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Self-regulation has been shown to play a protective role against youth substance abuse, but less is known about its influence on bullying behavior. In the present study, we examined several forms of bullying (physical, social, cyber, and all forms combined) and roles (bullies, victims, and bully-victims). Students (N = 1977, ages 11 to 13) from 27 middle schools throughout the United States (US) completed an online self-reported assessment of bullying and its hypothesized etiologic determinants. Across the outcomes, analyses revealed that social bullying was most prevalent, followed by physical bullying and cyberbullying. For bullying roles, almost two-thirds of students reported bullying victimization, nearly one-quarter reported bullying perpetration, and one in five students reported both. Of those reporting perpetration, 9 of 10 reported being victimized. Multivariate logistic regression models were used to examine the associations between self-regulation, bystander intervention skills, and bullying. For all forms of bullying combined, self-regulation was protective against bullying perpetration (OR 0.51, 95% CI: 0.42, 0.63) and perpetration/victimization (OR 0.55, 95% CI: 0.44, 0.68), while bystander intervention skills were not protective. Similar patterns emerged for physical, social, and cyberbullying. Collectively, these findings indicate that building self-regulation skills may be a critical component of interventions aimed at preventing bullying among school-aged youth.

Bullying is a widespread public health problem with significant behavioral and mental health consequences. The current study tested the effectiveness of combining interactive digital material for students, educators, and parents with class sessions to prevent bullying among middle school students. Fourteen middle schools were randomly assigned to intervention and comparison conditions. Both conditions received a classroom-based drug and violence prevention program that taught social skills, self-management skills, and social resistance skills. The intervention condition included class material on bullying and an educational video game for students that reinforced the classroom program; it also included digital material on bullying for parents and school staff. All students completed online pre- and post-test surveys to assess bullying-related behavior, knowledge, and life skills. Results indicated that students in the intervention schools reported significantly less bullying and cyberbullying perpetration and increased life skills knowledge relative to comparison schools. This study provides evidence that a school-based drug abuse and violence prevention program, when enhanced with a set of digital tools for students, parents, and school staff, holds considerable potential for addressing bullying among middle school adolescents.

A GWAS in a large case-control cohort of European ancestry identifies two genomic regions, the MHC class II gene HLA-DRB1 and an upstream locus of VRK1, that are associated with the most severe phenotype of spermatogenic failure.

Objectives The main goal of this study was to characterise the frequency and phenotype of B, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells in peripheral blood and the cytokine environment present in circulation in children with extended oligoarticular juvenile idiopathic arthritis (extended oligo JIA) and polyarticular JIA (poly JIA) when compared with healthy controls, children with persistent oligoarticular JIA (persistent oligo JIA) and adult JIA patients.Methods Blood samples were collected from 105 JIA patients (children and adults) and 50 age-matched healthy individuals. The frequency and phenotype of B, Tfh and Tfr cells were evaluated by flow cytometry. Serum levels of APRIL, BAFF, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-17A, IL-21, IL-22, IFN-γ, PD-1, PD-L1, sCD40L, CXCL13 and TNF were measured by multiplex bead-based immunoassay and/or ELISA in all groups included.Results The frequency of B, Tfh and Tfr cells was similar between JIA patients and controls. Children with extended oligo JIA and poly JIA, but not persistent oligo JIA, had significantly lower frequencies of plasmablasts, regulatory T cells and higher levels of Th17-like Tfh cells in circulation when compared with controls. Furthermore, APRIL, BAFF, IL-6 and IL-17A serum levels were significantly higher in paediatric extended oligo JIA and poly JIA patients when compared with controls. These immunological alterations were not found in adult JIA patients in comparison to controls.Conclusions Our results suggest a potential role and/or activation profile of B and Th17-like Tfh cells in the pathogenesis of extended oligo JIA and poly JIA, but not persistent oligo JIA.

While discourse surrounding decolonization is not new, in recent years it has gained significant momentum with many advocating for its implementation as a means to address historical injustices. However, Olúfẹ́mi Táíwò’s thought-provoking book, coupled with the movie “Mortu Nega”, invites us to critically examine the concept of decolonization. This article aims to present an argument that challenges decolonization narratives by exploring the potential limitations and unintended consequences of embracing decolonization as an absolute solution for humanitarian issues in African societies. To accomplish this, I will begin by providing historical context on Guinea-Bissau, the former Portuguese colony that serves as the focal point of the film. Furthermore, this article will provide a comprehensive description of Flora Gomes’ film, followed by a discussion addressing the trope of decolonization theory. I will use the persistent lack of women’s emancipation and their ongoing struggle for genuine liberation and gender justice in Guinea-Bissau as an example of the need, following Táíwò’s thought, to rethink the uses of decolonization as a tool for analyzing Africa’s issues.

