Effects of student-faculty interactions on persistence of underprepared community college students

The high concentration of underprepared students in community colleges presents a challenge to educators, policy-makers, and researchers. All have pointed to low completion rates and caution that institutional practices and policy ought to focus on improving retention and graduation rates. However, a multitude of inhibiting factors limits the educational opportunities of underprepared community college students. Using Tinto's (1993) and Astin's (1999) models of student departure as the primary theoretical framework, as well as faculty mentoring as a strategy to impact student performance and retention, the purpose of this study was to determine whether a mentoring program designed to promote greater student-faculty interactions with underprepared community college students is predictive of higher retention for such students. While many studies have documented the positive effects of faculty mentoring with 4-year university students, very few have examined faculty mentoring with underprepared community college students (Campbell and Campbell, 1997; Nora & Crisp, 2007). In this study, the content of student-faculty interactions captured during the mentoring experience was operationalized into eight domains. Faculty members used a log to record their interactions with students. During interactions they tried to help students develop study skills, set goals, and manage their time. They also provided counseling, gave encouragement, nurtured confidence, secured financial aid/grants/scholarships, and helped students navigate their first semester at college. Logistic regression results showed that both frequency and content of faculty interactions were important predictors of retention. Students with high levels of faculty interactions in the area of educational planning and personal/family concerns were more likely to persist. Those with high levels of interactions in time-management and academic concerns were less likely to persist. Interactions that focused on students' poor grades, unpreparedness for class, or excessive absences were predictive of dropping out. Those that focused on developing a program of study, creating a road map to completion, or students' self-perceptions, feelings of self-efficacy, and personal control were predictive of persistence.

Effects of student-faculty interactions on persistence of underprepared community college students.

The high concentration of underprepared students in community colleges presents a challenge to educators, policy-makers, and researchers. All have pointed to low completion rates and caution that institutional practices and policy ought to focus on improving retention and graduation rates. However, a multitude of inhibiting factors limits the educational opportunities of underprepared community college students. Using Tinto's (1993) and Astin's (1999) models of student departure as the primary theoretical framework, as well as faculty mentoring as a strategy to impact student performance and retention, the purpose of this study was to determine whether a mentoring program designed to promote greater student-faculty interactions with underprepared community college students is predictive of higher retention for such students. While many studies have documented the positive effects of faculty mentoring with 4-year university students, very few have examined faculty mentoring with underprepared community college students (Campbell and Campbell, 1997; Nora & Crisp, 2007). In this study, the content of student-faculty interactions captured during the mentoring experience was operationalized into eight domains. Faculty members used a log to record their interactions with students. During interactions they tried to help students develop study skills, set goals, and manage their time. They also provided counseling, gave encouragement, nurtured confidence, secured financial aid/grants/scholarships, and helped students navigate their first semester at college. Logistic regression results showed that both frequency and content of faculty interactions were important predictors of retention. Students with high levels of faculty interactions in the area of educational planning and personal/family concerns were more likely to persist. Those with high levels of interactions in time-management and academic concerns were less likely to persist. Interactions that focused on students' poor grades, unpreparedness for class, or excessive absences were predictive of dropping out. Those that focused on developing a program of study, creating a road map to completion, or students' self-perceptions, feelings of self-efficacy, and personal control were predictive of persistence.

Processo de transição da pessoa estomizada da depêndencia de cuidado ao autocuidado: subsídios à enfermagem

