Miracle-dz/UniFAR-FTUs huggingface dataset:
ErbB-1 and ErbB-2 Acquire Distinct Signaling Properties Dependent upon Their Dimerization Partner

ABSTRACT The different epidermal growth factor (EGF)-related peptides elicit a diverse array of biological responses as the result of their ability to activate distinct subsets of ErbB receptor dimers, leading to the recruitment of different intracellular signaling networks. To specifically examine dimerization-dependent modulation of receptor signaling, we constructed NIH 3T3 cell lines expressing ErbB-1 and ErbB-2 singly and in pairwise combinations with each other ErbB family member. This model system allowed the comparison of EGF-activated ErbB-1 with ErbB-1 activated by Neu differentiation factor (NDF)-induced heterodimerization with ErbB-4. In both cases, ErbB-1 coupled to the adaptor protein Shc, but only when activated by EGF was it able to interact with Grb2. Compared to the rapid internalization of EGF-activated ErbB-1, NDF-activated ErbB-1 showed delayed internalization characteristics. Furthermore, the p85 subunit of phosphatidylinositol kinase (PI3-K) associated with EGF-activated ErbB-1 in a biphasic manner, whereas association with ErbB-1 transactivated by ErbB-4 was monophasic. The signaling properties of ErbB-2 following heterodimerization with the other ErbB receptors or homodimerization induced by point mutation or monoclonal antibody treatment were also analyzed. ErbB-2 binding to peptides containing the Src homology 2 domain of Grb2 or p85 and the phosphotyrosine binding domain of Shc varied according to the mode of receptor activation. Finally, tryptic phosphopeptide mapping of both ErbB-1 and ErbB-2 revealed that receptor phosphorylation is dependent on the dimerization partner. Differential receptor phosphorylation may, therefore, be the basis for the differences in the signaling properties observed.
nmt2 of fission yeast: A second thiamine‐repressible gene co‐ordinately regulated with nmt1

We previously described a screen for thiamine‐repressible genes in Schizosaccharomyces pombe and reported on one such gene, nmt1, required for thiamine biosynthesis. Here we describe a second gene, nmt2, recovered in the same screen. Disruption of nmt2 also resulted in thiamine auxotrophy, indicating a role for the nmt2 gene product in thiamine biosynthesis. Both genes are highly transcribed in minimal medium and repressed in medium containing thiamine, and nuclear ‘run‐on’ experiments confirm that expression in both cases is controlled by the rate of transcription initiation. The virtually identical kinetics of induction and repression suggest that the two genes are co‐ordinately regulated. Sequence comparison of the two promoters reveals a canonical TATA box, downstream of which is a perfectly conserved 11 bp element. Transcript mapping experiments show that transcription initiation of both genes is centred on this element.
Neurobiology and phenotypic expression in early onset schizophrenia

Aim: Early‐onset schizophrenia (onset before adulthood) is a rare and severe form of the disorder that shows phenotypic and neurobiological continuity with adult‐onset schizophrenia. Here, we provide a synthesis of keynote findings in this enriched population to understand better the neurobiology and pathophysiology of early‐onset schizophrenia.
Intubation conditions with low dose rocuronium under sevoflurane induction for children.

