Miracle-dz/UniFAR-FTUs huggingface dataset:
IS911‐mediated intramolecular transposition is naturally temperature sensitive

It is shown here that the bacterial insertion sequence IS911 exhibits a temperature‐sensitive transposition phenotype. Previous results have demonstrated that elevated levels of the IS911 transposase OrfAB generate significant quantities of a figure‐eight form, created by cleavage and circularization of one of the transposon strands, and of an excised circular form, in which both transposon strands have been circularized. We show here that the level of both types of molecule observed in vivo was greatly reduced at 42°C compared with 37°C. On the other hand, reducing the temperature to 30°C resulted in a significant increase in production. Transposition activity at this temperature was sufficiently high to permit detection in vivo of an excised circular form of a defective single IS911 chromosomal copy when OrfAB is supplied in trans. A similar temperature–activity profile is observed for a cell‐free reaction that uses partially purified OrfAB and generates the figure‐eight form uniquely. Moreover, two point mutants of OrfAB were obtained, which render the reactions partially temperature resistant both in vivo and in vitro. These results suggest that some property of transposase itself is sensitive to elevated temperatures.
Lower genital tract intraepithelial neoplasia in HIV-infected women: guidelines for evaluation and management.

UNLABELLED Human immunodeficiency virus (HIV) and human papillomavirus (HPV) are both sexually transmitted viruses with many risk factors in common. Studies have found that HIV-seropositive women are at least five times as likely to be infected with HPV as seronegative controls. In immunocompromised HIV-seropositive women, the risk of cervical intraepithelial neoplasia (CIN) is almost as high as in women with squamous intraepithelial lesions on their Pap smear. Some studies have shown the false-negative rate of cervical cytology in HIV-seropositive women to be very high, although others have shown it to be comparable with the rate in seronegative controls. However, given the prevalence of CIN in this population, even a "normal" false-negative rate may result in many missed CIN lesions. Among HIV-seropositive women and especially among those who are immunocompromised, CIN is more likely to progress and recur after treatment. Recurrence rates may reach 87 percent 36 months after treatment in markedly immunosuppressed women. Cryotherapy is especially ineffective in these patients. Vulvar condyloma and vulvar intraepithelial neoplasia (VIN) are much more prevalent in HIV-seropositive women and especially in those who are markedly immunosuppressed or who have been immunosuppressed for a prolonged period of time. It is recommended that all HIV-seropositive women undergo periodic evaluation at intervals no less than every 6 months. Immunocompromised women should be followed with cytology and colposcopy of the cervix and vulva, although those with normal immune systems may be followed with cytology alone. Because the rates of recurrence and progression are so high after treatment of these women, they should be followed with colposcopy and cytology every 6 months. New approaches to treatment need to be explored in this population. TARGET AUDIENCE Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES After completion of this article, the reader will understand the association between the immune suppression of HIV and HPV-related diseases, be familiar with the treatment options for the HIV-seropositive woman with cervical intraepithelial neoplasia (CIN), understand the natural history of CIN in the patient with HIV-seropositivity, and become aware of the appropriate surveillance of the HIV-seropositive woman treated for CIN.
Accounting analyses of momentum and contrarian strategies in emerging markets *

Abstract We analyse the momentum and contrarian effects of stock markets in Brazil, Russia, India, China and South Africa (BRICS) using accounting data. The five markets show different characteristics with the Indian market having the strongest momentum effect. Stock markets in China and Brazil show significant short-term contrarian profit and intermediate to long-term momentum profit while South Africa shows short-term momentum effect and intermediate to long-term contrarian effect. The Russian stock market reveals largely insignificant momentum portfolio returns. We also find evidence that the contrarian profits in South Africa and China are caused by relatively high loser returns while positive momentum profit in India results from relatively high winner returns.
Regulation of organization and function of microtubules by the mitogen‐activated protein kinase cascade during plant cytokinesis