Objetivou-se conhecer como a pessoa com estomia vivência o processo de transição da dependência de cuidados ao autocuidado à luz da Teoria das Transições de Meleis. Pesquisa exploratória, descritiva com abordagem qualitativa no Serviço de Estomaterapia do Hospital Universitário Dr Miguel Riet Corrêa Jr do Rio Grande/ RS/ Brasil com 27 pessoas com estomias definitivas por câncer. Os dados foram coletados nos mês de janeiro e fevereiro de 2014 por meio de entrevista com roteiro semiestruturado e submetidos à Análise de Conteúdo apoiada nas ideias da Teoria das Transições de Afaf I. Meleis. Constatou-se que a natureza da transição situou-se no processo tipo saúde/doença. A entrada no processo de transição deu-se a partir da consciência desencadeada pelo diagnóstico de câncer, reforçado pela cirurgia de estomização. O empenhamento surge ao dedicarem-se a construção do conhecimento para o autocuidado frente às mudanças na sua vida e na sua nova relação com seu corpo, mudando a visão de si, do mundo e dos outros. Destacou-se o espaço temporal como algo dinâmico e variavelmente indeterminável, sendo fundamental para que se organizem e reflitam acerca do seu novo viver, fortalecendo-se para que a transição progrida. Verificaram-se como fatores facilitadores do autocuidado a construção de um significado positivo à estomização, o preparo dessa experiência ainda no pré-operatório, a estabilidade emocional, a fé e a religiosidade e a sensação de normalidade adquirida a partir de uma imagem próxima da anterior. Referiram-se, ainda, ao fornecimento de forma gratuita pelo governo das bolsas coletoras, adjuvantes e acessórios e ao atendimento da equipe multiprofissional. Como fatores inibidores do processo de transição encontraram-se a visão distorcida de seu corpo, o despreparo para viver com a estomia, a instabilidade emocional, a desmotivação com afastamento de atividades prazerosas, o cuidado excessivo e/ou estendido e até mesmo a superproteção da família, as complicações como hérnias e prolapsos, a falta de atitudes positivas quanto à vida, a negação da bolsa coletora, as tentativas frustradas de omitir o uso da bolsa coletora, a falta do domínio do manuseio dos equipamentos, o afastamento do trabalho e as dificuldades financeiras. Além destas, o abandono do parceiro, atitudes negativas e estigmatizantes por parte da família e a baixa qualidade dos materiais fornecidos pelo governo. Como indicadores de resultados identificaram-se a confiança para realizar atividades anteriores, aceitação de sua situação, uma visão positiva de sua vida e da capacidade de compartilhar o seu cuidado com sua família. Considera-se a saída da transição quando este for capaz de dominar novas competências tanto para o cuidado físico ao realizar a troca da bolsa coletora quanto readequando sua imagem e autoconceito. Concluiu-se que o processo de transição da dependência de cuidados ao autocuidado da pessoa com estomia é complexo e carregado de subjetividades. É necessário que o enfermeiro estabeleça ações terapêuticas de enfermagem eficazes e eficientes, contribuindo para a promoção e reabilitação da saúde deste, auxiliando-o na aquisição de sua autonomia e independência, subsidiando seu autocuidado e bem-estar.

Beyond Blame: cultural barriers to medical reporting

The paper explores the attitudes of medical physicians towards adverse incident reporting in health care, with particular focus on the inhibiting factors or barriers to participation. It is recognised that there are major barriers to medical reporting, such as the ‘culture of blame’. There are, however, few detailed qualitative accounts of medical culture as it relates to incident reporting. Drawing on a 2-year qualitative case study in the UK, this paper presents data gathered from 28 semi-structured interviews with specialist physicians. The findings suggest that blame certainly inhibits medical reporting, but other cultural issues were also significant. It was commonly accepted by doctors that errors are an ‘inevitable’ and potentially unmanageable feature of medical work and incident reporting was therefore ‘pointless’. It was also found that reporting was discouraged by an anti-bureaucratic sentiment and rejection of excessive administrative duties. Doctors were also apprehensive about the increased potential for managers and non-physicians to engage in the regulation of medical quality through the use of incident data. The paper argues that the promotion of incident reporting must engage with more than the ubiquitous ‘culture of blame’ and instead address the ‘culture of medicine’, especially as it relates to the collegial and professional control of quality.

An exploratory study of the factors enhancing and inhibiting export growth in the Chilean wine industry

The objective of this exploratory study is to investigate the main drivers that enhance and inhibit the export performance of Chilean wineries. Based on survey data collected from Chilean wineries, the findings of this study suggest that the main constraints within the Chilean wineries in developing exports is the lack of financial resources, limited quantities of stocks for market expansion, management’s lack of knowledge and experience, and the high cost of travelling and participating in trade shows. The main drivers of wine export performance according to the respondents are high quality of the wines, well established network of international distributors, and marketing skills. The major inhibitors of developing wine exports are exchange rate variability, problems in selecting a reliable international distributor, and limited government support to promote wine exports. This study also shows that export managers of Chilean wineries have high educational levels and have international experience. The findings have important implications for export development efforts of both governments and managers.

