bluuebunny/crossref_metadata_2025 huggingface dataset:
Placental Growth Factor Promotes Ovarian Cancer Cell Invasion via ZEB2
Authors: Song Ning , Liu Hao , Ma Xiaoxin , Zhang Shulan
Published: January 2016

Background/Aims: The aggressive manner of ovarian cancer (OVC) cells accounts for the majority of its lethality. Recently, we have shown that placental growth factor (PLGF) promotes metastases of OVC cells through miR-543-regulated MMP7. In the current study, we analyzed the effects of PLGF on another cell invasion associated protein, ZEB2, in OVC cells. Methods: The PLGF and ZEB2 levels in OVC tissues were compared to the paired adjacent non-tumor ovary tissue. We modified ZEB2 levels in OVC cells, and examined its effects on PLGF mRNA and protein levels by RT-qPCR and by Western blot, respectively. We also modified PLGF levels in OVC cells, and examined its effects on ZEB2 mRNA and protein levels by RT-qPCR and by Western blot, respectively. Then, we examined the cell invasiveness in PLGF-modified OVC cells in a transwell cell invasion assay. Finally, we used specific signal pathway inhibitors to treat PLGF-modified OVC cells and examined the effects on ZEB2 activation. Results: PLGF and ZEB2 levels were both significantly increased in OVC tissues, compared to the paired adjacent non-tumor ovary tissue. The PLGF and ZEB2 levels were strongly correlated. ZEB2 modification did not alter PLGF levels. Overexpression of PLGF in OVC cells significantly increased ZEB2 levels and cell invasiveness, while PLGF depletion in OVC cells significantly decreased ZEB2 levels and cell invasiveness. Application of a specific MAPK-p38 inhibitor, but not application of specific inhibitors for MAPK-p42/p44, PI3k/Akt, or JNK signaling pathways, to PLGF-overexpressing OVC cells substantially abolished the PLGF-induced ZEB2 activation. Conclusion: PLGF enhances OVC cell invasion through MAPK-p38-dependent activation of ZEB2.
The Effects of Indoxyl Sulfate on Human Umbilical Cord-Derived Mesenchymal Stem Cells In Vitro
Authors: Wang Wei , Liu Xueyong , Wang Wei , Li Jinghua , Li Yuanyuan , Li Liping , Wang Shaohua , Zhang Jianchun , Zhang Youkang , Huang Haichang
Published: January 2016

Background/Aims: Indoxyl sulfate, an important protein-bound uremic toxin, can damage stem cells, thus hampering stem cell-based regenerative medicine approaches targeting chronic kidney diseases (CKD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are thought to have promising clinical application because of their high proliferative potential and ease of isolation than MSCs from other sources. In the present study, we aimed to determine the harmful effects of indoxyl sulfate on the phenotype and functional potential of hUC-MSCs in vitro. Methods: The toxicity and cell viability was examined by Trypan blue exclusion and MTT assay. The cellular surface markers and the percentage of apoptotic cells by Annexin-V/PI staining were analyzed by flow cytometry. Proliferation was evaluated based on cell number counting and Ki-67 immunostaining. Cell senescence was measured using senescence-associated β-Galactosidase activity. The ability to stimulate the development of CD4+CD25+FoxP3+ regulatory T cells was assessed by incubating hUC-MSCs with peripheral blood mononuclear cells from the healthy volunteers. Results: Our results demonstrated that the immunophenotype of hUC-MSCs was not affected by indoxyl sulfate flow cytometry. However, a significant decrease in cell numbers and fraction of Ki-67 positive proliferating cells, along with a significant increase in cellular senescence were detected in hUC-MSCs after exposure to indoxyl sulfate. Additionally, their ability to stimulate CD4+CD25+FoxP3+ regulatory T cell production was compromised when hUC-MSCs were pretreated with indoxyl sulfate. Conclusion: Taken together, our study clearly demonstrated that the molecular alterations and functional incompetence in hUC-MSCs under the challenge of indoxyl sulfate in vitro.
Dopamine D1-Like Receptors Suppress the Proliferation of Macrophages Induced by Ox-LDL
Authors: Yao Yonggang , Yang Di , Han Yu , Wang Wei , Wang Na , Yang Jian , Zeng Chunyu
Published: January 2016

Background/Aims: Oxidized low-density lipoprotein (Ox-LDL) induces macrophage proliferation, a key physiological process which leads to atherosclerosis. The aim of this study was to determine the effects of dopamine D1-like receptors on macrophage proliferation induced by Ox-LDL. Methods: The expression of dopamine D1-like receptors was determined by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting. The effect of D1-like receptors on macrophage proliferation induced by Ox-LDL was measured by 3[H]-thymidine incorporation and cell number count. Results: Dopamine D1-like receptors were present in macrophages as determined by immunohistochemistry, RT-PCR and immunoblotting. A D1-like receptor agonist, fenoldopam, which by itself had no effect on macrophage proliferation, inhibited the stimulatory effect of Ox-LDL on macrophage proliferation. This was further confirmed by the D1-like receptor antagonist SCH 23390 blocking the effect of fenoldopam, thereby indicating that the fenoldopam action was receptor specific. Phosphatidylinositol 3-kinase (PI3K/Akt) and mitogen-activated protein kinase (MAPK/ERK) pathways were also involved in the proliferative effect of Ox-LDL because in the presence of PI3K/Akt or MAPK/ERK inhibitors, LY294002 or PD98059, the stimulatory effects of Ox-LDL were blocked. Moreover, the stimulatory effect of Ox-LDL on the phosphorylation of ERK and Akt was significantly reduced by fenoldopam in macrophages. Additional experiments found that both D1 and D5 receptor expression was lower in the peritoneal macrophages from Apolipoprotein E-deficient mice compared to the control C57Bl/6J mice. Conclusions: Macrophages express D1-like receptors. The activation of the D1-like receptors significantly inhibits Ox-LDL-induced macrophage proliferation, possibly through the inhibition of the PI3K/Akt and MAPK/ERK signaling pathways.
Identification of a Small Benzamide Inhibitor of Influenza Virus Using a Cell-Based Screening
Authors: Shin Woo-Jin , Nam Ky-Youb , Kim Nam-Doo , Kim Sei-Hwan , No Kyoung-Tai , Seong Baik-Lin
Published: January 2016

