Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognitive impairment in Crohn’s disease is associated with systemic inflammation, symptom burden and sleep disturbance

Background Patients with Crohn’s disease (CD) frequently complain of cognitive difficulties such as problems with concentration and clouding of thought, yet this has scarcely been objectively defined and underlying mechanisms remain unknown. Objective The objective of this article is to objectively measure cognitive impairments in patients with CD compared with healthy controls, and if present, to identify potentially modifiable, contributing factors associated with cognitive impairment. Methods CD patients and healthy age-/sex-matched controls completed surveys encompassing clinical, demographic, psychiatric, fatigue and sleep parameters. Contemporaneously, disease activity assessment with serum CRP, faecal calprotectin, Harvey–Bradshaw Index and the Subtle Cognitive Impairment test (SCIT) were performed, with the primary measure of response time (SCIT-RT) compared between groups. Multiple linear regression assessed for factors associated with slower SCIT-RT, denoting subtle cognitive impairment. Results A total of 49 CD and 31 control individuals participated, with median age 44 years (range 22–65) and 43 years (21–63), respectively. Compared to controls, SCIT-RT was slower across all timepoints in CD patients (ANOVA p < 0.001). In multivariate analysis, serum CRP (standardised beta coefficient 0.27, 95% CI (0.02, 0.51)), abdominal pain (0.43 (0.16, 0.70)), plasma haemoglobin (1.55 (1.42, 1.68)), and concurrent fatigue (0.56 (0.25, 0.88)) were each independently associated with slower SCIT-RT in CD (each p < 0.05), with a trend for poorer sleep quality 0.54 (−0.03, 1.11) (p = 0.06), yet conversely, higher faecal calprotectin titres were associated with faster SCIT-RT (−1.77 (−1.79, −1.76), p < 0.01). Conclusions Patients with CD demonstrated subtle cognitive impairment utilising the objective SCIT, correlating with systemic inflammation and other disease burden measures, although higher faecal calprotectin titres were unexpectedly associated with less cognitive impairment.
A Cell-Autonomous Molecular Cascade Initiated by AMP-Activated Protein Kinase Represses Steroidogenesis

ABSTRACT Steroid hormones regulate essential physiological processes, and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by luteinizing hormone (LH) via its receptor leading to increased cyclic AMP (cAMP) production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Steroidogenesis then passively decreases with the degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP-to-AMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis, including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutively steroidogenic R2C cells. We have also determined that maximum AMPK activation following stimulation of steroidogenesis in MA-10 Leydig cells occurs when steroid hormone production has reached a plateau. Our data identify AMPK as a molecular rheostat that actively represses steroid hormone biosynthesis to preserve cellular energy homeostasis and prevent excess steroid production.
Management of desmoid tumours: A large national database of familial adenomatous patients shows a link to colectomy modalities and low efficacy of medical treatments

Background Desmoid tumours represent a major complication of familial adenomatous polyposis. Our aims were to study the factors associated with the development of desmoid tumours in familial adenomatous polyposis patients, and to describe presentation and management of desmoid tumours. Methods and patients We reviewed all patients with familial adenomatous polyposis followed at our institution between 1965–2013, with either identified adenomatous polyposis coli gene mutation, or a personal and family history suggesting adenomatous polyposis coli-related polyposis. Response to treatment of desmoid tumours was assessed by Response Evaluation Criteria In Solid Tumor (RECIST) criteria. Results A total of 180 patients with familial adenomatous polyposis were included with a median follow-up of 19 years since diagnosis. Thirty-one (17%) patients developed 58 desmoid tumours, a median (range) 4.7 (0.8–41.6) years after their diagnosis of familial adenomatous polyposis. The only factor significantly associated with occurrence of desmoid tumours was the type of surgery: 12 (12%) desmoid tumours in 104 patients treated by colectomy, versus 19 (25%) desmoid tumours in 76 patients treated by proctocolectomy, p = 0.027. The localisation of desmoid tumours was: mesenteric (n = 25), abdominal wall (n = 30) or extra-abdominal (n = 3). Nineteen patients underwent 36 surgical procedures for desmoid tumours. Recurrence occurred in 26 (72%) cases and the recurrence-free survival was 2.6 (95% confidence interval (CI), 0.2–5.9) years. Thirteen patients received 27 medical treatments over a median 14 months. Objective response was observed in four (15%) patients and the median progression-free survival was nine (95% CI, 1.1–16.9) months. Conclusion If confirmed, colectomy (versus proctocolectomy) should be performed in adenomatous polyposis coli-related familial adenomatous polyposis patients to avoid desmoid tumours. We show that there is a high prevalence of post-surgical recurrence and the low efficacy of available medical treatments for desmoid tumours.
Interaction between 25S rRNA A Loop and Eukaryotic Translation Initiation Factor 5B Promotes Subunit Joining and Ensures Stringent AUG Selection

