Miracle-dz/UniFAR-FTUs huggingface dataset:
Design of an Escherichia coli Expressed HIV-1 gp120 Fragment Immunogen That Binds to b12 and Induces Broad and Potent Neutralizing Antibodies

Background: b12 is a broadly neutralizing human antibody that targets the conserved receptor binding site on HIV-1 gp120. Results: Designed gp120 fragment immunogens (b121a/b122a) targeting the b12 binding site were tested in rabbit immunization studies. Conclusion: Priming with b122a and boosting with gp120 elicited broadly neutralizing sera. Significance: gp120 fragment immunogens can elicit broadly neutralizing sera in small animals. b12, one of the few broadly neutralizing antibodies against HIV-1, binds to the CD4 binding site (CD4bs) on the gp120 subunit of HIV-1 Env. Two small fragments of HIV-1 gp120, b121a and b122a, which display about 70% of the b12 epitope and include solubility-enhancing mutations, were designed. Bacterially expressed b121a/b122a were partially folded and could bind b12 but not the CD4bs-directed non-neutralizing antibody b6. Sera from rabbits primed with b121a or b122a protein fragments and boosted with full-length gp120 showed broad neutralizing activity in a TZM-bl assay against a 16-virus panel that included nine Tier 2 and 3 viruses as well as in a five-virus panel previously designed to screen for broad neutralization. Using a mean IC50 cut-off of 50, sera from control rabbits immunized with gp120 alone neutralized only one virus of the 14 non-Tier 1 viruses tested (7%), whereas sera from b121a- and b122a-immunized rabbits neutralized seven (50%) and twelve (86%) viruses, respectively. Serum depletion studies confirmed that neutralization was gp120-directed and that sera from animals immunized with gp120 contained lower amounts of CD4bs-directed antibodies than corresponding sera from animals immunized with b121a/b122a. Competition binding assays with b12 also showed that b121a/2a sera contained significantly higher amounts of antibodies directed toward the CD4 binding site than the gp120 sera. The data demonstrate that it is possible to elicit broadly neutralizing sera against HIV-1 in small animals.
The Viroporin Activity of the Minor Structural Proteins VP2 and VP3 Is Required for SV40 Propagation*

Background: Viruses must interact with membranes to access host cell machinery for replication. Results: SV40 VP2 and VP3 are shown to form pores in membranes and pore formation is required for viral propagation. Conclusion: VP2 and VP3 act as viral-encoded membrane pore forming proteins or viroporins. Significance: These versatile proteins have evolved to function as both soluble and membrane proteins to support viral propagation. For nonenveloped viruses such as Simian Virus 40, the mechanism used to translocate viral components across membranes is poorly understood. Previous results indicated that the minor structural proteins, VP2 and VP3, might act as membrane proteins during infection. Here, purified VP2 and VP3 were found to form pores in host cell membranes. To identify possible membrane domains, individual hydrophobic domains from VP2 and VP3 were expressed in a model protein and tested for their ability to integrate into membranes. Several domains from the late proteins supported endoplasmic reticulum membrane insertion as transmembrane domains. Mutations in VP2 and VP3 were engineered that inhibited membrane insertion and pore formation. When these mutations were introduced into the viral genome, viral propagation was inhibited. This comprehensive approach revealed that the viroporin activity of VP2 and VP3 was inhibited by targeted disruptions of individual hydrophobic domains and the loss of membrane disruption activity impaired viral infection.
Cyclopia (synophthalmia) in Smith–Lemli–Opitz syndrome: First reported case and consideration of mechanism