Scavenger receptors are part of a complex surveillance system expressed by host cells to efficiently orchestrate innate immune response against bacterial infections. Stabilin-1 (STAB-1) is a scavenger receptor involved in cell trafficking, inflammation, and cancer; however, its role in infection remains to be elucidated. Listeria monocytogenes (Lm) is a major intracellular human food-borne pathogen causing severe infections in susceptible hosts. Using a mouse model of infection, we demonstrate here that STAB-1 controls Lm-induced cytokine and chemokine production and immune cell accumulation in Lm-infected organs. We show that STAB-1 also regulates the recruitment of myeloid cells in response to Lm infection and contributes to clear circulating bacteria. In addition, whereas STAB-1 appears to promote bacterial uptake by macrophages, infection by pathogenic Listeria induces the down regulation of STAB-1 expression and its delocalization from the host cell membrane. We propose STAB-1 as a new SR involved in the control of Lm infection through the regulation of host defense mechanisms, a process that would be targeted by bacterial virulence factors to promote infection.

Non-muscle myosin 2A (NM2A) is a key cytoskeletal enzyme that, along with actin, assembles into actomyosin filaments inside cells. NM2A is fundamental for cell adhesion and motility, playing important functions in different stages of development and during the progression of viral and bacterial infections. Phosphorylation events regulate the activity and the cellular localization of NM2A. We previously identified the tyrosine phosphorylation of residue 158 (pTyr158) in the motor domain of the NM2A heavy chain. This phosphorylation can be promoted by Listeria monocytogenes infection of epithelial cells and is dependent on Src kinase; however, its molecular role is unknown. Here, we show that the status of pTyr158 defines cytoskeletal organization, affects the assembly/disassembly of focal adhesions, and interferes with cell migration. Cells overexpressing a non-phosphorylatable NM2A variant or expressing reduced levels of Src kinase display increased stress fibers and larger focal adhesions, suggesting an altered contraction status consistent with the increased NM2A activity that we also observed. We propose NM2A pTyr158 as a novel layer of regulation of actomyosin cytoskeleton organization.

BackgroundEffective school-based programs for preventing substance abuse offer considerable public health potential. Yet limited class time and uneven implementation fidelity can be barriers to widespread adoption and high-quality implementation. A hybrid digital approach may be effective and help address these barriers.ObjectiveTo evaluate the effectiveness of a hybrid substance abuse prevention program for middle school students consisting of e-learning modules and in-person class sessions.DesignTwenty-three United States (U.S.) middle schools were randomly assigned either to an intervention condition (13 schools) or a treatment-as-usual control condition (10 schools) where standard health education material was delivered. There were 1,447 participants who completed the pre-test and post-test assessments, of which 48.3% were male and 51.7% female.InterventionThe hybrid digital intervention consisted of 14 brief e-learning modules and six classroom sessions adapted from an evidence-based program designed for classroom implementation to increase knowledge of adverse consequences of substance use and improve social skills, personal coping skills, and skills for resisting social influences to smoke, drink, or use drugs.MeasuresParticipating students completed online pre-test and post-test surveys to assess substance use, knowledge, and life skills.ResultsThere were significant reductions in substance use for the hybrid digital condition compared to the control condition as well as significant increases in health knowledge, skills knowledge, and life skills.ConclusionsA hybrid digital approach to substance abuse prevention is effective and offers potential for overcoming common barriers to widespread adoption and high-quality implementation.

É meu objetivo neste espaço analisar o mais recente livro de Teolinda Gersão, O Regresso de Júlia Mann a Paraty (2021), à luz do conceito de psicologia negra desenvolvido por Wade W. Nobles. Pretendo, assim, complexificar uma das questões centrais do romance, proferida por Sigmund Freud, o pai da psicanálise, tornado por Gersão (2021) em personagem-narrador fictícia: “será possível que sejamos incapazes de progredir no plano ético, do mesmo modo que, afinal, parecemos incapazes de amor e compaixão?” (p. 14). Ao mesmo tempo, pretendo também desconstruir o que o romance nos aponta como os erros de dois dos mais significativos agentes da história, tanto no campo científico como no literário. Influenciados e influenciadores intelectualmente, as grandes figuras da história literária, científica e do pensamento presentes no livro de Gersão foram alvo do mesmo lapso: o não questionamento crítico de um mundo apoiado na hegemonia branca, em que a diferença e a dignidade do “outro” foram rasuradas. Basendo-me no trabalho de Catherine Hall e Corinna McLeod, entre outros, sobre o processo da escrita da história como um processo reparatório demonstro ainda como O Regresso de Júlia Mann a Paraty efetua um diálogo crítico e reparador com o passado que se espelha no presente.

Pneumolysin (PLY) is a pore-forming toxin produced by the human pathobiont Streptococcus pneumoniae, the major cause of pneumonia worldwide. PLY, a key pneumococcal virulence factor, can form transmembrane pores in host cells, disrupting plasma membrane integrity and deregulating cellular homeostasis. At lytic concentrations, PLY causes cell death. At sub-lytic concentrations, PLY triggers host cell survival pathways that cooperate to reseal the damaged plasma membrane and restore cell homeostasis. While PLY is generally considered a pivotal factor promoting S. pneumoniae colonization and survival, it is also a powerful trigger of the innate and adaptive host immune response against bacterial infection. The dichotomy of PLY as both a key bacterial virulence factor and a trigger for host immune modulation allows the toxin to display both “Yin” and “Yang” properties during infection, promoting disease by membrane perforation and activating inflammatory pathways, while also mitigating damage by triggering host cell repair and initiating anti-inflammatory responses. Due to its cytolytic activity and diverse immunomodulatory properties, PLY is integral to every stage of S. pneumoniae pathogenesis and may tip the balance towards either the pathogen or the host depending on the context of infection.