ABSTRACT In yeast, 25S rRNA makes up the major mass and shape of the 60S ribosomal subunit. During the last step of translation initiation, eukaryotic initiation factor 5B (eIF5B) promotes the 60S subunit joining with the 40S initiation complex (IC). Malfunctional 60S subunits produced by misfolding or mutation may disrupt the 40S IC stalling on the start codon, thereby altering the stringency of initiation. Using several point mutations isolated by random mutagenesis, here we studied the role of 25S rRNA in start codon selection. Three mutations changing bases near the ribosome surface had strong effects, allowing the initiating ribosomes to skip both AUG and non-AUG codons: C2879U and U2408C, altering the A loop and P loop, respectively, of the peptidyl transferase center, and G1735A, mapping near a Eukarya-specific bridge to the 40S subunit. Overexpression of eIF5B specifically suppressed the phenotype caused by C2879U, suggesting functional interaction between eIF5B and the A loop. In vitro reconstitution assays showed that C2879U decreased eIF5B-catalyzed 60S subunit joining with a 40S IC. Thus, eIF5B interaction with the peptidyl transferase center A loop increases the accuracy of initiation by stabilizing the overall conformation of the 80S initiation complex. This study provides an insight into the effect of ribosomal mutations on translation profiles in eukaryotes.
Health Associations with Transport-Related Physical Activity and Motorized Travel to Destinations

ABSTRACT This study explores the relationships between health-risk indicators compared by transport-related physical activity (TPA) and motorized travel modes to two destinations. A population-representative telephone survey was conducted with adults (n = 1,989) residing in New Zealand. Those who engaged in motorized travel to place of work/study were less likely to be classified as sufficiently physically active (odds ratio [OR] = 0.5; 95% CI = 0.2 to 0.9) and normal body mass index (BMI) classification (OR = 0.6; 95% CI = 0.3 to 0.9) than were respondents who engaged in TPA. No significant physical activity or BMI associations were found for convenience shop travel. TPA travel to at least the place of work/study confers physical activity and BMI health benefits in an adult population-representative sample.
Athletes (and Coaches) Say the Darndest Things

P roviding nutrition counseling to athletes and coaches is a rewarding experience, but every once in a while, an athlete or a coach will say something that makes even the most seasoned nutrition professional say ‘‘huh? ’’ Like the time an exhausted distance runner swore she had iron deficiency anemia when the problem turned out to be the low-carbohydrate diet she was consuming because her mom insisted that she follow the meal plan outlined in the Dr Atkin’s weight loss program. The distance runner’s hematological profile was normal, but she was consuming only 50 g of carbohydrate per day or 1 g of carbohydrate per kilogram of body weight, compared with 7 to 8 g of carbohydrate per kilogram that is recommended for an endurance athlete. Then there was the baseball coach who watched a late night television infomercial and ordered a case of a supplement that purported to ‘‘tan and trim’’ his athletes. He subsequently found out that the supplement contained synephrineVa substance banned by the National Collegiate Athletic Association. The ‘‘tanning’’ ingredient gave him an odd orange tint; the ‘‘money back’’ guarantee never materialized. In this article, we examine some of the ‘‘darndest’’ things said by athletes and coaches. Sports Drinks and High-Fructose Corn Syrup
MBD2 and Multiple Domains of CHD4 Are Required for Transcriptional Repression by Mi-2/NuRD Complexes

