Miracle-dz/UniFAR-FTUs huggingface dataset:
Contortrostatin, a Homodimeric Snake Venom Disintegrin, Is a Potent Inhibitor of Osteoclast Attachment

Disintegrins are small disulfide‐rich proteins containing an Arg‐Gly‐Asp (RGD) sequence near their carboxyl terminus. These polypeptides inhibit binding of adhesion molecules to their receptors (integrins) on the surface of cells. Osteoclasts express integrins, heterodimeric cell surface adhesion receptors, that have been shown to be involved in interactions with the extracellular matrix (ECM), including attachment to bone and bone resorption. It has recently been shown that disintegrins effectively inhibit attachment of osteoclasts to components of the ECM and also disrupt osteoclast‐mediated bone resorption. Here we characterize the effects of contortrostatin (CTS), a novel homodimeric snake venom disintegrin, on osteoclast attachment. Plastic dishes coated with CTS were able to support osteoclast attachment with a high affinity (EC50,CTS = 86 ± 6.7 nM) similar to that of vitronectin (VTN; EC50,VTN = 80 ± 20 nM). Further, CTS was observed to inhibit completely osteoclast attachment to fetal bovine serum (FBS; IC50,FBS = 0.36 ± 0.04 nM) and VTN (IC50,VTN = 0.85 ± 0.13 nM). We used monoclonal antibodies directed against the β1 (monoclonal antibody [MAb] CD29) and β3 (MAb F11) integrin subunits to explore the mechanism of osteoclast attachment to immobilized CTS. Only MAb F11 inhibited attachment to immobilized CTS (IC50 = 0.41 ± 0.12 μg/ml), suggesting that binding to CTS is mediated in part by a β3 integrin, presumably the αvβ3 VTN receptor. In further support of an integrin‐mediated mechanism, binding of osteoclasts to CTS is inhibited by the RGD peptide, GRGDSP. CTS was also more potent (IC50,FBS = 0.36 ± 0.04 nM) at inhibiting osteoclast attachment to FBS‐coated wells than the monomeric snake venom disintegrin echistatin (IC50,FBS = 8.9 ± 1.5 nM) or VTN (IC50,FBS = 97.5 ± 25.5 nM). Taken together, these data suggest that the snake venom disintegrin CTS is a potent inhibitor of β3 integrin‐mediated osteoclast attachment, presumably involving the VTN receptor (an αvβ3 integrin). Further studies of the mechanism of CTS–osteoclast interactions may aid in the design of peptide mimetics to act as antiresorptive agents for the treatment of osteoporosis and other skeletal pathology.
A Quantified Past: Toward Design for Remembering With Personal Informatics

This article questions how people will interact with a quantified past—the growing historical record generated by the increasing use of sensor-based technologies and, in particular, personal informatics tools. In a qualitative study, we interviewed 15 long-term users of different self-tracking tools about how they encountered and made meaning from historical data they had collected. Our findings highlight that even if few people are self-tracking as a form of deliberate lifelogging, many of them generate data and records that become meaningful digital possessions. These records are revealing of many aspects of people’s lives. Through considerable rhetorical data-work, people can appropriate such records to form highly personal accounts of their pasts. We use our findings to identify six characteristics of a quantified past and map an emerging design space for the long-term and retrospective use of personal informatics. Principally, we propose that design should seek to support people in making account of their data and guard against the assumption that more, or “better,” data will be able to do this for them. To this end, we speculate on design opportunities and challenges for experiencing, curating, and sharing historical personal data in new ways.
Chemoarchitecture of GABAergic neurons in the ferret superior colliculus