Here we present a 24‐week fetus with Smith–Lemli–Opitz syndrome (SLOS), alobar holoprosencephaly (HPE) and cyclopia (synophthalmia). Following birth, we suspected SLOS in this fetus due to the additional findings of ambiguous genitalia and bilateral 2–3 toe syndactyly. The diagnosis of SLOS was confirmed by finding an elevated amniotic fluid 7‐dehydrocholesterol level (9,890 ng/ml; normal range = 3–9 ng/ml), and molecularly by detecting two different mutations in the DHCR7 gene, the gene causing SLOS. The first mutation was an IVS8‐1G>T change and the second was a deletion of exons 3 and 4; this latter mutation has not been reported previously. The mother carries the deletion, while the father carries the splice‐site mutation. Also of note, the father has an abnormally low total plasma cholesterol level (104–109 mg/dl). This is the most severe case of HPE described in any patient with SLOS. We postulate that the HPE in this case resulted from severe impairment of Sonic Hedgehog signaling secondary to abnormal cholesterol metabolism; however, the unique combination of mutations in the fetus functionally appears to be no different from other homozygous null mutations reported in DHCR7. Therefore, there must be other yet to be identified factors that contributed to the severity of HPE in SLOS. © 2010 Wiley‐Liss, Inc.
Cocoa Intake, Blood Pressure, and Cardiovascular Mortality

Background: Small, short-term, intervention studies indicate that cocoa-containing foods improve endothelial function and reduce blood pressure. We studied whether habitual cocoa intake was cross-sectionally related to blood pressure and prospectively related with cardiovascular mortality. Methods: Data used were of 470 elderly men participating in the Zutphen Elderly Study and free of chronic diseases at baseline. Blood pressure was measured at baseline and 5 years later, and causes of death were ascertained during 15 years of follow-up. Habitual food consumption was assessed by the cross-check dietary history method in 1985, 1990, and 1995. Cocoa intake was estimated from the consumption of cocoa-containing foods. Results: One third of the men did not use cocoa at baseline. The median cocoa intake among users was 2.11 g/d. After adjustment, the mean systolic blood pressure in the highest tertile of cocoa intake was 3.7 mm Hg lower (95% confidence interval [CI], �7.1 to �0.3 mm Hg;P=.03 for trend) and the mean diastolic blood pressure was 2.1 mm Hg lower (95% CI, �4.0 to �0.2 mm Hg; P=.03 for trend) compared with the lowest tertile. During followup, 314 men died, 152 of cardiovascular diseases. Compared with the lowest tertile of cocoa intake, the adjusted relative risk for men in the highest tertile was 0.50 (95% CI, 0.32-0.78; P=.004 for trend) for cardiovascular mortality and 0.53 (95% CI, 0.39-0.72; P.001) for all-cause mortality. Conclusion: In a cohort of elderly men, cocoa intake is inversely associated with blood pressure and 15-year cardiovascular and all-cause mortality. Arch Intern Med. 2006;166:411-417
Impacts of unit-level nurse practice environment and burnout on nurse-reported outcomes: a multilevel modelling approach.

AIM To investigate impacts of practice environment factors and burnout at the nursing unit level on job outcomes and nurse-assessed quality of care in acute hospital nurses. BACKGROUND Prior research has consistently demonstrated correlations between nurse practice environments and nurses' job satisfaction and health at work, but somewhat less evidence connects practice environments with patient outcomes. The relationship has also been more extensively documented using hospital-wide measures of environments as opposed to measures at the nursing unit level. DESIGN Survey. METHOD Data from a sample of 546 staff nurses from 42 units in four Belgian hospitals were analysed using a two-level (nursing unit and nurse) random intercept model. Linear and generalised linear mixed effects models were fitted including nurse practice environment dimensions measured with the Revised Nursing Work Index and burnout dimensions of the Maslach Burnout Inventory as independent variables and job outcome and nurse-assessed quality of care variables as dependent variables. RESULTS Significant unit-level associations were found between nurse practice environment and burnout dimensions and job satisfaction, turnover intentions and nurse-reported quality of care. Emotional exhaustion is a predictor of job satisfaction, nurse turnover intentions and assessed quality of care as well besides various nurse work practice environment dimensions. Nurses 'ratings of unit-level management and hospital-level management and organisational support had effects in opposite directions on assessments of quality of care at the unit; this suggests that nurses' perceptions of conditions on their nursing units relative to their perceptions of their institutions at large are potentially influential in their overall job experience. CONCLUSION Nursing unit variation of the nurse practice environment and feelings of burnout predicts job outcome and nurse-reported quality of care variables. RELEVANCE TO CLINICAL PRACTICE The team and environmental contexts of nursing practice play critical roles in the recruitment and retention of nurses, and as well as in the quality of care delivered. Widespread burnout as a nursing unit characteristic, reflecting a response to chronic organisational stressors, merits special attention from staff nurses, physicians, managers and leaders.
The stress in nursing students scale (SINS): principal components analysis of longitudinal data from Hong Kong.