This paper describes a study comparing four educational videogames designed for second language acquisition (SLA) of Portuguese vocabulary terms: three versions (one VR and two PC versions with different perspectives) of an endless-runner called ELLE the EndLess LEarner and a control game This or That, which is a digitized flashcard system. A total of 68 university students took a pre-test assessing vocabulary knowledge, played one of the four versions for a total of 20 minutes, and took a post-test that assessed vocabulary knowledge and player experience. The study showed significant learning gains for all participants, regardless of which version of the game they played, with the highest increases coming from the group playing the control flashcard game. Possible explanations for these results are discussed, along with the results from post-test gameplay items of playability, engrossment, enjoyment, gratification, and immersion.

Abstract Background The vasculitides are a group of rare diseases with different manifestations and outcomes. New therapeutic options have led to the need for long-term registries. The Rheumatic Diseases Portuguese Register, Reuma.pt, is a web-based electronic clinical record, created in 2008, which currently includes specific modules for 12 diseases and > 20,000 patients registered from 79 rheumatology centres. On October 2014, a dedicated module for vasculitis was created as part of the European Vasculitis Society collaborative network, enabling prospective collection and central storage of encrypted data from patients with this condition. All Portuguese rheumatology centres were invited to participate. Data regarding demographics, diagnosis, classification criteria, assessment tools, and treatment were collected. We aim to describe the structure of Reuma.pt/vasculitis and characterize the patients registered since its development. Results A total of 687 patients, with 1945 visits, from 13 centres were registered; mean age was 53.4 ± 19.3 years at last visit and 68.7% were females. The most common diagnoses were Behçet’s disease (BD) (42.5%) and giant cell arteritis (GCA) (17.8%). Patients with BD met the International Study Group criteria and the International Criteria for BD in 85.3 and 97.2% of cases, respectively. Within the most common small- and medium-vessel vasculitides registered, median [interquartile range] Birmingham Vasculitis Activity Score (BVAS) at first visit was highest in patients with ANCA-associated vasculitis (AAV) (17.0 [12.0]); there were no differences in the proportion of patients with AAV or polyarteritis nodosa who relapsed (BVAS≥1) or had a major relapse (≥1 major BVAS item) during prospective assessment (p = 1.00, p = 0.479). Biologic treatment was prescribed in 0.8% of patients with GCA, 26.7% of patients with AAV, and 7.6% of patients with BD. There were 34 (4.9%) deaths reported. Conclusions Reuma.pt/vasculitis is a bespoke web-based registry adapted for routine care of patients with this form of rare and complex diseases, allowing an efficient data-repository at a national level with the potential to link with other international databases. It facilitates research, trials recruitment, service planning and benchmarking.

The plasma membrane (PM) protects cells from extracellular threats and supports cellular homeostasis. Some pathogens produce pore-forming toxins (PFTs) that disrupt PM integrity by forming transmembrane pores. High PFT concentrations cause massive damage leading to cell death and facilitating infection. Sub-lytic PFT doses activate repair mechanisms to restore PM integrity, support cell survival and limit disease. Shedding of extracellular vesicles (EVs) has been proposed as a key mechanism to eliminate PFT pores and restore PM integrity. We show here that cholesterol-dependent cytolysins (CDCs), a specific family of PFTs, are at least partially eliminated through EVs release, and we hypothesize that proteins important for PM repair might be included in EVs shed by cells during repair. To identify new PM repair proteins, we collected EVs released by cells challenged with sub-lytic doses of two different bacterial CDCs, listeriolysin O and pneumolysin, and determined the EV proteomic repertoire by LC-MS/MS. Intoxicated cells release similar EVs irrespectively of the CDC used. Also, they release more and larger EVs than non-intoxicated cells. A cluster of 70 proteins including calcium-binding proteins, molecular chaperones, cytoskeletal, scaffold and membrane trafficking proteins, was detected enriched in EVs collected from intoxicated cells. While some of these proteins have well-characterized roles in repair, the involvement of others requires further study. As proof of concept, we show here that Copine-1 and Copine-3, proteins abundantly detected in EVs released by intoxicated cells, are required for efficient repair of CDC-induced PM damage. Additionally, we reveal here new proteins potentially involved in PM repair and give new insights into common mechanisms and machinery engaged by cells in response to PM damage.

