Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Immunodeficiency Virus Type 1 Envelope gp120 Induces a Stop Signal and Virological Synapse Formation in Noninfected CD4+ T Cells

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-infected T cells form a virological synapse with noninfected CD4+ T cells in order to efficiently transfer HIV-1 virions from cell to cell. The virological synapse is a specialized cellular junction that is similar in some respects to the immunological synapse involved in T-cell activation and effector functions mediated by the T-cell antigen receptor. The immunological synapse stops T-cell migration to allow a sustained interaction between T-cells and antigen-presenting cells. Here, we have asked whether HIV-1 envelope gp120 presented on a surface to mimic an HIV-1-infected cell also delivers a stop signal and if this is sufficient to induce a virological synapse. We demonstrate that HIV-1 gp120-presenting surfaces arrested the migration of primary activated CD4 T cells that occurs spontaneously in the presence of ICAM-1 and induced the formation of a virological synapse, which was characterized by segregated supramolecular structures with a central cluster of envelope surrounded by a ring of ICAM-1. The virological synapse was formed transiently, with the initiation of migration within 30 min. Thus, HIV-1 gp120-presenting surfaces induce a transient stop signal and supramolecular segregation in noninfected CD4+ T cells.
Does surgery for deep infiltrating bowel endometriosis improve fertility? A systematic review

Reduced fertility is a major concern in women with endometriosis. The influence of surgery of deep infiltrating endometriosis (DIE) affecting the bowel wall on fertility is controversial and the literature on this field is heterogeneous. In this review we addressed whether surgery for bowel DIE improves the spontaneous pregnancy rate, and the results of in vitro fertilization (IVF), and the potential risk of such surgery.
Metformin Increases Insulin Sensitivity and Plasma β-endorphin in Human Subjects

Metformin has been widely used in clinical type 2 diabetes treatment and prevention. The present study was designed to explore the effect on people with a sedentary lifestyle at therapeutic doses. Twenty-two physically-inactive volunteers with normal glucose tolerance were studied. Escalating doses of metformin in low-dose (250 mg), intermediate-dose (500 mg), and high-dose (750 mg) treatment three times per day were administrated into each subject for a three-week treatment period. Fasting plasma glucose, A1C, HOMA-IR for insulin resistance, lipid profile, and plasma beta-endorphin-like immunoreactivity (BER) were measured before treatment and weekly at the end of each dosing period. Metformin significantly reduced fasting plasma glucose and HOMA-IR in healthy humans after receiving this treatment at therapeutic doses including low-dose (5 %, 17 %), intermediate-dose (6 %, 25 %) and high-dose treatment (6 %, 21 %). Plasma BER was also increased from 135.46 +/- 61.73 pg/ml to 137.52 +/- 66.11 pg/ml by low-dosing (p = 0.39), to 139.17 +/- 64.08 pg/ml by intermediate-dosing (p = 0.32), and to 149.59 +/- 63.32 pg/ml by high-dosing (p < 0.05). Also, serum cholesterol decreased significantly using metformin at therapeutic doses including low-dose (4 %), intermediate-dose (8 %) and high-dose treatment (7 %). However, metformin failed to modify levels of serum HDL-cholesterol and C-reactive protein (CRP) in healthy subjects. Also, the reduction of serum cholesterol by metformin did not correlate to the increase in insulin sensitivity. In conclusion, metformin causes a significant parallel increase in insulin sensitivity and plasma beta-endorphin level in human subjects.
LOW BONE MINERAL DENSITY AMONG PATIENTS WITH NEWLY DIAGNOSED RHEUMATOID ARTHRITIS.

BACKGROUND Osteoporosis is an early and common feature in rheumatoid arthritis. Apart from other manifestations, Osteoporosis is an extra-articular manifestation of rheumatoid arthritis whichmay result in increased risk of fractures, morbidity mortality, and associated healthcare costs. This study evaluates bone mineral density changes in patients withrheumatoid arthritis of recent-onset. METHODS This cross sectional descriptive study was conducted in the Rheumatology Department of a tertiary care hospital in Karachi. Data was collected from 76 patients presenting with seropositive or seronegative rheumatoid arthritis. Bone mineral density of these patients measured at lumbar spine and hip by using dual energy x-ray absorptiometrys can. Variables like age, gender, BMI, menstrual status, disease duration, erythrocyte sedimentation rate, vitamin D level, clinical disease activity index and seropositivity for rheumatoid arthritis were measured along with outcome variables. RESULTS A total of 104 patients fulfilling inclusion criteria were registered with 28 excluded from study. A mong the remaining 76 patients, 68 (89.50%) were female, with mean age of patients (with low bone mineral density) as 50.95 ± 7.87 years. Nineteen (25%) patients had low bone mineral density, 68.52% had low BMD at spine while 10.52% at hip and 21.05% at spine and hip both. Low bone mineral density was found higher in patients with seronegative 7 (50%) as compared to seropositive patients 12 (19.4%) (p-value 0.017), whereas low bone mineral d ensity was found higher 12 (70.6%) among post-menopausal women. CONCLUSION Low BMD was found in 25% of patients at earlier stage of the rheumatoid arthritis with seropositivity, age and menopausal status as significant risk factors.
Innovation and the State: Thinking of Government as “Technology Maker” and Implications for Public Administration Research