The aim of this study is to investigate the psychometric structure of the Stress in Nursing Students Scale (SINS) using a cohort of nursing students in Hong Kong who were tested on two occasions and to compare the structure obtained with a previously derived structure in a separate and culturally contrasting sample. © 2010 Blackwell Publishing Ltd
Health literacy, self-reported status and health promoting behaviours for adolescents in Taiwan.

AIM AND OBJECTIVE The objective of this study was to analyse the associations between health literacy, health status and health-promoting behaviours among Taiwan adolescents. BACKGROUND Limited health literacy is associated with poor health outcomes such as low use of preventive services, poor self-reported health conditions and absence of health-promoting behaviours in adults. However, these factors have not been analysed in adolescents. The associations between health literacy and health outcome in adolescents provide helpful insights in conducting health education programmes for health professionals. DESIGN A cross-sectional survey. METHODS The survey analysed a purposive sample of 1601 senior/vocational high school students from six counties in Taiwan. Data for health literacy and health-promoting behaviours were collected by the Chinese version (short form) of the Test of Functional Health Literacy in Adolescents (c-sTOFHLAd) and health-promoting behaviour scale with subscales for the following health-promoting behaviours: nutrition, exercise, stress management, interpersonal relations, health responsibility and self-actualisation. RESULTS Adolescents with low health literacy were less likely to perceive good health status [adjusted odd ratio, (AOR) = 0·59, 95%CI = 0·41-0·86] and less likely to exhibit health-promoting behaviours (AOR = 0·58, 95%CI = 0·39-0·86) than those with high health literacy were, especially in nutrition (AOR = 0·62, 95%CI = 0·43-0·89) and interpersonal relations (AOR = 0·61, 95%CI = 0·43-0·87) subscales. Adolescents with high and low health literacy did not significantly differ in the following health-promoting behaviours: exercise, stress management, health responsibility and self-actualisation. CONCLUSION Health literacy is vital for promoting health in adolescents, especially in the domains of nutrition and interpersonal relations. RELEVANCE TO CLINICAL PRACTICE Health professionals should conduct health literacy assessments for adolescents prior to designing health education programmes for those with low health literacy to develop health literacy skills as to perform health promoting behaviours.
Endothelial Nitric-oxide Synthase Activation Generates an Inducible Nitric-oxide Synthase-like Output of Nitric Oxide in Inflamed Endothelium*

Background: In healthy endothelium, agonist-induced eNOS activation results in transient, calcium-dependent NO production. Results: In inflamed endothelium, bradykinin stimulates prolonged eNOS-derived NO that depends on Gαi, MEK1/2, and JNK, resulting in reduced migration. Conclusion: eNOS activation is mediated differently in normal and inflamed endothelium, resulting in divergent NO production and effects. Significance: High eNOS-derived NO may impair angiogenesis and wound healing in inflammation. High levels of NO generated in the vasculature under inflammatory conditions are usually attributed to inducible nitric-oxide synthase (iNOS), but the role of the constitutively expressed endothelial NOS (eNOS) is unclear. In normal human lung microvascular endothelial cells (HLMVEC), bradykinin (BK) activates kinin B2 receptor (B2R) signaling that results in Ca2+-dependent activation of eNOS and transient NO. In inflamed HLMVEC (pretreated with interleukin-1β and interferon-γ), we found enhanced binding of eNOS to calcium-calmodulin at basal Ca2+ levels, thereby increasing its basal activity that was dependent on extracellular l-Arg. Furthermore, B2R stimulation generated prolonged high output eNOS-derived NO that is independent of increased intracellular Ca2+ and is mediated by a novel Gαi-, MEK1/2-, and JNK1/2-dependent pathway. This high output NO stimulated with BK was blocked with a B2R antagonist, eNOS siRNA, or eNOS inhibitor but not iNOS inhibitor. Moreover, B2R-mediated NO production and JNK phosphorylation were inhibited with MEK1/2 and JNK inhibitors or MEK1/2 and JNK1/2 siRNA but not with ERK1/2 inhibitor. BK induced Ca2+-dependent eNOS phosphorylation at Ser1177, Thr495, and Ser114 in cytokine-treated HLMVEC, but these modifications were not dependent on JNK1/2 activation and were not responsible for prolonged NO output. Cytokine treatment did not alter the expression of B2R, Gαq/11, Gαi1,2, JNK, or eNOS. B2R activation in control endothelial cells enhanced migration, but in cytokine-treated HLMVEC it reduced migration. Both responses were NO-dependent. Understanding how JNK regulates prolonged eNOS-derived NO may provide new therapeutic targets for the treatment of disorders involving vascular inflammation.
Goltz syndrome and PORCN: A view from Europe