Cytokinesis in eukaryotes involves specific arrays of microtubules (MTs), which are known as the central spindle in animals, the anaphase spindle in yeasts, and the phragmoplast in plants. In plants, a mitogen‐activated protein kinase (MAPK) cascade stimulates the turnover of phragmoplast MTs, which allows the expansion of the phragmoplast that is essential for cytokinesis including the formation of cell plates. A prerequisite for activation of this cascade is the interaction between mitotic kinesin NACK1 in tobacco (HINKEL in Arabidopsis) and MAPK kinase kinase NPK1 (ANP1, 2, 3 in Arabidopsis). Other members of this cascade are NQK1 MAPK kinase and NRK1/NTF6 MAPK in tobacco and the respective orthologs in Arabidopsis. All the components in the pathway (designated the NACK‐PQR pathway) concentrate at the midzone of the phragmoplast in plant cells during cytokinesis. Downstream MAPKs in both plant species phosphorylate microtubule‐associated protein 65 (MAP65). Interestingly, activities of components in the NACK‐PQR pathway are downregulated by depolymerization of MTs. In the present review, we summarize current views on the mechanisms involved in activating the kinase cascade, a role of MAP65 phosphorylation by MAPK during cytokinesis, and the feedback mechanism for regulating inactivation of the kinase cascade. © 2012 Wiley Periodicals, Inc
Stress-enhanced fear learning in rats is resistant to the effects of immediate massed extinction

Enhanced fear learning occurs subsequent to traumatic or stressful events and is a persistent challenge to the treatment of post-traumatic stress disorder (PTSD). Facilitation of learning produced by prior stress can elicit an exaggerated fear response to a minimally aversive event or stimulus. Stress-enhanced fear learning (SEFL) is a rat model of PTSD; rats previously exposed to the SEFL 15 electrical shocks procedure exhibit several behavioral responses similar to those seen in patients with PTSD. However, past reports found that SEFL is not mitigated by extinction (a model of exposure therapy) when the spaced extinction began 24 h after stress. Recent studies found that extinction from 10 min to 1 h subsequent to fear conditioning “erased” learning, whereas later extinction, occurring from 24 to 72 h after conditioning did not. Other studies indicate that massed extinction is more effective than spaced procedures. Therefore, we examined the time-dependent nature of extinction on the stress-induced enhancement of fear learning using a massed trial's procedure. Experimental rats received 15 foot shocks and were given either no extinction or massed extinction 10 min or 72 h later. Our present data indicate that SEFL, following traumatic stress, is resistant to immediate massed extinction. Experimental rats showed exaggerated new fear learning regardless of when extinction training occurred. Thus, post-traumatic reactivity such as SEFL does not seem responsive to extinction treatments.
Defining the Importance of Phosphatidylserine Synthase-1 (PSS1)

Phosphatidylserine (PS) is a quantitatively minor, but physiologically important, phospholipid in mammalian cells. PS is synthesized by two distinct base-exchange enzymes, PS synthase-1 (PSS1) and PS synthase-2 (PSS2), that are encoded by different genes. PSS1 exchanges serine for choline of phosphatidylcholine, whereas PSS2 exchanges ethanolamine of phosphatidylethanolamine for serine. We previously generated mice lacking PSS2 (Bergo, M. O., Gavino, B. J., Steenbergen, R., Sturbois, B., Parlow, A. F., Sanan, D. A., Skarnes, W. C., Vance, J. E., and Young, S. G. (2002) J. Biol. Chem. 277, 47701–47708) and found that PSS2 is not required for mouse viability. We have now generated PSS1-deficient mice. In light of the markedly impaired survival of Chinese hamster ovary cells lacking PSS1 we were surprised that PSS1-deficient mice were viable, fertile, and had a normal life span. Total serine-exchange activity (contributed by PSS1 and PSS2) in tissues of Pss1–/– mice was reduced by up to 85%, but except in liver, the PS content was unaltered. Despite the presumed importance of PS in the nervous system, the rate of axonal extension of PSS1-deficient neurons was normal. Intercrosses of Pss1–/– mice and Pss2–/– mice yielded mice with three disrupted Pss alleles but no double knockout mice. In Pss1–/–/Pss2–/– and Pss1–/–/Pss2–/– mice, serine-exchange activity was reduced by 65–91%, and the tissue content of PS and phosphatidylethanolamine was also decreased. We conclude that (i) elimination of either PSS1 or PSS2, but not both, is compatible with mouse viability, (ii) mice can tolerate as little as 10% of normal total serine-exchange activity, and (iii) mice survive with significantly reduced PS and phosphatidylethanolamine content.
Purification and characterization of an exo-beta-1,4-glucanase from Ruminococcus flavefaciens FD-1

