Miracle-dz/UniFAR-FTUs huggingface dataset:
Negative regulation of TLR signaling in myeloid cells—implications for autoimmune diseases

Toll‐like receptors (TLR) are transmembrane pattern recognition receptors that recognize microbial ligands and signal for production of inflammatory cytokines and type I interferon in macrophages and dendritic cells (DC). Whereas TLR‐induced inflammatory mediators are required for pathogen clearance, many are toxic to the host and can cause pathological inflammation when over‐produced. This is demonstrated by the role of TLR‐induced cytokines in autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. Because of the potent effects of TLR‐induced cytokines, we have diverse mechanisms to dampen TLR signaling. Here, we highlight three pathways that participate in inhibition of TLR responses in macrophages and DC, and their implications in autoimmunity; A20, encoded by the TNFAIP3 gene, Lyp encoded by the PTPN22 gene, and the BCAP/PI3K pathway. We present new findings that Lyp promotes TLR responses in primary human monocytes and that the autoimmunity risk Lyp620W variant is more effective at promoting TLR‐induced interleukin‐6 than the non‐risk Lyp620R protein. This suggests that Lyp serves to downregulate a TLR inhibitory pathway in monocytes, and we propose that Lyp inhibits the TREM2/DAP12 inhibitory pathway. Overall, these pathways demonstrate distinct mechanisms of negative regulation of TLR responses, and all impact autoimmune disease pathogenesis and treatment.
The Cigarette, Risk, and American Culture

On Saturday, January 11, 1964, Surgeon General Luther Terry stepped to the podium of the State Department auditorium to begin a nationally televised press conference. Seated directly behind him were ten eminent physicians and scien tists, the members of his Advisory Committee on Smoking and Health. This group of individuals had met regularly over the last eighteen months to evaluate the evidence about the risks of cigarette smoking. Although the results of this investigation had been held top secret, signs prohibiting smoking hung in the auditorium, a harbinger of the coming announcement. In the outside corridors, members of the press puffed away. Reporters were offered copies of the report in the closed auditorium for an hour before the press conference. At the conclusion of the session, they rushed to phones to call in the story. The next day, the report received front-page coverage throughout the country. For the 70 million regular smokers in the United States, the report constituted bad news. It found that among men who smoke cigarettes the death rate from cancer of the lung was 1,000 percent higher than among nonsmokers. The report also cited chronic bronchitis and emphysema to be of far greater incidence among smokers. Addition ally, the committee found that the incidence of coronary artery disease, the leading cause of death in the United States, was 70
Appropriate healthcare technologies for low resource settings: use of m-technology in rural health care and education

The use of m-phones is rapidly spreading worldwide, reaching also the most isolated and socially marginalised communities. The opportunities it offers in public health are increasingly described in literature, however its potential in the training of, and support to local health workers has been only partially explored, less so its use in combination with innovative active learning approaches. The MobileDiagnosis experience shows that m-phones may be considered as an appropriate technology to educate, empower and mentoring local healthworkers, enabling team-work and collaboration among peers, contributing to improved health care quality locally, and making knowledge and experience widely accessible and shared globally. The m-phone is just a tool, its potential for the Common Good depends on the use we make of it, on our imagination and creativity. Our approach and experience is but a very small attempt to use it as a tool of liberating education.
MicroRNA‐140‐5p impairs zebrafish embryonic bone development via targeting BMP‐2

MicroRNA‐140‐5p (miRNA‐140‐5p) is important for embryonic bone development. In this study, we found that miRNA‐140‐5p and its binding site in the 3′UTR of bone morphogenetic protein 2 (BMP‐2) are highly conserved among vertebrates, and miRNA‐140‐5p negatively regulates both zebrafish and human BMP‐2 genes. Microinjection of miRNA‐140‐5p or BMP‐2b morpholino into zebrafish embryos led to a similar phenotype, including shortened tails, curved trunks, and defects in cranial cartilage. Moreover, miRNA‐140‐5p injection induced zebrafish embryo malformation that could be significantly rescued by microinjection of BMP‐2 mRNA. In conclusion, our results indicated that miRNA‐140‐5p regulates zebrafish embryonic bone development via targeting BMP‐2.
Psychosocial issue among office workers: a case study at a Public Higher Education Institution in Malaysia