Goltz syndrome (focal dermal hypoplasia) is an X‐linked dominant, multisystem birth defect with lethality for male embryos. The hypoplastic skin lesions follow Blaschko's lines and often show herniation of subcutaneous fatty tissue. Extracutaneous defects mainly involve the brain, the bones, the teeth, and the eyes. All of these anomalies show a segmental arrangement reflecting functional X‐chromosome mosaicism. The present contribution tells the story how the molecular cause of Goltz syndrome was investigated and found by the group of the geneticist Karl–Heinz Grzeschik from Marburg, Germany. © 2016 Wiley Periodicals, Inc.
Selection of line‐transect methods for estimating the density of group‐living animals: lessons from the primates

We review the four major contemporary methods for estimating density of group‐living animals from line‐transect sampling: perpendicular modelling of group centers, perpendicular modelling of center of measurable individuals, strip transects and animal–observer distance. The efficacy of each method is evaluated to produce a simple selection guide. We review the literature and use field data from the Udzungwa Mountains, Tanzania. The review is relevant to all group‐living animals; however, examples are drawn from the primates. Perpendicular methods have better mathematical justification than non‐perpendicular methods. For perpendicular methods using detection function models, it is preferable to measure group location using center of measurable individuals, as group centers are hard to estimate. The assumptions of detection function models are often broken in poor visibility habitats or with unhabituated animals. Alternatively strip transects may be used where there are reliable data on group spread and/or visibility. Strip transects are also the most practical, along with the animal–observer method; however, the latter lacks mathematical justification. We conclude that there are arguments for continued use of all four methods. In certain situations the use of raw encounter rates may also be considered. The appropriate method is determined by minimizing bias and considering time, resources and field conditions. Am. J. Primatol. 70:452–462, 2008. © 2008 Wiley‐Liss, Inc.
Inducible Interleukin 32 (IL-32) Exerts Extensive Antiviral Function via Selective Stimulation of Interferon λ1 (IFN-λ1)*

Background: Interleukin-32 participates in responses to viral infection, but how virus induces its expression and the mechanisms of its antiviral activities remain unclear. Results: Interleukin-32 selectively stimulates IFN-λ1 via activating distinct regulatory elements in the promoter. Conclusion: Interleukin-32 promotes IFN-λ1-mediated antiviral response. Significance: Interleukin-32 is one immune response factor and plays an important role in the control of viral infection. Interleukin (IL)-32 has been recognized as a proinflammatory cytokine that participates in responses to viral infection. However, little is known about how IL-32 is induced in response to viral infection and the mechanisms of IL-32-mediated antiviral activities. We discovered that IL-32 is elevated by hepatitis B virus (HBV) infection both in vitro and in vivo and that HBV induced IL-32 expression at the level of both transcription and post-transcription. Furthermore, microRNA-29b was found to be a key factor in HBV-regulated IL-32 expression by directly targeting the mRNA 3′-untranslated region of IL-32. Antiviral analysis showed that IL-32 was not sufficient to alter HBV replication in HepG2.2. 15 cells. To mimic the viremic phase of viral infection, freshly isolated peripheral blood mononuclear cells were treated with IL-32γ, the secretory isoform, and the supernatants were used for antiviral assays. Surprisingly, these supernatants exhibited extensive antiviral activity against multiplex viruses besides HBV. Thus, we speculated that the IL-32γ-treated peripheral blood mononuclear cells produced and secreted an unknown antiviral factor. Using antibody neutralization assays, we identified the factor as interferon (IFN)-λ1 and not IFN-α. Further studies indicated that IL-32γ effectively inhibited HBV replication in a hydrodynamic injection mouse model. Clinical data showed that elevated levels of IFN-λ1 both in serum and liver tissue of HBV patients were positively correlated to the increased levels of IL-32. Our results demonstrate that elevated IL-32 levels during viral infection mediate antiviral effects by stimulating the expression of IFN-λ1.
Using peer mentoring for people with spinal cord injury to enhance self-efficacy beliefs and prevent medical complications.