An exo-beta-1,4-glucanase (Exo A) from Ruminococcus flavefaciens FD-1 was purified to homogeneity and characterized. Enzyme activity was monitored during purification by using the substrate p-nitrophenyl-beta-D-cellobioside (NPC). Over 85% of the NPC activity was found to be extracellular once the filter paper was degraded (7 days). Culture supernatant was harvested, and the protein was concentrated by ultrafiltration. The retentate (greater than or equal to 300,000 Mr), containing most of the activity against NPC, was then fractionated with a TSK DEAE-5PW column. This yielded a sharp major peak of NPC enzyme activity, followed by a broader, less active area that appeared to contain at least six minor peaks of lower enzymatic activity. Further purification was achieved by chromatography with a hydroxylapatite column. Finally, gel filtration chromatography yielded a homogeneous enzyme (Exo A) as determined by silver stains of both sodium dodecyl sulfate- and nondenaturing electrophoresis gels. Substrate specificity experiments and the products of cellulose digestion indicate that the enzyme was an exo-beta-1,4-glucanase. Exo A required Ca2+ for maximal activity and had an apparent Km of 3.08 mM for NPC, with a Vmax of 0.298 mumol/min per mg of protein. The enzyme had an Mr of 230,000, as determined by gel filtration chromatography, and was a dimer of 118,000-Mr subunits. The N-terminal amino acid sequence of the enzyme is presented.
Review: Heat Shock Proteins and Systemic Lupus Erythematosus

This review briefly defines the heat shock proteins (hsps), their classification and their functions. The hypothesis that links hsps to the development of autoimmunity is explored, together with the rationale for investigation of the relationship between hsps and systemic lupus erythematosus (SLE). Thus, published work on this subject falls into three main categories: the overexpression of hsps in SLE, the development of autoantibodies to hsps in SLE, and the surface expression of hsps in peripheral blood mononuclear cells in SLE. This work is reviewed in detail. In conclusion, we describe areas for further study and outline ways in which this is being approached.
Web-based recruiting’s impact on organizational image and familiarity: too much of a good thing?

Abstract Little is known about the efficacy of many of the newer forms of online recruitment. Using a quasi-experimental design, we tested the impact of individual exposure to corporate recruitment websites and Facebook on perceptions of organizational familiarity and organizational image over time. Most interestingly, we found evidence of a curvilinear or non-linear relationship between frequency of exposure to organizational communications and perceptions of organizational familiarity across time. Implications of our findings for HR theory and practice are discussed.
Does elevated parathyroid hormone concentration predict cognitive decline in older people?

Background and aims: Increased parathyroid activity has been associated with impaired cognitive function, although the predictive value of parathyroid hormone (PTH) for cognitive decline has not yet been fully investigated. This association was evaluated in random persons of age cohorts of 75, 80 and 85 years in a 10-year longitudinal prospective study. Methods: Cognition of patients (n=514) was assessed with the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) at baseline and at intervals of one, five and ten years. Clinical data were collected and serum PTH, ionized calcium (Ca2+) and creatinine as well as apolipoprotein E (APOE) alleles were determined at baseline. Results: Impaired cognition (MMSE<24 or CDR≥1) was associated with older age, impaired renal function, and elevated PTH (≥62 ng/L, IV-quartile) at baseline. Elevated PTH indicated a 2-fold risk of an at least 4-point decrease in MMSE (OR 2.20) and a 3-fold risk of an increase in CDR-class (OR 3.20) within the first year of follow-up. The risk remained significantly elevated even after controlling for age, gender, baseline cognition, serum Ca2+, creatinine, and AP0E4 (OR 2.24 for MMSE; OR 2.12 for CDR). High PTH also predicted cognitive decline within a five-year follow-up (OR 3.20), but the association disappeared at ten years. Conclusions: Elevated PTH concentrations are associated with a five-year cognitive decline in a general aged population, independently of Ca2+ and renal function. The role of vitamin D deficiency, the most common cause of elevated PTH in the elderly, needs to be further investigated.
Corticosteroids for Bell's palsy (idiopathic facial paralysis).