Self-awareness of workers’ own health status had been proven can prevent work-related harm and injury and also mental health problems. Both mental and physical health improvements (physical and psychosocial factors) should be the main focused in any research. Workload and work-related stress are the examples of psychosocial factors that may exist in each organization. A case study related to safety and health was conducted among staff at Human Resources Management Division (HRMD) at a public higher education institution (Institut Pengajian Tinggi Awam -IPTA) in Malaysia. Total numbers of 22 staff were employed. However, only 21 staffs were participated in this study which contributed to about 95% of the response rate. A set of self-administered questionnaires which consist of questions on socio demographics information, questions on working hour, questions on workload and also questions on work-related stress were used as the study instruments. Result shows that office workers in HRMD, work in long hours in a week to keep up with workload. The availability of supplies, equipment and materials to do the work however, helps the workers to manage their works in a proper way. The relationship of inter-staff also found in a good condition. This study will be useful for other researcher to conduct a psychosocial study among office workers in a bigger sample size. This finding also can be as a guidance to manage workload and work-related stress in workplace.
Nipah virus matrix protein: expert hacker of cellular machines

Nipah virus (NiV, Henipavirus) is a highly lethal emergent zoonotic paramyxovirus responsible for repeated human outbreaks of encephalitis in South East Asia. There are no approved vaccines or treatments, thus improved understanding of NiV biology is imperative. NiV matrix protein recruits a plethora of cellular machinery to scaffold and coordinate virion budding. Intriguingly, matrix also hijacks cellular trafficking and ubiquitination pathways to facilitate transient nuclear localization. While the biological significance of matrix nuclear localization for an otherwise cytoplasmic virus remains enigmatic, the molecular details have begun to be characterized, and are conserved among matrix proteins from divergent paramyxoviruses. Matrix protein appropriation of cellular machinery will be discussed in terms of its early nuclear targeting and later role in virion assembly.
Initial steps of the pathogenesis of the infection caused by Streptococcus suis: fighting against nonspecific defenses

Interactions between a bacterial pathogen and its potentially susceptible host are initiated with the colonization step. During respiratory/oral infection, the pathogens must compete with the normal microflora, resist defense mechanisms of the local mucosal immunity, and finally reach, adhere, and breach the mucosal epithelial cell barrier in order to induce invasive disease. This is the case during infection by the swine and zoonotic pathogen Streptococcus suis, which is able to counteract mucosal barriers to induce severe meningitis and sepsis in swine and in humans. The initial steps of the pathogenesis of S. suis infection has been a neglected area of research, overshadowed by studies on the systemic and central nervous phases of the disease. In this Review article, we provide for the first time, an exclusive focus on S. suis colonization and the potential mechanisms involved in S. suis establishment at the mucosa, as well as the mechanisms regulating mucosal barrier breakdown. The role of mucosal immunity is also addressed. Finally, we demystify the extensive list of putative adhesins and virulence factors reported to be involved in the initial steps of pathogenesis by S. suis.
N‐Glycosylation is essential for the secretion of extracellular superoxide dismutase

Extracellular superoxide dismutase (EC‐SOD or SOD3) protects against various oxidative stress‐related diseases by scavenging reactive superoxides in the extracellular space. It is the only SOD isozyme that is secreted and glycosylated (at asparagine 89). However, the physiological roles of its glycosylation are poorly understood. In this study, we found that the glycosylation site on EC‐SOD is well conserved and that a glycosylation‐deficient EC‐SOD mutant retains its enzymatic activity, but is not secreted. This impairment in secretion may, in part, be due to the ability of the mutants to form unusual higher order oligomers. Our findings reveal that the glycan modification is a key regulator of EC‐SOD secretion and contributes to the understanding of the roles of glycans in EC‐SOD‐related diseases.
Biyokimyasal Özellikleri ile L - Karnitin