In this essay we summarize the historical roots and development of public sector innovation research and discuss its main current weakness – lack of explicit evolutionary perspective. To remedy this weakness, we develop a co-evolutionary perspective on public administration, technological development and innovation. Relying on Christopher Pollitt’s framework of government as “placemaker”, we propose a complementary framework of government as “technology maker”. In the concluding section, we discuss the implications of the proposed framework for PA research.
Head and neck squamous cell carcinoma is not associated with interleukin-18 promoter gene polymorphisms: a case-control study.

OBJECTIVE To investigate the association of two functional single nucleotide polymorphisms in the promoter region of the interleukin-18 gene, at positions -607 and -137, with head and neck squamous cell carcinoma. DESIGN Genomic deoxyribonucleic acid was extracted, by the salting-out method, from peripheral blood leukocytes. Single nucleotide polymorphisms of the interleukin-18 gene at positions -607 (cytosine/adenine) and -137 (guanine/cytosine) were analysed by sequence-specific polymerase chain reaction. SUBJECTS One hundred and eleven patients (86 men and 25 women; mean age 56.7+/-13.7 years) and 212 regional controls (165 men and 47 women; mean age 53.3+/-12.2 years) were studied. Control subjects comprised healthy volunteers or cancer-free individuals presenting with otolaryngological disease. The diagnosis of squamous cell carcinoma was confirmed histopathologically. Various clinical parameters were collected at diagnosis, including tumour site, tumour size, lymph node involvement, distant metastasis and stage. RESULTS There was no significant association between the allele, genotype or haplotype frequencies of the two single nucleotide polymorphisms of the interleukin-18 promoter and the head and neck squamous cell carcinoma susceptibility or clinical parameters at diagnosis. CONCLUSION Interleukin-18 polymorphisms at positions -607 and -137 did not confer susceptibility to head and neck squamous cell carcinoma in southern Iranian patients.
Current trends in brain-computer interface research at the Neil Squire foundation

The Neil Squire Foundation (NSF) is a Canadian nonprofit organization whose purpose is to create opportunities for independence for individuals who have significant physical disabilities. Over the last ten years, our team in partnership with researchers at the Electrical and Computer Engineering Department, the University of British Columbia, has been working to develop a direct brain-controlled switch for individuals with significant physical disabilities. The NSF Brain Interface Project primarily focuses on the development of brain-computer interface switch technologies for intermittent (or asynchronous) control in natural environments. That is, technologies that will work when the user intends control but also remains in a stable off state when there is no intent to control. A prototype of such a switch has successfully been developed. This switch has demonstrated classification accuracies greater than 94%. The initial results are promising, but further research is required to improve switch accuracies and reliability and to test these switch technologies over a larger population of users and operating conditions. This paper provides an overview of the NSF brain-switch technologies and details our approach to future work in this area.
Information and Communication Technology in Education in China: Policies and Practices

This seminar is co-organised by the Centre for Information Technology in Education (CITE) and Faculty of Education, HKU Current policies and practices in ICT in education in China were developed on the basis of its achievements in the area of instructional technology. Therefore, past policies and implementation strategies in instructional technology provided the foundation for the fast development in the area of ICT in education. This seminar will start with a brief review of the history of ICT in education in China. The current state of development in integration ICT into the school curriculum will be examined from five perspectives: curriculum development, resources development, contemporary distance education, application of information technology and teacher professional development. Finally, the seminar will discuss problems, challenges and strategies for further developments in this area in China.
Renal auto-transplantation promotes cortical microvascular network remodeling in a preclinical porcine model