γ‐Aminobutyric acid (GABA)ergic neurons are thought to play a key role both in visual processing and in the complex sensory‐motor transformations that take place in the mammalian superior colliculus. To understand the organization of GABAergic neurons in the ferret superior colliculus, we applied antisera to several markers of GABAergic function, including GABA, two isoforms of its synthetic enzyme glutamic acid decarboxylase (GAD‐65 and GAD‐67), and the GABA transporter, GAT‐1. We also applied antisera to several calcium binding proteins (calbindin [CB], calretinin [CR], and parvalbumin [PV]) and neuronal nitric oxide synthase (NOS), chemical markers that colocalize with GABA in some areas of the central nervous system. The distribution of GABAergic neurons in the ferret is similar to that of other mammalian species. GABAergic neurons in the ferret superior colliculus were small, morphologically diverse, and widely distributed throughout all layers of the colliculus. As has been shown in other mammalian species, neurons expressing PV, CB, CR, and NOS were differentially distributed in layers and patches throughout the ferret colliculus. None of these markers, however, showed a distribution that mirrored that of GABAergic neurons. Furthermore, few GABAergic neurons colocalized these neurochemical markers. Only 14% of GABAergic neurons in the superficial layers and 18% of neurons in the deeper layers colocalized PV, 14% of GABAergic neurons in the superficial layers and 10% in the deeper layers colocalized CB, and only 1% of GABAergic neurons in both the superficial and deep layers colocalized nitric oxide synthase. Thus, the arrangement of GABAergic neurons in the ferret superior colliculus is broadly distributed and is distinct from other recognized organizational patterns in the superior colliculus. J. Comp. Neurol. 452:334–359, 2002. © 2002 Wiley‐Liss, Inc.
Adaptation to Marginal Habitats

The ability to adapt to marginal habitats, in which survival and reproduction are initially poor, plays a crucial role in the evolution of ecological niches and species ranges. Adaptation to marginal habitats may be limited by genetic, developmental, and functional constraints, but also by consequences of demographic characteristics of marginal populations. Marginal populations are often sparse, fragmented, prone to local extinctions, or are demographic sinks subject to high immigration from high-quality core habitats. This makes them demographically and genetically dependent on core habitats and prone to gene flow counteracting local selection. Theoretical and empirical research in the past decade has advanced our understanding of conditions that favor adaptation to marginal habitats despite those limitations. This review is an attempt at synthesis of those developments and of the emerging conceptual framework.
Effects of aerobic training in adolescents with Down syndrome.

The purpose of this study was to evaluate the effects that aerobic training has on adolescents and young adults with Down syndrome. Fourteen individuals with Down syndrome (mean age = 17.7 yr) participated in a 10-wk walking/jogging exercise training study. A pre- and post-training walking treadmill test was performed to determine the following parameters: peak oxygen uptake (VO2, absolute and relative), minute ventilation (VE, l.min-1), heart rate HR, b.min-1), RER (VCO2/VO2), and time and grade to exhaustion. Following the pre-training evaluations, subjects were assigned to a control group (N = 4) or an exercise group (N = 10). The exercise group underwent a 10-wk walk/jog training program at a frequency of 3 times per week, for a duration of 30 min, and at an intensity of approximately 65-75% peak HR. Following training, both control and experimental groups showed no changes in peak VO2 (absolute and relative), VE, HR, and RER. The exercise group, however, did demonstrate a significant improvement in peak exercise time (and grade). Although the training program did not produce improvements in aerobic capacity, it did produce gains in walking capacity. It was concluded that the adolescents and young adults may not be able to improve their aerobic capacity when performing a walk/jog training program.
MK0787 (N-formimidoyl thienamycin): evaluation of in vitro and in vivo activities

The practical application of thienamycin, a novel beta-lactam antibiotic with a broad activity spectrum, was compromised by problems of instability. MK0787, N-formimidoyl thienamycin, does not have this liability. As reported, bacterial species resistant to most beta-lactam antibiotics, such as Pseudomonas aeurginosa, Serratis, Enterobacter, Enterococcus, and Bacteroides spp. , are uniformly susceptible to MK0787, usually at one-half the inhibitory level of thienamycin. Bactericidal activity usually occurs at the minimal inhibitory concentration endpoint. Activity was reduced only at the highest inoculum densities tested and by a lessor factor than was observed with reference beta-lactam antibiotic active against P. aeruginosa and beta-lactamase-bearing strains. MK0787 exhibits a broad spectrum of in vivo activity when evaluated parenterally for efficacy against systemic infections in mice. The order of potency in vivo, 0.03 to 0.06 mg/kg for gram-positive species and 0.65 to 3.8 mg/kg for gram-negative infections including Pseudomonas, exceeded that of thienamycin and was at least 10-fold superior to reference beta-lactam antibiotics including two recently developed agents with antipseudomonal activity, cefotaxime and LY127935.
Political and socioeconomic instability: how does it affect HIV? A case study in the Democratic Republic of Congo.