BACKGROUND During short surgical procedures and when there is a need to avoid the use of anticholinesterase at the end of surgery, the use of a smaller intubation dose of neuromuscular blocking drug is preferred. The aim of this study was to evaluate tracheal intubation conditions using smaller doses of rocuronium for children under sevoflurane induction. METHODS Eighty American Society of Anesthesiologists classification physical status I or II children were enrolled. After mask induction with sevoflurane with nitrous oxide for 3 minutes, 0.3 mg/kg of rocuronium was given. Intubation was performed 60 or 90 seconds thereafter. Study group A included children aged 1 to 3 years and 90 seconds between rocuronium injection and intubation. Group B included children aged 1 to 3 years who had 60 seconds between rocuronium injection and intubation. Group C included children aged 4 to 6 years who had 90 seconds between rocuronium injection and intubation. Group D included children aged 4 to 6 years who had 60 seconds between rocuronium injection and intubation. Intubation conditions were judged based on the scoring of ease of jaw opening and laryngoscopy, position of the vocal cords, and degree of straining after tracheal intubation. RESULTS All 80 children underwent successful tracheal intubation without laryngospasm or any complications. Intubation conditions were judged as optimal in all children in group A, 95% in group B, 80% in group C, and 65% in group D. CONCLUSIONS A total of 0.3 mg/kg of rocuronium was sufficient for tracheal intubation for children 1 to 6 years old under sevoflurane induction. To guarantee optimal intubation conditions for elder children, allow 90 seconds waiting time after rocuronium administration was recommended.
Effects of inhibin-related peptides and oestradiol on androstenedione and progesterone secretion by bovine theca cells in vitro.

Primary monolayer cultures of bovine theca cells isolated from pooled ovarian follicles (3-10 mm diameter) were used to examine the effects of various granulosa cell-derived substances on basal and luteinizing hormone (LH)-induced androgen and progesterone secretion. After an overnight pretreatment period, cells were incubated with a range of treatments including LH, oestradiol-17 beta, inhibin, activin and follistatin. Media were collected after 48 h and assessment of androstenedione and progesterone secretion made by radioimmunoassay. Addition of LH (5-50 ng/ml) to the cells resulted in a dose-dependent stimulation of both androstenedione (2.5- to 3-fold rise; P < 0.01) and progesterone (approximately 1.6-fold rise; P < 0.001) production. Secretion of androstenedione was also raised (up to 5-fold; P < 0.001) by addition of oestradiol-17 beta (0.3-300 ng/ml), whilst levels of the androgen in the presence of both LH (20 ng/ml) and oestradiol (300 ng/ml) were up to 12-fold higher (P < 0.001) than control values. In contrast, oestradiol treatment inhibited by up to 50% both basal (P < 0.001) and LH-stimulated (P < 0.001) secretion of progesterone. Exposure of cells to purified bovine inhibin (5-125 ng/ml) consistently raised androstenedione secretion by up to 42% over basal levels (P < 0.001). Inhibin also enhanced both LH-stimulated (approximately 35%; P < 0.001) and oestradiol-stimulated (approximately 20%; P < 0.05) secretion of androstenedione. In direct contrast, treatment of theca cells with human recombinant activin-A (1-50 ng/ml) inhibited both LH-stimulated (approximately 50%; P < 0.001) and oestradiol-stimulated (approximately 30%; P < 0.005) androstenedione secretion. Activin also reversed the positive effect of inhibin on basal (P < 0.01), LH-stimulated (P < 0.001) and oestradiol-stimulated (P < 0.001) androstenedione secretion, though activin alone did not affect basal steroid output. Simultaneous addition of human recombinant follistatin reversed the inhibitory effects of activin on LH- and oestradiol-induced androstenedione secretion but did not modify the effects of inhibin. Follistatin alone did not alter either basal or LH-stimulated androstenedione output. Neither basal nor LH-stimulated secretion of progesterone were consistently affected by inhibin, activin or follistatin. As well as confirming the stimulatory effects of both LH and oestradiol on bovine thecal cell androgen production, these observations are indicative of opposing intrafollicular paracrine roles for granulosa cell-derived inhibin and activin in modulating thecal cell responses to gonadotrophins and steroids in the bovine ovary. (ABSTRACT TRUNCATED AT 400 WORDS)
Cross-Site Evaluation of the Alliance to Reduce Disparities in Diabetes