Background: The zoonotic transmission of highly pathogenic avian influenza viruses and the global pandemic of H1N1 influenza in 2009 signified the need for a wider coverage of therapeutic options for the control of influenza. Methods: An in-house compound library was screened using a cytopathic effect inhibition assay. Selected hits were then tested in vivo and used as a core skeleton for derivative synthesis. Results: The hit compound (BMD-2601505) was effective [50% effective concentration (EC50) of 60-70 μM] in reducing the death rate of cells infected with human influenza A and B viruses as well as avian influenza A virus. Furthermore, BMD-2601505 reduced the weight loss and increased the survival after lethal infection. The compound was further modified to enhance its antiviral potency. Results show that one derivative with bromobenzene moiety was most effective (EC50 of 22-37 μM) against the influenza viruses tested. Conclusion: We identified a small benzamide compound exhibiting antiviral activity against influenza viruses. The results warrant further evaluation of antiviral activities against drug-resistant influenza isolates.
Benign Cardiac Effects of Hemoglobin H Disease
Authors: Sheeran Claire , Bowden Donald K. , Pasricha Sant-Rayn , Cheng Ken , Romanelli Giovanni , Peverill Roger E.
Published: January 2016

Background/Aims: Hemoglobin H (HbH) disease is associated with iron overload, but whether this results in serious cardiac or vascular sequelae is unresolved. Methods: We identified 39 adult subjects (age 42 ± 12 years, 13 men) with HbH disease who had undergone echocardiography, 27 of whom had also undergone cardiac and liver magnetic resonance assessment of iron loading using T2*-weighted imaging. Results: None of the subjects had a history of heart failure or arrhythmias. There were 13/39 subjects with a ferritin level within the sex-based normal range and only 4/39 had ferritin >1,000 ng/ml. Left ventricular (LV) and left atrial dilatation was common, but LV ejection fraction was normal (≥55%) in all subjects. Age was positively correlated with log ferritin in the 27 nontransfused subjects (r = 0.43) and was inversely correlated with the transmitral E wave and E/A ratio (r = -0.69 and r = -0.79, respectively), but no relation of log ferritin with E or E/A was evident. The peak tricuspid regurgitation velocity was normal in 24/29 subjects for whom this was obtained, and it was no more than mildly elevated in the other 5. None of the tested subjects had an abnormal cardiac T2* reading, but half had evidence of liver iron loading. Conclusion: No myocardial iron loading or serious cardiac or vascular sequelae were identified in this cohort with HbH disease.
Proteomics of Secretory-Stage and Maturation-Stage Enamel of Genetically Distinct Mice
Authors: Charone Senda , De Lima Leite Aline , Peres-Buzalaf Camila , Silva Fernandes Mileni , Ferreira de Almeida Lucas , Zardin Graeff Marcia Sirlene , Cardoso de Oliveira Rodrigo , Campanelli Ana Paula , Groisman Sonia , Whitford Gary Milton , Everett Eric T. , Buzalaf Marília Afonso Rabelo
Published: January 2016

The mechanisms by which excessive ingestion of fluoride (F) during amelogenesis leads to dental fluorosis (DF) are still not precisely known. Inbred strains of mice vary in their susceptibility to develop DF, and therefore permit the investigation of underlying molecular events influencing DF severity. We employed a proteomic approach to characterize and evaluate changes in protein expression from secretory-stage and maturation-stage enamel in 2 strains of mice with different susceptibilities to DF (A/J, i.e. ‘susceptible' and 129P3/J, i.e. ‘resistant'). Weanling male and female susceptible and resistant mice fed a low-F diet were divided into 2 F-water treatment groups. They received water containing 0 (control) or 50 mg F/l for 6 weeks. Plasma and incisor enamel was analyzed for F content. For proteomic analysis, the enamel proteins extracted for each group were separated by 2-dimensional electrophoresis and subsequently characterized by liquid-chromatography electrospray-ionization quadrupole time-of-flight mass spectrometry. F data were analyzed by 2-way ANOVA and Bonferroni's test (p < 0.05). Resistant mice had significantly higher plasma and enamel F concentrations when compared with susceptible mice in the F-treated groups. The proteomic results for mice treated with 0 mg F/l revealed that during the secretory stage, resistant mice had a higher abundance of proteins than their susceptible counterparts, but this was reversed during the maturation stage. Treatment with F greatly increased the number of protein spots detected in both stages. Many proteins not previously described in enamel (e.g. type 1 collagen) as well as some uncharacterized proteins were identified. Our findings reveal new insights regarding amelogenesis and how genetic background and F affect this process.
Detection of Human Papillomavirus Infections at the Single-Cell Level
Authors: Shen Zhenping , Liu Xia , Morihara Janice , Hulbert Ayaka , Koutsky Laura A. , Kiviat Nancy B. , Xi Long Fu
Published: January 2016

