Miracle-dz/UniFAR-FTUs huggingface dataset:
Two-step processing for activation of the cytolysin/hemolysin of Vibrio cholerae O1 biotype El Tor: nucleotide sequence of the structural gene (hlyA) and characterization of the processed products

Vibrio cholerae O1 biotype El Tor produces and secretes a 65-kDa cytolysin/hemolysin into the culture medium. We cloned the structural gene (hlyA) for the cytolysin from the total DNA of a V. cholerae O1 El Tor strain, N86. Nucleotide sequence analysis of hlyA revealed an open reading frame consisting of 2,223 bp which can code for a protein of 741 amino acids with a molecular weight of 81,961. Consistent with this, a 79-kDa protein was identified as the product of hlyA by maxicell analysis in Escherichia coli. N-terminal amino acids of this 79-kDa HlyA protein and those of a 65-kDa El Tor cytolysin purified from V. cholerae were Asn-26 and Asn-158, respectively. The 82- and 79-kDa precursors of the 65-kDa mature cytolysin were found in V. cholerae by pulse-chase labeling and Western blot (immunoblot) analysis of hlyA products. Hemolytic activity of the 79-kDa HlyA protein from E. coli was less than 5% that for the 65-kDa cytolysin from V. cholerae. Our results suggest that in V. cholerae, the 82-kDa preprotoxin synthesized in the cytoplasm is secreted through the membranes into the culture medium as the 79-kDa inactive protoxin after cleavage of the signal peptide and is then further processed into the 65-kDa active cytolysin by release of the N-terminal 15-kDa fragment.
Age‐related intrinsic changes in human bone‐marrow‐derived mesenchymal stem cells and their differentiation to osteoblasts

In vivo and in vitro studies indicate that a subpopulation of human marrow‐derived stromal cells (MSCs, also known as mesenchymal stem cells) has potential to differentiate into multiple cell types, including osteoblasts. In this study, we tested the hypothesis that there are intrinsic effects of age in human MSCs (17–90 years). We tested the effect of age on senescence‐associated β‐galactosidase, proliferation, apoptosis, p53 pathway genes, and osteoblast differentiation in confluent monolayers by alkaline phosphatase activity and osteoblast gene expression analysis. There were fourfold more human bone MSCs (hMSCs) positive for senescence‐associated β‐galactosidase in samples from older than younger subjects (P < 0.001; n = 17). Doubling time of hMSCs was 1.7‐fold longer in cells from the older than the younger subjects, and was positively correlated with age (P = 0.002; n = 19). Novel age‐related changes were identified. With age, more cells were apoptotic (P = 0.016; n = 10). Further, there were age‐related increases in expression of p53 and its pathway genes, p21 and BAX. Consistent with other experiments, there was a significant age‐related decrease in generation of osteoblasts both in the STRO‐1+ cells (P = 0.047; n = 8) and in adherent MSCs (P < 0.001; n = 10). In sum, there is an age‐dependent decrease in proliferation and osteoblast differentiation, and an increase in senescence‐associated β‐galactosidase‐positive cells and apoptosis in hMSCs. Up‐regulation of the p53 pathway with age may have a critical role in mediating the reduction in both proliferation and osteoblastogenesis of hMSCs. These findings support the view that there are intrinsic alterations in human MSCs with aging that may contribute to the process of skeletal aging in humans.
Statins and neuroprotection

The beneficial effect of β-hydroxy-β-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in primary prevention of coronary artery disease in those with hypercholesterolaemia and in secondary prevention in those with established coronary vascular disease are now well known. A growing body of evidence suggests that statins also possess important additional clinical benefits, such as stroke risk reduction. In this article we review the evidence that statins may be neuroprotective, especially in the brain parenchyma during stroke. We also review the observational data that statins may prevent the onset of dementia.
In vitro cytotoxicity assessment of roundup (glyphosate) in L-02 hepatocytes