OZET Karnitin, organizmada yaglarin enerjiye donusumunu saglayan bir maddedir. Karaciger ve bobrekte sentezlenerek, iskelet kaslari, kalp, beyin gibi dokularda depolanir. Genellikle canli organizma kendisine yetecek oranda karnitini sentezleyebilir. Ancak bazi organizmalarda ise bu sentez miktari ya da kullanilabilecek oranda karnitin dokulara transferi yeterli olamayabilir. Karnitin, oksidatif stresi azaltan bir faktor olarak degisik sartlarda tedavi edici bir faktor olarak etkindir ve doktor kontrollu olmak uzere geleneksel tedavide ilave ajanlar olarak kullanilabilmektedir. Yorgunluk, fiziksel performansin artirilmasi, kalp - damar sisteminin korunmasi gibi farkli amaclarla karnitin kullanimi guvenli ve pozitif etkilere sahip gibi gorunmektedir. Anahtar Kelimeler: Karnitin, biyokimyasal fonksiyon, medikal kullanim ABSTRACT L - CARNITINE AND BIOCHEMICAL CHARACTERISTICS Carnitine is a nutrient that helps the body turn fat into energy. It is produced by the body in the liver and kidneys and stored in the skeletal muscles, heart and brain. Usually, the body can make all the carnitine it needs. However, some organisms may be deficient in carnitine because their bodies cannot make enough carnitine or transport it into tissues so it can be used. Carnitine has been proposed as a treatment for many conditions because it helps reduce oxidative stress. Some of the conditions carnitine may help treat are serious, and it should be take the supplement under the supervision of doctor, as an adjunct therapy to conventional medicine. For other conditions, such as fatigue or improving exercise performance, protection of heart diseases, carnitine appears safe and seems to have positive effects. Key Words: Carnitine, biochemical function, medical usage
NMR study of the antifreeze activities of active and inactive isoforms of a type III antifreeze protein

The quaternary‐amino‐ethyl 1 (QAE1) isoforms of type III antifreeze proteins (AFPs) prevent the growth of ice crystals within organisms living in polar regions. We determined the antifreeze activity of wild‐type and mutant constructs of the Japanese notched‐fin eelpout (Zoarces elongates Kner) AFP8 (nfeAFP8) and characterized the structural and dynamics properties of their ice‐binding surface using NMR. We found that the three constructs containing the V20G mutation were incapable of stopping the growth of ice crystals and exhibited structural changes, as well as increased conformational flexibility, in the first 310 helix (residues 18–22) of the sequence. Our results suggest that the inactive nfeAFP8s are incapable of anchoring water molecules due to the unusual and flexible backbone conformation of their primary prism plane‐binding surface.
Composition and immunological significance of the upper respiratory tract microbiota

The intestinal microbiota is essential for nutrient acquisition, immune development, and exclusion of invading pathogens. The upper respiratory tract (URT) microbiota is less well studied and does not appear to abide by many of the paradigms of the gastrointestinal tract. Decades of carriage studies in children have demonstrated that microbe–microbe competition and collusion occurs in the URT. Whether colonization with common pathogens (e.g., Staphylococcus aureus and Streptococcus pneumoniae) alters immune development or susceptibility to respiratory conditions is just beginning to be understood. Herein, we discuss the biogeography of the URT microbiota, the succession and evolution of the microbiota through the life course, and discuss the evidence for microbe–microbe interactions in colonization and infection.
Promoting Adherence to Medical Treatment in Chronic Childhood Illness : Concepts, Methods, and Interventions