Modulation of dermal microvascular endithelial cell responses to growth factors and haemostatic factors in the presence of vitronectin

In order to effect permanent closure in burns patients suffering from full thickness wounds, replacing their skin via split thickness autografting, is essential. Dermal substitutes in conjunction with widely meshed split thickness autografts (+/- cultured keratinocytes) reduce scarring at the donor and recipient sites of burns patients by reducing demand for autologous skin (both surface area and thickness), without compromising dermal delivery at the wound face. Tissue engineered products such as Integra consist of a dermal template which is rapidly remodelled to form a neodermis, at which time the temporary silicone outer layer is removed and replaced with autologous split thickness skin. Whilst provision of a thick tissue engineered dermis at full thickness burn sites reduces scarring, it is hampered by delays in vascularisation which results in clinical failure. The ultimate success of any skin graft product is dependent upon a number of basic factors including adherence, haemostasis and in the case of viable tissue grafts, success is ultimately dependent upon restoration of a normal blood supply, and hence this study. Ultimately, the goal of this research is to improve the therapeutic properties of tissue replacements, through impregnation with growth factors aimed at stimulating migration and proliferation of microvascular endothelial cells into the donor tissue post grafting. For the purpose of my masters, the aim was to evaluate the responsiveness of a dermal microvascular endothelial cell line to growth factors and haemostatic factors, in the presence of the glycoprotein vitronectin. Vitronectin formed the backbone for my hypothesis and research due to its association with both epithelial and, more specifically, endothelial migration and proliferation. Early work using a platform technology referred to as VitroGro (Tissue Therapies Ltd), which is comprised of vitronectin bound BP5/IGF-1, aided keratinocyte proliferation. I hypothesised that this result would translate to another epithelium - endothelium. VitroGro had no effect on endothelial proliferation or migration. Vitronectin increases the presence of Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) receptors, enhancing cell responsiveness to their respective ligands. So, although Human Microvascular Endothelial Cell line 1 (HMEC-1) VEGF receptor expression is generally low, it was hypothesised that exposure to vitronectin would up-regulate this receptor. HMEC-1 migration, but not proliferation, was enhanced by vitronectin bound VEGF, as well as vitronectin bound Epidermal Growth Factor (EGF), both of which could be used to stimulate microvascular endothelial cell migration for the purpose of transplantation. In addition to vitronectin's synergy with various growth factors, it has also been shown to play a role in haemostasis. Vitronectin binds thrombin-antithrombin III (TAT) to form a trimeric complex that takes on many of the attributes of vitronectin, such as heparin affinity, which results in its adherence to endothelium via heparan sulfate proteoglycans (HSP), followed by unaltered transcytosis through the endothelium, and ultimately its removal from the circulation. This has been documented as a mechanism designed to remove thrombin from the circulation. Equally, it could be argued that it is a mechanism for delivering vitronectin to the matrix. My results show that matrix-bound vitronectin dramatically alters the effect that conformationally altered antithrombin three (cATIII) has on proliferation of microvascular endothelial cells. cATIII stimulates HMEC-1 proliferation in the presence of matrix-bound vitronectin, as opposed to inhibiting proliferation in its absence. Binding vitronectin to tissues and organs prior to transplant, in the presence of cATIII, will have a profound effect on microvascular infiltration of the graft, by preventing occlusion of existing vessels whilst stimulating migration and proliferation of endothelium within the tissue.

Inhibiting Eph kinase activity may not be “Eph”ective for cancer treatment

Several Eph receptor tyrosine kinases (RTKs) are commonly over-expressed in epithelial and mesenchymal cancers and are recognized as promising therapeutic targets. Although normal interaction between Eph receptors and their ephrin ligands stimulates kinase activity and is generally tumor suppressive, significant Eph over-expression allows activation of ligand- and/or kinase-independent signaling pathways that promote oncogenesis. Single-agent kinase inhibitors are widely used to target RTK-driven tumors but acquired and de novo resistance to such agents is a major limitation to effective clinical use. Accumulating evidence suggests that Ephs can be inhibited by “leaky” or low-specificity kinase inhibitors targeted at other RTKs. Such off-target effects may therefore inadvertently promote ligand- and/or kinase-independent oncogenic Eph signaling, thereby providing a new mechanism by which resistance to the RTK inhibitors can emerge. We propose that combining specific, non-leaky kinase inhibitors with tumor-suppressive stimulators of Eph signaling may provide more effective treatment options for overcoming treatment-induced resistance and clinical failure.

Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18

Background: Implantation and growth of metastatic cancer cells at distant organs is promoted by inflammation-dependent mechanisms. A hepatic melanoma metastasis model where a majority of metastases are generated via interleukin-18-dependent mechanisms was used to test whether anti-inflammatory properties of resveratrol can interfere with mechanisms of metastasis. Methods: Two experimental treatment schedules were used: 1) Mice received one daily oral dose of 1 mg/kg resveratrol after cancer cell injection and the metastasis number and volume were determined on day 12. 2) Mice received one daily oral dose of 1 mg/kg resveratrol along the 5 days prior to the injection of cancer cells and both interleukin-18 (IL-18) concentration in the hepatic blood and microvascular retention of luciferase-transfected B16M cells were determined on the 18(th) hour. In vitro, primary cultured hepatic sinusoidal endothelial cells were treated with B16M-conditioned medium to mimic their in vivo activation by tumor-derived factors and the effect of resveratrol on IL-18 secretion, on vascular cell adhesion molecule-1 (VCAM-1) expression and on tumor cell adhesion were studied. The effect of resveratrol on melanoma cell activation by IL-18 was also studied. Results: Resveratrol remarkably inhibited hepatic retention and metastatic growth of melanoma cells by 50% and 75%, respectively. The mechanism involved IL-18 blockade at three levels: First, resveratrol prevented IL-18 augmentation in the blood of melanoma cell-infiltrated livers. Second, resveratrol inhibited IL-18-dependent expression of VCAM-1 by tumor-activated hepatic sinusoidal endothelium, preventing melanoma cell adhesion to the microvasculature. Third, resveratrol inhibited adhesion-and proliferation-stimulating effects of IL-18 on metastatic melanoma cells through hydrogen peroxide-dependent nuclear factor-kappaB translocation blockade on these cells. Conclusions: These results demonstrate multiple sites for therapeutic intervention using resveratrol within the prometastatic microenvironment generated by tumor-induced hepatic IL-18, and suggest a remarkable effect of resveratrol in the prevention of inflammation-dependent melanoma metastasis in the liver.

Factors affecting the protease activity of venom from jellyfish Rhopilema esculentum Kishinouye

In this paper, the effects of some chemical and physical factors such as temperature, pH values, glycerol, and divalent metal cations on the protease activity of venom from jellyfish, Rhopilema esculentum Kishinouye, were assayed. Protease activity was dependent on temperature and pH values. Zn2+, Mg2+, and Mn2+ in sodium phosphate buffer (0.02 M, pH 8.0) could increase protease activity. Mn2+ had the best effects among the three metal cations and the effect was about 20 times of that of Zn2+ or Mg2+ and its maximal protease activity was 2.3 x 10(5) U/mL. EDTA could increase protease activity. PMSF had hardly affected protease activity. O-Phenanthroline and glycerol played an important part in inhibiting protease activity and their maximal inhibiting rates were 87.5% and 82.1%, respectively. (c) 2005 Elsevier Ltd. All rights reserved.

Involvement of Rel/Nuclear Factor-κB Transcription Factors in Keratinocyte Senescence

After a finite doubling number, normal cells become senescent, i.e. nonproliferating and apoptosis resistant. Because Rel/nuclear factor (NF)-κB transcription factors regulate both proliferation and apoptosis, we have investigated their involvement in senescence. cRel overexpression in young normal keratinocytes results in premature senescence, as defined by proliferation blockage, apoptosis resistance, enlargement, and appearance of senescence-associated β-galactosidase (SA-β-Gal) activity. Normal senescent keratinocytes display a greater endogenous Rel/NF-κB DNA binding activity than young cells; inhibiting this activity in presenescent cells decreases the number of cells expressing the SA-β-Gal marker. Normal senescent keratinocytes and cRel-induced premature senescent keratinocytes overexpressed manganese superoxide dismutase (MnSOD), a redox enzyme encoded by a Rel/NF-κB target gene. MnSOD transforms the toxic O2.- into H2O2, whereas catalase and glutathione peroxidase convert H2O2 into H2O. Neither catalase nor glutathione peroxidase is up-regulated during cRel-induced premature senescence or during normal senescence, suggesting that H 2O2 accumulates. Quenching H2O2 by catalase delays the occurrence of both normal and premature cRel-induced senescence. Conversely, adding a nontoxic dose of H2O2 to the culture medium of young normal keratinocytes induces a premature senescence-like state. All these results indicate that Rel/NF-κB factors could take part in the occurrence of senescence by generating an oxidative stress via the induction of MnSOD.