BACKGROUND Inflammation and oedema of the facial nerve are implicated in causing Bell's palsy. Corticosteroids have a potent anti-inflammatory action which should minimise nerve damage and thereby improve the outcome of patients suffering from this condition. OBJECTIVES The objective of this review was to assess the effect of steroid therapy in the recovery of patients with Bell's palsy. SEARCH STRATEGY We searched the Cochrane Neuromuscular Disease Group register for randomised trials, as well as MEDLINE, EMBASE and LILACS (to December 2000). We contacted known experts in the field to identify additional published or unpublished trials. SELECTION CRITERIA Randomised trials comparing different routes of administration and dosage schemes of corticosteroid or adrenocorticotrophic hormone therapy versus a control group where no therapy considered effective for this condition was administered, unless it was also given in a similar way to the experimental group. DATA COLLECTION AND ANALYSIS Two reviewers independently assessed eligibility, trial quality, and extracted the data. MAIN RESULTS Three trials with a total of 117 patients were included. One trial compared cortisone acetate with placebo; one compared prednisone plus vitamins, with vitamins alone; and one, not-placebo controlled, tested the efficacy of methylprednisolone. Allocation concealment was appropriate in two trials, and the data reported allowed an intention-to-treat analysis. Overall 13/59 (22%) of the patients allocated to steroid therapy had incomplete recovery of facial motor function six months after randomisation, compared with 15/58 (26%) in the control group. This reduction was not significant (relative risk 0.86, 95% confidence interval 0.47 to 1.59). The reduction in the proportion of patients with cosmetically disabling sequelae six months after randomisation was also not significant (relative risk 0.86, 95% confidence interval 0.38 to 1.98). REVIEWER'S CONCLUSIONS The available evidence from randomised controlled trials does not show significant benefit from treating Bell's palsy with corticosteroids. More randomised controlled trials with a greater number of patients are needed to determine reliably whether there is real benefit (or harm) from the use of steroid therapy in patients with Bell's palsy.
Hypoxia-inducible factor 1alpha in the glaucomatous retina and optic nerve head.

OBJECTIVE To examine tissue hypoxia in the retina and optic nerve head of glaucomatous eyes by the assessment of a transcription factor, hypoxia-inducible factor 1alpha (HIF-1alpha), which is tightly regulated by the cellular oxygen concentration. METHODS Using immunohistochemical analysis, the cellular localization of HIF-1alpha was studied in the retina and optic nerve head of 28 human donor eyes with glaucoma compared with 20 control eyes from healthy donors matched for several characteristics. The relationship between the retinal regions that exhibited immunostaining for HIF-1alpha and functional damage was examined using visual field data. RESULTS There was an increase in the immunostaining for HIF-1alpha in the retina and optic nerve head of glaucomatous donor eyes compared with the control eyes. In addition, the retinal location of the increased immunostaining for HIF-1alpha in some of the glaucomatous eyes was closely concordant with the location of visual field defects recorded in these eyes. CONCLUSIONS Because the regions of HIF-1alpha induction represent the areas of decreased oxygen delivery and hypoxic stress, information obtained from this study provides direct evidence that tissue hypoxia is present in the retina and optic nerve head of glaucomatous eyes, and hypoxic signaling is a likely component of the pathogenic mechanisms of glaucomatous neurodegeneration. Clinical Relevance These findings support the presence of tissue hypoxia in the retina and optic nerve head of glaucomatous patients.
Environment‐specific amino acid substitution tables: Tertiary templates and prediction of protein folds

The local environment of an amino acid in a folded protein determines the acceptability of mutations at that position. In order to characterize and quantify these structural constraints, we have made a comparative analysis of families of homologous proteins. Residues in each structure are classified according to amino acid type, secondary structure, accessibility of the side chain, and existence of hydrogen bonds from the side chain. Analysis of the pattern of observed substitutions as a function of local environment shows that there are distinct patterns, especially for buried polar residues. The substitution data tables are available on diskette with Protein Science. Given the fold of a protein, one is able to predict sequences compatible with the fold (profiles or templates) and potentially to discriminate between a correctly folded and misfolded protein. Conversely, analysis of residue variation across a family of aligned sequences in terms of substitution profiles can allow prediction of secondary structure or tertiary environment.
Taking aim at Alzheimer's disease through the mammalian target of rapamycin