Five years ago we reported a low and stable HIV prevalence in selected population groups despite the poor environment and political instability in the Democratic Republic of Congo (DRC). Since then the central government has lost control of almost one third of the country and war is waging across DRC. We hereby report to what extent the ongoing conflict could impact on the stability of HIV prevalence reported in our previous study. From March to May 2002 we conducted HIV serosurveys in four major cities: Kinshasa Mbuji-Mayi Lubumbashi located in the government-held areas and Kisangani under the control of the rebels Rwandan and Ugandan armies. Convenient sampling was obtained among pregnant women attending antenatal clinics tuberculosis patients clinic outpatients blood donors sexually transmitted infection (STI) patients sex workers and internally displaced people (IDP). After informed consent 3090 individuals 2201 women (72.1%) and 889 men (28.8%) were screened for HIV antibody by a rapid assay (Abbott Determine HIV-1/2; Abbott Laboratory Tokyo Japan) or a commercial enzyme-linked immunosorbent assay (Organon Technika Belgium). All reactive specimens were discriminated and confirmed by a line immunoassay (Innolia HIV-1/2; Innogenetics Ghent Belgium). (excerpt)
Effects of Capital Structure on Firmâ€™s Performance: Empirical Study of Manufacturing Companies in Nigeria

This research examines the effect of capital structure on firmâ€™s performance with a case study of manufacturing companies in Nigeria from 2003 to 2012 with the purpose of providing a critical appraisal of the need and importance of capital structure. Descriptive and regression research technique was employed to consider the impact of some key variables such as Returns on asset (ROA), Returns on equity(ROE),Total debt to total asset(TD), Total debt to equity ratio(DE) on firm performance. Secondary data was employed using data derived from ten (10) manufacturing companies. From our findings, we observe that capital structure measures (total debt and debt to equity ratio) are negatively related to firm performance. It is hereby recommended that firms should use more of equity than debt in financing their business activities, in as much as the value of a business can be enhanced using debt capital. Hence firms should establish the point at which the weighted average cost of capital is minimal and maintain that gearing ratio so that the companyâ€™s value will not be eroded, as the firmâ€™s capital structure is optimal at this point ceteris paribus.
Suicide and suicide attempts in Ankara in 1998: results of the WHO/EURO Multicentre Study of Suicidal Behaviour.

BACKGROUND The rates and associated basic demographic features of attempted and completed suicides in a catchment area in Turkey were investigated as part of the WHO/Euro Multicentre Study of Suicidal Behaviour. METHOD All hospitals in the catchment area were screened in order to identify attempted suicides. Statistics for completed suicides were obtained from the State Institute of Statistics (SIS). RESULTS The rates of attempted and completed suicides per 100,000 inhabitants over 15 years of age were 31.9 for males and 85.6 for females, and 9.9 for males and 5.6 for females, respectively. The majority of attempted suicides were in the 15-24-year-old age group, as is the case in all other European countries. The majority of completed suicides were also in the 15-24-year-old age group, although in other European centers most completed suicides occur in the 40+ age group. The most frequent methods were overdose for attempted suicide and hanging for completed suicide. The rates of both attempted and completed suicides were lower than those of other participating centers in Europe. CONCLUSION Male sex is a risk factor for completed suicide and female sex is a risk factor for attempted suicide, while an age of 15-24 years may be a risk factor for both groups.
Sequential Binding of SeqA to Paired Hemi-methylated GATC Sequences Mediates Formation of Higher Order Complexes*

Preferential binding of the SeqA protein to hemi-methylated GATC sequences functions as a negative regulator for Escherichia coli initiation of chromosomal replication at oriC and is implicated in segregating replicated chromosomes for cell division. We demonstrate that sequential binding of one SeqA tetramer to a set of two hemi-methylated sites mediates formation of higher-order complexes. The absence of cross-binding to separate DNAs suggests that two monomers of a SeqA tetramer bind to two hemi-methylated sites on DNA. The interaction among SeqA proteins bound to at least six adjacent hemi-methylated sites induces aggregation of free proteins to bound proteins. Aggregation might be indicative of SeqA foci, which appear to track replication forks in vivo. Studies of the properties of SeqA binding will contribute to our understanding of the function of SeqA.
Efficacy of poly-unsaturated fatty acid therapy on patients with nonalcoholic steatohepatitis.