ABSTRACT The goal of the present study was to elucidate the in vitro cytotoxicity of Roundup and to reveal the possible related mechanisms in L-02 hepatocytes. By detecting reactive oxygen species (ROS) production, glutathione (GSH)/superoxide dismutase (SOD) levels, mitochondrial permeability transition pore (PTP) open rate, apoptosis-inducing factor (AIF) release, intracellular Ca2+ concentration, and alanine aminotransferease (ALT)/aspartate aminotransferase (AST) leakage, we determined that Roundup induced anti-oxidant system inhibition, mitochondria damage, DNA damage, membrane integrity and permeability changes, and apoptosis in L-02 hepatocytes. By revealing the mechanistic insights of Roundup-induced cytotoxicity, our results are valuable for the design of preventive and therapeutic strategies for the occupational population exposed to Roundup and other pesticides.
Female Mate Choice in Mammals

Studies of mate choice in vertebrates have focused principally on birds, in which male ornaments are often highly developed, and have shown that females commonly select mates on the basis of particular phenotypic characteristics that may reflect their genetic quality. Studies of female mate choice in mammals are less highly developed, and they have commonly focused on female mating preferences that are likely to be maintained by benefits to the female's own survival or breeding success. However, recent experimental studies of mate choice in mammals—especially rodents—provide increasing evidence of consistent female preferences that appear likely to generate benefits to the fitness of offspring. As yet, there is no compelling evidence that female mating preferences are less highly developed in female mammals than in female birds, although these preferences may more often be masked by the effects of male competition or of attempts by males to constrain female choice.
CD40 Activates NF-κB and c-Jun N-Terminal Kinase and Enhances Chemokine Secretion on Activated Human Hepatic Stellate Cells1

Activated hepatic stellate cells (HSCs) are the main producers of extracellular matrix in the fibrotic liver and contribute to hepatic inflammation through the secretion of chemokines and the recruitment of leukocytes. This study assesses the function of CD40 on human HSCs. Activated human HSCs express CD40 in culture and in fibrotic liver, as determined by flow cytometry, RT-PCR, and immunohistochemistry. CD40 expression is strongly enhanced by IFN-γ. Stimulation of CD40 with CD40 ligand (CD40L)-transfected baby hamster kidney cells induces NF-κB, as demonstrated by the activation of I-κB kinase (IKK), increased NF-κB DNA binding, and p65 nuclear translocation. CD40-activated IKK also phosphorylates a GST-p65 substrate at serine 536 in the transactivation domain 1. Concomitant with the activation of IKK, CD40L-transfected baby hamster kidney cell treatment strongly activates c-Jun N-terminal kinase. CD40 activation increases the secretion of IL-8 and monocyte chemoattractant protein-1 by HSCs 10- and 2-fold, respectively. Adenovirally delivered dominant negative (dn) IKK2 and TNFR-associated factor 2dn inhibit IKK-mediated GST-I-κB and GST-p65 phosphorylation, NF-κB binding, and IL-8 secretion, whereas IKK1dn and NF-κB-inducing kinase dominant negative do not have inhibitory effects. We conclude that the CD40-CD40L receptor-ligand pair is involved in a cross-talk between HSCs and immune effector cells that contributes to the perpetuation of HSC activation in liver fibrosis through TNFR-associated factor 2- and IKK2-dependent pathways.
Risk-Minimizing Belief: Its Association with Smoking and Risk of Harm From Smoking in Northern Thailand

Risk-minimizing beliefs refer to the underestimation of the health risks of particular behaviors. The aim of the study was to investigate the associations between risk-minimizing belief with smoking and the risk of harms from smoking in Northern Thailand (N=3,865). Adjusting for potential confounders, risk-minimizing belief was inversely associated with lifelong abstinence, positively associated with increased risk of being a current smoker, and weakly associated with increased risk of harm from smoking. Targeting risk-minimizing beliefs in current smokers and those who have never smoked may be useful in the Northern Thai population.
Simulation of oligopeptide dynamics and folding. The use of NMR chemical shifts to analyse the MD trajectories