Introduction: MD is considered a rare disease. An adequate model that explains MD's pathophysiology is not well established. Recently, the vascular theory of the disease has been revived. Objectives: To characterize a MD population according to its cardiovascular risk and correlate it to the MD clinical course. Methods: In this retrospective chart study the data of 31 MD patients observed between January 2017 and April 2018 in a tertiary university hospital were reviewed. Patients included in the study were diagnosed according to the Bárány Society criteria. Lost follow-ups, patients with autoimmune disease, atopy or allergy, major psychiatric disease and migraine were excluded. Age, gender, cardiovascular risk factors, audiometric and vestibular parameters, occurrence of MD attacks in the previous 6 months, vestibular medication in course and time course of MD were recorded and compared between groups (with and without cardiovascular risk factors). Results: 31 patients (61.3% females) mean aged 60.3 years (±9.7) were studied. 74% of the population had at least one risk factor and 51.6% of patients had attacks in the last 6 months. There was a statistically significant difference in the occurrence of MD attacks in the last 6 months (p = 0.014) between MD patients with and without risk factors. Mean PTA thresholds were higher and speech discrimination was lower in individuals with more cardiovascular risk factors. Conclusions: Treatment of MD focusing on vascular risk factors may allow a better control of symptoms and result in a decreased need for ablative procedures in this disorder. Keywords: Ménière disease, Cardiovascular disease, Hypertension, Prognosis

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A tradição literária e artística ocidental foi particularmente despiciente no que toca à representação da épica batalha travada por Aquiles e Pentesileia, cuja representação não encontra lugar nos poemas homéricos. O mito desta amazona não constituiu alvo de nenhum texto dramático ou épico, ao contrário do que aconteceu com outras heroínas da tradição clássica, nomeadamente Medeia, Antígona e Helena. Sendo raros os registos literários do mito (na Grécia arcaica, no Ciclo Épico, Etiópida; no século I a. C., por Diodoro Sículo e Apolodoro; pelo poeta épico Quinto de Esmirna, que viveu entre os séculos III e IV d. C.), o empenho pela sua revitalização tem-se mostrado particularmente escasso ao longo dos séculos. Neste sentido, torna-se pertinente notar o interesse que a batalha entre estes dois heróis gregos, Aquiles e Pentesileia, que põe tradicionalmente em relevo as fragilidades amorosas do rei dos mirmidões e as qualidades bélicas da amazona, suscitou em dois autores portugueses, Vasco Graça Moura e Hélia Correia. Pretendemos, neste sentido, abordar as releituras do mito nas obras sombras com aquiles e pentesileia (1999), de Vasco Graça Moura, e na breve prosa Penthesiléa, retirada de um pequeno conjunto de textos intitulado Apodera-te de Mim (2002), de Hélia Correia, à luz da tradição clássica, compreendendo assim os contributos para o fortalecimento da presença de mitos clássicos na literatura portuguesa contemporânea.

The results of radiographic and visual examinations of four mummies originating from Deir el-Bahari, now kept in different museums throughout Egypt, are presented here. One individual dates to the Twenty-second Dynasty, and the remaining three date to the Twenty-fifth Dynasty, and were possibly related. Some of the mummies possessed amulets, with one individual having unusual accouterments in addition to the amulets.

In this article I explore the connections between colonial literature and an­thropology during the first decades of the twentieth century. Through the analysis of Brito Camacho’s Pretos e Brancos (1926), I argue that some of the literary works that won the Contest of Colonial Literature are imbued with an anthropologic gaze. By this, I mean that colonial literature and anthropology were constituted as two intertwined colonial “knowledges” from the beginning of the colonial project. Both “knowledges” -literary and anthropological- served the objective of the construction and legitimi­zation of the Portuguese colonial empire.

Introduction: Cryptogenic stroke is present in about 40% of ischemic stroke patients. Extracardiac shunt related to pulmonary arteriovenous fistula (PAVF) could be a rare potential risk factor for embolic stroke. Most PAVFs are multiple, congenital, and associated with hereditary conditions. On the other hand, isolated PAVFs are rare conditions and an uncommon cause of cryptogenic stoke. Case Report: We describe a case of a young woman without history of respiratory diseases or vascular risk factors, who presented with acute onset of transitory aphasia and right hemiplegia. She had a history of a transient ischemic attack, 3 years before, and migraine headaches. Brain MRI showed an acute cortical ischemic lesion and a chronic ischemic lesion. Diagnostic workup with transcranial Doppler ultrasonography revealed a significant right-to-left shunt with curtain pattern, and echocardiogram did not show structural abnormalities. An isolated small PAVF was diagnosed on pulmonary angiogram. Despite the rare association between isolated small PAVF and stroke, we decided to treat it with coil embolization because of recurrence of stroke, cortical lesions suggestive of embolic source, significant right-left shunt, and risk of future complications. Conclusions: This case highlights the importance of search, identification, and interpretation of causes of cryptogenic strokes to better choose therapy to reduce the stroke recurrence risk. Although unusual, PAVF detection is a treatable cause of stroke and the therapeutic decisions should take into account the characteristics of the PAVF and the degree of suspicion regarding the cause-effect relationship between PAVF and stroke.