AIM To examine whether poly-unsaturated fatty acid (PUFA) therapy is beneficial for improving nonalcoholic steatohepatitis (NASH). METHODS In total, 78 patients pathologically diagnosed with NASH were enrolled and were randomly assigned into the control group and the PUFA therapy group (added 50 mL PUFA with 1:1 ratio of EHA and DHA into daily diet). At the initial analysis and after 6 mo of PUFA therapy, parameters of interest including liver enzymes, lipid profiles, markers of inflammation and oxidation, and histological changes were evaluated and compared between these two groups. RESULTS At the initial analysis, in patients with NASH, serum levels of alanine aminotransferase (ALT) and aspartase aminotransferase (AST) were slightly elevated. Triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol levels, markers of systemic inflammation [C-reactive protein (CRP)] and oxidation [malondialdehyde (MDA)], as well as fibrosis parameters of type IV collagen and pro-collagen type III pro-peptide were also increased beyond the normal range. Six months later, ALT and AST levels were significantly reduced in the PUFA group compared with the control group. In addition, serum levels of TG and TC, CRP and MDA, and type IV collagen and pro-collagen type III pro-peptide were also simultaneously and significantly reduced. Of note, histological evaluation showed that steatosis grade, necro-inflammatory grade, fibrosis stage, and ballooning score were all profoundly improved in comparison to the control group, strongly suggesting that increased PUFA consumption was a potential way to offset NASH progression. CONCLUSION Increased PUFA consumption is a potential promising approach for NASH prevention and reversal.
Bacillus Calmette‐Guérin immunotherapy for genitourinary cancer

The administration of Bacillus Calmette‐Guérin (BCG) immunotherapy has become the standard of care for high‐grade non‐muscle invasive bladder cancer (NMIBC) and carcinoma in‐situ (CIS) in terms of prevention of recurrence and progression. While most agree on a 6 week induction cycle, various maintenance schedules (if any at all) have been implemented without a unifying consensus. This review assesses the historical emergence of BCG immunotherapy, beginning with its discovery as a vaccinatin for tuberculosis to its effect on the host immune system and potential therapeutic benefits for various oncologic conditions. The data establishing BCG immunotherapy as the standard of care for high‐grade NMIBC and CIS over other bladder instillation modalities is presented in addition to the effect maintenance BCG therapy has on sustaining the immuno‐protective effect.
African American Adolescent Females' Perceptions of Neighborhood Safety, Familial Strategies, and Sexual Debut

Sexual debut represents a developmental transition that holds possibility for growth and for risk. Family and neighborhood may impact timing of debut. This qualitative study examined family strategies (e.g., moving, parental monitoring), perceptions of neighborhood, and attitudes about sex and sexual debut among sexually experienced and inexperienced African American adolescent females living in disadvantaged urban neighborhoods. Findings show that more familial strategies were reported by sexually inexperienced females, suggesting that strategies may delay sexual debut. Furthermore, experiences with neighborhood violence related to attitudes about sex and sexual debut, suggesting a linkage between death anxiety and sexual debut among female youth.
CXCL12–CXCR7 axis is important for tumor endothelial cell angiogenic property