Hydrogen peroxide sensing, signaling and regulation of transcription factors

The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm-nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and, (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M-1s−1 and ≥ 1.3 × 103 M-1s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.

The inflammatory role of angiogenic growth factors : a neutrophil perspective

De par sa présence dans tous les vaisseaux sanguins, l'endothélium joue un rôle clef dans le processus d’hémostase, tant par sa libération de facteurs anticoagulants que par ses changements protéiques qui permettent à l’organisme de déclencher la réparation tissulaire. La fonction anticoagulante de l’endothélium peut être mise en défaut en cas d’atteinte de son intégrité, entrainant la formation de thrombus, le rejet précoce de greffes ou encore l’induction de l’athérosclérose. L’intégrité de l’endothélium est donc capitale pour la prévention de nombreuses maladies cardiovasculaires. Chez l’adulte, les cellules endothéliales (CE), normalement quiescentes, sont rapidement activées en cas d’hypoxie ou d’inflammation, leur permettant ainsi d’amorcer le processus angiogénique comme suit: Tout d’abord, l’induction de l’hyperperméabilité vasculaire permet l’extravasation des protéines plasmatiques. Ensuite, la dégradation de la lame basale par des métalloprotéases permet aux CE de se détacher, de proliférer, de migrer et de s’organiser pour former l’ébauche du futur vaisseau. La dernière étape consiste en la maturation du vaisseau, c’est-à-dire son recouvrement par des cellules murales, telles que les cellules musculaires lisses et les péricytes. Ces processus sont régulés par de nombreux facteurs angiogéniques tels que les membres de la famille Notch, du vascular endothelial growth factor (VEGF), du fibroblast growth factor (FGF), des angiopoïétines, et des matrix metalloproteases (MMP). L’angiogenèse pathologique, soit une insuffisance ou un excès de vascularisation, est impliquée dans les blessures chroniques, les accidents cardiovasculaires, les pathologies coronariennes artérielles, les pathologies tumorales, l’arthrite rhumatoïde, la rétinopathie diabétique, l’athérosclérose, le psoriasis et l’asthme. Ces pathologies sont souvent issues d’une dérégulation de l’activité endothéliale, fréquemment observée conjointement à l’expression continue de molécules d’adhésion leucocytaires, à l’augmentation de la perméabilité vasculaire, et aux anomalies de la vasoréactivité. L’activation non-contrôlée de l’endothélium entraîne ainsi une inflammation chronique et la formation de structures vasculaires anarchiques. Les premiers leucocytes à répondre à l’appel inflammatoire sont les neutrophiles. Equippées d’une panoplie de produits antibactériens puissants mais aussi nocifs pour les tissus qui les entourent, ces cellules polylobées participent à chaque étape du processus inflammatoire, depuis l’induction de l’hyperperméabilité vasculaire jusqu’à la résolution. En effet, grâce à leurs récepteurs, les neutrophiles détectent et interprètent les signaux biochimiques présents dans la circulation et à la surface de l’endothélium, et libèrent aussi leurs propres médiateurs tels le VEGF, les MMP, et l’interleukine-8 (IL-8), dont les effets sont à la fois paracrines et autocrines. Existent-ils d’autres modulateurs typiques de la fonction endothéliale capables d’influencer le comportement des neutrophiles? En effet, notre laboratoire a démontré que chez l’humain, une stimulation directe aux angiopoïétines incitait les neutrophiles à adhérer aux CE, à migrer, à synthétiser et à relâcher l’IL-8, voire même à vivre plus longtemps. La présence du récepteur des angiopoïétines, Tie2, à la surface des neutrophiles laisse présager que la famille possèderait d’autres fonctions leucocytaires encore non-identifiées. Par ailleurs, dans un modèle classique de l’angiogenèse in vivo (matrigel), nous avons observé que sous l’effet du FGF1 et 2, les ébauches des nouveaux vaisseaux étaient parfois accompagnées d’une infiltration de cellules granulocytaires. Ainsi, en partant de ces observations, l’objectif de nos études (présentées ci-après) était d’approfondir nos connaissances sur la relation entre neutrophiles et facteurs angiogéniques, notamment les FGF et les angiopoïétines. Par tests in vitro, nous avons confirmé que les neutrophiles humains exprimaient plusieurs récepteurs du FGF (FGFR1-4) d’une façon hétérogène, et qu’ils migraient vers un gradient des ligands FGF1 et 2. Par ailleurs, nous nous sommes intéressés aux voies de signalisation inflammatoires activées par les ligands FGF1, FGF2, Ang1 et Ang2. Grâce à une stratégie génique ciblant 84 gènes inflammatoires, nous avons identifié plusieurs cibles d’intérêt touchées par Ang1, dont certains membres de la famille de l’IL-1, alors qu’aucun des gènes testés n’avait changé de façon significative sous l’effet des FGF ou d’Ang2. Suite à des cinétiques approfondies, nous avons démontré qu’Ang1 stimulait la transcription de l’ARN messager de l’IL-1β, et augmentait simultanément la quantité de protéine immature (pro-IL-1β; inactive) et clivée (IL-1β « mature »; active). En parallèle, Ang1 augmentait la sécrétion de l’antagoniste naturel de l’IL-1β, l’IL-1RA, sans pour autant stimuler la relâche de l’IL-1β. A l’instar des endotoxines bactériennes dont les effets liés à l’IL-1 dépendaient de la kinase p38, ceux d’Ang1 découlaient presque entièrement des voies de signalisation du p42/44.

