Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune Synapses Between Lymphocytes and Target Cells in Autoimmune Thyroid Diseases

The immune synapse is the interface between an antigen-presenting cell and a lymphocyte [1-4] as well as the interface between different lymphocytes, Natural Killer cells, and target cells [5]. This intercellular connection serves as a focal point for exocytosis and endocytosis [6]. Numerous investigations have elucidated the structure of the immunological synapse. The synapse is composed of a central region: a central supramolecular activation complex SMAC [cSMAC], a T cell receptor (TCR) cluster and associated signaling proteins, and peripheral SMAC ( pSMAC) of a ring of tight adhesion between the reacting cells [7]. The separated space of SMAC is the place of exocytic and endocytic events in this site but the precise site of signaling is not known [8]. The early signaling process occurs in peripheral microclusters in the pSMAC and the cSMAC in T and B cell synapses [9-12]. CD4 T cells form long-lived synapses with APCs – the synapses live few hours. CD8 T cells form transient synapses, lasting only minutes, because the target cells are killed [13,14]. In this cytotoxic synapse, activated Src kinases were detected in the cSMAC [13]. The cSMACs play an important role not only in signaling but also in receptor recycling because endosomal compartments polarize to the point immediately beneath the cSMAC of the immunological synapse [15]. The endosome comes to lie underneath the cSMAC as polarization of the microtubule skeletons occurs during synapse formation. This polarization is antigen-dependent. The receptor activation leads to accumulation of actin across the synapse and formation of an outer ring around the synapse [16,17]. The cytotoxic reaction of lymphocytes CD8 is connected with release of specialized lysosomes containing the lytic pore-forming protein perforin, which enables gransymes to lead to rapid apoptosis of the target cell [17]; the centrosome in the lymphocytes is polarized right up to the plasma membrane containing the synapse cSMAC [18]. The lytic granules are delivered to a specialized secretory domain within the synapse by moving along the microtubules toward the centro‐
Multiple sclerosis: chemokine receptor expression on circulating lymphocytes in correlation with radiographic measures of tissue injury

Background Leukocytes expressing inflammatory chemokine receptors (CKRs), most consistently CCR2, CCR5, and CXCR3, have been identified in multiple sclerosis (MS) tissue lesions and provide attractive therapeutic targets. Our previous studies found large inter-individual differences in expression of these CKRs but stable levels over time within subjects. This observation suggests a CKR “set-point” within individuals, which might relate to inflammatory injury in MS. We evaluated the correlation between CKR levels and magnetic resonance imaging (MRI) measures of disease activity. Methods Fifty-five relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients were prospectively followed with annual CKR and MRI studies. Multiparameter flow cytometry was used to determine CCR2, CCR5, and CXCR3 expression on CD4 and CD8 cells. Simultaneous cranial MRIs were performed, and quantitative measures of T2, T1, and gadolinium lesions, brain parenchymal fraction (BPF), and whole brain and fractionated magnetization transfer ratio (MTR) were performed using automated software. Spearman’s rank correlations evaluated the relationship between CKR levels and MRI measures. Results Significant correlations were observed between CXCR3 expression on CD8 cells and measures of new (T1) and total (T1, T2) lesion volumes, lesion MTR, and BPF; higher levels of CXCR3 expression were correlated with greater injury on MRI (|r| = 0.27–0.42). In contrast, CD4 cell CKR expression was only minimally correlated with MRI measures. Conclusions Over 2 years, we observed significant correlations between the percent of CD8 cells expressing CXCR3 and MRI measures of MS inflammatory activity and tissue destruction. These observations are consistent with a pathogenic role for cytotoxic T cells in MS brain and have significant implications regarding T-cell targeted therapeutic strategies.
Rotavirus Types in Europe and Their Significance for Vaccination

The degree of diversity of cocirculating human rotavirus wild-type strains is high. This article reviews the occurrence and frequency of rotavirus types in European children younger than 5 years of age during the past 10–15 years. To enable greater understanding of the overall epidemiologic situation, rotavirus types found in animals in Europe are described. In addition, rotavirus types occurring in children outside Europe are considered. Taken together, these data provide an essential background to the development of rotavirus vaccines. The different concepts of immunization with the 2 main rotavirus candidate vaccines are briefly discussed, and their potential impact on the epidemiology of cocirculating rotavirus wild-type viruses is considered. A case is made for comprehensive surveillance of cocirculating human rotavirus types in Europe after the implementation of rotavirus vaccination.
Enhancement of survivability of mammalian cells by overexpression of the apoptosis-suppressor gene bcl-2.

