Miracle-dz/UniFAR-FTUs huggingface dataset:
An atomic force microscopy analysis of yeast mutants defective in cell wall architecture

Yeast cells are surrounded by a thick cell wall, the composition and structure of which have been characterized by biochemical and genetic methods. In this study, we used atomic force microscopy (AFM) to visualize the cell surface topography and to determine cell wall nanomechanical properties of yeast mutants defective in cell wall architecture. While all mutants investigated showed some alteration in cell surface topography, this alteration was particularly salient in mutants defective in β‐glucan elongation (gas1), chitin synthesis (chs3) and cross‐linkages between chitin and β‐glucan (crh1crh2). In addition, these alterations in surface topology were accompanied by increased roughness of the cell. From force–indentation curves, the Young's modulus was determined, as it gives a measure of the elasticity of the cell wall. A value of ∼1.6 MPa was obtained for the cell walls of the wild‐type strain in exponential and stationary phases of growth. The same value was measured in a mnn9 mutant defective in protein mannosylation, and was two‐fold reduced in a mutant with reduced β‐glucan (fks1Δ and knr4Δ), only in the stationary phase of growth. In contrast, the elasticity was dramatically reduced in mutants defective in chitin synthesis (chs3Δ), β‐glucan elongation (gas1Δ) and, even more remarkably, in a crh1Δcrh2Δ mutant defective in the enzymes that catalyse cross‐linkages of chitin to β‐glucan. Taken together, these results provide direct physical evidence that the nanomechanical properties of the yeast cell wall are mainly dependent on cross‐links and cell wall remodelling, rather than on cell wall composition or thickness. Copyright © 2010 John Wiley & Sons, Ltd.
Pediatric cardiac readmissions: An opportunity for quality improvement?

OBJECTIVE Hospital readmissions are increasingly becoming a metric for quality in the current landscape of changing and cost effective medicine. However, no 30-d readmission rates have been established for pediatric cardiac medical patients in the United States. Thus, the objective was to determine 30 d readmission rates and risk factors associated with readmission for pediatric cardiac patients, hypothesizing that pediatric cardiac patients would have significantly higher readmission rates than their general pediatric counterparts. DESIGN This was a retrospective cohort study. SETTING The study took place at a large urban academic children's hospital. PATIENTS The 1124 included patients were discharged from the medical cardiology service and had an unplanned readmission within 30 d during the period of 2012-2014. MEASURES Admissions, readmissions, diagnoses, demographics, weights, medications, procedures, length of stay, were all measured. RESULTS There were 1993 visits and 408 (20.5%) 30-d readmissions in our study. Among the 1124 patients, 219 (19.5%) had at least one 30-d readmission. Patient factors associated with increased likelihood of 30-d readmission were younger age (median: 197.5 vs 1365.5 d, P < .0001), lower discharge weight (6.2 v 14.5 kg, P < .0001) and greater number of diagnoses (P < .0001). The encounter factor associated with a 30-d readmission was longer length of stay (4 vs 2 d, P < 0.0001). Factors associated with decreased readmissions were having had an electrophysiology procedure during their stay, taking an angiotensin converting enzyme inhibitor/angiotensin receptor blocker or taking an antibiotic. CONCLUSIONS Readmissions within 30 d among pediatric cardiology patients are common. The most common factors associated with readmissions are not likely to be modifiable but may serve as important prognostic indicators and as a basis for counseling.
Extracellular Signal-Regulated Kinase Binds to TFII-I and Regulates Its Activation of the c-fosPromoter

