The research highlights shared synergies in policy objectives for broadband deployment at multiple levels of governance – EU, UK, regional and local authority. Tensions, however, are found in the deployment process at the regional level, as broadband policy objectives interact with those for highways and planning agendas. In seeking to manage these tensions it highlights three coordination roles – champion, troubleshooter and monitor - and shows how these help to address conflicts and tensions that emerge. While the research suggests such tensions are impossible to fully eliminate, the findings show how the work of these informal actors helps to mediate their effects and support the deployment of broadband. These findings are drawn from an in-depth study of broadband policy in Wales between 2012 and 2017, including interviews with the policy community, analysis of news articles and review of policy documentation.