The vascular network is a major target of ischemia-reperfusion, but has been poorly investigated in renal transplantation. The aim of this study was to characterize the remodeling of the renal vascular network that follows ischemia-reperfusion along with the most highly affected cortex section in a preclinical renal transplantation model. There were two experimental groups. The first was a grafted kidney group consisting of large white pigs for which the left kidney was harvested, cold flushed, preserved for 24 h in the University of Wisconsin’s preservation solution, and then auto-transplanted (n = 5); the right kidney was removed to mimic the situation of human kidney transplantation. The second group (uni-nephrectomized kidney group) consisted of animals that underwent only right nephrectomy, but not left renal transplantation (n = 5). Three months after autotransplantation, the kidneys were studied by X-ray microcomputed tomography. Vessel morphology and density and tortuosity of the network were analyzed using a 3D image analysis method. Cortical blood flow was determined by laser doppler analysis and renal function and tissue injury assessed by plasma creatinine levels and histological analysis. Renal ischemia-reperfusion led to decreased vascular segment volume associated with fewer vessels of less than 30 μm, particularly in the inner cortex:0.79 ± 0.54% in grafted kidneys vs. 7.06 ± 1.44% in uni-nephrectomized kidneys, p < 0.05. Vessels showed higher connectivity throughout the cortex (the arborescence factor of the whole cortex was less in grafted than uni-nephrectomized kidneys 0.90 ± 0.04 vs. 1.07 ± 0.05, p < 0.05, with an increase in the number of bifurcations). Furthermore, cortical blood flow decreased early in kidney grafts and remained low three months after auto-transplantation. The decrease in microvasculature correlated with a deterioration of renal function, proteinuria, and tubular dysfunction, and was associated with the development of fibrous tissue. This work provides new evidence concerning the impact of ischemia-reperfusion injuries on the spectrum of renal vascular diseases and could potentially guide future therapy to preserve microvessels in transplantation ischemia-reperfusion injury.
Autoimmune mechanisms activating the angiotensin AT1 receptor in 'primary' aldosteronism.

CONTEXT The mechanisms causing excessive aldosterone production and hypertension in primary aldosteronism (PA) are complex and often incompletely recognized. Autoantibodies to the angiotensin AT1 receptor (AT1R) have been reported in some PA patients with an aldosterone-producing adenoma but not with idiopathic adrenal hyperplasia. OBJECTIVE We investigated whether these autoantibodies will activate AT1R and thereby potentially contribute to the pathophysiology of PA. DESIGN AT1R autoantibody activity in sera and/or IgG purified from 13 biochemically confirmed PA patients was measured using AT1R-transfected cells, and their contractile effects were assayed using perfused rat cremaster arterioles. Aldosterone stimulation was measured in vitro using isolated human adrenal carcinoma (HAC15) adrenal cells. These data were compared with sera obtained from a group of normotensive control subjects who were expected to have negligible AT1R autoantibodies. RESULTS Sera from each of the 13 PA patients significantly increased AT1R activation in AT1R-transfected cells compared with 20 control subjects, and this activity was inhibited by the selective AT1R blocker losartan. Sera and IgG purified from AT1R autoantibody-positive sera demonstrated significant vasoconstrictive effects in isolated rat cremaster arterioles and were blocked by losartan. Moreover, the AT1R autoantibody-positive IgG directly stimulated aldosterone production in the cultured adrenal cells and enhanced angiotensin-induced aldosterone production in these cells, and these effects were blocked by candesartan. CONCLUSIONS These data support a probable pathophysiological role for AT1R autoantibodies in PA and thereby raise important etiological and therapeutic implications.
Acetylation of FOXM1 is essential for its transactivation and tumor growth stimulation

Forkhead box transcription factor M1 (FOXM1) plays crucial roles in a wide array of biological processes, including cell proliferation and differentiation, the cell cycle, and tumorigenesis by regulating the expression of its target genes. Elevated expression of FOXM1 is frequently observed in a multitude of malignancies. Here we show that FOXM1 can be acetylated by p300/CBP at lysines K63, K422, K440, K603 and K614 in vivo. This modification is essential for its transactivation on the target genes. Acetylation of FOXM1 increases during the S phase and remains high throughout the G2 and M phases, when FOXM1 transcriptional activity is required. We find that the acetylation-deficient FOXM1 mutant is less active and exhibits significantly weaker tumorigenic activities compared to wild-type FOXM1. Mechanistically, the acetylation of FOXM1 enhances its transcriptional activity by increasing its DNA binding affinity, protein stability, and phosphorylation sensitivity. In addition, we demonstrate that NAD-dependent histone deacetylase SIRT1 physically binds to and deacetylates FOXM1 in vivo. The deacetylation of FOXM1 by SIRT1 attenuates its transcriptional activity and decreases its protein stability. Together, our findings demonstrate that the reversible acetylation of FOXM1 by p300/CBP and SIRT1 modulates its transactivation function.
Hepatitis C incidence—a comparison between injection and noninjection drug users in New York City