Alliance programs implemented multilevel, multicomponent programs inspired by the chronic care model and aimed at reducing health and health care disparities for program participants. A unique characteristic of the Alliance programs is that they did not use a fixed implementation strategy common to programs using the chronic care model but instead focused on strategies that met local community needs. Using data provided by the five programs involved in the Alliance, this evaluation shows that of the 1,827 participants for which baseline and follow-up data were available, the program participants experienced significant decreases in hemoglobin A1c and blood pressure compared with a comparison group. A significant time by study group interaction was observed for hemoglobin A1c as well. Over time, more program participants met quality indicators for hemoglobin A1c and blood pressure. Those participants who attended self-management classes and experienced more resources and support for self-management attained more benefit. In addition, program participants experienced more diabetes competence, increased quality of life, and improvements in diabetes self-care behaviors. The cost-effectiveness of programs ranged from $23,161 to $61,011 per quality-adjusted life year. In sum, the Alliance programs reduced disparities and health care disparities for program participants.
Angiotensinogen as a biomarker of acute kidney injury

Abstract Early recognition of acute kidney injury (AKI) is critical to prevent its associated complications as well as its progression to long term adverse outcomes like chronic kidney disease. A growing body of evidence from both laboratory and clinical studies suggests that inflammation is a key factor contributing to the progression of AKI regardless of the initiating event. Biomarkers of inflammation are therefore of interest in the evaluation of AKI pathogenesis and prognosis. There is evidence that the renin angiotensin aldosterone system is activated in AKI, which leads to an increase in angiotensin II (Ang II) formation within the kidney. Ang II activates pro-inflammatory and pro-fibrotic pathways that likely contribute to the progression of AKI. Angiotensinogen is the parent polypeptide from which angiotensin peptides are formed and its stability in urine makes it a more convenient marker of renin angiotensin system activity than direct measurement of Ang II in urine specimens, which would provide more direct information. The potential utility of urinary angiotensinogen as a biomarker of AKI is discussed in light of emerging data showing a strong predictive value of AKI progression, particularly in the setting of decompensated heart failure. The prognostic significance of urinary angiotensinogen as an AKI biomarker strongly suggests a role for renin–angiotensin system activation in modulating the severity of AKI and its outcomes.
Manufacturing Molecules Through Metabolic Engineering

Metabolic engineering has the potential to produce from simple, readily available, inexpensive starting materials a large number of chemicals that are currently derived from nonrenewable resources or limited natural resources. Microbial production of natural products has been achieved by transferring product-specific enzymes or entire metabolic pathways from rare or genetically intractable organisms to those that can be readily engineered, and production of unnatural specialty chemicals, bulk chemicals, and fuels has been enabled by combining enzymes or pathways from different hosts into a single microorganism and by engineering enzymes to have new function. Whereas existing production routes use well-known, safe, industrial microorganisms, future production schemes may include designer cells that are tailor-made for the desired chemical and production process. In any future, metabolic engineering will soon rival and potentially eclipse synthetic organic chemistry.
Optimized noninvasive procedures to measure DNA damage in comet assay

The comet assay is a well-established, simple and sensitive method to measure DNA damage in single cell and is commonly used in human trials to investigate the effects of pollution, occupational hazards and potential genoprotective agents. Peripheral blood lymphocytes are most commonly used in human biomonitoring studies, but lymphocytes collected from the mouth offer a potentially attractive, noninvasive alternative. The aim of the current study was to develop a buccal cell lymphocyte comet assay procedure. Cells were collected from mouthwash of three healthy volunteers and tested individually. The comet assay was performed under different pH and times of alkaline treatment, electrophoresis run times and hydrogen peroxide concentrations. Optimal conditions for buccal lymphocytes in comet assay were found to be pH >13 for unwinding and electrophoresis buffers, 10-min alkaline unwinding treatment and 20-min electrophoresis run time. We successfully utilized our optimized assay conditions to demonstrate the genoprotective activity of quercetin. This newly established procedure offers an alternative noninvasive sampling method for the investigation of DNA protection and/or damaging effect.
A SDN-based energy saving strategy in wireless access networks