Contents: Part I:Overview and Introduction. K.A. Riekert, D. Drotar, Adherence to Medical Treatment in Pediatric Chronic Illness: Critical Issues and Answered Questions. Part II:Historical Foundations. J.A. Trostle, The Ideology of Adherence: An Anthropological and Historical Perspective. B.M. Korsch, Pediatric Compliance From a Patient/Family Perspective. Part III:Conceptual Models of Adherence and Compliance for Clinical Care and Research. T.L. Creer, Self-Management and the Control of Chronic Pediatric Illness. L.J. Bauman, A Patient-Centered Approach to Adherence: Risks for Nonadherence. Part IV:Measurement Issues. D.M. Matsui, Children's Adherence to Medication Treatment. B.G. Bender, H. Milgrom, C. Rand, F.S. Wamboldt, Measurement of Treatment Nonadherence in Children With Asthma. A.M. Delamater, Critical Issues in the Assessment of Regimen Adherence in Children With Diabetes. Part V:Influences on Adherence to Treatment in Childhood Chronic Illness. N. Walders, C. Nobile, D. Drotar, Promoting Adherence to Treatment in Childhood Chronic Illness: Challenges in a Managed Care Environment. M.R. DiMatteo, Practitioner-Family-Patient Communication in Pediatric Adherence: Implications for Research and Clinical Practice. C.E. Ievers-Landis, D. Drotar, Parental and Child Knowledge of the Treatment Regimen for Childhood Chronic Illnesses: Related Factors and Adherence to Treatment. Part VI:Impact of Adherence to Treatment on Child Health Outcomes and Research Findings. J.W. Varni, J.R. Jacobs, M. Seid, Adherence to Treatment as a Predictor of Health-Related Quality of Life. S.B. Johnson, Compliance Behavior in Clinical Trials: Error or Opportunity? Part VII:Interventions to Promote Adherence to Treatment in Childhood Chronic Illness. M.A. Rapoff, Facilitating Adherence to Medical Regimens for Pediatric Rheumatic Diseases: Primary, Secondary, and Tertiary Prevention. B.J. Anderson, J. Brackett, J. Ho, L.M. B. Laffel, An Intervention to Promote Family Teamwork in Diabetes Management Tasks: Relationships Among Parental Involvement, Adherence to Blood Glucose Monitoring, and Glycemic Control in Young Adolescents With Type 1 Diabetes. T. Wysocki, P. Greco, M. Harris, N.H. White, Behavioral Family Systems Therapy for Adolescents With Diabetes. A.L. Quittner, D. Drotar, D. Seidner, N. Slocum, J. Jacobsen, Adherence to Medical Treatments in Adolescents With Cystic Fibrosis: The Development and Evaluation of Family-Based Interventions. L.J. Stark, Adherence to Diet in Chronic Conditions: The Example of Cystic Fibrosis. D.E. Sandberg, T. Mazur, R.A. Hazen, D.E. Alliger, J. Buchlis, M.H. MacGillivray, Promoting Adherence to Growth Hormone Among Children With Growth Failure. Part VIII:Summary of Recommendations to Enhance Practice, Research, and Training Concerning Adherence to Treatment in Childhood Chronic Illness. D. Drotar, K.A. Riekert, E. Burgess, R. Levi, C. Nobile, A. Seja, N. Walders, Adherence to Treatment in Childhood Chronic Illness: Issues and Recommendations to Enhance Practice, Research, and Training.
Dynamic sitting to prevent pressure ulcers in spinal cord injured

At present, clinical interventions and research efforts are not fully successful in defining the risk of pressure ulcer development and as such in eventually preventing pressure ulcers. As a result, the prevalence and incidence values of pressure ulcers remain unacceptably high. It is common sense that healthy subjects do not develop pressure ulcers due to a dynamic variation in sitting posture. This dynamic sitting behavior can be identified and used as a reference values for the optimal sitting behavior of individuals that use a wheelchair and are at risk of developing pressure ulcer. The main research question that has been answered in this thesis is if imposing dynamic sitting behavior by means of the Dynasit chair in Spinal Cord Injured individuals results in elevated tissue viability? In order to define a reference values for the sitting behavior of spinal cord injured individuals, an analysis of healthy sitting behavior has been performed. It was found that healthy subjects change their sitting posture at least every eight minutes. To impose this dynamic sitting behavior on spinal cord injured individuals, the Dynasit chair has been developed. The Dynasit chair is an experimental sitting device developed to investigate the effects of different sitting postures, alternating tuberal support and pelvic orientations on the (sub-) cutaneous tissue viability. Two studies on healthy subjects demonstrated the positive effect of actuation with the Dynasit chair on the tissue load. Regarding the main research question of this thesis, a study performed in 10 male spinal cord injured individuals, confirmed the ability of the Dynasit chair to impose dynamic sitting behavior, based on healthy sitting behavior, in spinal cord injured individuals. This imposed dynamic sitting behavior resulted in significant elevation of the (sub-) cutaneous tissue oxygenation. This elevated tissue oxygenation implies that due to the dynamic sitting, the wheelchair user can sit for prolonged periods of time without tissue breakdown.
Frequent Loss of Estrogen Receptor-β Expression in Prostate Cancer