Oxygen-dependent hydroxylation by Factor Inhibiting HIF (FIH) regulates the TRPV3 ion channel

Factor Inhibiting HIF (FIH) is an oxygen-dependent asparaginyl hydroxylase that regulates the hypoxia-inducible factors (HIFs). Several proteins containing ankyrin repeat domains have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ankyrin repeat domain. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygendependent asparaginyl hydroxylation is likely to extend to other ion channels.

Correlation between antigenemia of Paracoccidioides brasiliensis and inhibiting effects of plasma in patients with paracoccidioidomycosis

Metabolites produced by pathogenic fungi may be involved in the pathogenesis of fungal infections consequently altering the defence mechanisms of the host. In this study the levels of Paracoccidioides brasiliensis antigens detected in the plasma of patients with paracoccidioidomycosis correlated with the suppression index detected by the low mitogenic response of peripheral blood mononuclear cells (PBMC) to phytohaemaglutinin (PHA). This inhibitory effect on lymphoproliferation was observed in the plasma of 58% of the patients, suggesting the presence of inhibitory factors. Plasma samples from paracoccidioidomycosis patients having or not having inhibitory factors showed no significant effect on chromosomes of lymphocytes from healthy individuals, However, these plasmas had a suppressive activity on the blastogenic response of these lymphocytes stimulated with PHA, that was independent of a cytotoxic effect. P. brasiliensis antigens added to the proliferative response of PBMC from healthy individuals stimulated or not stimulated with PHA showed a dose-dependent suppressor effect, reproducing the inhibitory effect of patients' plasma. We suggest that the antigens of P, brasiliensis present in the plasma of patients, even at low concentrations, can play an important role in the reduction of the cellular immune response and in the genesis of the immuneregulatory disturbances observed in paracoccidioidomycosis.

Human microbiota-secreted factors inhibit shiga toxin synthesis by enterohemorrhagic Escherichia coli O157:H7

Escherichia coli O157:H7 is a food-borne pathogen causing hemorrhagic colitis and hemolytic-uremic syndrome, especially in children. The main virulence factor responsible for the more serious disease is the Shiga toxin 2 (Stx2), which is released in the gut after oral ingestion of the organism. Although it is accepted that the amount of Stx2 produced by E. coli O157:H7 in the gut is critical for the development of disease, the eukaryotic or prokaryotic gut factors that modulate Stx2 synthesis are largely unknown. In this study, we examined the influence of prokaryotic molecules released by a complex human microbiota on Stx2 synthesis by E. coli O157:H7. Stx2 synthesis was assessed after growth of E. coli O157:H7 in cecal contents of gnotobiotic rats colonized with human microbiota or in conditioned medium having supported the growth of complex human microbiota. Extracellular prokaryotic molecules produced by the commensal microbiota repress stx(2) mRNA expression and Stx2 production by inhibiting the spontaneous and induced lytic cycle mediated by RecA. These molecules, with a molecular mass of below 3 kDa, are produced in part by Bacteroides thetaiotaomicron, a predominant species of the normal human intestinal microbiota. The microbiota-induced stx(2) repression is independent of the known quorum-sensing pathways described in E. coli O157:H7 involving SdiA, QseA, QseC, or autoinducer 3. Our findings demonstrate for the first time the regulatory activity of a soluble factor produced by the complex human digestive microbiota on a bacterial virulence factor in a physiologically relevant context.