ABSTRACT We have previously shown that TFII-I enhances transcriptional activation of the c-fos promoter through interactions with upstream elements in a signal-dependent manner. Here we demonstrate that activated Ras and RhoA synergize with TFII-I for c-fospromoter activation, whereas dominant-negative Ras and RhoA inhibit these effects of TFII-I. The Mek1 inhibitor, PD98059 abrogates the enhancement of the c-fos promoter by TFII-I, indicating that TFII-I function is dependent on an active mitogen-activated protein (MAP) kinase pathway. Analysis of the TFII-I protein sequence revealed that TFII-I contains a consensus MAP kinase interaction domain (D box). Consistent with this, we have found that TFII-I forms an in vivo complex with extracellular signal-related kinase (ERK). Point mutations within the consensus MAP kinase binding motif of TFII-I inhibit its ability to bind ERK and its ability to enhance the c-fos promoter. Therefore, the D box of TFII-I is required for its activity on the c-fos promoter. Moreover, the interaction between TFII-I and ERK can be regulated. Serum stimulation enhances complex formation between TFII-I and ERK, and dominant-negative Ras abrogates this interaction. In addition, TFII-I can be phosphorylated in vitro by ERK and mutation of consensus MAP kinase substrate sites at serines 627 and 633 impairs the phosphorylation of TFII-I by ERK and its activity on the c-fos promoter. These results suggest that ERK regulates the activity of TFII-I by direct phosphorylation.
Antecedents of adolescent initiation of sex, contraceptive use, and pregnancy.

OBJECTIVE To identify the most important antecedents associated with adolescent initiation of sex, contraceptive use, and pregnancy. METHODS Statistically significant antecedents in more than 250 studies were identified and summarized. RESULTS More than 100 antecedents create a complex and detailed picture of the correlates of adolescent sexual behaviors. They describe characteristics of the adolescents themselves, their partners, peers, families, schools, and communities, as well as relationships to these entities. They included antecedents that were inherently sexual and nonsexual. CONCLUSIONS To reduce teen pregnancy substantially, multiple sexual and nonsexual antecedents in different clusters may need to be addressed.
Antibody profile to Borrelia burgdorferi in veterinarians from Nuevo León, Mexico, a non-endemic area of this zoonosis

Objectives Lyme disease is a tick-borne disease caused by infections with Borrelia. Persons infected with Borrelia can be asymptomatic or can develop disseminated disease. Diagnosis and recognition of groups at risk of infection with Borrelia burgdorferi is of great interest to contemporary rheumatology. There are a few reports about Borrelia infection in Mexico, including lymphocytoma cases positive to B. burgdorferi sensu stricto by PCR and a patient with acrodermatitis chronica atrophicans. Veterinarians have an occupational risk due to high rates of tick contact. The aim of this work was to investigate antibodies to Borrelia in students at the Faculty of Veterinary Medicine and Zootechnics, at Nuevo León, Mexico, and determine the antibody profile to B. burgdorferi antigens. Material and methods Sera were screened using a C6 ELISA, IgG and IgM ELISA using recombinant proteins from B. burgdorferi, B. garinii and B. afzelii. Sera with positive or grey-zone values were tested by IgG Western blot to B. burgdorferi sensu stricto. Results All volunteers reported tick exposures and 72.5% remembered tick bites. Only nine persons described mild Lyme disease related symptoms, including headaches, paresthesias, myalgias and arthralgias. None of the volunteers reported erythema migrans. Nine samples were confirmed by IgG Western blot. The profile showed 89% reactivity to OspA, 67% to p83, and 45% to BmpA. Conclusions Positive sera samples shared antibody reactivity to the markers of late immune response p83 and BmpA, even if individuals did not present symptoms of Lyme arthritis or post-Lyme disease. The best criterion to diagnose Lyme disease in our country remains to be established, because it is probable that different strains coexist in Mexico. This is the first report of antibodies to B. burgdorferi in Latin American veterinarians. Veterinarians and high-risk people should be alert to take precautionary measures to prevent tick-borne diseases.
Relationships Between Cognitive and Behavioral Measures of Executive Function in Children With Brain Disease

This study addressed the clinical and construct validity of the Behavior Rating Inventory of Executive Function. (BRIEF: Gioia, Isquith, Guy, & Kenworthy, 2000), a questionnaire designed to tap behavioral aspects of executive functions in children. BRIEF profiles in early treated phenylketonuria (PKU; n = 44), early treated hydrocephalus (n = 45), frontal focal lesions (n = 20) and controls (n = 80) were examined. Clinical validity was supported through significant between-group comparisons, especially between the frontal focal lesion group and other groups. To examine construct validity, raw scores on cognitive executive function measures including the Contingency Naming Test (CNT), Rey Complex Figure (RCF), Tower of London (TOL), and Controlled Oral Word Association Test (COWAT), were correlated with BRIEF scale scores. Few significant correlations were found, indicating cognitive and behavioral measures appear to tap different constructs within the executive function domain. A dissociation was found between behavioral and cognitive impairments in the frontal as opposed to PKU and hydrocephalus groups. This is discussed in relation to underlying pathology, the cognitive measures used, and possible limitations in the BRIEF's usefulness for measuring behavioral executive dysfunction in groups only mildly affected by neurological compromise.
The Antitumor Effect of GDC-0941 Alone and in Combination with Rapamycin in Breast Cancer Cells