Objective: To explore the possibility of single-cell analysis of human papillomavirus (HPV) infection. Methods: Two hundred and twenty cells were isolated by laser capture microdissection from formalin-fixed and paraffin-embedded cervical tissue blocks from 8 women who had HPV DNA detected in their cervical swab samples. The number of type-specific HPV copies in individual cells was measured by quantitative polymerase chain reaction with and without a prior reverse transcription. The cells were assayed and counted for more than once if the corresponding swab sample was positive for ≥2 HPV types. Results: Infection with HPV16, HPV39, HPV51, HPV52, HPV58, HPV59 and HPV73 was detected in 12 (5.5%) of 220, 3 (9.4%) of 32, 3 (5.8%) of 52, 11 (22.9%) of 48, 9 (18.8%) of 48, 3 (9.4%) of 32 and none of 20 cells, respectively. The numbers of HPV genome copies varied widely from cell to cell. The coexistence of multiple HPV types was detected in 6 (31.6%) of 19 positive cells from 1 of the 6 women who had 2 or 3 HPV types detected in their swab samples. Conclusion: Given the heterogeneity of HPV status in individual cells, further clarification of HPV infection at the single-cell level may refine our understanding of HPV-related carcinogenesis.
Prior Cannabis Use Is Associated with Outcome after Intracerebral Hemorrhage
Authors: Di Napoli Mario , Zha Alicia M. , Godoy Daniel A. , Masotti Luca , Schreuder Floris H.B.M. , Popa-Wagner Aurel , Behrouz Réza ,   from the MNEMONICH Registry
Published: January 2016

Objective: Recent evidence suggests that a potential harmful relationship exists between cannabis use and ischemic stroke. The purpose of this study was to determine the implications of cannabis use in intracerebral hemorrhage (ICH) patients. Methods: An analysis of an international, multicenter, observational database of consecutive patients with spontaneous ICH was conducted. We extracted the following characteristics on presentation: demographics, risk factors, antiplatelet or anticoagulant use, Glasgow Coma Scale, ICH score, neuroimaging parameters, and urine toxicology screen (UTS) results. Modified Rankin Scale (mRS) score was utilized for determination of outcome at discharge. Adjusted logistic ordinal regression was used as shift analysis to assess the impact of cannabis use on mRS score at discharge. The adjusted common OR measured the likelihood that cannabis use would lead to lower mRS scores. Results: Within a cohort of 725 spontaneous ICH patients, UTS was positive for cannabinoids in 8.6%. Cannabinoids-positive (CB+) patients were more frequently Caucasian (p < 0.001), younger (p < 0.001), and had lower median ICH scores on admission (p = 0.017) than those who were cannabinoids-negative. CB+ patients also showed a shift toward better outcome in the distribution of mRS categories, with an adjusted common OR of 0.544 (95% CI 0.330-0.895, p = 0.017). Conclusion: In this multinational cohort, cannabis use was discovered in nearly 10% of patients with spontaneous ICH. Although there was no relationship between cannabis use and specific ICH characteristics, CB+ patients had milder ICH presentation and less disability at discharge.
Computed Tomography Perfusion Improves Diagnostic Accuracy in Acute Posterior Circulation Stroke
Authors: Sporns Peter , Schmidt Rene , Minnerup Jens , Dziewas Rainer , Kemmling André , Dittrich Ralf , Zoubi Tarek , Heermann Philipp , Cnyrim Christian , Schwindt Wolfram , Heindel Walter , Niederstadt Thomas , Hanning Uta
Published: January 2016

Background and Purpose: Computed tomography perfusion (CTP) has a high diagnostic value in the detection of acute ischemic stroke in the anterior circulation. However, the diagnostic value in suspected posterior circulation (PC) stroke is uncertain, and whole brain volume perfusion is not yet in widespread use. We therefore studied the additional value of whole brain volume perfusion to non-contrast CT (NCCT) and CT angiography source images (CTA-SI) for infarct detection in patients with suspected acute ischemic PC stroke. Methods: This is a retrospective review of patients with suspected stroke in the PC in a database of our stroke center (n = 3,011) who underwent NCCT, CTA and CTP within 9 h after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and pc-ASPECTS locations of ischemia. Three imaging models - A (NCCT), B (NCCT + CTA-SI) and C (NCCT + CTA-SI + CTP) - were compared with regard to the misclassification rate relative to gold standard (infarction in follow-up imaging) using the McNemar's test. Results: Of 3,011 stroke patients, 267 patients had a suspected stroke in the PC and 188 patients (70.4%) evidenced a PC infarct on follow-up imaging. The sensitivity of Model C (76.6%) was higher compared with that of Model A (21.3%) and Model B (43.6%). CTP detected significantly more ischemic lesions, especially in the cerebellum, posterior cerebral artery territory and thalami. Conclusions: Our findings in a large cohort of consecutive patients show that CTP detects significantly more ischemic strokes in the PC than CTA and NCCT alone.
Partial Response to Platinum Doublets in Refractory EGFR-Positive Non-Small Cell Lung Cancer Patients after RRx-001: Evidence of Episensitization
Authors: Carter Corey A. , Oronsky Bryan T. , Caroen Scott Z. , Scicinski Jan J. , Cabrales Pedro , Reid Tony , Degesys Aiste , Jenkins John , Brzezniak Christina
Published: January 2016