In this paper, a simulation of the folding process, based on a random perturbations of the ϕ, ψ, χ1 dihedral angles, is proposed to approach the formation at the atom level of both principal elements of protein secondary structure, the α‐helix and the β‐hairpin structures. Expecting to understand what may happen in solution during the formation of such structures, the behaviour of large sets of random conformations that are generated for small oligopeptides was analysed. Different factors that may influence the folding (as conformational propensity, hydrophobic interactions and side‐chain mobility) were investigated. The difference between the corresponding theoretical folding and the real conformational diversity that is observed in solution is appraised by a comparison between the calculated and observed NMR secondary chemical shifts. From this study it appears that hydrophobic interactions and mobility represent the principal factors that initiate folding and determine the observed hydrogen‐bond pattern, which subsequently allows packing between the peptide side chains. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.
What's in a Name: False Assumptions about DNS Names

The Domain Name System (DNS) provides an essential service on the Internet, mapping structured names to a variety of data, usually IP addresses. These names appear in email addresses, Uniform Resource Identifiers (URIs), and other application-layer identifiers that are often rendered to human users. Because of this, there has been a strong demand to acquire names that have significance to people, through equivalence to registered trademarks, company names, types of services, and so on. There is a danger in this trend; the humans and automata that consume and use such names will associate specific semantics with some names and thereby make assumptions about the services that are, or should be, provided by the hosts associated with the names. Those assumptions can often be false, resulting in a variety of failure conditions. This document discusses this problem in more detail and makes recommendations on how it can be avoided. This memo provides information for the Internet community.
The Zoomorphic Figurines from Sha'ar Hagolan: Hunting Magic Practices in the Neolithic Near East

Abstract While much attention has been paid to the anthropomorphic figurines of the Yarmukian culture, very little is known about the zoomorphic representations made by the same people. This paper fills the gap by presenting a full corpus of the zoomorphic figurines uncovered at Sha'ar Hagolan, the type site of the Yarmukian culture. There are 38 items, all illustrated by drawings and a few by photographs. In addition, several zoomorphic figurines from Pre-Pottery Neolithic B Munhata have been re-examined and are discussed here.
Entrustability of professional activities and competency‐based training

The idea of competency-based training (CBT) seems to have entered medical education with a speed and impact that has outperformed problem-based learning in the 1980s and 1990s. Within less than 10 years, the CanMEDS competencies in Canada, the ACGME competencies in the United States and similar frameworks in other countries have been introduced for postgraduate medical training countrywide, and examples of competency-based undergraduate medical training have now begun to emerge. The growing number and impact of medical education journals and medical education conferences have helped in the spread of what could almost be called a ‘competencies hype’. It is likely that 2000–10 will be remembered as the decade of CBT in medical education. Competencybased training could remain in our memories as a lasting change that really advanced medical training. However, if we do not want to end up 10 years from now with the conclusion that a ‘competency’ was essentially nothing but a label, replacing what we conveniently used to call ‘educational objective’, it will now be necessary to specify its definition and translate it into daily practice. Signs of confusion about the concept of competency are already visible in the literature from fields other than medical education. The way in which we succeed in defining competencies, implement competency-based education and – most crucially ) assess competencies will be critical.
PKC-selectively controls the adhesion-stimulating molecule Rap 1

