Miracle-dz/UniFAR-FTUs huggingface dataset:
dGNaC1, a Gonad-specific Amiloride-sensitive Na+Channel*

Amiloride-sensitive sodium channels have been implicated in reproductive and early developmental processes of several species. These include the fast block of polyspermy inXenopus oocytes that follows the sperm binding to the egg or blastocoel expansion in mammalian embryo. We have now identified a gene called dGNaC1 that is specifically expressed in the gonads and early embryo in Drosophila melanogaster. The corresponding protein belongs to the superfamily of cationic channels blocked by amiloride that includesCaenorhabditis elegans degenerins, the Helix aspersa FMRF-amide ionotropic receptor (FaNaC), the mammalian epithelial Na+ channel (ENaC), and acid-sensing ionic channels (ASIC, DRASIC, and MDEG). Expression of dGNaC1 inXenopus oocytes generates a constitutive current that does not discriminate between Na+ and Li+, but is selective for Na+ over K+. This current is blocked by amiloride (IC50 = 24 μm), benzamil (IC50 = 2 μm), and ethylisopropyl amiloride (IC50 = 49 μm). These properties are clearly different from those obtained after expression of the previously cloned members of this family, including ENaC and the human αENaC-like subunit, δNaC. Interestingly, the pharmacology of dGNaC1 is not very different from that found for the Na+ channel characterized in rabbit preimplantation embryos. We postulate that this channel may participate in gametogenesis and early embryonic development inDrosophila.
Clinicians’ perspective on key domains in ANCA-associated vasculitis: a Delphi exercise

Objectives: The existing set of outcomes for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) needs to incorporate views of outcome measure stakeholders to meet the current standards of outcome measurement proposed by the Outcome Measures in Rheumatology (OMERACT) initiative. This study identifies domains that clinical experts (one group of stakeholders) consider to be important to determining the impact of AAV using the International Classification of Functioning, Disability and Health (ICF), a framework that describes health along four components: body functions, body structures, activities and participation, and contextual factors. Method: An international group of clinicians with expertise in the clinical care of patients with vasculitis were identified through consultation with three major vasculitis societies. The relevant domains were determined using a three-round e-mail-based Delphi questionnaire. Results: Eighty-two clinicians were invited to participate in this study and 41 responded. Nineteen domains were identified as important by > 80% of participants: six body functions (energy, seeing, hearing, pain, respiratory, and renal function), seven body structures (peripheral nerves, eye, ear, nose, sinuses, lungs (and airways), and kidneys), three activities and participation (carrying out daily routine, remunerative employment, and recreation and leisure), and three environmental factors (medications, support and relationships, and health services, systems, and policies). Conclusions: Clinical experts focus on the physiological effects of AAV with less importance given to the effect of AAV on patients’ activities and participation in life situations and the role of contextual factors. This study represents a step towards incorporating views of a range of stakeholders into disease assessment in AAV.
The effect of different fluoride application methods on the remineralization of initial carious lesions

Objectives The purpose of this study was to assess the effect of single and combined applications of fluoride on the amount of fluoride release, and the remineralization and physical properties of enamel. Materials and Methods Each of four fluoride varnish and gel products (Fluor Protector, FP, Ivoclar Vivadent; Tooth Mousse Plus, TM, GC; 60 Second Gel, A, Germiphene; CavityShield, CS, 3M ESPE) and two fluoride solutions (2% sodium fluoride, N; 8% tin(ii) fluoride, S) were applied on bovine teeth using single and combined methods (10 per group), and then the amount of fluoride release was measured for 4 wk. The electron probe microanalysis and the Vickers microhardness measurements were conducted to assess the effect of fluoride application on the surface properties of bovine teeth. Results The amount of fluoride release was higher in combined applications than in single application (p < 0.05). Microhardness values were higher after combined applications of N with FP, TM, and CS than single application of them, and these values were also higher after combined applications of S than single application of A (p < 0.05). Ca and P values were higher in combined applications of N with TM and CS than single application of them (p < 0.05). They were also increased after combined applications of the S with A than after single application (p < 0.05). Conclusions Combined applications of fluoride could be used as a basis to design more effective methods of fluoride application to provide enhanced remineralization.
The effects of oxytocin and milk removal on milk secretion in the goat