This paper investigates on the base stations (BSs) sleeping control and energy saving in wireless network. The objective is to find the sleeping control and energy saving configuration between total power consumption and average video's quality. On the Software Defined Network (SDN) access network architecture, a type of sleeping control and active BSs' optimal transmitting time strategy is considered, the BS sleeps when there is no active users, and wakes up after a period of vacation time. In this paper, we study the active users grouping strategy, In order to spare more BSs into sleeping mode. Then this paper proposes an active BS transmitting time optimal strategy according to the users' QoS. In the proposed strategy, the active BSs' transmitting time is minimized in order to save energy. This paper employs the mixed integer-programming model to present this optimization problem. Then we utilized a novel algorithm to save the energy in access networks and also meet the QoS requirements. Both the analytical and simulation results show that the algorithm can effectively save energy in the access network BSs.
A phenotype‐based genetic association study reveals the contribution of neuregulin1 gene variants to age of onset and positive symptom severity in schizophrenia

By pure endpoint diagnosis of the disease, the risk of developing schizophrenia has been repeatedly associated with specific variants of the neuregulin1 (NRG1) gene. However, the role of NRG1 in the etiology of schizophrenia has remained unclear. Since Nrg1 serves vital functions in early brain development of mice, we hypothesized that human NRG1 alleles codetermine developmentally influenced readouts of the disease: age of onset and positive symptom severity. We analyzed 1,071 comprehensively phenotyped schizophrenic/schizoaffective patients, diagnosed according to DSM‐IV‐TR, from the GRAS (Göttingen Research Association for Schizophrenia) Data Collection for genetic variability in the Icelandic region of risk in the NRG1 gene. For the case‐control analysis part of the study, we included 1,056 healthy individuals with comparable ethnicity. The phenotype‐based genetic association study (PGAS) was performed on the GRAS sample. Instead of a risk constellation, we detected that several haplotypic variants of NRG1 were, unexpectedly, less frequent in the schizophrenic than in the control sample (mean OR = 0.78, range between 0.68 and 0.85). In the PGAS we found that these “protective” NRG1 variants are specifically underrepresented in subgroups of schizophrenic subjects with early age of onset and high positive symptom load. The GRAS Data Collection as a prerequisite for PGAS has enabled us to associate protective NRG1 genotypes with later onset and milder course of schizophrenia. © 2011 Wiley‐Liss, Inc.
Influence of obesity on left ventricular midwall mechanics in arterial hypertension.

The evaluation of the effect of obesity on left ventricular systolic performance may differ in relation to the method used to measure left ventricular function and to the type of study population. Whether obesity worsens left ventricular midwall mechanics in arterial hypertension has never been investigated. Accordingly, we assessed echocardiographic left ventricular midwall shortening-circumferential end-systolic stress relations in 156 normotensive and normal-weight (reference) adults, 94 normotensive and overweight (1985 National Institutes of Health partition values) to obese (body mass index > 30 kg/m2) adults, 263 hypertensive and normal-weight adults, and 224 hypertensive and overweight-to-obese adults. There was an inverse relation of midwall shortening to circumferential end-systolic stress in all groups (all P < .005). Left ventricular performance as a ratio of observed to predicted midwall shortening fell below the fifth percentile in 4 of 94 (4%) of overweight-to-obese normotensive individuals. Eighty-eight of 487 hypertensive subjects (18.1%) exhibited depressed midwall shortening as a percentage of the value predicted from wall stress, with no difference between normal-weight (50 of 263 [19%]) and overweight (38 of 224 [17%]) subjects. Sixty-one normotensive and 131 hypertensive subjects were frankly obese. After adjustment for sex and age, midwall shortening, as either absolute values or a percentage of predicted, was not statistically different among obese, overweight, and normal-weight subjects in both normotensive and hypertensive groups. For each quartile of observed-to-predicted midwall shortening ratio, obese subjects had greater left ventricular end-diastolic volume than normal-weight subjects among both normotensive and, more evidently, hypertensive subjects. A predicted midwall shortening was generated from both wall stress and left ventricular volume with the use of multiple regression analysis. High body mass index, mean blood pressure, aging, and male sex independently predicted low afterload and left ventricular volume-independent midwall left ventricular performance (multiple R = .31, P < .0001). Thus, (1) midwall left ventricular systolic performance in asymptomatic overweight or frankly obese individuals is comparable to that in normal-weight individuals in both the presence and absence of arterial hypertension; (2) however, maintenance of normal life ventricular performance in obese individuals is associated with the use of Starling reserve; and (3) this compensatory mechanism is especially evident when arterial hypertension and obesity coexist.
Local Termination of 3′-5′-Cyclic Adenosine Monophosphate Signals: The Role of A Kinase Anchoring Protein–Tethered Phosphodiesterases