AIMS AND OBJECTIVES Individuals with spinal cord injury/disease are faced with a myriad of psychosocial adjustment challenges. This article describes the implementation of a peer-mentoring programme designed to support this adjustment process for people with SCI/disease and the programme's believed impact on self-efficacy and prevention of medical complications. BACKGROUND With shorter length of stay in acute inpatient rehabilitation after spinal cord injury/disease, peer mentor programmes are becoming an important component to assist with education and community re-integration. DESIGN Quasi-experimental non-controlled pretest/post-test. METHOD Patients with newly acquired spinal cord injury/disease participated in a one-year spinal cord injury peer-mentoring programme. Peer mentors met with their assigned participants regularly during inpatient care and on discharge to track medical complications and assist with adjusting to life after spinal cord injury/disease. RESULTS In all, of 37 mentees enrolled, 24 successfully completed the programme. Sixty-seven per cent showed improved self-efficacy score between the two time points. Medical complications and doctor visits all decreased significantly between 0-6 months and 7-12 months. Our findings indicate that the older an individual is, the lower the likelihood of having a urinary tract infection (p = 0.006). The programme was well received by all mentees who felt they could connect well with their peer mentor. CONCLUSION Peer mentoring in a rehabilitation setting enhances the understanding of challenges that patients and medical staff deal with on a day-to-day basis. Our findings suggest it is important to monitor and educate individuals with spinal cord injury/disease at the acute stage to improve medical outcomes. Caution is advised in the interpretation of these results as they were obtained in a small non-random sample using self-report data. RELEVANCE TO CLINICAL PRACTICE Peer mentors play an increasingly important role in nurse-delivered education in the spinal cord injury/disease population.
Annexin A2 Regulates β1 Integrin Internalization and Intestinal Epithelial Cell Migration*

Background: Intestinal epithelial wound closure requires dynamic regulation/turnover of cell-matrix adhesions. Results: Down-regulation of annexin A2 increases cell-matrix adhesion and delays β1 integrin internalization from the plasma membrane. Conclusion: Annexin A2 promotes wound closure by regulating internalization of β1 integrin in migrating epithelial cells. Significance: This study identifies a novel role of annexin A2 in regulating β1 integrin internalization required for intestinal epithelial cell migration. The gastrointestinal epithelium functions as an important barrier that separates luminal contents from the underlying tissue compartment and is vital in maintaining mucosal homeostasis. Mucosal wounds in inflammatory disorders compromise the critical epithelial barrier. In response to injury, intestinal epithelial cells (IECs) rapidly migrate to reseal wounds. We have previously observed that a membrane-associated, actin binding protein, annexin A2 (AnxA2), is up-regulated in migrating IECs and plays an important role in promoting wound closure. To identify the mechanisms by which AnxA2 promotes IEC movement and wound closure, we used a loss of function approach. AnxA2-specific shRNA was utilized to generate IECs with stable down-regulation of AnxA2. Loss of AnxA2 inhibited IEC migration while promoting enhanced cell-matrix adhesion. These functional effects were associated with increased levels of β1 integrin protein, which is reported to play an important role in mediating the cell-matrix adhesive properties of epithelial cells. Because cell migration requires dynamic turnover of integrin-based adhesions, we tested whether AnxA2 modulates internalization of cell surface β1 integrin required for forward cell movement. Indeed, pulse-chase biotinylation experiments in IECs lacking AnxA2 demonstrated a significant increase in cell surface β1 integrin that was accompanied by decreased β1 integrin internalization and degradation. These findings support an important role of AnxA2 in controlling dynamics of β1 integrin at the cell surface that in turn is required for the active turnover of cell-matrix associations, cell migration, and wound closure.