Cell lines derived from the hemopoetic lineages are widely used as hosts for the production of biologicals. These cell lines have been demonstrated to undergo high levels of the active death program commonly referred to as apoptosis. The effects of overexpression of the apoptosis suppressor gene bcl-2 on the properties of a Burkitt lymphoma were compared with the control cell line (transfected with a negative control plasmid) under a variety of conditions relevant to cell culture production technology. In stationary batch cultures, there was a clear reduction in both the rate of total cell death and the level of apoptosis during the decline phase of the bcl-2 transfected cell cultures as compared with that of the control cell cultures. Nutrient analysis revealed that the onset of death during the control cell cultures occurred following complete exhaustion of glutamine. However, the bcl-2 transfected cell cultures continued to grow even though glutamine had been exhausted, and a significant decline in viability only occurred when glucose had also been completely exhausted.When cells were cultured in suspension without prior adaptation, the bcl-2 transfected cells grew significantly better, suggesting that the bcl-2 gene protected the cells from apoptosis triggered by either the lack of substrate or the hydrodynamic environment. Fluorescence microscopy revealed that death of the control cells was almost entirely by apoptosis, whereas death was almost exclusively by necrosis in the delayed decline phase of the transfected cell cultures. In both instances, death occurred before total exhaustion of glucose and glutamine.The induction of apoptosis following growth arrest is a major impediment to the development of culture strategies that optimize specific productivity by reducing the growth rate. Results presented here suggest that suppression of apoptosis by bcl-2 under the condition of excess thymidine allows the maintenance of cells in a growth-arrested state for much longer than would otherwise be possible.When cells were transferred to a range of commercial serum-free media, cell growth was, in all cases, much better for the bcl-2 transfected cell line. Moreover, when cells were cultivated in glutamine-free medium, the control cells exhibited a decrease in viable cell number within the first 24 h whereas, for the bcl-2 transfected cell cultures, viable cell number did not exhibit any clear decrease until after 75 h. Clearly, these results indicate that the metabolic engineering approach can be used to alter advantageously the survival and proliferative capacity of cells in cell culture environments. (c) 1996 John Wiley & Sons, Inc.
High-speed exercise history and catastrophic racing fracture in thoroughbreds.

OBJECTIVE To investigate the relation between several racing speed history characteristics and risk of fatal skeletal injury (FSI) in racing Thoroughbreds. ANIMALS 64 Thoroughbreds euthanatized during a 9-month period in 1991 at a California racemeet because of a catastrophic fracture incurred while racing (cases), identified retrospectively. For each race in which an FSI occurred, 1 control horse was randomly selected from the noncatastrophically injured participants. PROCEDURE Racing and officially timed workout histories were obtained for each horse. Several history characteristics were calculated to summarize racing career patterns and high-speed exercise schedules prior to date of injury and included age at first race, proportion of career spent laid up, average duration of laid up periods, average lifetime racing frequency, time from last lay up to date of injury, and total and rate of distance accumulated 1 to 6 months prior to date of injury. History characteristics associated with FSI were screened by paired t-test and studied in detail, using conditional logistic regression. RESULTS High total and high average daily rates of exercise distance accumulation within a 2-month period were associated with higher risks for FSI during racing, yet career patterns, such as age at first race or total proportion of career spent laid up, were not found to be associated with risk for FSI. A horse that had accumulated a total of 35 furlongs of race and timed-work distance in 2 months, compared with a horse with 25 furlongs accumulated, had an estimated 3.9-fold increase in risk for racing-related FSI (95% confidence interval = 2.1, 7.1). A horse that had accumulated race and timed-work furlongs at an average rate of 0.6 furlong/d within a 2-month period, compared with a horse with an average of 0.5 furlong/d, had an estimated 1.8-fold increase in risk for racing-related FSI (95% confidence interval = 1.4, 2.6). CONCLUSIONS AND CLINICAL RELEVANCE Thoroughbred racehorses that either accumulate large total high-speed distances or rapidly accumulate high-speed distances within a 2-month period may be at increased risk for FSI during racing.
Adolescent and Young Adult Perceptions of Hookah and Little Cigars/Cigarillos: Implications for Risk Messages