ABSTRACT Mi-2/nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complexes are important regulators of chromatin structure and DNA accessibility. We examined requirements for individual domains of chromodomain helicase DNA-binding protein 4 (CHD4), a core catalytic component of NuRD complexes, as well as the NuRD subunit methyl-binding domain protein 2 (MBD2) and methylated DNA, for NuRD function in the context of tissue-specific transcription. By itself, loss of NuRD activity is not sufficient for transcriptional activation. However, NuRD complexes greatly reduce activation of the B cell-specific mb-1 (Cd79a) gene by the transcription factors EBF1 and Pax5. Using our B cell model system, we determined that the two chromodomains and ATPase/helicase and C-terminal domains (CTD) of CHD4 are all necessary for repression of mb-1 promoters by NuRD. All of these domains except the CTD are required for efficient association of CHD4 with mb-1 promoter chromatin. Loss of MBD2 expression or of DNA methylation impaired association of CHD4 with mb-1 promoter chromatin and enhanced its transcription. We conclude that repressive functions of MBD2-containing NuRD complexes are dependent on cooperative interactions between the major domains of CHD4 with histones and DNA and on binding of methylated DNA by MBD2.
Gender and Campus Violence: A Study of University of Lagos

This research is an attempt to investigate the incidence of violence among university students using University of Lagos as a case study. A questionnaire on different kinds of violence was administered to 446 students of the university. In addition, four focus group discussion sessions were conducted to assess the types of violence that occur in different settings on the campus. Most of the respondents were aged 21-25 years. The results show that verbal violence was more rampant than the other types of violence. However physical violence was recorded more among students in the first year than the higher levels. The findings show the need for proper orientation and guidance on social interaction for new students of tertiary institutions.
COCCIDIOIDES INFECTION (COCCIDIOIDOMYCOSIS): II. THE PRIMARY TYPE OF INFECTION

Ever since coccidioidal infection has been known to be due to a fungus,1it has been recognized that there are two distinct cycles of development of the infecting organism: the form which occurs when the organism has infected animal tissues, and the one which occurs when the organism grows on culture medium and, presumably, in nature. The first of these cycles was that observed when infected human beings came under clinical observation. The parasitic organism was seen as a double-contoured spherule, averaging about 30 microns in diameter, which reproduced by endosporulation, the endospores being released into the tissues by rupture of the wall of the mother spherule. The spherules so closely resembled Coccidia that it was at first believed that they belonged to the protozoan group, and they were called Coccidioides, i. e. , like Coccidia; hence the name. The second cycle occurs when the organism grows outside the body,
The Minimal Active Human SVA Retrotransposon Requires Only the 5′-Hexamer and Alu-Like Domains

ABSTRACT RNA-based duplication mediated by reverse transcriptase (RT), a process termed retrotransposition, is ongoing in humans and is a source of significant inter- and perhaps intraindividual genomic variation. The long interspersed element 1 (LINE-1 or L1) ORF2 protein is the genomic source for RT activity required for mobilization of its own RNA in cis and other RNAs, such as SINE/variable-number tandem-repeat (VNTR)/Alu (SVA) elements, in trans. SVA elements are ∼2-kb hominid-specific noncoding RNAs that have resulted in single-gene disease in humans through insertional mutagenesis or aberrant mRNA splicing. Here, using an SVA retrotransposition cell culture assay in U2OS cells, we investigated SVA domains important in L1-mediated SVA retrotransposition. Partial- and whole-domain deletions revealed that removal of either the Alu-like or SINE-R domain in the context of a full-length SVA has little to no effect, whereas removal of the CT hexamer or the VNTR domain can result in a 75% decrease in activity. Additional experiments demonstrate that the Alu-like fragment alone can retrotranspose at low levels while the addition of the CT hexamer can enhance activity as much as 2-fold compared to that of the full-length SVA. These results suggest that no SVA domain is essential for retrotransposition in U2OS cells and that the 5′ end of SVA (hexamer and Alu-like domain) is sufficient for retrotransposition.
Role of Double-Stranded DNA Translocase Activity of Human HLTF in Replication of Damaged DNA