RRx-001, an experimental systemically non-toxic epi-immunotherapeutic agent, which potentiates the resensitization of resistant cancer cells to formerly effective therapies, is under active investigation in several clinical trials that are based on sequential or concomitant rechallenge to resistant first- or second-line regimens. One of these trials is designated TRIPLE THREAT (NCT02489903), because it explores the conditioning or priming effect of RRx-001 on three tumor types - non-small cell lung cancer (NSCLC), small cell lung cancer and high-grade neuroendocrine tumors - prior to re-administration of platinum doublets. In follow-up to a recent case study, which describes early monotherapeutic benefit with RRx-001 in a refractory EGFR-mutated NSCLC tumor, we present subsequent evidence of a radiological partial response to reintroduced platinum doublets after RRx-001. For the 50% of patients with EGFR-mutated NSCLC who progress on EGFR-tyrosine kinase inhibitors (without evidence of a T790M mutations) as well as platinum doublets and pemetrexed/taxane, no other clinically established treatment options exist. A retrial of these therapies in EGFR-positive NSCLC patients via priming with epigenetic agents such as RRx-001 constitutes a strategy to ‘episensitize' tumors (i.e. reverse resistance by epigenetic means) and to extend overall survival.
The Epidural Treatment of Sciatica: Its Origin and Evolution
Authors: Ter Meulen Bastiaan C. , Weinstein Henry , Ostelo Raymond , Koehler Peter J.
Published: January 2016

Epidural injection with corticosteroids is a common treatment option for patients with lower back pain or sciatica. In this paper we review its origin and evolution. The first injections were given around 1900 in Paris by Jean Sicard (1872-1929) and Fernand Cathelin (1873-1945), who worked independently. They both injected small volumes of cocaine into the sacral hiatus. After a slow start, the epidural treatment of back pain and sciatica gradually spread to other parts of Europe and Northern America. In the early 1950s, corticosteroids were introduced for epidural use. Since the 1970s, there have been numerous clinical trials that show a significant, although small, effect of epidural corticosteroid injections compared with placebo for leg pain in the short term. Despite an ongoing debate about effectiveness and safety, epidural injections remain popular.
Increased Odds of Melanoma: Parkinson's Disease, Essential Tremor, Dystonia versus Controls
Authors: Shalaby Sherif Y. , Louis Elan D.
Published: January 2016

Objective: Patients with Parkinson's disease (PD) have an increased risk of melanoma, although the mechanisms are unclear. We are unaware of studies that have assessed the association between other movement disorders, such as essential tremor (ET) and dystonia, and melanoma. In this study, we assessed the association between ET, PD, dystonia and cancer (esp. melanoma). Methods: One hundred and eight PD cases, 139 ET cases, and 54 dystonia cases, and 124 controls were enrolled in a research study of the epidemiology of movement disorders (total n = 425). The groups were frequency matched on age and gender. Cancer diagnoses were made based on self-reports. Melanoma diagnoses were further validated. Results: The prevalence of melanoma was higher in PD cases than controls (13.9 vs. 1.6%, p < 0.001), and was marginally higher in ET cases (5.8%, p = 0.08) and dystonia cases (7.4%, p = 0.06) than controls. In adjusted logistic regression models, the odds of melanoma was 7.09-9.84 times higher in PD cases than controls (p values 0.01-0.003), 3.73-4.10 times higher in ET cases than controls (p values 0.08-0.10), and 4.88-5.27 times higher in dystonia cases than controls (p values 0.06-0.07). Conclusion: The links between neurological disorders and melanoma, long-known, may not be specific to PD and may extend to other movement disorders.
The class I phosphoinositide 3-kinases α and β control antiphospholipid antibodies-induced platelet activation
Authors: Laurent Pierre-Alexandre , Garcia Cédric , Gratacap Marie-Pierre , Vanhaesebroeck Bart , Sié Pierre , Payrastre Bernard , Terrisse Anne-Dominique
Published: January 2016

Antiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies (aPL) associated with increased thrombotic risk and pregnancy morbidity. Although aPL are heterogeneous auto-antibodies, the major pathogenic target is the plasma protein β2-glycoprotein 1. The molecular mechanisms of platelet activation by aPL remain poorly understood. Here, we explored the role of the class IA phosphoinositide 3-kinase (PI3K) α and β isoforms in platelet activation by aPL. Compared to control IgG from healthy individuals, the IgG fraction isolated from patients with APS potentiates platelet aggregation induced by low dose of thrombin in vitro and increases platelet adhesion and thrombus growth on a collagen matrix under arterial shear rate through a mechanism involving glycoprotein Ib (GPIb) and Toll Like Receptor 2 (TLR-2). Using isoforms-selective pharmacological PI3K inhibitors and mice with megakaryocyte/platelet lineage-specific inactivation of class IA PI3K isoforms, we demonstrate a critical role of the PI3Kβ and PI3Kα isoforms in platelet activation induced by aPL. Our data show that aPL potentiate platelet activation through GPIbα and TLR-2 via a mechanism involving the class IA PI3Kα and β isoforms, which represent new potential therapeutic targets in the prevention or treatment of thrombotic events in patients with APS.
Cognitive reserve in elderly: neuropsychological aspects and the education role in the latest findings
Authors: Dias João Gabriel Magalhães , Silva Pablo Rodrigo Andrade da , Alvez Tânia Corrêa de Toledo Ferraz
Published: January 2016

The elderly population is growing worldwide, and therefore cognitive decline and dementia is a major problem for healthcare system. However, many elders do not develop dementia or significant cognitive impairment even though present brain lesions, such as cortical atrophy and/or lesions, leading to the concept of Cognitive Reserve (CR). The main objective of this review is to establish the recent findings of CR in elderly cognition and explore some of the cognitive markers related to CR. In order to accomplish that we carried out a search for papers published either in English or Portuguese language in the last 5 years in the Medline database using as keywords cognitive reserve, elderly and aging/ageing. We filtered 14 studies that specifically approached the neuropsychological aspects (e.g, memory, attention, orientation, executive function) and reviewed them in detail. Based on these papers regarding old-aged individuals, education appears to have several implications on CR by strengthening cognitive abilities, however does not appear to impact on cognitive decline. Besides, we realized that cognitive performance is one of the form to measure CR, even though the methods cannot be standardized, which may be the cause of some varied conclusions. Regarding CR, education was the most prevalent measure, and CR seems to have a beneficial effect on executive function and episodic memory and it seems to act by both neural reserve and neural compensation. Print exposure appears as a potential variable positively related to cognitive performance and CR.
Neurobiologia das emoções
Authors: Ramos Renato T.
Published: January 2016