Use of hookah and little cigars/cigarillos (LCCs) is high among adolescents and young adults. Although these products have health effects similar to cigarettes, adolescents and young adults believe them to be safer. This study examined adolescent and young adult perceptions of hookah and LCCs to develop risk messages aimed at discouraging use among users and at-risk nonusers. Ten focus groups with 77 adolescents and young adults were conducted to explore their perceptions about the perceived risks and benefits of hookah and LCC use. Participants were users of other (non-cigarette) tobacco products (n = 47) and susceptible nonusers (n = 30). Transcripts were coded for emergent themes on participants’ perceptions of hookah and LCCs. Participants did not perceive health effects associated with hookah and LCC use to be serious or likely to happen given their infrequency of use and perceptions that they are less harmful than cigarettes. Participants generally had positive associations with smoking hookah and LCCs for several reasons, including that they are used in social gatherings, come in various flavors, and can be used to perform smoke tricks. Because adolescents and young adults underestimate and discount the long-term risks associated with hookah and LCC use, effective messages may be those that focus on the acute/immediate health and cosmetic effects.
Microbial profiles in saliva from children with and without caries in mixed dentition.

OBJECTIVE The purpose of this study was to determine the bacterial profiles in saliva of the isolated children for studying caries etiology. MATERIALS AND METHODS Samples were collected from isolated children from 6 to 8years old including 20 caries-free (dmfs=0) (healthy) and 30 caries-active individuals (dmfs>8) (patients). 16S rRNA genes were amplified by PCR from bacterial DNA of saliva sample and labeled via incorporation of Cy3-dCTP in second nested PCR. After hybridization of labeled amplicons on HOMIM, the microarray slides were scanned and original data acquired from professional software. RESULTS Collectively, 94 bacterial species or clusters representing six bacterial phyla and 30 genera were detected. A higher bacterial diversity was observed in patients than in healthy samples. Statistical analyses revealed eight species or clusters were detected more frequently in diseased patients than in healthy samples, while six different species were detected more frequently in healthy as compared to diseased patients. CONCLUSION The diversity of microbe within saliva derived from isolated population increased in caries-active status, and there are some bacteria in salivary flora can be as candidate biomarkers for caries prognosis in mixed dentition. The imbalances in the resident microflora may be the ultimate mechanism of dental caries.
Inverse Flexible Weibull Extension Distribution

paper, a new two parameters model is introduced. We called it the inverse flexible Weibull extension (IFW) distribution. Several properties of this distribution have been discussed. The maximum likelihood estimators of the parameters are derived. Two real data sets are analyzed using the new model, which show that the new model fits the data better than some other very well known models. KeywordsWeibull distribution; Hazard function; Moments; Maximum likelihood estimators; Median and mode.
Symmetric Graphs of Order a Product of Two Distinct Primes

A simple undirected graph ? is said to be symmetric if its automorphism group Aut ? is transitive on the set of ordered pairs of adjacent vertices of ? , and ? is said to be imprimitive if Aut ? acts imprimitively on the vertices of ? Let k and p be distinct primes with k < p. This paper gives a classification of all imprimitive symmetric graphs on kp vertices for k ? 5. The cases k < 5 have been treated previously by Cheng and Oxley (k = 2) and the second and third authors (k = 3), and the classification of primitive symmetric graphs on kp vertices with k ? 5 was done by the first and third authors.
Musculoskeletal complaints and psychosocial risk factors among Chinese hospital nurses.