We reported that tumor endothelial cells (TECs) differ from normal endothelial cells (NECs) in many aspects, such as gene expression profiles. Although CXCR7 is reportedly highly expressed in blood vessels of several tumors, its function in TECs is still unknown. To investigate this role, we isolated TECs from mouse tumor A375SM xenografts, and compared them with NECs from normal mouse dermis. After confirming CXCR7 upregulation in TECs, we analyzed its function using CXCR7 siRNA and CXCR7 inhibitor; CCX771. CXCR7 siRNA and CCX771 inhibited migration, tube formation and resistance to serum starvation in TECs but not in NECs. ERK1/2 phosphorylation was inhibited by CXCR7 knockdown in TECs. These results suggest that CXCR7 promotes angiogenesis in TECs via ERK1/2 phosphorylation. Using ELISA, we also detected CXCL12, a ligand of CXCR7, in conditioned medium from TECs, but not from NECs. CXCL12 neutralizing antibody significantly inhibited TEC random motility. VEGF stimulation upregulated CXCR7 expression in NECs, implying that VEGF mediates CXCR7 expression in endothelial cells. A CXCR7 inhibitor, CCX771 also inhibited tumor growth, lung metastasis and tumor angiogenesis in vivo. Taken together, the CXCL12–CXCR7 autocrine loop affects TEC proangiogenic properties, and could be the basis for an antiangiogenic therapy that specifically targets tumor blood vessels rather than normal vessels.
Treatment of rheumatoid arthritis with a peptide diet: a randomized, controlled trial.

Elemental diets provide food in its simplest formulation and have been used in the treatment of rheumatoid arthritis (RA) and other chronic inflammatory diseases. Such a diet is supposed to be less antigenic to the human immune system than normal food. The aim of this study was to evaluate the clinical effect of an artificial peptide diet as a temporary supplement to conventional treatment. Patients with active RA were single-blindly randomized either to a liquid elemental peptide-diet for four weeks or to continuation of the usual food (control group). In the diet group all normal foods were renounced. Thirty patients were included and followed for six months. The outcome measurements were pain intensity, morning stiffness, HAQ-score, number of swollen joints, joint tenderness, erythrocyte sedimentation rate, and patient's global assessment of health. Two of the fifteen patients assigned to the diet dropped out. The diet resulted in a transient but statistically significant improvement in the average level of pain (P = 0.02), in HAQ-score (P=0.03), and a significant reduction in Body Mass Index (P=0.001). Only one patient in the diet group had a clear remission. Side-effects were frequent but compliance good. The study showed that the peptide diet can improve some subjective and objective disease parameters. Due to the low remission ratio the peptide diet is not a treatment of choice in unselected RA-patients. but the peptide diet might be beneficial to a subset of RA-patients, e.g. patients where foods aggravate disease activity.
From insect eye to vertebrate muscle: redeployment of a regulatory network.

The redeployment of the same signaling systems at different places and times during embryogenesis, and the conservation of these systems across species, from inver-tebrates to vertebrates, has emerged as a major theme of biology. This conservation also applies to transcriptional regulation; the Hox genes are a classic example. More recently a striking illustration of the phenomenon was provided by the demonstration that homologous regulatory genes are responsible for the formation of the om-matidia, which constitute the eye of the fruit fly Drosophila and of the mammalian eye. Furthermore, the transcription factor Pax6, like its Drosophila homolog eyeless, which is at the top of the regulatory cascade, can induce ectopic eye formation in the fly (Halder et al. 1995). The article by Heanue and collegues in this issue of Genes & Development , demonstrates that the same combination of transcriptional regulators required for eye formation is redeployed elsewhere during vertebrate embryogenesis, in this case in the somite and its skeletal muscle derivatives. ,
Cardiopulmonary effects of diazepam

Eighteen patients with appreciable obstructive lung disease and 18 patients without measurable mechanical lung impairment were given intravenous diazepam to permit endoscopy. Doses of diazepam required for comparable level of anesthesia were used. There was an increase in the heart rate, and there were decreases in the blood pressure, stroke volume, left ventricular stroke work, and cardiac output in patients with normal pulmonary function. Total peripheral resistance was elevated after 15 minutes. In patients with obstructive lung disease, diazepam produced insignificant changes in heart rate, diastolic blood pressure, and total peripheral resistance. Left ventricular stroke work, stroke volume, and systolic blood pressure were markedly reduced. There was a depression in alveolar ventilation, associated with an increase ill the arterial carbon dioxide tension and a decrease in pH. The only significant differences in the effects of diazepam on cardiopulmonary function were in diastolic blood pressure and left ventricular stroke work, which were more affected in the control subjects than in the patients. O2 saturation was affected more in the patients than in the control subjects.