Este artigo revê alguns conceitos gerais sobre os mecanismos biológicos envolvidos na expressão das emoções. O foco da discussão é a relevância destas informações para a formação do médico em geral. A hipótese de que comportamentos inatos e geneticamente controlados interagem fortemente com elementos sociais, culturais e familiares na gênese dos transtornos afetivos e ansiosos é discutida a partir de dados de estudos com modelos animais e estudos utilizando técnicas de neuroimagem funcional. Embora, muitas questões de caráter psicodinâmico e sociológico não sejam discutidas, o artigo chama a atenção para a importância, dentro da prática clínica, da articulação destes conhecimentos humanísticos com os modelos neurofisiológicos do comportamento humano.
Bases moleculares e celulares das nefropatias hereditárias císticas
Authors: Amaral Andressa Godoy , Onuchic Luiz Fernando
Published: January 2016

As nefropatias hereditárias císticas (NHCs) são causadas por mutações gênicas determinantes ao desenvolvimento de anormalidades nas células renais epiteliais, alterações que criam as condições biológicas necessárias à formação cística. A identificação de genes mutados nessas enfermidades e a caracterização de seus produtos proteicos vêm permitindo a elucidação de mecanismos envolvidos em sua patogênese. Esta revisão tem como foco as bases genéticas e a patogênese molecular dessas enfermidades, embora também aborde brevemente aspectos clínicos e epidemiológicos das NHCs de maior impacto médico e socioeconômico. Dentro deste conjunto de moléstias, abordaremos a doença renal policística autossômica dominante, doença renal policística autossômica recessiva, nefronoftises, doença renal túbulo-intersticial autossômica dominante, doença de von Hippel-Lindau e complexo esclerose tuberosa. Essas NHCs possuem sobreposição de manifestações clínicas e compartilham vias e defeitos moleculares. Entre suas características comuns, destacaremos o papel central de anormalidades no cílio apical primário e de vias de sinalização intracelular responsáveis por alterações fundamentais do fenótipo celular. Ao apresentar os avanços obtidos na patogênese molecular e celular das NHCs, discutiremos criticamente o estabelecimento, os papeis e as implicações da homeostase defeituosa de cálcio citosólico; resposta celular hiperproliferativa ao AMP cíclico; taxas elevadas de proliferação celular e apoptose; alterações da matriz extracelular; alterações da polaridade celular; e secreção transepitelial de fluido. O conhecimento acumulado nas últimas duas décadas trouxe um novo contexto molecular e celular às NHCs, capaz de criar a plataforma de conhecimento necessária para o desenvolvimento de ensaios pré-clínicos. Tais ensaios, por sua vez, vêm amparando a condução de estudos clínicos robustos, os quais têm aberto perspectivas terapêuticas promissoras.
Critérios para avaliação de incapacidade laborativa na insuficiência cardíaca
Authors: Torres Rafael Augusto Tamasauskas , Cintra Raquel Barbosa , Sá Eduardo Costa
Published: January 2016

Introdução: A Previdência Social, no Brasil, é uma seguradora social que garante a renda do segurado quando ele perde sua capacidade laborativa. Dentre os benefícios concedidos temos a aposentadoria por invalidez, sendo que para sua concessão o segurado deve passar por perícia médica que comprove sua incapacidade total e permanente. Quatorze por cento das aposentadorias por invalidez concedidas nos últimos três anos ocorreram devido a doenças do aparelho circulatório, sendo que a via final das maiorias destas doenças é a insuficiência cardíaca. Objetivo: Identificar critérios para determinar incapacidade total e permanente em segurados portadores de insuficiência cardíaca congestiva em perícias previdenciárias. Metodologia: Revisão bibliográfica, sem limite de data, realizada de abril a agosto de 2014, utilizando os seguintes descritores: insuficiência cardíaca, seguro por invalidez e aposentadoria, nas seguintes bases de dados: Pubmed/Medline; BVS (Biblioteca Virtual de Saúde); Scopus; Web of Science; e Cochrane. A legislação previdenciária foi pesquisada. Resultados: Insuficiência cardíaca pode ser considerada incapacitante para mobilidade, tarefas complexas e tarefas de autocuidado, além de cursar com incapacidade cognitiva moderada ou severa. Insuficiência cardíaca como complicação pós-infarto é forte indicador para aposentadoria precoce, tendo como fator prognóstico positivo para retorno ao trabalho idade menor que 60 anos, fração de ejeção maior que 35%, ausência de financiamento durante o afastamento, ausência de ataques de ansiedade e trabalho com baixa exigência física. Discussão: O Grau III ou IV da insuficiência cardíaca, segundo NYHA e a Previdência Social, cursa com incapacidade que, se permanente, dará direito à aposentadoria por invalidez. Exames complementares não devem ser usados de forma isolada. Idade maior que 60 anos, sexo feminino e alta carga de trabalho são fatores de mau prognóstico. Conclusão: Para a avaliação de capacidade laborativa na insuficiência cardíaca devem ser levados em consideração os achados clínicos, a fração de ejeção, a cognição do examinado, a exigência física do trabalho e as condições de retorno a este, a idade do periciando e a classificação funcional utilizada pela NYHA ou da Previdência Social.
Lúpus eritematoso sistêmico diagnosticado durante a gestação: relato de caso
Authors: Coelho Junior Luilson Geraldo , Machado Gabrielly Borges , Figueiredo Estevão Tavares de , Faria Talitha Araújo
Published: January 2016