BACKGROUND Musculoskeletal complaints represent a common occupational problem for health care workers throughout the world. Despite their sizeable numbers, however, few epidemiological studies have investigated musculoskeletal complaints among Chinese hospital nurses. Objective To assess the prevalence of, and risk factors for, musculoskeletal complaints among hospital nurses in mainland China. METHODS A total of 282 female, registered nurses were surveyed (92% response rate) using a modified Chinese-language version of the Standardized Nordic Questionnaire. Body sites were divided into the neck, shoulder, upper back and lower back regions. RESULTS The 12 month period-prevalence of musculoskeletal complaints at any of the four regions was 70%. The lower back was the most commonly reported body site (56%), followed by the neck (45%), shoulder (40%) and upper back (37%). High mental pressure, boring or tedious tasks and limited work support were identified as significant risk factors (adjusted odds ratios: 1.79-2.52). No correlations were found between manual handling or perceived physical exertion and increased reporting of musculoskeletal complaints. CONCLUSION This study has shown that musculoskeletal complaints are prevalent among Chinese hospital nurses. The correlation with various psychosocial factors is also consistent with evidence from other countries.
Hepatitis B Virus Core Antigen: Enhancement of Its Production in Escherichia coli, and Interaction of the Core Particles with the Viral Surface Antigen

Abstract The core antigen (HBcAg) of hepatitis B Virus (HBV) can be expressed in Escherichia coli where it assembles into icosahedral particles containing 240 or 180 subunits. Analysis of the two kinds of particles by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) showed that a substantial proportion of their subunits were smaller than the full-length HBcAg monomer and of variable size, but all had the same N-terminal sequence showing that the smaller species were heterogeneous in their arginine-rich C-terminal regions. Around 50% of these arginine residues are encoded by the triplet AGA which is rare in E. coli. Supplementation of the level of AGA tRNA in the cell by transformation with plasmids expressing the T4 AGA tRNA gene significantly enhanced the yield of HBcAg. Fusion phage carrying a ligand specific for HBcAg showed no significant difference in the affinity for the two sizes of HBcAg particles, but in similar reactions in solution HBV surface antigen exhibited differential affinities for the same two HBcAg preparations.
Polyalanine-independent Conformational Conversion of Nuclear Poly(A)-binding Protein 1 (PABPN1)*

Background: Mutations in the gene of the nuclear polyadenylate-binding protein 1 (PABPN1) lead to oculopharyngeal muscular dystrophy (OPMD) and aggregation of PABPN1. Results: Fibrillar structures occur independently of the OPMD causing mutation. Conclusion: OPMD might be caused by processes other than fibrillation. Significance: Fibrils of full-length PABPN1 have been obtained which might have structures identical to those found in OPMD patients. Oculopharyngeal muscular dystrophy is a late-onset disease caused by an elongation of a natural 10-alanine segment within the N-terminal domain of the nuclear poly(A)-binding protein 1 (PABPN1) to maximally 17 alanines. The disease is characterized by intranuclear deposits consisting primarily of PABPN1. In previous studies, we could show that the N-terminal domain of PABPN1 forms amyloid-like fibrils. Here, we analyze fibril formation of full-length PABPN1. Unexpectedly, fibril formation was independent of the presence of the alanine segment. With regard to fibril formation kinetics and resistance against denaturants, fibrils formed by full-length PABPN1 had completely different properties from those formed by the N-terminal domain. Fourier transformed infrared spectroscopy and limited proteolysis showed that fibrillar PABPN1 has a structure that differs from native PABPN1. Circumstantial evidence is presented that the C-terminal domain is involved in fibril formation.
The Human “Treg MLR”: Immune Monitoring for FOXP3+ T Regulatory Cell Generation

Background. Controversy exists about the conditions effecting the development of forkhead/winghead helix transcription factor P3 (FOXP3) expressing T cells and their relevance in transplant recipients. Methods. We generated carboxy-fluorescein diacetate succinimidyl ester-labeled CD4+CD25high FOXP3+ cells in mixed lymphocyte reactions (MLRs) (“the Treg MLR”), with varying human leukocyte antigen (HLA) disparities and cell components. Five color flow cytometry and 3H-thymidine uptakes were the readouts. Results. (1) Despite lower stimulation indices (SIs) than two DR-mismatched MLRs, 2 DR-matched MLRs generated more than twofold higher percentages when gating on proliferating CD4+CD25high FOXP3+ cells; (2) Even with low numbers of proliferating cells, autologous and HLA identical MLRs generated the highest FOXP3+:FOXP3− cell ratios; (3) Elimination of either non-CD3+ responding cells (resulting in “direct presentation” only) or responding CD25+ (Treg generating) cells increased the SI but inhibited proliferating CD4+CD25high FOXP3+ cell development; (4) MLR-generated CD4+CD25high FOXP3+ cells added as third components specifically inhibited the same freshly set MLR SI and caused recruitment of new CD4+CD25high FOXP3+ cells. As an example of the “Treg MLR” immune monitoring potential, addition of third component peripheral blood mononuclear cell containing high percentages of CD4+CD25high FOXP3+ cells from an HLA identical kidney transplant recipient (in a tolerance protocol) caused donor-specific Treg MLR inhibition or recruitment. This was similar to the third component MLR Tregs generated entirely in vitro. Conclusion. In the Treg MLR, the generation of CD4+CD25High FOXP3+ cells is more pronounced in the context of self-recognition (HLA matching, indirect presentation). These cells can be assayed for MLR inhibitory and Treg recruitment functions, so as to immunologically monitor the allospecific regulation after transplantation.
Life stress and somatic symptoms among adolescents: gender as moderator.