In this essay I analyze the way in which the representation of hair, the part of the body chosen by Djaimilia Pereira de Almeida to be the focal point of her novel Esse cabelo (2015), enables a dialog among questions of gender, sexuality, class, race and ethnicity in Post-colonial Portugal.--- DOI: http://dx.doi.org/10.22409/abriluff.2017n18a371

Este estudo procura ser uma contribuição para a análise do género nas obras de dois dos autores mais relevantes da literatura brasileira do século XX, Graciliano Ramos e João Guimarães Rosa. Procura-se desmantelar, através da teoria do espaço, a ideologia de género que subjaz a São Bernardo e Buriti. Pretende-se igualmente verificar a ocorrência de dissonâncias no tratamento das personagens femininas nos dois autores. Procura-se, finalmente, contribuir para uma reavaliação da construção da feminilidade nas obras, construção essa que não é de forma nenhuma independente das visões que os autores tinham da sociedade da sua época.

Este artigo incide sobre os “silêncios no feminino” no Boletim da Agência Geral das Colónias, ou seja, sobre a ausência (ou quase) das mulheres como participantes na escrita de tão importante veículo da imprensa colonial. É aqui intenção pensar e avaliar sobre as razões disso, partindo-se do princípio de que os silêncios devem ser recuperados para uma melhor compreensão da história colonial portuguesa.

Non-muscle myosin 2A (NM2A) is a motor cytoskeletal enzyme with crucial importance from the early stages of development until adulthood. Due to its capacity to convert chemical energy into force, NM2A powers the contraction of the actomyosin cytoskeleton, required for proper cell division, adhesion and migration, among other cellular functions. Although NM2A has been extensively studied, new findings revealed that a lot remains to be discovered concerning its spatiotemporal regulation in the intracellular environment. In recent years, new functions were attributed to NM2A and its activity was associated to a plethora of illnesses, including neurological disorders and infectious diseases. Here, we provide a concise overview on the current knowledge regarding the structure, the function and the regulation of NM2A. In addition, we recapitulate NM2A-associated diseases and discuss its potential as a therapeutic target.

Listeria monocytogenes is among the best-characterized intracellular pathogens. Its virulence factors, and the way they interfere with host cells to hijack host functions and promote the establishment and dissemination of the infection, have been the focus of multiple studies over the last 30 years. During cellular infection, L. monocytogenes was shown to induce host DNA damage and delay the host cell cycle to its own benefit. However, whether the cell cycle stage would interfere with the capacity of Listeria to infect human cultured cell lines was never assessed. We found here that L. monocytogenes preferentially infects cultured cells in G2/M phases. Inside G2/M cells, the bacteria lead to an increase in the overall mitosis duration by delaying the mitotic exit. We showed that L. monocytogenes infection causes a sustained activation of the spindle assembly checkpoint, which we correlated with the increase in the percentage of misaligned chromosomes detected in infected cells. Moreover, we demonstrated that chromosome misalignment in Listeria-infected cells required the function of two Listeria virulence factors, ActA and InlC. Our findings show the pleiotropic role of Listeria virulence factors and their cooperative action in successfully establishing the cellular infection.

The cell wall of Listeria monocytogenes (Lm), a major intracellular foodborne bacterial pathogen, comprises a thick peptidoglycan layer that serves as a scaffold for glycopolymers such as wall teichoic acids (WTAs). WTAs contain non-essential sugar substituents whose absence prevents bacteriophage binding and impacts antigenicity, sensitivity to antimicrobials, and virulence. Here, we demonstrated, for the first time, the triple function of Lm WTA glycosylations in the following: (1) supporting the correct anchoring of major Lm virulence factors at the bacterial surface, namely Ami and InlB; (2) promoting Lm resistance to antimicrobial peptides (AMPs); and (3) decreasing Lm sensitivity to some antibiotics. We showed that while the decoration of WTAs by rhamnose in Lm serovar 1/2a and by galactose in serovar 4b are important for the surface anchoring of Ami and InlB, N-acetylglucosamine in serovar 1/2a and glucose in serovar 4b are dispensable for the surface association of InlB or InlB/Ami. We found that the absence of a single glycosylation only had a slight impact on the sensibility of Lm to AMPs and antibiotics, however the concomitant deficiency of both glycosylations (rhamnose and N-acetylglucosamine in serovar 1/2a, and galactose and glucose in serovar 4b) significantly impaired the Lm capacity to overcome the action of antimicrobials. We propose WTA glycosylation as a broad mechanism used by Lm, not only to properly anchor surface virulence factors, but also to resist AMPs and antibiotics. WTA glycosyltransferases thus emerge as promising drug targets to attenuate the virulence of bacterial pathogens, while increasing their susceptibility to host immune defenses and potentiating the action of antibiotics.

The host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the whole organism. Keratins are cytoskeletal proteins that are the major components of intermediate filaments in epithelial cells however, their role in bacterial infection has been disregarded. Here we investigate the role of the major epithelial keratins, keratins 8 and 18 (K8 and K18), in the cellular infection by Listeria monocytogenes. We found that K8 and K18 are required for successful InlB/cMet-dependent L. monocytogenes infection, but are dispensable for InlA/E-cadherin-mediated invasion. Both K8 and K18 accumulate at InlB-mediated internalization sites following actin recruitment and modulate actin dynamics at those sites. We also reveal the key role of K8 and K18 in HGF-induced signaling which occurs downstream the activation of cMet. Strikingly, we show here that K18, and at a less extent K8, controls the expression of cMet and other surface receptors such TfR and integrin β1, by promoting the stability of their corresponding transcripts. Together, our results reveal novel functions for major epithelial keratins in the modulation of actin dynamics at the bacterial entry sites and in the control of surface receptors mRNA stability and expression.