O lúpus eritematoso sistêmico (LES) é uma doença inflamatória crônica de etiologia autoimune, distribuição multissistêmica, cujas manifestações clínicas são bastante variáveis. Fatores genéticos, hormonais e ambientais estão correlacionados com o desenvolvimento da doença, a qual é caracterizada por períodos de remissão e exacerbação. No LES, os fenômenos imunológicos levam à produção de auto-anticorpos, os quais são dirigidos a antígenos nucleares do próprio organismo, resultando em diferentes manifestações clínicas, podendo acometer ossos, articulações, pulmões, fígado, rins e sistema nervoso central. Mulheres em período fértil têm alta prevalência, sendo que, na maior parte dos casos, não têm sua fertilidade comprometida. O início do quadro durante a gravidez é raro e indica pior prognóstico para mãe e feto. A gravidez está desaconselhada quando a doença está ativa durante a concepção, e quando se associa à nefrite lúpica. Mulheres portadoras de lúpus cursam com gestação de alto risco, haja vista, as gestantes lúpicas apresentarem maior taxa de abortamento espontâneo, restrição de crescimento intra-uterino e fetal, eclâmpsia, morte fetal, parto pré-termo. Há controvérsias sobre o efeito da gestação na atividade da doença, uma vez que, o LES pode afetar a gravidez, e o inverso também pode ocorrer; todavia, o LES não deve ser entendido como uma limitação à gestação, e o acompanhamento da mesma deve ser feito por equipe multiprofissional, assegurando uma gravidez segura para mãe e feto. Apresentamos o caso de uma paciente diagnosticada com LES no primeiro trimestre de gestação e que apresentou evolução clínica e laboratorial rápida e desfavorável, evoluindo com quadro de nefrite lúpica e abortamento.
Análise da Conversação e oralidade em textos escritos
Authors: Silva Luiz Antônio da
Published: January 2016

Marcuschi (1977) ressalta que a oralidade é um importante tópico a ser desenvolvido na sala de aula, mas, infelizmente, tem sido deixado de lado, pois professores e responsáveis pelo ensino não consideram a importância da oralidade no ensino de língua materna. A razão principal é o foco que é dado ao ensino de língua nas escolas brasileiras: a escola existe para ensinar a escrever e escrever bem. Apesar dos avanços dos estudos linguísticos sobre fala e escrita; apesar das contribuições da Sociolinguística e da Análise da Conversação; apesar dos preconceitos vencidos, especialmente sobre a distinção rigorosa entre as duas modalidades, há, ainda, um percurso a vencer. Dessa forma, é produtivo trazer à tona a discussão sobre fala e escrita. Decorridos vários anos da constatação de Marcuschi (1977), autores de livros didáticos, professores, pesquisadores e responsáveis pelo ensino de língua portuguesa têm outra postura teórica, mas, na prática, ainda, há muito que avançar, pois a escrita continua a ser o foco do ensino de língua portuguesa nas escolas brasileiras. Tudo indica que boa parte dos professores conhece a teoria, mas eles têm dificuldades na prática do cotidiano escolar. Este trabalho tem por objetivo analisar marcas de oralidade ou efeitos de oralidade em textos literários escritos, mais precisamente em diálogos produzidos. A partir dessas análises, busca-se dar subsídios ao professor de língua portuguesa, a fim de que ele possa trabalhar de forma coerente e produtiva. Para ilustrar nossas observações, escolhemos fragmentos de crônicas do escritor brasileiro Luís Fernando Veríssimo, publicadas em três obras: Comédias para se ler na escola,Sexo na cabeça e Amor Veríssimo.
Gêneros orais, argumentação e ensino de língua portuguesa
Authors: Aquino Zilda G. O.
Published: January 2016

A proposta deste trabalho é tratar de questões relacionadas à língua falada em sala de aula, centralizando-se nas práticas discursivas em que se destaque a argumentação. Entende-se que discussões que se fizeram em torno dos gêneros discursivos, especialmente orientados pelos estudos de Bakhtin e da Linguística de texto, vêm propiciando um avanço em torno da necessidade que tem a escola de promover o ensino da língua a partir da abordagem de gêneros discursivos. Nesta acepção, tanto a modalidade escrita quanto a falada merecem espaço no aprendizado, como se espera que venha ocorrendo; entretanto, acreditamos que os gêneros orais, por demandarem do professor conhecimentos específicos das características da língua falada e da interação que advém de seu uso em situações concretas, e em razão de esses estudos serem recentes entre nossos pesquisadores (não passam de três décadas), ainda devam estar muito presentes em nossas discussões. No caso deste trabalho, o recorte recai sobre  um gênero da oralidade específico – o debate, tendo em vista o fato de se constituir em um espaço privilegiado de construção de conhecimento, de posicionamento frente a questões que se apresentam na vida em sociedade – pontos de interesse da escola. Além de contribuir para o desenvolvimento de habilidades necessárias às práticas sociodiscursivas determinadas, propõe-se que o ensino da argumentação nos gêneros orais se atenha à observação de estratégias selecionadas em interações na quais se destaque o jogo interacional que se delineia quando se busca persuadir o(s) interlocutor(es). O corpus constitui-se de transcrições de debates, tanto a partir de sua ocorrência em sala de aula, quanto em outros contextos, como o da mídia. O tratamento metodológico faz-se a partir da identificação dos argumentos e de seu uso estratégico em situações específicas. A discussão teórica recai sobre os trabalhos de Orecchioni (2010), Marcuschi (2004), Dolz e  Schneuwly (2004),  Perelman e Olbrechts-Tyteca (1996[1958]), entre outros.
Expansão da capacidade do atendimento de ponta no Sistema Interligado Brasileiro
Authors: Ramos Dorel Soares , Morozowski Filho Marciano , Schilling Marcus Theodor , Rosa José Antonio de Oliveira
Published: January 2016