Background: The phosphatidylinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a key potential target in breast cancer therapy. Because some cancer cell lines are resistant to mTOR inhibition, we combined the mTOR inhibitor with the PI3K inhibitor and assayed the inhibitory effect of this combination versus that of a single inhibitor. Methods: The proliferation of MCF7, SK-BR-3, T-47D, and MDA-MB-231 cells was measured by MTT assay in the presence of GDC-0941 and/or rapamycin. Afterwards, we determined the visible changes in signaling in the PI3K/AKT/mTOR pathway by Western blotting. Results: GDC-0941 exhibited excellent inhibition on MCF7, T-47D and SK-BR-3 cells with different characteristics. In addition, GDC-0941 blocked the feedback of PI3K/Akt through S6K1, resulting in decreased Akt activity by rapamycin activation. The combination of GDC-0941 and rapamycin downregulated the key components of the cell cycle machinery, such as cyclin D1 and upregulated the apoptotic markers. Conclusion: Our findings suggest that GDC-0941, either alone or in combination with rapamycin, may serve as a new, promising approach for breast cancer treatment.
Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence

Significance Factors that influence the virulence of HIV are of direct relevance to ongoing efforts to contain, and ultimately eradicate, the HIV epidemic. We here investigate in Botswana and South Africa, countries severely affected by HIV, the impact on HIV virulence of adaptation of HIV to protective HLA alleles such as HLA-B*57. In Botswana, where the epidemic started earlier and reached higher adult seroprevalence than in South Africa, HIV replication capacity is lower. HIV is also better adapted to HLA-B*57, which in Botswana has no protective effect, in contrast to its impact in South Africa. Modelling studies indicate that increasing antiretroviral therapy access may also contribute to accelerated declines in HIV virulence over the coming decades. It is widely believed that epidemics in new hosts diminish in virulence over time, with natural selection favoring pathogens that cause minimal disease. However, a tradeoff frequently exists between high virulence shortening host survival on the one hand but allowing faster transmission on the other. This is the case in HIV infection, where high viral loads increase transmission risk per coital act but reduce host longevity. We here investigate the impact on HIV virulence of HIV adaptation to HLA molecules that protect against disease progression, such as HLA-B*57 and HLA-B*58:01. We analyzed cohorts in Botswana and South Africa, two countries severely affected by the HIV epidemic. In Botswana, where the epidemic started earlier and adult seroprevalence has been higher, HIV adaptation to HLA including HLA-B*57/58:01 is greater compared with South Africa (P = 7 × 10−82), the protective effect of HLA-B*57/58:01 is absent (P = 0.0002), and population viral replicative capacity is lower (P = 0.03). These data suggest that viral evolution is occurring relatively rapidly, and that adaptation of HIV to the most protective HLA alleles may contribute to a lowering of viral replication capacity at the population level, and a consequent reduction in HIV virulence over time. The potential role in this process played by increasing antiretroviral therapy (ART) access is also explored. Models developed here suggest distinct benefits of ART, in addition to reducing HIV disease and transmission, in driving declines in HIV virulence over the course of the epidemic, thereby accelerating the effects of HLA-mediated viral adaptation.
Improving prescription auxiliary labels to increase patient understanding.