In daily clinical practice, there is a growing number of patients receiving new biological agents used in the treatment of malignancies. Ipilimumab is a fully humanized monoclonal antibody approved for patients with melanoma. It acts as an immune checkpoint inhibitor, binding and blocking cytotoxic T-lymphocyte antigen-4 in order to increase the antitumor immune response. There are several reports of autoimmune responses after its use. A 74-year-old man developed a mild rash and pruritus a few hours after the second infusion of ipilimumab and 24 h after the third dose of ipilimumab, he presented with shortness of breath, proximal limb muscle weakness, and diplopia. Repetitive nerve stimulation was consistent with a postsynaptic neuromuscular junction disorder. He began therapy with corticosteroids and pyridostigmine and ipilimumab was discontinued. Following ipilimumab suspension, the patient started to improve gradually. Here, we describe a rare case of myasthenia gravis presumably related with ipilimumab’s therapy. A better knowledge of these agents is necessary, in order to identify characteristics or biomarkers that may be associated with the development of potentially serious autoimmune responses.

Following damage by pore forming toxins (PFTs) host cells engage repair processes and display profound cytoskeletal remodeling and concomitant plasma membrane (PM) blebbing. We have recently demonstrated that host cells utilize similar mechanisms to control cytoskeletal dynamics in response to PFTs and during cell migration. This involves assembly of cortical actomyosin bundles, reorganisation of the endoplasmic reticulum (ER) network, and the interaction between the ER chaperone Gp96 and the molecular motor Non-muscle Myosin Heavy Chain IIA (NMHCIIA). Consequently, Gp96 regulates actomyosin activity, PM blebbing and cell migration, and protects PM integrity against PFTs. In addition, we observed that PFTs increase association of Gp96 and ER vacuoles with the cell surface or within PM blebs loosely attached to the cell body. Similarly, gut epithelial cells damaged by PFTs in vivo were shown to release microvilli structures or directly purge cytoplasmic content. Cytoplasmic purging involves profound cytoskeletal remodeling and ER vacuolation, suggesting that our observations recapitulate recovery processes in vivo. Here, we discuss our findings in light of the current understanding of PM repair mechanisms and in vivo recovery responses to PFTs.

Clostridium perfringens produces an arsenal of toxins that act together to cause severe infections in humans and livestock animals. Perfringolysin O (PFO) is a cholesterol-dependent pore-forming toxin encoded in the chromosome of virtually all C. perfringens strains and acts in synergy with other toxins to determine the outcome of the infection. However, its individual contribution to the disease is poorly understood. Here, we intoxicated human epithelial and endothelial cells with purified PFO to evaluate the host cytoskeletal responses to PFO-induced damage. We found that, at sub-lytic concentrations, PFO induces a profound reorganization of the actomyosin cytoskeleton culminating into the assembly of well-defined cortical actomyosin structures at sites of plasma membrane (PM) remodeling. The assembly of such structures occurs concomitantly with the loss of the PM integrity and requires pore-formation, calcium influx, and myosin II activity. The recovery from the PM damage occurs simultaneously with the disassembly of cortical structures. PFO also targets the endoplasmic reticulum (ER) by inducing its disruption and vacuolation. ER-enriched vacuoles were detected at the cell cortex within the PFO-induced actomyosin structures. These cellular events suggest the targeting of the endothelium integrity at early stages of C. perfringens infection, in which secreted PFO is at sub-lytic concentrations.

The experiment was carried out in the Experimental farm of Unimontes in Janaúba, North of MinasGerais, aiming at determining characteristics of the silages of five sorghum genotypes cultivated in the winter.The genotypes Volumax, AG 2005E, Qualimax, BRS 610 and AG 2501 were used. The planting in the field wasaccomplished in blocks at random, with four replications per genotype. Data were subjected to analysis of varianceusing the Sisvar program and mean comparisons were done according to the Scott-Knott test at 5% significance. Aftercutting, part of the material was ensiled. After the silos opening, the samples were pre-dried, ground and packed inglass flasks for analyses of pH, NH3/NT, latic acid, acetic acid and dry matter digestibility in vitro. The pH values, NH3/NT, lactic acid and acetic acid of the silages were adequate for a good fermentation profile. The largest percentagesof DIVDM of the silages were found in the Qualimax, BRS 610 and AG 2005E genotypes that did not differ amongthemselves and were superior to the others. The data were submitted to variance analysis through the Sisvar programand mean comparisons were done in agreement with Scott-Knott test at 5%. The studied genotypes presented goodgreen mass yield and also agronomic characteristics and nutritional value appropriated to the production of silageswith good fermentative pattern when cultivated in the winter.