1. When goats were milked each hour after being given a dose of synthetic oxytocin within the range thought to be released by the pituitary, there was a progressive rise in milk yield becoming statistically significant by 5 hr. The effect was reduced if the milk was not removed from the gland each hour.
E‐cadherin quantititive immunocytochemical assays in breast carcinomas

The reduction of E‐cadherin expression, which is involved in the initial step of invasion and metastasis of cancer, was investigated in 218 human breast carcinomas. Quantitative immunohistochemical assays (ICAs) were performed on frozen sections. Quantitation was assessed by processing digitized microscopic images of immunoreactions using a computerized system of image analysis (SAMBA). The results were correlated with clinicopathological data and quantitative immunodetection of other molecules. E‐cadherin expression was significantly (P<0·001) stronger in ductal carcinomas than in lobular carcinomas and stronger (P<0·01) in low grades than in high grades, but E‐cadherin was independent of lymph node status and tumour size. Also an inverse significant (P<0·01) relationship was observed between E‐cadherin expression on tissue sections and positive immunoreactions with anti‐P53, MIB1 (growth fraction), and anti‐c‐erb‐B2 product. Conversely, strong positive and anti‐E‐cadherin immunoreactions correlated with strong positive anti‐ER and anti‐PR immunoreactions (P<0·01). No relationship was observed between E‐cadherin and the results of quantitative ICAs of cathepsin D, CD31, and P‐glycoprotein, assessed on consecutive sections from the same frozen tissue samples. The results show that preserved E‐cadherin expression correlates with high degree of tumour differentiation, low proliferative activity, and low expression of prognostic markers. The deregulation of E‐cadherin is independent of other steps of tumour invasion, such as protease digestion of extracellular matrix and angiogenesis. © 1997 John Wiley & Sons, Ltd.
A 5-year review of FIGO stage IB cervical cancer in an Asian population.

OBJECTIVE We studied the clinical patterns and outcome of patients with FIGO (1985) Stage 1b cervical cancer. In particular, looking at the clinico-pathological characteristics in relation with disease recurrence. PATIENTS & METHODS Ninety-nine Asian patients were managed at (the former) K K Hospital, Singapore, from 1987 to 1991. The mean and median follow-up periods were 67 and 60 months respectively. This study was performed in 1995. RESULTS The majority of the patients (81%) was treated by radical hysterectomy with or without adjuvant radiotherapy/chemotherapy while 15% were treated by radical pelvic radiotherapy alone and 4% of patients had pelvic radiotherapy following the diagnosis of cervical cancer after a simple hysterectomy. Thirteen patients developed tumour recurrence (13.1%). In these patients, there was a greater proportion of adenocarcinomas (31% vs 13%, p = 0.1065), lymph node metastases (45% vs 20%, p = 0.09) and surgical margins involvement (45% vs 7%) 7%, p = 0.004) while there seemed to be no difference in histological sub-types, vascular space involvement and cytological grading. The relative risks of developing tumour recurrence in patients with adenocarcinoma was 2.5 times (95% CI: 0.88-7.05), lymph-node metastasis: 2.3 times (95% CI: 0.96-4.93) and involved surgical margins; 5.9 times (95% CI: 2.27-15.5). The mean time to recurrence were 21.7 months with all of them detected within 36 months following primary therapy. All of them had abnormal physical findings while routine follow-up Pap smear was positive in only one patient (8%). In general, the outcome of salvage treatment was poor. CONCLUSIONS In our group of patients with FIGO Stage lb cervix cancer, majority had radical surgery performed initially. Thirteen percent had disease recurrence, in which there were greater proportions of patients with adenocarcinoma, lymph-node metastasis, and involved surgical margins. The mean time-to-recurrence was 21.7 months with all detected by 36 months. Routine follow-up Pap smear seemed to be a poor indicator of disease status.
Increased Expression of IL-33 in Severe Asthma: Evidence of Expression by Airway Smooth Muscle Cells1