OBJECTIVE To study the impact of life stress on somatic symptoms of adolescents and to explore the moderating role of gender. METHODS This cross-sectional study was conducted from September to December 2014 at secondary schools located in Islamabad, Pakistan. Data was collected by administering self-reported measures on a sample of adolescents including both males and females. SPSS 21 was used for data analysis. RESULTS Of the 663 participants, 228(34.4%) were girls and 435(65.6%) were boys. The overall mean age was 15.27±1.20 years (range: 12-16 years). There was a significant positive correlation between the experience of life stress and somatic symptoms among adolescents (p<0.01). The prevalence of somatic symptoms was 431(65.10%) among the adolescents who experienced school-related stressors. Gender was a significant moderator and the interaction effect of gender and life stress was significant (p<0.05). Female adolescents had higher level of life stress and experienced more somatic symptoms compared to male adolescents (p<0.05). CONCLUSIONS Life stress was found to be an important indicator of somatic complaints in adolescents, with greater risk for girls as compared to boys.
Association of NOD1 (CARD4) insertion/deletion polymorphism with susceptibility to IBD: a meta-analysis.

AIM To find evidences about whether NOD1/CARD4 insertion/deletion polymorphism is associated with inflammatory bowel disease by meta-analysis. METHODS We surveyed the studies on the association of NOD1/CARD4 insertion/deletion polymorphism with inflammatory bowel disease in PubMed. Meta-analysis was performed for genotypes GG/T vs T/T, GG/GG vs T/T, GG/T + GG/GG vs T/T, GG/GG vs T/T + GG/T, and GG allele vs T allele in a fixed/random effect model. RESULTS We identified 8 studies (6439 cases and 4798 controls) in Caucasian populations using PubMed search. We found no association between NOD1/CARD4 insertion/deletion polymorphism and inflammatory bowel disease, Crohn's disease, and ulcerative colitis. Stratification of cases by age showed that NOD1/CARD4 insertion/deletion polymorphism was associated with inflammatory bowel disease in younger age group at onset (< 40 years) (GG vs T: OR = 0.68, 95% CI: 0.50-0.93, P = 0.02; GG/T + GG/GG vs T/T: OR = 0.71, 95% CI: 0.59-0.85, P = 0.0003). CONCLUSION This meta-analysis demonstrates an association between NOD1/CARD4 insertion/deletion polymorphism and inflammatory bowel disease in the younger age group at onset (< 40 years) in Caucasian populations.
A Second-Generation Integrated Map of the Silkworm Reveals Synteny and Conserved Gene Order Between Lepidopteran Insects

A second-generation linkage map was constructed for the silkworm, Bombyx mori, focusing on mapping Bombyx sequences appearing in public nucleotide databases and bacterial artificial chromosome (BAC) contigs. A total of 874 BAC contigs containing 5067 clones (22% of the library) were constructed by PCR-based screening with sequence-tagged sites (STSs) derived from whole-genome shotgun (WGS) sequences. A total of 523 BAC contigs, including 342 independent genes registered in public databases and 85 expressed sequence tags (ESTs), were placed onto the linkage map. We found significant synteny and conserved gene order between B. mori and a nymphalid butterfly, Heliconius melpomene, in four linkage groups (LGs), strongly suggesting that using B. mori as a reference for comparative genomics in Lepidotera is highly feasible.