The antigen-specific interaction of a T cell with an antigen-presenting cell (APC) results in the formation of an immunologic synapse (IS) between the membranes of the 2 cells. 2 integrins on the T cell, namely, leukocyte function-associated antigen 1 (LFA-1) and its counter ligand, namely, immunoglobulin-like cell adhesion molecule 1 (ICAM-1) on the APC, critically stabilize this intercellular interaction. The small GTPase Rap1 controls T-cell adhesion through modulating the affinity and/or spatial organization of LFA-1; however, the upstream regulatory components triggered by the T-cell receptor (TCR) have not been resolved. In the present study, we identified a previously unknown function of a protein kinase C(PKC)/RapGEF2 complex in LFA-1 avidity regulation in T lymphocytes. After T-cell activation, the direct phosphorylation of RapGEF2 at Ser960 by PKCregulates Rap1 activation as well as LFA-1 adhesiveness to ICAM-1. In OT-II TCRtransgenic CD4 T cells, clustering of LFA-1 after antigen activation was impaired in the absence of PKC. These data define that, among other pathways acting on LFA-1 regulation, PKCand its effector RapGEF2 are critical factors in TCR signaling to Rap1. Taken together, PKCsets the threshold for T-cell activation by positively regulating both the cytokine responses and the adhesive capacities of T lymphocytes. (Blood. 2008;112: 4617-4627)
Evidence-based re-design of an introductory course “programming in C”

This paper describes the step-wise re-design of a traditional introductory programming course into a blended learning course. By combining lectures with an online programming environment, short instructional videos, and Tutorial-worksheets, we intend to increase student learning and help students develop the ability to write software. To ensure a successful revision of the course, student learning is closely monitored. The course is changed in separate steps spread over several semesters. By administering a German translation of the SCS1 Assessment at each step, the effects of the changes to the course can be analyzed. The translation of the SCS1 and the data gathering process are described and preliminary data on student learning in the course are shown.
Modelos microfinancieros latinoamericanos: una experiencia para la inclusión social y el desarrollo

Introduccion: en Latinoamerica, las instituciones microfinancieras han sido las encargadas de apalancar mediante pequenos prestamos a millones de individuos para financiar el capital de trabajo y la inversion de pequenas maquinas. El objetivo del trabajo es mostrar los resultados que las microfinanzas arrojan en la mejoria de los indicadores de pobreza y en el crecimiento de la economia. Metodologia: para el analisis cuantitativo, se utilizaron los datos de pobreza, crecimiento de los paises medidos segun su pbi, la tasa de ahorro, el crecimiento de empresas, entre otros indicadores de paises de America Latina, los cuales fueron correlacionados entre si para buscar las variables que podrian ser motoras o explicativas de la disminucion de los indices de pobreza. Resultados: luego del analisis de correlacion entre las distintas variables, se hallo una relacion fuerte entre el aumento de los montos promedios otorgados y la disminucion de las tasas de pobreza; pudo probarse la profundizacion del mercado microcrediticio y su relacion con la pobreza en los paises analizados. Conclusiones: las microfinanzas se convirtieron en una herramienta poderosa de lucha contra la pobreza en los paises que las practicaron, respetando la dignidad humana de aquellas personas que sufren de exclusion economica y social.
An Essential Tryptophan of Escherichia coli DnaA Protein Functions in Oligomerization at the E. coli Replication Origin*

In the initiation of bacterial DNA replication, DnaA protein recruits DnaB helicase to the chromosomal origin, oriC, leading to the assemble of the replication fork machinery at this site. Because a region near the N terminus of DnaA is required for self-oligomerization and the loading of DnaB helicase at oriC, we asked if these functions are separable or interdependent by substituting many conserved amino acids in this region with alanine to identify essential residues. We show that alanine substitutions of leucine 3, phenylalanine 46, and leucine 62 do not affect DnaA function in initiation. In contrast, we find on characterization of a mutant DnaA that tryptophan 6 is essential for DnaA function because its substitution by alanine abrogates self-oligomerization, resulting in the failure to load DnaB at oriC. These results indicate that DnaA bound to oriC forms a specific oligomeric structure, which is required to load DnaB helicase.
High rates of genital mycoplasma infection in the highlands of Papua New Guinea determined both by culture and by a commercial detection kit