Hepatitis C virus (HCV) burdens injection drug users (IDUs) with prevalence estimated from 60–100% compared to around 5% among noninjection drug users (non-IDUs). We present preliminary data comparing the risk for HCV among IDUs and non-IDUs to inform new avenues of HCV prevention and intervention planning. Two cohorts, new IDUs (injecting ≤3 years) and non-IDUs (smoke/sniff heroine, crack or cocaine ≤10 years) ages 15–40, were street-recruited in New York City. Participants underwent risk surveys and HCV serology at baseline and 6-month follow-up visits. Person-time analysis was used to estimate annual HCV incidence. Of 683 non-IDUs, 653 were HCV seronegative, 422 returned for at least 1 follow-up visit, and 1 became HCV seropositive. Non-IDUs contributed 246.3 person-years (PY) yielding an annual incident rate of 0.4/100 PY (95% Confidence Interval [CI]=0.0–1.2). Of 260 IDUs, 114 were HCV seronegative, 62 returned for at least 1 follow-up visit, and 13 became HCV seropositive. IDUs contributed 36.3 PY yielding an annual incidence rate of 35.9/100 PY (95% CI=19.1–61.2). Among IDUs, HCV seroconverters tended to be younger (median age 25 vs. 28, respectively), and inject more frequently (61.5% vs. 34.7%, respectively) than nonseroconverters. These interim data suggest that IDUs may have engaged in high-risk practices prior to being identified for prevention services. Preventing or at least delaying transition into injection could increase opportunity to intervene. Identifying risk factors for transition into injection could inform early prevention to reduce onset of injection and risk of HCV.
Microbial characterization of artificial sediment and comparisons with natural sediments—implication for toxicity testing

The development and activity of microbiota in artificial sediment may have strong implications for the fate of test compounds and the outcome of toxicity tests. In this study, we compare a number of microbial variables in the artificial sediment commonly used in toxicity testing with that of natural sediments. Bacterial abundance of artificial sediment ranged 5.7 to 7.1 × 108 cells/g wet weight, which is about two orders of magnitude lower than values commonly reported for natural sediments. Similarly, alternative estimates of microbial biomass (sum of phospholipid fatty acid, ergosterol, adenosine triphosphate) were several times lower for artificial sediment compared with natural sediment. Bacterial activity (3H‐thymidine incorporation) ranged 4.0 to 7.4 pmol g−1 h−1 (or 0.062–0.113 μg C g−1 h−1) in artificial sediments, which is low compared with values commonly reported for freshwater sediments. Community respiration in artificial sediment was 34 to 93 μg CO2 g−1 d−1. Bacterial community composition assessed by terminal restriction fragment length polymorphism of polymerase chain reaction amplified 16S rRNA genes demonstrated that natural bacterial communities appear to be more diverse than their counterparts in artificial sediment. The average similarity of the microbial communities obtained by this method was less than 40%, and different operational taxonomic units appeared to dominate the artificial and natural sediment, respectively. These results and supporting data from previous studies in natural sediments suggest that the artificial sediment has a poorly developed microbial component that differs substantially from that in natural sediments.
Phenotype-Stratified Genetic Linkage Study Demonstrates that IBD2 Is an Extensive Ulcerative Colitis Locus

OBJECTIVES:The complete elucidation of genetic variants that contribute to inflammatory bowel disease (IBD) will likely include variants that increase risk to both Crohn's disease and ulcerative colitis as well as variants that increase risk for particular phenotypic subsets. The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci.METHODS:This linkage study encompassed 904 affected relative pairs, representing the largest combined phenotyped cohort to date, and allowing for meaningful subset analyses. Genetic linkage data were stratified by disease location and age at diagnosis.RESULTS:We establish that some loci, notably the IBD3 and chromosome 3q linkage regions demonstrate contributions from both small intestine and colon cohorts, whereas others, notably the IBD1 (NOD2/CARD15) and IBD2 regions increase risk for small intestine or colon inflammation, respectively. The strongest linkage evidence in this study was for the subset of extensive ulcerative colitis in the region of IBD2 (lod 3.27; p < 0.001). Evidence for linkage in the region of NOD2/CARD15 (IBD1) was stronger for the subset of Crohn's patients with ileal disease (lod 2.56; P = 0.035) compared to the overall Crohn's group, consistent with previous findings that NOD2/CARD15 variants are associated with ileal disease.CONCLUSIONS:Analyses incorporating disease location in IBD increase the power and enhance the accuracy of genomic localization. Our data provide strong evidence that extensive ulcerative colitis represents a pathophysiologic subset of IBD.
S-R compatibility between response position and destination of apparent motion: evidence of the detection of affordances.

In choice reaction time, stimuli and responses in some combinations (e.g., based on spatial arrangement) are faster than in other combinations. To test whether motion toward a position yields faster responses at that position, a computer-generated square in front of one hand appeared to move either toward that hand or toward the other hand. Compatible responses (e.g., motion toward left hand/left response) were faster than incompatible responses, even when that opposed traditional positional compatibility. In Experiment 2, subjects responded to the same stimuli but with both hands left, right, or on the body midline. Medial responses were the fastest, showing that destination, rather than mere relative position, was a critical variable. It was suggested that spatial compatibility effects are not unique to position but apply to a variety of task situations, describable by J.J. Gibson's theory of affordances, in which he claims that one perceives the actions (e.g., catching) permitted in a situation.