Within the current regulatory model of the Brazilian electricity sector, the lack of specific regulation for the market power reserve services in the long term leads to the underestimation of generation assets, especially in cases where additional investment would enable increasing the installed capacity of existing hydroelectric plants at low cost. A correct evaluation of such investment would have important consequences in the medium term, it would reduce the social energy shortage costs, both preventive, reflected by thermal dispatch, as well corrective, incurred in the recovery of production losses and others due to long-duration interruptions of energy supply.
Dimensão da crise e a explosão das tarifas de energia elétrica
Authors: Kirchner Carlos Augusto Ramos
Published: January 2016

We cannot in any way attribute the crisis the electrical sector is going through only to the lack of rain; or solely impute the rising electricity tariffs to the need for granting permits for building thermoelectric power plants. The electrical sector is currently in a topsy-turvy state; in which its players, namely state-owned energy generation companies have stopped selling their energy, and are speculating and liquidating in the shortterm market. The reason for implementing costly thermoelectric plants when an option could have been made for low-cost thermoelectric plants is the reason why costs of energy transmission have risen. Tariff skyrocketing has been followed by a risk of rationing; and many industries are making their productive activity impossible, and many electrical power players are making a lot of money.
Universidade em movimento
Authors: Marcovitch Jacques
Published: January 2016

The lessons from the university financial crisis triggered in 2013 are reviewed, and preventive actions for resource management are proposed. These actions are analyzed from the perspective of a university as a complex organizational system. The role of compliance and its forms of control are also described and discussed. The text addresses, above all, the importance of ethical values for the fulfillment of an academic mission.
Avaliação: resultados, tendências e desafios
Authors: Oliveira Luiz Nunes de
Published: January 2016

A critical review of faculty evaluation at the University of São Paulo is presented. In view of the difficulties plaguing the qualitative assessment of teaching and outreach activities, promotions and distribution of fellowships and other benefits have traditionally been decided by focusing on research records, often on the number of articles published in scientific journals with impact parameters exceeding predefined minimum criteria. Here it is argued that the university needs more comprehensive, reliable evaluation methods to implement plans targeting the improvement of teaching, outreach, and research. We discuss general principles on which the evaluation processes should be based, and show that making use of them will make it considerably easy to set guidelines to rebuild the system.
Alguns desafios para o financiamento das universidades públicas estaduais do estado de São Paulo
Authors: Luque Carlos Antonio
Published: January 2016

This article discusses the main challenges faced in financing the three state-owned universities in São Paulo over the past few years. These challenges can be separated into three different dimensions. First of all, there is a dispute between the various sectors of public policy receiving public funding (education, health, security, transport, social welfare, etc.). Second, the education and health sector budgets are determined by provisions in the federal constitution; and that leads to intense disputes between sectors subject to such links and other sectors. Finally, there is competition for funding among the three universities themselves and other institutions which cannot count on the same budgetary linkages. These conflicts can be lessened when the state of São Paulo’s tax income is significantly higher than it has been, and that depends on how the economy will evolve.
Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor
Authors: Howangyin Kiave-Yune , Zlatanova Ivana , Pinto Cristina , Ngkelo Anta , Cochain Clément , Rouanet Marie , Vilar José , Lemitre Mathilde , Stockmann Christian , Fleischmann Bernd K. , Mallat Ziad , Silvestre Jean-Sébastien
Published: January 2016

Background—

In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction.

Methods and Results—

We generated double-deficient mice for Mertk and Mfge8 (Mertk
−/−
/Mfge8
−/−
) and challenged them with acute coronary ligature. Compared with wild-type, Mertk-deficient (Mertk
−/−
), or Mfge8-deficient (Mfge8
−/−
) animals, Mertk
−/−
/Mfge8
−/−
mice displayed greater alteration in cardiac function and remodeling. Mertk and Mfge8 were expressed mainly by cardiac Ly6C
High and Low
monocytes and macrophages. In parallel, Mertk
−/−
/Mfge8
−/−
bone marrow chimeras manifested increased accumulation of apoptotic cells, enhanced fibrotic area, and larger infarct size, as well as reduced angiogenesis. We found that the abrogation of efferocytosis affected neither the ability of circulating monocytes to infiltrate cardiac tissue nor the number of resident Ly6C
High
and Ly6C
How
monocytes/macrophages populating the infarcted milieu. In contrast, combined Mertk and Mfge8 deficiency in Ly6C
High
/Ly6C
Low
monocytes/macrophages either obtained from in vitro differentiation of bone marrow cells or isolated from infarcted hearts altered their capacity of efferocytosis and subsequently blunted vascular endothelial growth factor A (VEGFA) release. Using LysMCre
+
/VEGFA
fl/fl
mice, we further identified an important role for myeloid-derived VEGFA in improving cardiac function and angiogenesis.