In this essay, I compare two narratives from different nations, Haiti and Mozambique, in order to analyze intersections between the postcolonial contexts in which each fiction is embedded. Two theoretical perspectives inform my reading of Nadine Pinede’s “Departure Lounge” (2011) and João Paulo Borges Coelho’s Campo de trânsito (2007). I draw first on Vivek Chibber’s argument that postcolonial studies fail to provide an adequate basis for a theory of human rights and a practice of global solidarity. I then introduce the Warwick Research Collective’s elaboration of a new theory of world literature constructed around the concept of “combined and uneven development”. My discussion of “Departure Lounge” and Campo de trânsito subsequently focuses on the fictional portrayal of emergent practices within traditional societies experiencing a process of modernization and the effects of the world capitalist system. I conclude by proposing a way out of the limitations of postcolonial studies.

This essay analyzes João Paulo Borges Coelho’s latest novel, Rainhas da Noite (2013), from the perspective of its portrayal of colonial women. My argument begins by recalling Laura Calvacante Padilha’s inspired insights into the representation of voices from pre-colonial traditions in modern African fiction. I then develop and extend Padilha’s work by including voices from the historically more recent colonial past within the fictional repertory of recovered voices. Borges Coelho’s writings indeed allude to spaces and “voices” of African tradition, as Padilha argues. I suggest, however, that it is the memory of the past of Mozambican colonial time, as well as the relation between that past and a present defined by post-independence, that constitutes the axis of aesthetic and social meaning in Rainhas da Noite. The recent past of Portuguese colonial domination permeates Borges Coelho’s novels. --- Original in English.

Introduction: Polycystic ovary syndrome is the most frequent cause of anovulatory infertility and management involves a multistep approach. Laparoscopic ovarian diathermy is accepted as a second-line treatment of patients who failed to respond to clomiphene citrate. The aims of this study were to determine the efficacy of this technique at short and long-term and to perform an analysis of predictive factors of spontaneous pregnancy. Material and Methods: This retrospective study involved 76 women who underwent laparoscopic ovarian diathermy between 2004 and 2013 in a university hospital. Main outcomes were cycle regularity and pregnancy. Short-term outcomes recorded during followup in our centre were reviewed and long-term outcomes were evaluated by a telephone interview to all women whose surgery was undertaken more than three years ago. Clinical and biochemical data were analysed as predictive factors of spontaneous conception in patients without other infertility factors. Results: Menstrual cycle regularity was initially achieved in 53 (70%) women and in the long-term follow-up subgroup, 52% (12/23) had regular periods. In general, 53 (70%) women conceived and 77 pregnancies were achieved, 60% of which were spontaneous. The only prognostic factor found to be significantly associated with spontaneous conception was a shorter duration of infertility (< 3 years) (p < 0.05). Discussion: Laparoscopic ovarian diathermy showed pregnancy rates comparable to other ovulation induction treatments with the advantage of having a long lasting beneficial effect in menstrual regularity and fertility. Conclusion: Laparoscopic ovarian diathermy is a safe and effective treatment option for anovulatory infertility in women with polycystic ovary syndrome.

Understanding the strategies used by pathogens to infect, survive, and proliferate in their hosts requires the identification of virulence factors. We developed PCR-based screening of targeted mutants to facilitate quick, simultaneous detection of multiple novel bacterial virulence genes. Based on direct PCR screening of pooled targeted mutants, this approach provides a fast and sensitive measure of virulence attenuation while significantly reducing the number of animals and time required. We demonstrate that the careful design of gene-specific primers allows the direct relative quantification of mixed mutants in infected mouse organs. Indeed, we show that the band intensity of the PCR product is directly related to the quantity of the corresponding strain in a pool of mutants. We applied the PCR-based screening of targeted mutants to the murine model of listeriosis and revealed new genes required for full pathogenicity of Listeria monocytogenes, a facultative human intracellular pathogen. PCR-based screening is a simple, useful, and fast technique to test pools of targeted bacterial mutants in vivo, without the requirements for a rigorous purification step, complicated PCR set-up, or special equipment. This approach can be adapted to other bacterial systems, constituting a significant advance in the field of infection biology.

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Objective: To estimate the prevalence of young people's involvement in violence measured as participation in physical fights or being physically, sexually or emotionally abused. We also aimed to understand the role of social, demographic and other behavioural characteristics in violence. Methods: We evaluated 7511 adolescents (4243 girls and 3268 boys) aged 15 to 19 years old, enrolled in public schools. Information was obtained using an anonymous, self-administrated questionnaire. Results: The most frequently reported type of violence was emotional abuse (15.6%). Boys reported greater involvement in fights (3.6 vs. 13.6%, pObjetivo: Estimar la prevalencia de la participación de los jóvenes en peleas, y de ser físicamente, sexualmente o emocionalmente maltratados. Analizar la función de las características sociales, demográficas y de comportamiento sobre la violencia. Métodos: Se evaluaron 7.511 adolescentes (4.243 chicas y 3.268 chicos) de 15 a 19 años de edad, matriculados en escuelas públicas. La información se obtuvo por cuestionario anónimo auto-administrado. Resultados: La violencia emocional fue la más notificada (15,6%). Los chicos indicaron más peleas (3,6 frente a 13,6%, p

Palavras-chave: Criança; Escleroderma Sistémica.