The role of estrogen and its receptors in the etiology and progression of prostate cancer (PC) is poorly understood. In normal and malignant human prostate, estrogen receptor-α is expressed only in the stroma, whereas estrogen receptor-β (ERβ) is present in both normal stroma and epithelium. Because loss of ERβ expression is associated with prostate hyperplasia in ERβ-null mice, this study determined patterns of ERβ expression in normal, hyperplastic, and malignant human prostate and associations with clinical outcome. Five normal prostates from organ donors and 159 radical prostatectomy specimens from patients with clinically localized PC were assessed for ERβ expression using immunohistochemistry. ERβ-positivity was defined as ≥5% of cells demonstrating nuclear immunoreactivity. All of the five normal prostates showed strong ERβ-nuclear staining in >95% of the epithelium and 35% of the stromal cells. The number of ERβ-positive cases declined to 24.2% (38/157) in hyperplasia adjacent to carcinoma and 11.3% (18/159) in PCs. ERβ-positivity was related to decreased relapse-free survival (log-rank P = 0.04). Thus, loss of ERβ expression is associated with progression from normal prostate epithelium to PC, whereas those cancers that retained ERβ expression were associated with a higher rate of recurrence. These data identify the need to further investigate the potential role of ERβ in the regulation of prostate epithelial cell proliferation and the functional consequences of decreased ERβ expression in the evolution of PC.
Modulation of Escherichia coli serine acetyltransferase catalytic activity in the cysteine synthase complex

In bacteria and plants, serine acetyltransferase (CysE) and O‐acetylserine sulfhydrylase‐A sulfhydrylase (CysK) collaborate to synthesize l‐Cys from l‐Ser. CysE and CysK bind one another with high affinity to form the cysteine synthase complex (CSC). We demonstrate that bacterial CysE is activated when bound to CysK. CysE activation results from the release of substrate inhibition, with the Ki for l‐Ser increasing from 4 mm for free CysE to 16 mm for the CSC. Feedback inhibition of CysE by l‐Cys is also relieved in the bacterial CSC. These findings suggest that the CysE active site is allosterically altered by CysK to alleviate substrate and feedback inhibition in the context of the CSC.
Management of Antiviral Induced Anemia in HCV Infected Patients

H C virus (HCV) infection affects more than 170 million people worldwide(1, 2). Approximately 80% of patients with acute infection will subsequently develop chronic disease, and an estimated 20% to 30% will develop cirrhosis and hepatocellular carcinoma(3). The maost effective therapeutic regimen for chronic hepatitis C is the combination of pegylated interferon alpha and ribavirin, which yields a sustained virologic response (SVR) in up to 56% of patients(4, 5). However, combination therapy is also associated with significant adverse events and is contraindicated in certain patient populations. Development of side effects, particularly hematologic ones, may result in suboptimal dosing or discontinuation of therapy that can reduce the likelihood of SVR.
Chromatin accessibility and guide sequence secondary structure affect CRISPR‐Cas9 gene editing efficiency

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)‐associated protein 9 (CRISPR‐Cas9) systems have emerged as the method of choice for genome editing, but large variations in on‐target efficiencies continue to limit their applicability. Here, we investigate the effect of chromatin accessibility on Cas9‐mediated gene editing efficiency for 20 gRNAs targeting 10 genomic loci in HEK293T cells using both SpCas9 and the eSpCas9(1.1) variant. Our study indicates that gene editing is more efficient in euchromatin than in heterochromatin, and we validate this finding in HeLa cells and in human fibroblasts. Furthermore, we investigate the gRNA sequence determinants of CRISPR‐Cas9 activity using a surrogate reporter system and find that the efficiency of Cas9‐mediated gene editing is dependent on guide sequence secondary structure formation. This knowledge can aid in the further improvement of tools for gRNA design.
The effect of slightly warm temperature on work performance and comfort in open-plan offices - a laboratory study.

The aim of the study was to determine the effect of a temperature of 29°C on performance in tasks involving different cognitive demands and to assess the effect on perceived performance, subjective workload, thermal comfort, perceived working conditions, cognitive fatigue, and somatic symptoms in a laboratory with realistic office environment. A comparison was made with a temperature of 23°C. Performance was measured on the basis of six different tasks that reflect different stages of cognitive performance. Thirty-three students participated in the experiment. The exposure time was 3.5 h in both thermal conditions. Performance was negatively affected by slightly warm temperature in the N-back working memory task. Temperature had no effect on performance in other tasks focusing on psychomotor, working memory, attention, or long-term memory capabilities. Temperature had no effect on perceived performance. However, slightly warm temperature caused concentration difficulties. Throat symptoms were found to increase over time at 29°C, but no temporal change was seen at 23°C. No effect of temperature on other symptoms was found. As expected, the differences in thermal comfort were significant. Women perceived a temperature of 23°C colder than men.