A deficit in zinc availability can cause alterations in tubulin thiol redox status in cultured neurons and in the developing fetal rat brain

Zinc (Zn) deficiency during early development can result in multiple brain abnormalities and altered neuronal functions. In rats, a gestational deficit of Zn can affect the fetal brain cytoskeleton, and signaling cascades involved in cellular processes that are central to brain development. In the current paper, we tested the hypothesis that oxidative stress is involved in Zn deficiency-induced altered tubulin dynamics and the associated dysregulation of transcription factor NF-êB.For this purpose, we used two cell culture models (rat cortical neurons, human IMR-32 neuroblastoma cells) and an animal model of Zn deficiency. A low rate of in vitro tubulin polymerization, an increase in tubulin oligomers and a higher protein cysteine oxidation were observed in the Zn deficient neuronal cells, and in gestation day 19 fetal brains obtained from dams fed marginal Zn diets throughout pregnancy. These alterations could be prevented by treating the Zn deficient cells with the reducing agen tris (2-carboxyethyl)phosphine, or the presence of N-acetyl cysteine (NAC) and á-lipoic acid (LA) Consistent with the above, Zn deficiency-induced tubulin-mediated alterations in transcription factor NF-êB nuclear translocation were prevented by treating IMR-32 cells with LA and NAC. Binding of the NF-êB protein p50, dynein and karyopherin alpha (components of the NF-êB transport complex) to â-tubulin as well as the expression of NF-êB dependent genes (bcl-2, cyclin D1 and c-myc) were also restored by the addition of LA and NAC to Zn deficient cells. In conclusion, a deficit in Zn viability could affect early brain development through: 1) an induction of oxidative stress; 2) tubulin oxidation; 3) altered tubulin dynamics, and 4) deregulation of signals (e.q. NF-êB) involved in critical developmental events.Fil: Mackenzie, Gerardo G.. University Of California At Davis; Estados UnidosFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Cientificas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Instituto de Investigaciones Bioquímicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Romero, Carolina. University Of California At Davis; Estados UnidosFil: Keen, Carl L.. University Of California At Davis; Estados UnidosFil: Oteiza, Patricia Isabel. University Of California At Davis; Estados Unido

Through the legal maze: An Act Respecting Research

Introduction The New Brunswick Institute for Research, Data and Training (NB-IRDT) is a recently established provincial research data centre and data custodian hosting anonymized linkable administrative data from the Government of New Brunswick (GNB) and other public bodies. GNB has committed to transferring research-relevant data from across GNB operations to NB-IRDT. Objectives and Approach Although NB-IRDT had received a small number of administrative data sets from the GNB Department of Health as of the end of 2016, transfers of other datasets from the Department of Health, Department of Social Development and other Departments was halted because of a series of legal opinions citing a lack of legislative authority to do so. This presentation details an innovative and transformative approach that overcame these obstacles to facilitate continued data sharing with NB-IRDT not just from those Departments but from across the spectrum of government operations. Results Passed in the NB Legislature in March 2017 and proclaimed in May 2017, An Act Respecting Research modified 12 different pieces of existing legislation to define a clear legal authority through which pseudo-anonymized data from all of the Provincial Government plus numerous other public bodies could be transferred to NB-IRDT in linkable form. This included Acts as disparate as the Education Act, Mental Health Act, the Nursing Homes Act, the New Brunswick Housing Act, etc. An Act Respecting Research was the culmination of more than a year of collaborative effort between NB-IRDT and the Executive Council Office plus 14 different provincial line departments. The Act also permits the collection of the Medicare health insurance numbers by departments and public for data matching and transfer purposes. Conclusion/Implications The Act Respecting Research is unique in Canada and would not have occurred without GNB’s commitment to the principle and practice of evidence-based policymaking. After the Act’s passage, NB-IRDT has received numerous datasets and work is ongoing on many more, from postsecondary education to road accidents and workers compensation claims

Transcriptome profiles associated to VHSV infection or DNA vaccination in turbot (Scophthalmus maximus)

DNA vaccines encoding the viral G glycoprotein show the most successful protection capability against fish rhabdoviruses. Nowadays, the molecular mechanisms underlying the protective response remain still poorly understood. With the aim of shedding light on the protection conferred by the DNA vaccines based in the G glycoprotein of viral haemorrhagic septicaemia virus (VHSV) in turbot (Scophthalmus maximus) we have used a specific microarray highly enriched in antiviral sequences to carry out the transcriptomic study associated to VHSV DNA vaccination/infection. The differential gene expression pattern in response to empty plasmid (pMCV1.4) and DNA vaccine (pMCV1.4-G860) intramuscular administration with regard to non-stimulated turbot was analyzed in head kidney at 8, 24 and 72 hours post-vaccination. Moreover, the effect of VHSV infection one month after immunization was also analyzed in vaccinated and non-vaccinated fish at the same time points. Genes implicated in the Toll-like receptor signalling pathway, IFN inducible/regulatory proteins, numerous sequences implicated in apoptosis and cytotoxic pathways, MHC class I antigens, as well as complement and coagulation cascades among others were analyzed in the different experimental groups. Fish receiving the pMCV1.4-G860 vaccine showed transcriptomic patterns very different to the ones observed in pMCV1.4-injected turbot after 72 h. On the other hand, VHSV challenge in vaccinated and non-vaccinated turbot induced a highly different response at the transcriptome level, indicating a very relevant role of the acquired immunity in vaccinated fish able to alter the typical innate immune response profile observed in non-vaccinated individuals. This exhaustive transcriptome study will serve as a complete overview for a better understanding of the crosstalk between the innate and adaptive immune response in fish after viral infection/vaccination. Moreover, it provides interesting clues about molecules with a potential use as vaccine adjuvants, antiviral treatments or markers for vaccine efficiency monitoring