ABSTRACT Unrepaired DNA lesions can block the progression of the replication fork, leading to genomic instability and cancer in higher-order eukaryotes. In Saccharomyces cerevisiae, replication through DNA lesions can be mediated by translesion synthesis DNA polymerases, leading to error-free or error-prone damage bypass, or by Rad5-mediated template switching to the sister chromatid that is inherently error free. While translesion synthesis pathways are highly conserved from yeast to humans, very little is known of a Rad5-like pathway in human cells. Here we show that a human homologue of Rad5, HLTF, can facilitate fork regression and has a role in replication of damaged DNA. We found that HLTF is able to reverse model replication forks, a process which depends on its double-stranded DNA translocase activity. Furthermore, from analysis of isolated dually labeled chromosomal fibers, we demonstrate that in vivo, HLTF promotes the restart of replication forks blocked at DNA lesions. These findings suggest that HLTF can promote error-free replication of damaged DNA and support a role for HLTF in preventing mutagenesis and carcinogenesis, providing thereby for its potential tumor suppressor role.
Factors Influencing Sleep Quality in Nursing Students and non Nursing Students

Purpose: The purpose of this study was to identify sleep quality according to a sleep model, to examine factors influencing sleep quality in nursing students and non nursing students. Methods: A cross sectional study was conducted with 154 nursing students and 155 non nursing students at several universities and college in Seoul. A self administrated questionnaire was used for data collection and data were analyzed descriptive statistics, t test or ANOVA, and regression with SPSS/WIN 14.0 program. Results: Sleep quality of nursing students is lower than non nursing students. Sleep qualities showed significant differences according to academic self efficacy, stress, depression and daytime sleepiness in nursing students and stress, depression and daytime sleepiness in non nursing students. Significant factors influencing sleep quality of nursing students was stress and for non nursing students, daytime sleepiness. Conclusion: The findings indicated the importance of sleep hygiene education for nursing students is that results in sleep quality.
Direct Interplay among Histones, Histone Chaperones, and a Chromatin Boundary Protein in the Control of Histone Gene Expression

ABSTRACT In Saccharomyces cerevisiae, the histone chaperone Rtt106 binds newly synthesized histone proteins and mediates their delivery into chromatin during transcription, replication, and silencing. Rtt106 is also recruited to histone gene regulatory regions by the HIR histone chaperone complex to ensure S-phase-specific expression. Here we showed that this Rtt106:HIR complex included Asf1 and histone proteins. Mutations in Rtt106 that reduced histone binding reduced Rtt106 enrichment at histone genes, leading to their increased transcription. Deletion of the chromatin boundary element Yta7 led to increased Rtt106:H3 binding, increased Rtt106 enrichment at histone gene regulatory regions, and decreased histone gene transcription at the HTA1-HTB1 locus. These results suggested a unique regulatory mechanism in which Rtt106 sensed the level of histone proteins to maintain the proper level of histone gene transcription. The role of these histone chaperones and Yta7 differed markedly among the histone gene loci, including the two H3-H4 histone gene pairs. Defects in silencing in rtt106 mutants could be partially accounted for by Rtt106-mediated changes in histone gene repression. These studies suggested that feedback mediated by histone chaperone complexes plays a pivotal role in regulating histone gene transcription.
Downlink Capacity and Optimal Power Allocation in Hybrid Underlay–Interweave Secondary Networks