OBJECTIVES To develop new, easy-to-understand prescription auxiliary labels, assess patient understanding of both new and existing labels, and compare the effectiveness of existing labels with the newly developed ones. DESIGN Cross-sectional study. SETTING Semistructured interviews. PARTICIPANTS Convenience sample of adults from minority populations who were currently taking or had previously taken a prescription medication and could understand English. INTERVENTION Easy-to-understand prescription auxiliary labels were developed. Both these newly created labels and existing labels were shown to participants. Participants' health literacy levels and understanding of the information provided on the labels were determined. The reading difficulty of the auxiliary labels was determined using a Lexile Score. MAIN OUTCOME MEASURES Interpretation and understanding of prescription auxiliary labels. RESULTS The study included 120 participants with a mean age of 40 years (SD = 14). All existing prescription auxiliary labels yielded less than 50% "excellent" interpretations except for those indicating "Take with food" and "Do not chew or crush. " The newly designed labels were better understood compared with existing labels. Some existing labels yielded Lexile scores above the sixth-grade reading level. There was an association between higher levels of education (χ2 = 20.86, P = 0.02) or higher REALM-R (Rapid Estimate of Adult Literacy in Medicine, Revised) scores (χ2 = 26.79, P = 0.02) and better interpretation of auxiliary labels. CONCLUSION Simpler auxiliary labels with improved patient comprehension can be developed. Auxiliary label understanding and interpretation is low for commonly used labels. Pharmacies should consider using existing manufacturer auxiliary labels that meet the criteria for patients with low literacy.
Bone Morphogenetic Protein 7 (BMP-7) Influences Tendon-Bone Integration In Vitro

Introduction Successful graft ingrowth following reconstruction of the anterior cruciate ligament is governed by complex biological processes at the tendon-bone interface. The aim of this study was to investigate in an in vitro study the effects of bone morphogenetic protein 7 (BMP-7) on tendon-bone integration. Materials and Methods To study the biological effects of BMP-7 on the process of tendon-bone-integration, two independent in vitro models were used. The first model involved the mono- and coculture of bovine tendon specimens and primary bovine osteoblasts with and without BMP-7 exposure. The second model comprised the mono- and coculture of primary bovine osteoblasts and fibroblasts. Alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lactate and osteocalcin (OCN) were analyzed by ELISA. Histological analysis and electron microscopy of the tendon specimens were performed. Results In both models, positive effects of BMP-7 on ALP enzyme activity were observed (p<0.001). Additionally, similar results were noted for LDH activity and lactate concentration. BMP-7 stimulation led to a significant increase in OCN expression. Whereas the effects of BMP-7 on tendon monoculture peaked during an early phase of the experiment (p<0.001), the cocultures showed a maximal increase during the later stages (p<0.001). The histological analysis showed a stimulating effect of BMP-7 on extracellular matrix formation. Organized ossification zones and calcium carbonate-like structures were only observed in the BMP-stimulated cell cultures. Discussion This study showed the positive effects of BMP-7 on the biological process of tendon-bone integration in vitro. Histological signs of improved mineralization were paralleled by increased rates of osteoblast-specific protein levels in primary bovine osteoblasts and fibroblasts. Conclusion Our findings indicated a role for BMP-7 as an adjuvant therapeutic agent in the treatment of ligamentous injuries, and they emphasized the importance of the transdifferentiation process of tendinous fibroblasts at the tendon-bone interface.
Recovery of Egomotion and Segmentation of Independent Object Motion Using the EM Algorithm

Motion in image sequences can result from the motion of the observer (egomotion) and from the presence of independently moving objects (IMOs) within the field of view of the observer. Any vision system intended for all observer capable of motion needs the ability to distinguish between these two possibilities in order to successfully perform navigation and collision avoidance tasks. One approach to motion segmentation is to perform a statistical clustering on a set of local constraints on 3-D motion in the image. This thesis proposes two new methods, based on the EM algorithm, to perform robust motion segmentation on image sequences that contain IMOs. The first method uses statistical clustering of linear and bilinear constraints (derived from computed optical flow using subspace methods) on 3-D translation and rotation. The problems of outlier detection and determining number of processes and their initial parameters for the EM algorithm are considered. Also, analysis of the effects of IMO boundaries on linear constraints, as well as a derivation for the removal of bias inherent in translation estimates from linear constraints, are presented. Effects of fixation on detection of IMOs are considered. A framework for hypothesizing about motions underlying a set of constraint clusters is detailed. There exist situations in which 3-D motion constraints are not sufficient to perform segmentation. The second method tracks depth-structure over time and evaluates rigidity allowing IMOs to be identified as outliers. Results obtained from four image sequences are presented. The first sequence is synthetic optic flow generated from a depth map and contains one IMO. The second sequence was captured from a robot moving in an industrial environment. The third sequence is similar to the second, except the flow has been generated using a regularly spaced grid which assumes no prior segmentation of the image. The fourth sequence illustrates a case in which the 3-D constraints are insufficient to perform the segmentation, and the estimation of depth structure is needed to solve the problem. Finally, directions for future research into this problem are presented.
Chronic exposure to nicotine impairs cholinergic angiogenesis