Duplicate vaginal swabs were collected from 100 women, and comparisons were made between an in-house broth-agar culture system and a commercially available kit, the Mycoplasma IST kit (bioMérieux), for the detection of Mycoplasma hominis and Ureaplasma urealyticum. There was good agreement between the two systems for detection of the genital mycoplasmas in terms of sensitivity, with values of > 92% being obtained. In terms of specificity, the mutual comparisons were less favorable, though specificity values of > 72% were obtained. Statistically there was no significant difference in the performance of the two tests (P < 0.1 for both M. hominis and U. urealyticum). While the broth-agar culture system was considerably less expensive than the kit, the Mycoplasma IST kit provided additional information on antibiotic susceptibilities and had the advantages of a shelf life of up to 12 months and not requiring the preparation of culture media. The prevalences of colonization obtained for M. hominis and U. urealyticum were extremely high in this randomly selected group of women from periurban and rural settlements in the Eastern Highlands of Papua New Guinea, being > or = 70% for M. hominis and > or = 78% for U. urealyticum. colonization with both genital mycoplasmas simultaneously was also very common, with > or = 60% of women being colonized by both M. hominis and U. urealyticum.
The impending crisis awaiting cardiac transplantation. Modeling a solution based on selection.

BACKGROUND Each month, the number of transplant candidates added to the waiting list exceeds the number of transplantations performed, and many outpatients deteriorate to require transplantation urgently. The current list of 2400 candidates and the average wait of 8 months continue to increase. METHODS AND RESULTS To determine the size at which the outpatient and critical candidate pools will stabilize, population models were constructed using current statistics for donor hearts, candidate listing, sudden death, and outpatient decline to urgent status and revised to predict the impact of alterations in policies of candidate listing. If current practices continue, within 48 months the predicted list will stabilize as the sum of an estimated 270 hospitalized candidates, among whom, together with newly listed urgent candidates, all hearts will be distributed and 3700 outpatient candidates with virtually no chance of transplantation unless they deteriorate to an urgent status. Decreasing the upper age limit now to 55 years would reduce the number listed each month by 30% and result within 48 months in a list of only 1490. The list could also be decreased by 30%, however, if it were possible to list only a candidate group with an 80% chance (compared with 52% estimated currently) of sudden death or deterioration during the next year. With this strategy, the waiting list would equilibrate within 48 months to one-third the current size, with 50% of hearts for outpatient candidates, who would then have an 11% chance each month of receiving a heart compared with 0% if recent policies prevail. Total deaths, with and without transplantation, would be minimized by this rigorous selection of outpatient candidates. CONCLUSIONS This study implies that immediate provisions should be made to limit candidate listing and revise expectations to reflect the diminishing likelihood of transplantation for outpatient candidates. Future emphasis should be on improved selection of candidates at highest risk without transplantation.
An Assessment and Archaeological Application of Cortex Measurement in Lithic Assemblages

We describe an experimental test and archaeological application of the solid geometry method for the interpretation of cortical surface area in lithic assemblages proposed by Dibble et al. (2005). Experimental results support the method's accuracy while archaeological application to assemblages from western New South Wales, Australia suggests a repeated pattern of the selective removal of artifacts away from their location of manufacture. These findings shed light on the role curation and mobility play in the use and eventual discard of those artifact classes for which conventional measures of curation are not applicable. The results raise new questions about Aboriginal technological organization and land use, while simultaneously highlighting the complex relationship between past human behavior and archaeological assemblage content.
Standardising curved carapace length measurements for leatherback turtles, Dermochelys coriacea, to investigate global patterns in body size

There are two commonly utilised, but distinct, methods for measuring carapace length of leatherback turtles (Dermochelys coriacea). Either the carapace is measured along the central ridge or to the side of the central ridge. Here, we demonstrate that these two measurements produce differing results. Moreover, we formulate a globally-applicable correction factor to standardise between these two measurements. Standardised curved carapace length measurements from leatherback turtles at nesting sites worldwide generally fit into 3 size categories: small (<150 cm; Atlantic: Southeast and Pacific: East), mid-sized (150-157.5 cm; Atlantic: Northwest), and large (>157.5 cm; Indian: Southwest, Indian: Northeast, and Pacific: West).