In this paper, the downlink capacity region of a secondary network in a multiuser spectrum sharing system is obtained for a hybrid underlay-interweave paradigm, where the current channel side information (CSI) of the channel between a secondary transmitter-receiver pair is assumed at the secondary transmitter, whereas the outdated CSI of the interference channel is available to the secondary transmitter. In the hybrid paradigm, the secondary network cycles through the interweave or the underlay paradigms depending on whether spectrum holes are detected or the primary network is active, respectively. The outdated CSI is described via a correlation model, and the interference outage probability constraint (IOPC) and the average interference power constraint are considered. In general, determining the boundary of this region is a nonconvex problem. To navigate around solving this nonconvex problem, we replace the IOPC with its equivalent constraint on the peak transmit power, and we propose a power allocation algorithm for solving the latter problem. Simulations show that utilizing the outdated CSI of the interference channel reduces the secondary network's capacity as compared with when the current CSI is utilized. This reduction is a function of the correlation between the current and outdated CSI values, the interference outage probability in the primary network, and imperfect spectrum sensing.
PLEKHG2 Promotes Heterotrimeric G Protein βγ-Stimulated Lymphocyte Migration via Rac and Cdc42 Activation and Actin Polymerization

ABSTRACT PLEKHG2 is a Dbl family Rho guanine nucleotide exchange factor (RhoGEF) whose gene was originally identified as being upregulated in a leukemia mouse model and was later shown to be activated by heterotrimeric G protein βγ (Gβγ) subunits. However, its function and activation mechanisms remain elusive. Here we show that, compared to its expression in primary human T cells, its expression is upregulated in several leukemia cell lines, including Jurkat T cells. Downregulation of PLEKHG2 in Jurkat T cells by small interfering RNAs (siRNAs) specifically inhibited Gβγ-stimulated Rac and Cdc42, but not RhoA, activation. Consequently, suppressing PLEKHG2 expression blocked actin polymerization and SDF1α-stimulated lymphocyte migration. Additional studies indicate that Gβγ likely activates PLEKHG2, in part by binding the N terminus of PLEKHG2 to release an autoinhibition imposed by its C terminus, which interacts with a region encompassing the catalytic Dbl homology (DH) domain. As a result, overexpressing either the N terminus or the C terminus of PLEKHG2 blocked Gβγ-stimulated Rac and Cdc42 activation and prevented Jurkat T cells from forming membrane protrusions and migrating. Together, our studies have provided the first evidence for the endogenous function of PLEKHG2, which may serve as a key Gβγ-stimulated RhoGEF that regulates lymphocyte chemotaxis via Rac and Cdc42 activation and actin polymerization.
Fendiline Inhibits K-Ras Plasma Membrane Localization and Blocks K-Ras Signal Transmission

ABSTRACT Ras proteins regulate signaling pathways important for cell growth, differentiation, and survival. Oncogenic mutant Ras proteins are commonly expressed in human tumors, with mutations of the K-Ras isoform being most prevalent. To be active, K-Ras must undergo posttranslational processing and associate with the plasma membrane. We therefore devised a high-content screening assay to search for inhibitors of K-Ras plasma membrane association. Using this assay, we identified fendiline, an L-type calcium channel blocker, as a specific inhibitor of K-Ras plasma membrane targeting with no detectable effect on the localization of H- and N-Ras. Other classes of L-type calcium channel blockers did not mislocalize K-Ras, suggesting a mechanism that is unrelated to calcium channel blockade. Fendiline did not inhibit K-Ras posttranslational processing but significantly reduced nanoclustering of K-Ras and redistributed K-Ras from the plasma membrane to the endoplasmic reticulum (ER), Golgi apparatus, endosomes, and cytosol. Fendiline significantly inhibited signaling downstream of constitutively active K-Ras and endogenous K-Ras signaling in cells transformed by oncogenic H-Ras. Consistent with these effects, fendiline blocked the proliferation of pancreatic, colon, lung, and endometrial cancer cell lines expressing oncogenic mutant K-Ras. Taken together, these results suggest that inhibitors of K-Ras plasma membrane localization may have utility as novel K-Ras-specific anticancer therapeutics.