Abstract A significant portion of the world's population suffers from sporadic Alzheimer's disease (AD) with available present therapies limited to symptomatic care that does not alter disease progression. Over the next decade, advancing age of the global population will dramatically increase the incidence of AD and severely impact health care resources, necessitating novel, safe, and efficacious strategies for AD. The mammalian target of rapamycin (mTOR) and its protein complexes mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2) offer exciting and unique avenues of intervention for AD through the oversight of programmed cell death pathways of apoptosis, autophagy, and necroptosis. mTOR modulates multi-faceted signal transduction pathways that involve phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), hamartin (tuberous sclerosis 1)/ tuberin (tuberous sclerosis 2) (TSC1/TSC2) complex, proline-rich Akt substrate 40 kDa (PRAS40), and p70 ribosomal S6 kinase (p70S6K) and can interface with the neuroprotective pathways of growth factors, sirtuins, wingless, forkhead transcription factors, and glycogen synthase kinase-3β. With the ability of mTOR to broadly impact cellular function, clinical strategies for AD that implement mTOR must achieve parallel objectives of protecting neuronal, vascular, and immune cell survival in conjunction with preserving networks that determine memory and cognitive function.
Single nucleotide polymorphism genomic arrays analysis of t(8;21) acute myeloid leukemia cells

Translocation of chromosomes 8 and 21, t(8;21), resulting in the AML1-ETO fusion gene, is associated with acute myeloid leukemia (AML). The findings of this study indicate that genomic alterations and KIT-D816 mutation confer a poor prognosis in t(8;21) AML patients. Translocation of chromosomes 8 and 21, t(8;21), resulting in the AML1-ETO fusion gene, is associated with acute myeloid leukemia. We searched for additional genomic abnormalities in this acute myeloid leukemia subtype by performing single nucleotide polymorphism genomic arrays (SNP-chip) analysis on 48 newly diagnosed cases. Thirty-two patients (67%) had a normal genome by SNP-chip analysis (Group A), and 16 patients (33%) had one or more genomic abnormalities including copy number changes or copy number neutral loss of heterozygosity (Group B). Two samples had copy number neutral loss of heterozygosity on chromosome 6p including the PIM1 gene; and one of these cases had E135K mutation of Pim1. Interestingly, 38% of Group B and only 13% of Group A samples had a KIT-D816 mutation, suggesting that genomic alterations are often associated with a KIT-D816 mutation. Importantly, prognostic analysis revealed that overall survival and event-free survival of individuals in Group B were significantly worse than those in Group A.
West Nile Virus and Greater Sage-Grouse: Estimating Infection Rate in a Wild Bird Population

Abstract Understanding impacts of disease on wild bird populations requires knowing not only mortality rate following infection, but also the proportion of the population that is infected. Greater sage-grouse (Centrocercus urophasianus) in western North America are known to have a high mortality rate following infection with West Nile virus (WNv), but actual infection rates in wild populations remain unknown. We used rates of WNv-related mortality and seroprevalence from radiomarked females to estimate infection rates in a wild greater sage-grouse population in the Powder River basin (PRB) of Montana and Wyoming from 2003 to 2005. Minimum WNv-related mortality rates ranged from 2.4% to 13.3% among years and maximum possible rates ranged from 8.2% to 28.9%. All live-captured birds in 2003 and 2004 tested seronegative. In spring 2005 and spring 2006, 10.3% and 1.8% respectively, of newly captured females tested seropositive for neutralizing antibodies to WNv. These are the first documented cases of sage-grouse surviving infection with WNv. Low to moderate WNv-related mortality in summer followed by low seroprevalence the following spring in all years indicates that annual infection rates were between 4% and 29%. This suggests that most sage-grouse in the PRB have not yet been exposed and remain susceptible. Impacts of WNv in the PRB in the near future will likely depend more on annual variation in temperature and changes in vector distribution than on the spread of resistance. Until the epizootiology of WNv in sagebrush-steppe ecosystems is better understood, we suggest that management to reduce impacts of WNv focus on eliminating man-made water sources that support breeding mosquitoes known to vector the virus. Our findings also underscore problems with using seroprevalence as a surrogate for infection rate and for identifying competent hosts in highly susceptible species.