Testing QCD Sum Rules on the Light-Cone in D->(pi,K) l nu Decays

We compare the predictions for the form factors f_+^{D->pi,K}(0) from QCD sum rules on the light-cone with recent experimental results. We find f_+^{D->pi}(0) = 0.63\pm 0.11, f_+^{D->K}(0) = 0.75\pm 0.12 and f_+^{D->pi}(0)/f_+^{D->K}(0)= 0.84\pm 0.04 in very good agreement with experiment. Although the uncertainties of the form factors themselves are larger than the current experimental errors and difficult to reduce, their ratio is determined much more accurately and with an accuracy that matches that of experiment.Comment: 12 page

Therapeutic Targeting of Replicative Immortality

One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy

O Trabalho do Médico no Brasil na Perspectiva da Constituição de 1988 e do Direito Social ao Trabalho

MEDICAL WORK IN BRAZIL IN THE PERSPECTIVE OF 1998´S CONSTITUTION AND THE SOCIAL RIGHT TO WORK O presente artigo tem como objetivo discutir a relação de trabalho em que se inserem historicamente os médicos brasileiros, bem como compreender como essas relações influenciam o papel do médico, sob o ponto de vista da cidadania, utilizando-se de uma análise qualitativa-descritiva do fenômeno estudado. São consideradas as normas jurídicas de caráter constitucional e do direito social do trabalho que se aplicam à relação em destaque, notadamente as concernentes aos direitos fundamentais e ao requisito legal de subordinação inserto na Consolidação das Leis do Trabalho. Matrizes de pensamento sócio-histórico são visitadas, a partir das interpretações fundantes de K. Marx, N. Bobbio e H. Arendt. Por fim, o artigo aponta para algumas reflexões críticas necessárias, no sentido de transformar e construir um novo paradigma nas relações de trabalho médico, e sugere uma proposta para a carreira médica nos moldes de carreiras como a magistratura, a defensoria pública e a advocacia geral da união, como também uma relação mais equilibrada dos médicos com os planos e seguradoras de saúde no Brasil. PALAVRAS-CHAVE: Relação de trabalho; direitos fundamentais; sociologia do trabalho; trabalho médico; medicina. ABSTRACT This paper aims to discuss the historical labour relationship of brazilian physicians as well as to understand how this relationship influence the physician's role from the point of view of citizenship, using a qualitative descriptive analysis of the phenomenon studied. Some legal and constitutional rules are considered to understand the character of social labor law that apply to this specific relationship, notably those concerning the fundamental rights and the legal requirement to insert in the Consolidation of Labor Laws . Socio-historical thought are examined, from interpretation of K. Marx , N. Bobbio and H. Arendt . Finally , the article points to some critical thinking necessary to transform and build a new paradigm in relations of medical work , and suggests a proposal for a medical career in the terms of similar careers magistrates, public defenders and public attorneys, as well as a more balanced relationship with the medical plans and health insurers in Brazil . KEYWORDS: Employment relationship; fundamental rights; work´s sociology; medical work; medicine. Data da Submissão: 18/04/2014 Data da Aceitação: 27/05/201

Education sector response to early and unintended pregnancy: A review of country experiences in sub-Saharan Africa

In Sub-Saharan Africa (SSA), early and unintended pregnancy leads to a colossal loss of educational opportunities for girls. Existing studies that show associations between early/unintended pregnancy and school dropout lead to critical questions about how the education sector is responding to the issue in SSA. Conducted from August 2014 to April 2015, this review was devoted to an examination of such responses across six countries: Botswana, Kenya, Malawi, Tanzania, Uganda, and Zambia. The review focused on several key issues, including: education-sector policies for pregnant students and adolescent mothers; integration of pregnancy prevention into sexuality education curricula; the school environment as it pertains to pregnant students and adolescent mothers; and education-sector efforts to improve gender equality. The report concludes that the existence of national policies and guidelines (whether in official or draft form) to promote education-sector responses to early/unintended pregnancy demonstrates the commitment of countries to respond to this critical issue, however countries in the East and Southern Africa region would benefit from intensive support to address the gaps identified

Computing Nash Equilibrium in Wireless Ad Hoc Networks: A Simulation-Based Approach

This paper studies the problem of computing Nash equilibrium in wireless networks modeled by Weighted Timed Automata. Such formalism comes together with a logic that can be used to describe complex features such as timed energy constraints. Our contribution is a method for solving this problem using Statistical Model Checking. The method has been implemented in UPPAAL model checker and has been applied to the analysis of Aloha CSMA/CD and IEEE 802.15.4 CSMA/CA protocols.Comment: In Proceedings IWIGP 2012, arXiv:1202.422

Therapeutic targeting of replicative immortality

One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy