Miracle-dz/UniFAR-FTUs huggingface dataset:
Specific Asparagine-Linked Glycosylation Sites Are Critical for DC-SIGN- and L-SIGN-Mediated Severe Acute Respiratory Syndrome Coronavirus Entry

ABSTRACT Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus (CoV) designated SARS-CoV. The virus utilizes angiotensin-converting enzyme 2 (ACE2) as the primary receptor. Although the idea is less clear and somewhat controversial, SARS-CoV is thought to use C-type lectins DC-SIGN and/or L-SIGN (collectively referred to as DC/L-SIGN) as alternative receptors or as enhancer factors that facilitate ACE2-mediated virus infection. In this study, the function of DC/L-SIGN in SARS-CoV infection was examined in detail. The results of our study clearly demonstrate that both proteins serve as receptors independently of ACE2 and that there is a minimal level of synergy between DC/L-SIGN and ACE2. As expected, glycans on spike (S) glycoprotein are important for DC/L-SIGN-mediated virus infection. Site-directed mutagenesis analyses have identified seven glycosylation sites on the S protein critical for DC/L-SIGN-mediated virus entry. They include asparagine residues at amino acid positions 109, 118, 119, 158, 227, 589, and 699, which are distinct from residues of the ACE2-binding domain (amino acids 318 to 510). Amino acid sequence analyses of S proteins encoded by viruses isolated from animals and humans suggest that glycosylation sites N227 and N699 have facilitated zoonotic transmission.
Social workers’ experiences with whistleblowing: To speak or not to speak?

INTRODUCTION: Reporting perceived inadequate and/or harmful practice has become known internationally as whistleblowing. Social workers have a responsibility to uphold ethical standards and may blow the whistle when faced with what they perceive as unethical conduct. METHOD : A small-scale, qualitative study explored the experiences of 10 social workers in Aotearoa New Zealand who, having observed what they believed to be poor or unsafe practice, attempted to have their concerns addressed by reporting to a third party or blowing the whistle. FINDINGS : The research reveals common experiences of limited support for, and retaliation from colleagues and organisations towards, those who spoke out. Participants experienced both personal and professional consequences. CONCLUSIONS : The research identifies the need for appropriate processes and support for whistleblowing social workers and their employing agencies. Social workers need to be better informed about their rights and responsibilities under the Protected Disclosures Act (2000).
Functional interactions between monomers of the retroviral envelope protein complex

Retroviral vectors have been widely used in human gene therapy protocols. Entry into target cells is directed by the retroviral envelope protein, with receptor binding and postbinding fusion functions contributed mainly by the SU and TM subunits, respectively. We have generated mutants of the Moloney murine leukemia virus (MoMuLV) envelope protein with mutations in both the receptor binding domain of SU and throughout the TM subunit that are functionally inactive when expressed individually. However, the coexpression of these two classes of mutants partially restores envelope protein function and allows transduction. Several lines of evidence indicate that this complementation occurs in trans within envelope protein heterooligomers. The finding that the binding and postbinding functions of a retroviral envelope protein can be contributed by two different monomers should assist in the engineering of envelope proteins for tissue-specific gene delivery.
Hepatitis B and C Virus Infection in Crohn's Disease

Patients with Crohn's disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-&agr; (IFN-&agr;) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00–2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04–11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61–3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37–3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37–3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06–1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-&agr; for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.
Role of the Estrogen Antagonist ICI 182,780 in Vessel Assembly and Apoptosis of Endothelial Cells

Angiogenesis is required during tumor progression. Emerging data, including the presence of estrogen receptors in endothelium, suggests that estrogens can mediate endothelial proliferation and differentiation. Therefore, it is likely that anti-estrogenic drugs can also exert their effects in endothelial cells. The purpose of this work was to evaluate the effect of one anti-estrogenic agent, ICI 182,780, in human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs with 5 different concentrations of ICI 182,780 resulted in decreased cell viability and increase in apoptosis. Gene expression profile of these ICI-treated cells evaluated by cDNA array presented an upregulation of 68 newly expressed genes, whose expression was absent from both control and 17β-estradiol-treated HUVECs. Most of these genes were implicated in both intrinsic and extrinsic apoptotic pathways. Furthermore, ICI 182,780 incubation prevented HUVECs from formity capillary-like tubules in a Matrigel assay. These findings suggest that besides blocking tumor cell proliferation in an estrogen receptor-dependent manner, ICI 182,780 impaired angiogenesis by preventing branching and capillary-like tubule formation and by activating apoptotic pathways in endothelial cells.
How Global Financial Crisis Affected the Financial Development and Economic Growth?

A growing body of theoretical and empirical literature analyses the relationship between finance and economic growth. The relationship has been strongly supported by many empirical analyses. However, Global Financial Crisis, 2008 and significantly improved econometric techniques made scholars to revisit this relationship. The main motivation of this paper is to empirically revisit the traditional financial development proxies relationship with economic growth after world’s second greatest financial crisis. In this study, both fixed effect and dynamic panel data analysis are conducted by using 147 countries over the period of 2000- 2013. The analysis results prove the destructive effect of GFC, 2008 on the relationship between financial development and economic growth. Also, the finding showed that the significance of traditional financial development proxies has lowered after the crisis.
Glucocorticoid regulation of preproglucagon transcription and RNA stability during stress

Stress elicits a synchronized response of the endocrine, sympathetic, and central nervous systems to preserve homeostasis and well-being. Glucagon-like peptide-1 (GLP-1), a primary posttranslational product of the preproglucagon (PPG) gene, activates both physical and psychological stress responses. The current study examined mechanisms regulating expression of PPG gene products in the hindbrain. Our results indicate that PPG mRNA decreases rapidly after exposure to acute stressors of multiple modalities. Reduced mRNA levels are accompanied by reduced GLP-1 immunoreactivity in the paraventricular nucleus of hypothalamus, suggesting release at PPG terminals. Stress-induced decrements in PPG mRNA were attenuated in adrenalectomized-corticosterone-replaced rats, suggesting that mRNA down-regulation is due at least in part to glucocorticoid secretion. In contrast, acute stress increased levels of PPG heteronuclear RNA (hnRNA) in a glucocorticoid-dependent manner, suggesting that decreases in PPG mRNA are due to increased degradation rather than reduced transcription. Glucocorticoid administration to unstressed rats is sufficient to cause decrements in PPG mRNA and increments in PPG hnRNA. These findings suggest that glucocorticoids deplete the pool of transcribed PPG mRNA and concurrently stimulate PPG gene transcription, with the latter allowing a mechanism for replenishment of PPG mRNA after stress cessation. The combination of rapid PPG mRNA depletion and initiation of PPG transcription within 30 min is consistent with a rapid action of glucocorticoids on GLP-1 bioavailability, resulting in a transient reduction in the capacity for neuropeptidergic excitation of stress responses.
Treating Women Who Are Pregnant and Parenting for Opioid Use Disorder and the Concurrent Care of Their Infants and Children: Literature Review to Support National Guidance

Objectives: The prevalence of opioid use disorder (OUD) during pregnancy is increasing. Practical recommendations will help providers treat pregnant women with OUD and reduce potentially negative health consequences for mother, fetus, and child. This article summarizes the literature review conducted using the RAND/University of California, Los Angeles Appropriateness Method project completed by the US Department of Health and Human Services Substance Abuse and Mental Health Services Administration to obtain current evidence on treatment approaches for pregnant and parenting women with OUD and their infants and children. Methods: Three separate search methods were employed to identify peer-reviewed journal articles providing evidence on treatment methods for women with OUD who are pregnant or parenting, and for their children. Identified articles were reviewed for inclusion per study guidelines and relevant information was abstracted and summarized. Results: Of the 1697 articles identified, 75 were included in the literature review. The perinatal use of medication for addiction treatment (MAT, also known as medication-assisted treatment), either methadone or buprenorphine, within comprehensive treatment is the most accepted clinical practice, as withdrawal or detoxification risks relapse and treatment dropout. Medication increases may be needed with advancing pregnancy, and are not associated with more severe neonatal abstinence syndrome (NAS). Switching medication prenatally is usually not recommended as it can destabilize opioid abstinence. Postnatally, breastfeeding is seen as beneficial for the infant for women who are maintained on a stable dose of opioid agonist medication. Less is known about ideal pain management and postpartum dosing regimens. NAS appears generally less severe following prenatal exposure to buprenorphine versus methadone. Frontline NAS medication treatments include protocol-driven methadone and morphine dosing in the context of nonpharmacological supports. Conclusions: Women with OUD can be treated with methadone or buprenorphine during pregnancy. NAS is an expected and manageable condition. Although research has substantially advanced, opportunities to guide future research to improve maternal and infant outcomes are provided.
[The effect of clonidine on the intrapulmonary right-to-left shunt in one-lung ventilation in the dog].

Many vasoactive drugs--vasoconstrictors as well as vasodilators--impair the efficiency of hypoxic pulmonary vasoconstriction (HPV) and may cause dangerous hypoxemia during one-lung ventilation (1-LV). The effect of clonidine, a widely used alpha 2-agonistic antihypertensive agent, on intrapulmonary right-to-left shunt (Qs/Qt) during 1-LV has not yet been studied. METHODS. Twenty anesthetized beagle dogs were instrumented with a 7F Swan-Ganz catheter and an arterial line. A left thoracotomy in the lateral position was performed and the left main bronchus was prepared for clamping. Intravenous clonidine (5 micrograms/kg) was administered to 10 dogs. Anesthesia was maintained with either thiopental and fentanyl or halothane (0.8 insp. vol%) and fentanyl. The ventilatory frequency (100% O2, tidal volume 150 ml/kg) was adjusted to obtain an end-expiratory CO2 of 4.5%. Each dog underwent the following experimental sequence: (1) baseline measurements with 2-LV; (2) 20 min 1-LV (left lung atelectasis was achieved by clamping the left main bronchus); and (3) 20 min 2-LV. After allowing 30 min for conversion from i.v. to halothane anesthesia or vice versa, the procedure was repeated (5 dogs in each group received first i.v. and 5 dogs first halothane anesthesia). RESULTS. Qs/Qt was slightly but not significantly higher under halothane anesthesia in both groups during 1-LV as well as 2-LV (Table 1). No differences existed between the halothane and i.v. groups with regard to arterial pO2 and cardiac index. In the control group (i.v. or halothane, n = 20) Qs/Qt increased during 1-LV from 10.8 +/- 2.8% (mean +/- S.D.) to 26.6 +/- 5.5%, and in the clonidine group (i.v. or halothane, n = 20) from 7.2 +/- 2.3% to 18.3 +/- 5.4%. These differences between the control and clonidine groups are significant (P less than 0.001) for 1-LV as well as 2-LV. Arterial pO2 during 1-LV was reduced less in the clonidine group (573 +/- 48 to 390 +/- 99 mmHg) than in the control group (550 +/- 44 to 323 +/- 94 mmHg) (P less than 0.05). During 1-LV no significant differences between the two groups could be detected with regard to pulmonary artery pressure, mixed-venous pO2, pCO2, and pH. Heart rate, cardiac index, and oxygen uptake were significantly lower and arteriovenous O2 difference was significantly greater in the clonidine group, indicating better control of sympathoadrenergic activity under clonidine. CONCLUSIONS. We conclude that pretreatment with clonidine improves HPV during 1-LV. This effect of clonidine is probably due to reduced sympathetic nervous system activity.
Competitive Positioning of Complementors on Digital Platforms: Evidence from the Sharing Economy

Various platforms have recently emerged within the sharing economy and the phenomenon has started to affect several industries. While platforms such as Airbnb and BlaBlaCar are providing convenience and economic benefits to end-users, their success also turned them into crowded and competitive markets. With increasing numbers of products and services offered via the platforms, signals such as popularity and reputation have become critical market mechanisms that affect the decision-making processes of end-users. In this paper, we examine the positioning strategies of new hosts on Airbnb, a platform focused on accommodation sharing, to understand how they attempt to cope with the inherent lack of credible quality signals as they join the platform. By analyzing close to 47,000 listings, we find that new hosts follow a cost-leadership strategy rather than trying to differentiate their offerings. We also analyze how this strategy changes depending on prior platform-specific experience of hosts.
The SAM Domains of Anks Family Proteins Are Critically Involved in Modulating the Degradation of EphA Receptors

ABSTRACT We recently reported that the phosphotyrosine-binding (PTB) domain of Anks family proteins binds to EphA8, thereby positively regulating EphA8-mediated signaling pathways. In the current study, we identified a potential role for the SAM domains of Anks family proteins in EphA signaling. We found that SAM domains of Anks family proteins directly bind to ubiquitin, suggesting that Anks proteins regulate the degradation of ubiquitinated EphA receptors. Consistent with the role of Cbl ubiquitin ligases in the degradation of Eph receptors, our results revealed that the ubiquitin ligase c-Cbl induced the ubiquitination and degradation of EphA8 upon ligand binding. Ubiquitinated EphA8 also bound to the SAM domains of Odin, a member of the Anks family proteins. More importantly, the overexpression of wild-type Odin protected EphA8 and EphA2 from undergoing degradation following ligand stimulation and promoted EphA-mediated inhibition of cell migration. In contrast, a SAM domain deletion mutant of Odin strongly impaired the function of endogenous Odin, suggesting that the mutant functions in a dominant-negative manner. An analysis of Odin-deficient primary embryonic fibroblasts indicated that Odin levels play a critical role in regulating the stability of EphA2 in response to ligand stimulation. Taken together, our studies suggest that the SAM domains of Anks family proteins play a pivotal role in enhancing the stability of EphA receptors by modulating the ubiquitination process.
Does the Authenticity of Preclinical Teaching Format Affect Subsequent Clinical Clerkship Outcomes? A Prospective Randomized Crossover Trial

Background: Educational theories predict conflicting results for the effect of increasing the authenticity of the teaching format of complex information on educational outcomes. We sought to determine the effect of increasingly authentic small-group, preclerkship teaching format on clerkship outcomes to further enlighten this debate. Summary: Students enrolled in a prospective randomized crossover trial that involved three content areas. For each content area, three teaching formats were tested. Participants were randomized to teaching format by content area. Clerkship outcomes were performance on an objective structured clinical exam, a DVD exam, internal medicine clerkship grades, and performance on the subject examination. The data were analyzed using a multivariate analysis of covariance. One hundred and thirty-three (78%) students participated. Teaching format did not have a statistically significant effect on any of the specified clerkship outcomes. However, number of patients seen was significantly associated with higher scores in respective outcomes by topic. Conclusions: Second-year teaching format did not directly influence subsequent clerkship performance. Our study adds to the literature by demonstrating that the authenticity of preclinical teaching format does not appear to matter for clerkship performance; however, the number of actual patients seen does appear to influence related clerkship outcomes.
Ending the microfoundations hegemony

The New Classical Counter Revolution changed macromodelling methodology and ushered in the hegemony of microfounded models. Yet, in reality, at any particular point in time there is a trade-off between data coherence and theoretical coherence, and insisting that all academically respectable modelling should be at one extreme of this trade-off is a major mistake. The paper argues that if more traditional structural econometric models (SEMs) had been developed alongside microfounded models, links between finance and the real economy would have been more thoroughly explored before the financial crisis, allowing macroeconomists to respond better to the Great Recession. Just as microfoundations hegemony held back macroeconomics on that occasion, it is likely to do so again. Macroeconomics will develop more rapidly in useful directions if microfounded models and more traditional SEMs work alongside each other, and are accorded equal academic respect.
Mammographic screening in women more than 64 years old: a comparison of 1- and 2-year intervals.

OBJECTIVE The purpose of our study was to determine if annual mammographic screening was superior to biennial screening in women more than 64 years old by examining differences in various prognostic indicators. MATERIALS AND METHODS We reviewed the records of 119 consecutive women 65 years old and older with 120 cases of breast cancer who had a previous normal screening evaluation for breast cancer that included mammography and physical examination 8-30 months before diagnosis. A search of the computerized tumor registry, clinical records, and breast imaging records from November 1988 to April 1995 provided our cases. Screening intervals were defined as 6-18 months (annual) and 19-30 months (biennial). Mammographic, histologic, and clinical features were reviewed. Disease severity (DS) levels were assigned to each tumor as follows: DS-1 included minimal disease (ductal carcinoma in situ [TisNO], T1aN0, and T1bN0 tumors), DS-2 included all T1cN0 tumors, DS-3 included tumors larger than 2 cm in diameter with lymph nodes that were negative for cancer, and DS-4 included all metastatic disease. Statistically significant differences were calculated using the Wilcoxon rank sum test, Fisher's exact test, and the chi-square test. RESULTS Ninety-three tumors were found in the group of patients who were annually screened, and 27 were found in the group of patients who were screened biennially. The women who underwent yearly screening mammography had significantly smaller invasive tumors (average, 10.7 mm; median, 9.5 mm versus 16.5 mm and 15.0 mm, respectively; p = .0086). The women who were screened annually also had significantly less advanced disease than women screened biennially (annually screened patients versus biennially screened patients: DS-1, 72% versus 44%; DS-2, 23% versus 37%; DS-3, 2% versus 11%; DS-4, 3% versus 7%; p = .0071). The group of patients screened annually had fewer cases of lymph node metastases (3% versus 8%; p = .12) and three times as many cases of ductal carcinoma in situ (22% versus 7%, p = .10). CONCLUSION Annual screening mammography revealed significantly smaller tumors and less advanced cases of cancer than biennial screening, providing inferential support for annual mammographic screening of women more than 64 years old.
The impact of attitudes and aspirations on educational attainment and participation

The ‘poverty gap’ in education means that children from poorer families tend to do less well at school and beyond. It is crucial to know whether this situation can be improved by activities to enhance the beliefs and behaviour of the most educationally marginalised families. If attitudes and aspirations do cause higher levels of attainment, then appropriate interventions can be developed. But if they do not, then money and effort is being wasted on approaches that may even have damaging side effects. This all-encompassing review of existing evidence provides summaries on a range of areas, from parental expectations to child substance abuse.