Listeria monocytogenes is an opportunistic Gram-positive bacterial pathogen responsible for listeriosis, a human foodborne disease. Its cell wall is densely decorated with wall teichoic acids (WTAs), a class of anionic glycopolymers that play key roles in bacterial physiology, including protection against the activity of antimicrobial peptides (AMPs). In other Gram-positive pathogens, WTA modification by amine-containing groups such as D-alanine was largely correlated with resistance to AMPs. However, in L. monocytogenes, where WTA modification is achieved solely via glycosylation, WTA-associated mechanisms of AMP resistance were unknown. Here, we show that the L-rhamnosylation of L. monocytogenes WTAs relies not only on the rmlACBD locus, which encodes the biosynthetic pathway for L-rhamnose, but also on rmlT encoding a putative rhamnosyltransferase. We demonstrate that this WTA tailoring mechanism promotes resistance to AMPs, unveiling a novel link between WTA glycosylation and bacterial resistance to host defense peptides. Using in vitro binding assays, fluorescence-based techniques and electron microscopy, we show that the presence of L-rhamnosylated WTAs at the surface of L. monocytogenes delays the crossing of the cell wall by AMPs and postpones their contact with the listerial membrane. We propose that WTA L-rhamnosylation promotes L. monocytogenes survival by decreasing the cell wall permeability to AMPs, thus hindering their access and detrimental interaction with the plasma membrane. Strikingly, we reveal a key contribution of WTA L-rhamnosylation for L. monocytogenes virulence in a mouse model of infection.

In the past thirty years GIS technology has progressed from computer mapping to spatial database management, and more recently, to quantitative map analysis and modeling. However, most applications still rely on visual analysis for determining similarity within and among maps. The aim of this study is to compare maps of homogenous areas computed from estuarine sediment characterization indicators, using different approaches. These maps were defined using three different interpolation methods. Different Kappa statistics, visual map overlays or components of agreement and disagreement due to chance, quantity and location were used for single cell and/or neighborhood (hard and soft) map comparison. Although the three methods were computed with different statistical techniques, their results are similar, supporting the choice of any of the methods as equivalent and thus of equal value to be used as management units of the estuary. Hence the significance of choosing one of the methods is reduced.

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Neste artigo analisa-se a circulação de expectativas e racionalidades de decisores políticos e de casais em procriação medicamente assistida, em Portugal, em torno da decisão quanto à doação de embriões para investigação científica. As interpenetrações entre a esfera política e a leiga serão discutidas com base na análise de conteúdo das seguintes fontes de informação: discursos políticos que suportaram a proposta de criação de um sistema de informação para os dadores de embriões idêntico ao sistema dos dadores de órgãos biológicos; entrevistas conduzidas entre Agosto 2011 e Agosto 2012 a 221 casais e 93 mulheres envolvidos em fertilização in vitro ou injeção intracitoplasmática de espermatozoides, no Hospital de S. João, Porto, sobre doação de embriões para investigação. Decisores políticos e casais partilham uma elevada recetividade ao progresso científico e depositam elevadas expectativas e confiança no poder terapêutico da investigação científica em células estaminais embrionárias. Se os casais usam a ética da reciprocidade, responsabilidade social e altruísmo para justificar as suas decisões; os decisores políticos realçam os contributos dos avanços da ciência para a esfera económica e promoção da imagem do país. Estes resultados consolidam a necessidade de reforçar a participação de diversos públicos na construção de princípios éticos e de responsabilidade social na regulação das práticas de investigação em embriões de origem humana.

Listeria monocytogenes is a human intracellular pathogen able to colonize host tissues after ingestion of contaminated food, causing severe invasive infections. In order to gain a better understanding of the nature of host-pathogen interactions, we studied the L. monocytogenes genome expression during mouse infection. In the spleen of infected mice, approximately 20% of the Listeria genome is differentially expressed, essentially through gene activation, as compared to exponential growth in rich broth medium. Data presented here show that, during infection, Listeria is in an active multiplication phase, as revealed by the high expression of genes involved in replication, cell division and multiplication. In vivo bacterial growth requires increased expression of genes involved in adaptation of the bacterial metabolism and stress responses, in particular to oxidative stress. Listeria interaction with its host induces cell wall metabolism and surface expression of virulence factors. During infection, L. monocytogenes also activates subversion mechanisms of host defenses, including resistance to cationic peptides, peptidoglycan modifications and release of muramyl peptides. We show that the in vivo differential expression of the Listeria genome is coordinated by a complex regulatory network, with a central role for the PrfA-SigB interplay. In particular, L. monocytogenes up regulates in vivo the two major virulence regulators, PrfA and VirR, and their downstream effectors. Mutagenesis of in vivo induced genes allowed the identification of novel L. monocytogenes virulence factors, including an LPXTG surface protein, suggesting a role for S-layer glycoproteins and for cadmium efflux system in Listeria virulence.