Cholinergic angiogenesis is mediated by an endothelial nicotinic acetylcholine receptor (EC nAChR). Short-term administration of nicotine stimulates angiogenesis via EC nAChRs.The long-term effects of nicotine upon cholinergic angiogenesis are unknown. The objective of this study was to determine whether chronic nicotine exposure blunts angiogenesis. We exposed C57/Bl6 male mice (n = 42) to nicotine (200 μg/ml drinking water) or vehicle for 8 or 16 weeks. Subsequently, hindlimb ischemia was induced by ligation of the left femoral artery. After surgery, animals in the vehicle-treated group were re-randomized to vehicle (vehicle group) or nicotine (acute exposure group) for 2 weeks; whereas animals that had been previously treated (for 8 or 16 weeks with nicotine) continued to receive nicotine (8 WK or 16 WK groups). After 2 weeks, animals were sacrificed for immunohistochemical, gene expression, and angiogenesis studies. Capillary density of the ischemic hindlimb was increased by nicotine in naïve animals (vehicle vs acute exposure: 2.40 ± 0.09 vs 2.82 ± 0.10 capillaries/myocyte, p < 0.05). However, prior exposure to nicotine for 16 weeks (16 WK) abolished the effects of nicotine to increase capillary density in the ischemic hindlimb (acute vs 16 WK: 2.82 ± 0.10 vs 2.47 ± 0.03 capillaries/ myocyte; p < 0.05). The impairment of cholinergic angiogenesis was associated with a reduction in nAChR expression and plasma VEGF levels. Chronic exposure to nicotine impaired capillary sprouting of aortic segments ex vivo (vehicle vs 16 WK: 0.303 ± 0.029 vs 0.204 ± 0.017 mm2, p < 0.05, n = 3 in each group). In conclusion, the current study shows for the first time that chronic exposure to nicotine impairs cholinergic angiogenesis, an effect mediated by downregulation of the vascular nAChR, and attenuation of nicotine-induced VEGF release. These studies may explain the impairment in angiogenic processes observed in long-term smokers.
Human cellular and humoral immune responses to Phlebotomus papatasi salivary gland antigens in endemic areas differing in prevalence of Leishmania major infection

Background Sand fly saliva compounds are able to elicit specific immune responses that have a significant role in Leishmania parasite establishment and disease outcome. Characterizing anti-saliva immune responses in individuals living in well defined leishmaniasis endemic areas would provide valuable insights regarding their effect on parasite transmission and establishment in humans. Methodology/Principal findings We explored the cellular and humoral immune responses to Phlebotomus (P.) papatasi salivary gland extracts (SGE) in individuals living in cutaneous leishmaniasis (CL) old or emerging foci (OF, EF). OF was characterized by a higher infection prevalence as assessed by higher proportions of leishmanin skin test (LST) positive individuals compared to EF. Subjects were further subdivided into healed, asymptomatic or naïve groups. We showed anti-SGE proliferation in less than 30% of the individuals, regardless of the immune status, in both foci. IFN-γ production was higher in OF and only observed in immune individuals from OF and naïve subjects from EF. Although IL-10 was not detected, addition of anti-human IL-10 antibodies revealed an increase in proliferation and IFN-γ production only in individuals from OF. The percentage of seropositive individuals was similar in immune and naïves groups but was significantly higher in OF. No correlation was observed between anti-saliva immune responses and LST response. High anti-SGE-IgG responses were associated with an increased risk of developing ZCL. No differences were observed for anti-SGE humoral or cellular responses among naïve individuals who converted or not their LST response or developed or not ZCL after the transmission season. Conclusions/Significance These data suggest that individuals living in an old focus characterized by a frequent exposure to sand fly bites and a high prevalence of infection, develop higher anti-saliva IgG responses and IFN-γ levels and a skew towards a Th2-type cellular response, probably in favor of parasite establishment, compared to those living in an emerging focus.