IL-33, a new member of the IL-1 cytokine family, promotes Th2 inflammation, but evidence on the implications of this cytokine in asthma is lacking. IL-33 would be mainly expressed by structural cells, but whether proinflammatory cytokines modulate its expression in airway smooth muscle cells (ASMC) is unknown. Endobronchial biopsies were obtained from adults with mild (n = 8), moderate (n = 8), severe (n = 9), asthma and from control subjects (n = 5). Immunocytochemistry, laser-capture microdissection, reverse transcriptase, and real-time quantitative PCR were used for determining IL-33 expression in the lung tissues. ASMC isolated from resected lung specimens were cultured with proinflammatory cytokines and with dexamethasone. IL-33 expression by ASMC was determined by PCR, ELISA, and Western blotting. Higher levels of IL-33 transcripts are detected in biopsies from asthmatic compared with control subjects, and especially in subjects with severe asthma. ASMC show IL-33 expression at both protein and mRNA levels. IL-33 and TNF-α transcript levels correlate in the lung tissues, and TNF-α up-regulates IL-33 expression by cultured ASMC in a time- and dose-dependent manner. IFN-γ also increases IL-33 expression and shows synergistic effect with TNF-α. Dexamethasone fails to abolish TNF-α-induced IL-33 up-regulation. IL-33 expression increases in bronchial biopsies from subjects with asthma compared with controls, as well as subjects with asthma severity. ASMC are a source of the IL-33 cytokine. Our data propose IL-33 as a novel inflammatory marker of severe and refractory asthma.
Gender Diversity on U.S. Corporate Boards

Despite rhetoric supporting the advancement of women on corporate boards, meager evidence supports significant progress over the past decade in the United States. The authors examine archival board data (for more than 3,000 U.S. publicly traded firms) from 2002 to 2011 and find that a female is most likely to be appointed to a corporate board when a woman has just exited the position. A similar propensity occurs to reappoint a male when a man leaves, although the effect is smaller than for women. The authors argue that this “gender-matching heuristic” can impede progress in attaining gender diversity, regardless of intention, because it emphasizes the replacement of existing women rather than changing board composition. The authors replicate this effect in follow-up laboratory studies and show that “what works” to increase the representation of women on boards, irrespective of gender matching, is to increase the number of women in the candidate pool.
Viscosity rather than quantity of dietary fibre predicts cholesterol-lowering effect in healthy individuals

The well-documented lipid-lowering effects of fibre may be related to its viscosity, a phenomenon that has been understudied, especially when fibre is given against the background of a typical North American (NA) diet. In this three-arm experiment, we compared the lipid-lowering effect of low-viscosity wheat bran (WB), medium-viscosity psyllium (PSY) and a high-viscosity viscous fibre blend (VFB), as part of a fibre intervention aimed at increasing fibre intake to recommended levels within the context of a NA diet in apparently healthy individuals. Using a randomised cross-over design, twenty-three participants (twelve males and eleven females; age 35 (sd 12) years; LDL-cholesterol (C) 2·9 (sem 0·6) mmol/l) consuming a typical NA diet received a standard, fibre-enriched cereal, where approximately one-third of the fibre was either a low-viscosity (570 centipoise (cP)) WB, medium-viscosity (14 300 cP) PSY or a high-viscosity (136 300 cP) novel VFB, for 3 weeks separated by washout periods of ≥ 2 weeks. There were no differences among the treatments in the amount of food consumed, total dietary fibre intake, reported physical activity and body weight. Final intake of the WB, PSY and VFB was 10·8, 9·0 and 5·1 g, respectively. Reduction in LDL-C was greater with the VFB compared with the medium-viscosity PSY ( − 12·6 (sem 3·5) %, P = 0·002) and low-viscosity WB ( − 14·6 (sem 4·2) %, P = 0·003). The magnitude of LDL-C reduction showed a positive association with fibre apparent viscosity (r − 0·41, P = 0·001). Despite the smaller quantity consumed, the high-viscosity fibre lowered LDL-C to a greater extent than lower-viscosity fibres. These data support the inclusion of high-viscosity fibre in the diet to reduce plasma lipids among apparently healthy individuals consuming a typical NA diet.
Epidural Anesthesia Enhances Sympathetic Nerve Activity in the Unanesthetized Segments in Cats