Conclusions—

After myocardial infarction, Mertk- and Mfge8-expressing monocyte/macrophages synergistically engage the clearance of injured cardiomyocytes, favoring the secretion of VEGFA to locally repair the dysfunctional heart.
Multiple estimation methods suggest similar repertoire sizes for Gulf Coast and eastern marsh wrens with no correlation between repertoire size and migratory distance
Authors: Luttrell Sarah A.M. , Gallagher Megan E. , Lohr Bernard
Published: January 2016

There are many ways for signalling systems to be complex, one of which is a large signal repertoire. However, it is frequently challenging to estimate larger repertoires accurately. We present the first description of repertoire size for a subspecies of marsh wren on the Gulf Coast of North America,Cistothorus palustris thryophilus, using four repertoire estimation techniques (simple enumeration, Wildenthal curve-fitting, Davidson & Wilkinson curve-fitting, and the Coupon Collector model). We demonstrate that the repertoire estimation methods in question perform with varying degrees of accuracy under natural conditions, and propose that rather than establishing an absolute repertoire size for a given individual it may instead be necessary to use multiple techniques to establish a repertoire range. We find thatC. p. thryophilushas a song repertoire size falling well within the range of repertoires produced by other marsh wren subspecies in eastern North America, although it may be on the larger end of this range. We find no evidence supporting a correlation between migratory distance and increased repertoire size in this species, as might be predicted under a sexual selection hypothesis.
Life history traits, liquid culture production and storage temperatures of Steinernema yirgalemense
Authors: Addis Temesgen , Mijušković Nevena , Strauch Olaf , Ehlers Ralf-Udo
Published: January 2016

Using the hanging drop technique with nematode growth gelrite medium, life history traits of Steinernema yirgalemense (strain Sy 157-C) were investigated at a bacterial density of 10 × 109 cells ml−1 of Xenorhabdus indica at 25°C. With the same technique, the exit of dauer juveniles (DJ) from the arrested stage (recovery) was assessed at 5 × 109, 10 × 109 and 20 × 109 cells ml−1 of X. indica. Additionally, S. yirgalemense was incubated in nematode liquid medium at 25, 27 and 30°C. At each culture temperature, DJ recovery, sex ratio at 3 days post DJ inoculation and DJ yield and DJ as a percentage of non-DJ stages at 15 days post DJ inoculation were assessed. DJ survival in Ringer’s solution stored at 4, 15 and 25°C was assessed for 66 days. Steinernema yirgalemense has a total fertility rate and net reproductive rate of 487 and 314 offspring per female, respectively. The intrinsic rate of natural increase was 0.98 day−1, population doubling time PDT = 0.71 days and mean generation time days. The average lifespan of S. yirgalemense females starting from first-stage juveniles was 6.55 days. In liquid culture, DJ recovery ranged from 63-75% at 72 h post DJ inoculation and was not significantly different between the incubation temperatures. Parental male to female ratio was not influenced by incubation temperature and usually was at a ratio of 1:2. The percentage of females that entered into endotokia matricida at 72 h post DJ inoculation was 61% at 25°C, whereas at 27 and 30°C it was 24% and 0.5%, respectively. The highest DJ yield was recorded at 25°C (284 114 DJ ml−1) followed by 27°C (176 932 DJ ml−1) and the lowest at 30°C with 26 298 DJ ml−1. At a storage temperature of 4°C, DJ survival did not exceed 42 days, whereas at 15 and 25°C more than 95% of the DJ survived 66 days. Although S. yirgalemense DJ survived for long periods at both 15 and 25°C in liquid storage, their survival in formulated product and virulence after storage needs further investigation.
New Jurassic Sinopalaeocossus and related genera with notes on their evolutionary implications (Hemiptera, Palaeontinidae)
Authors: Chen Jun , Zhang Haichun , Wang Bo , Zheng Xiaoting , Wang Xiaoli
Published: January 2016

SinopalaeocossusHong, 1983 and related genera (Hemiptera, Palaeontinidae) are revised on the basis of newly discovered materials from the Middle Jurassic of Daohugou, northern China. The genusHamicossusWang and Ren, 2007 is considered to be a junior synonym ofSinopalaeocossus, resulting inS. laevis(Wang and Ren, 2007), comb. nov. The new speciesSinopalaeocossus amoenusChen, Zhang and Wang is described based on fore and hindwings. TheSinopalaeocossusand related genera resembleMartynovocossusWang and Zhang, 2008 and were likely derived from the latter. TheSinopalaeocossusand related genera bear high diversity on wing venations. As compared toMartynovocossus, the crossveinm3+4-cuaof hindwing is absent forSynapocossusWang, Shih and Ren, 2013 and certain species ofSinopalaeocossus, and the crossveinr-mof forewing is absent forSynapocossus. The rapid evolution of wing venations is likely due to intense predation pressures of the newly evolved flying and insectivorous vertebrates.
Unraveling cryptic species diversity in an aposematic sap beetle genus (Coleoptera: Nitidulidae: Cryptarchinae) from northern Europe
Authors: Clayhills Tom , Audisio Paolo , Cline Andrew R. , Mancini Emiliano , Trizzino Marco , Sabatelli Simone
Published: January 2016

The saproxylic sap beetleGlischrochilus(Glischrochilus)quadripunctatus(Linnaeus, 1758), is associated with subcortical habitats of coniferous trees. This species is widely distributed across Europe and Siberia, and is the best known and largest European nitidulid species. A closely related cryptic species,G.(G.)tremulaesp. nov.has been discovered in a xerothermic area of SE Finland in association with old aspens. The two species exhibit a sympatric occurrence in SE Finland, on their respective host trees. We analyze the COI barcode region to compareG.(G.)quadripunctatus,G.(G.)tremulaesp. nov., andG. (Librodor) hortensis(Fourcroy, 1785). Morphological, ecological, and molecular data confirm the presence in SE Finland of twoGlischrochiluss.str. species. We provide a description of the new species. The newGlischrochilusapparently represents a relictual taxon associated with old hollow aspens, and should be considered a species with inherent conservation value within European saproxylic beetle communities.