A kinase anchoring proteins (AKAPs) belong to a family of functionally related proteins capable of binding protein kinase A (PKA) and tether it to relevant targets. In this way, AKAPs organize macromolecular complexes to segregate PKA activity and retain signal specificity. In the heart, AKAP–PKA interaction is central to the regulation of cardiac contractility. Phosphodiesterases belong to a large superfamily of enzymes that degrade 3′-5′-cyclic adenosine monophosphate (cAMP). They possess diverse catalytic properties and multiple regulatory mechanisms and control the duration and amplitude of the cAMP signal, including its propagation in space. AKAPs, together with PKA, can also assemble phosphodiesterases thereby providing a means to locally control cAMP dynamics at the level of single macromolecular complexes. This allows for the fine tuning of the cAMP response to the specific demands of the cell.
Differential expression of CD180 and IgM by B‐cell chronic lymphocytic leukaemia cells using mutated and unmutated immunoglobulin VH genes

We have studied the surface expression of the Toll‐like receptor family member CD180 on cells from 78 patients with B‐chronic lymphocytic leukaemia (B‐CLL). B‐CLL cells had variable levels of CD180 expression, but this was always less than that expressed by normal blood B cells and was stable for 24 months. Significantly higher levels of CD180 were expressed by B‐CLL cells with mutated IGVH genes compared with those using unmutated IGVH genes. This was in contrast to the higher levels of expression of surface immunoglobulin M by B‐CLL cells using unmutated, rather than mutated IGVH genes. CD180 was functional on B‐CLL cells from some of the patients, as shown by the increased expression of CD86 following incubation in vitro with anti‐CD180. The differential expression of CD180 amongst B‐CLL patients is one more marker that may define more precisely the different biological properties of this heterogeneous disease.
Bank Responses to Corporate Reorganization: Evidence from an Emerging Economy

This study analyzes a unique dataset of 125 corporate reorganization filings in Brazil from 2006 to 2016 to understand the role of bank creditor seniority in bankruptcy outcomes of smalland medium-sized companies. We find that conflict between bank creditor classes is relevant for explaining reorganization outcomes and that it occurs when organizations are in the money. Additionally, bank seniority matters more than the bank’s debt share for explaining bankruptcy outcomes in creditor-oriented regimes. Finally, we find a concave relationship between favorable votes and the number of banks involved and between favorable votes and a company’s age.
Breaking bad news in inpatient clinical settings: role of the nurse.

AIM This paper is a report of an exploration of the role of the nurse in the process of breaking bad news in the inpatient clinical setting and the provision of education and support for nurses carrying out this role. BACKGROUND The term 'breaking bad news' is mostly associated with the moment when negative medical information is shared with a patient or relative. However, it can also be seen as a process of interactions that take place before, during and after bad news is broken. Little research has been conducted exploring the role of the nurse in the process of breaking bad news in the inpatient clinical setting. METHODS A questionnaire was developed using Likert scales and open text questions. Data collection took place in 2007. Fifty-nine inpatient areas took part in the study; 335 questionnaires were distributed in total and 236 were completed (response rate 70%). RESULTS Nurses engaged in diverse breaking bad news activities at many points in care pathways. Relationships with patients and relatives and uncontrolled and unplanned events shaped the context in which they provided this care. Little formal education or support for this work had been received. CONCLUSION Guidance for breaking bad news should encompass the whole process of doing this and acknowledge the challenges nurses face in the inpatient clinical area. Developments in education and support are required that reflect the challenges that nurses encounter in the inpatient care setting.