To evaluate compensatory sympathetic excitation during epidural anesthesia, we measured cardiac and renal sympathetic nerve activity during thoracic or lumbar epidural anesthesia in cats.Thirteen cats were divided into three groups: five cats received thoracic epidural anesthesia, five received lumbar epidural anesthesia, and three received lumbar epidural anesthesia after the carotid sinus and vagoaortic nerves were severed (denervated lumbar group). Heart rate (HR), mean arterial pressure (MAP), and cardiac and renal sympathetic nerve activity were measured repeatedly after administration of a single dose of 0.1 mL/kg of 1% lidocaine via the epidural catheter. Epidural solution spread from a median of C-8 to T-6 in the thoracic epidural group, T-8 to L-3 in the lumbar epidural group, and T-7 to L-3 in the denervated lumbar group. During thoracic epidural anesthesia, HR, MAP, and cardiac sympathetic nerve activity decreased, while renal nerve activity increased. Similarly, HR, MAP, and renal sympathetic nerve activity decreased during lumbar epidural anesthesia, and cardiac activity increased. In the denervated lumbar group, HR, MAP, and renal sympathetic nerve activity decreased but cardiac activity remained unchanged. Sympathetic nerve activity in corresponding unanesthetized segments increased during thoracic or lumbar epidural anesthesia in association with significant decreases in MAP and HR. After severance of the carotid sinus and vagoaortic nerves, the absence of sympathetic excitation in the unanesthetized segments during lumbar epidural anesthesia suggests that the compensatory response is produced by the baroreceptor reflex response to anesthesia-induced hypotension. (Anesth Analg 1997;84:391-7)
Glucose‐dependent insulinotropic polypeptide–producing K cells in dexamethasone‐treated rats

Some studies indicate that diabetes mellitus exerts an influence on the gastrointestinal tract and its diffuse neuroendocrine system (DNES) in regard to cellular density and neuroendocrine content. Since there is no data about relationship between experimentally induced non–insulin‐dependent (type 2) diabetes mellitus (NIDDM) on the gut K cells, the aim of our study was to investigate immunohistochemical, stereological and ultrastructural changes of rat K cells after 12 days of dexamethasone treatment. Twenty male Wistar rats aged 30 days were given daily intraperitoneally 2 mg kg–1 dexamethasone (group DEX, 10 rats) or saline (group C, 10 rats) for 12 days. Tissue specimens were obtained from each antrum with corpus and different parts of the small (SI) and large intestine (LI) of all animals. Immunohistochemistry was carried out using antisera against the GIP and insulin. Transmission electron microscopy was also used. Although, according to the literature data, rat K cells are present in the duodenum and jejunum and, to a lesser extent, in the ileum, in the present study we observed that those cells were abundant also in all parts of the LI. We observed generally that GIP‐producing K cells were augmented in all parts of SI and decreased in the LI of DEX rats. Insulin immunoreactivity (ir) coexpressed with GIP‐ir in K cells and was stronger in the SI of DEX rats as compared with C rats. We also found by electron microscopy that small intestinal K cells have features not only of GIP‐secreted but also of insulin‐secreted cells. We concluded that dexamethasone treatment caused proliferation of K cells in the rat SI, and simultaneously transformation of GIP‐producing K cells to insulin‐synthesizing cells.
Minimal mechanistic model of siRNA-dependent target RNA slicing by recombinant human Argonaute 2 protein

Significance Argonaute (Ago) proteins are the key component of the RNA-induced silencing complex (RISC) and mediate RNA interference (RNAi) in association with small RNAs. Although overall the mechanism of RNAi is well understood, many molecular details of this complex process are not. The implementation of pre-steady-state kinetic techniques enabled us to develop a comprehensive minimal mechanistic model for human Ago 2 (hAgo2)-mediated target RNA binding and cleavage, dissecting binary as well as ternary complex formation and target RNA cleavage into individual substeps. The model presented provides in-depth insights into the complicated interplay of hAgo2 with small RNAs and corresponding target molecules, which in combination with available X-ray structures will eventually lead to better understanding of the underlying mechanisms of RNAi. Argonaute (Ago) proteins are the key component of the RNA-induced silencing complex and mediate RNA interference (RNAi) in association with small RNAs. Although overall the mechanism of RNAi is well understood, many molecular details of this complex process are not. Here we report about in-depth steady-state and, in particular, pre-steady-state characterization of siRNA binding, target RNA recognition, sequence-specific cleavage and product release by recombinant human Ago 2 (hAgo2). In combining our biochemical studies with crystal structures of bacterial Ago proteins and of recently released hAgo2, we relate kinetic data to conformational changes along the pathway and propose a comprehensive minimal mechanistic model describing fundamental steps during RNAi. Furthermore, in contrast to the current conception, our hAgo2 preparations are programmable with double-stranded siRNA. Accordingly, the system investigated represents a functional minimal RNA-induced silencing complex.
Comparison of Levosimendan versus Dobutamine in Patients with Moderate to Severe Left Ventricular Dysfunction Undergoing Off-pump Coronary Artery Bypass Grafting: A Randomized Prospective Study

Context: Recent upsurge in referral of patients with compromised left ventricular (LV) function for cardiac surgery has led to an increasing use inotropes to achieve improvement of tissue perfusion in the perioperative period. Aims and Objectives: To compare the hemodynamic effects and immediate postoperative outcomes with levosimendan and dobutamine in patients with moderate to severe LV dysfunction undergoing off-pump coronary artery bypass grafting (OPCAB). Settings and Design: University teaching hospital, randomized control study. Materials and Methods: Eighty patients were randomly divided into two groups of 40 each. Group I received levosimendan at 0.1 μg/kg/min and Group II received dobutamine at 5 μg/kg/min. Hemodynamic data were noted at 30 min, during obtuse marginal grafting, 1, 6, 12, and 24 h after surgery. Heart rate (HR), mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI), left ventricular stroke work index (LVSWI) and right ventricular stroke work index (RVSWI), mixed venous oximetry (SvO2), and lactate were measured. Statistical Analysis Used: Chi-square and Student's t-test. Results: The HR, MAP, PCWP, SVRI, and PVRI were lower in Group I when compared to Group II. Group I patients showed a statistically significant increase in LVSWI, RVSWI, and CI, when compared to Group II. Comparatively, Group I patients maintained higher SvO2and lower lactate levels. Duration of ventilation, Intensive Care Unit (ICU), and hospital stay were lower in Group I. Conclusions: Levosimendan was associated with statistically significant increase in indices of contractility (CI, LVSWI, and RVSWI) and decrease in PCWP during and after OPCAB. Levosimendan group had lower incidence of atrial fibrillation, shorter length of ICU, and hospital stay.
Leadership and organizational performance : State of the art and research agenda

A large portion of the everyday discourse about leadership and leaders takes it for granted that leaders make a big difference in terms of performance. The football managers discussion is one clear example, the wider fascination with business leaders likewise marks this association – and so too the fascination with political leaders. However, the academic literature finds it hard to find reliable evidence for a clear association, because both main concepts (leadership and performance) are broad and difficult to define and because of many confounding variables that make it difficult to demonstrate clear cause and effect. But while some academics have seemingly abandoned the attempt to tackle this difficult but central subject, there are some who seek to trace the relationship. It can be shown that a change of leader does produce some kind of performance outcome. For example, appointments of some leaders and the dismissal of others can trigger dramatic shifts in stock prices. In this chapter we will systematically examine the relationship between leadership and performance, both theoretically (section 2) and empirically (section 3). In section 4 we will use public leadership and performance as illustrative of our analysis. We will conclude with an overview of the current state of the literature and we will outline a research agenda. Overall, we show that empirical studies have mainly found positive relationships between leadership and performance, although effect sizes vary considerably. However, cross-sectional designs with subjective performance measures tend to find relatively strong effects. Therefore, we advocate a systematic approach to studying the leadership-performance relationship with attention to research designs, and we urge that more panel designs and experimental designs are applied in future studies, because these enable scholars to assess changes over time and getter a much better grasp of causality.