SISTEMAS DE CONTROLE GERENCIAL EM EMPRESAS BRASILEIRAS INTERNACIONALIZADAS: O CASO DE UMA EMPRESA DE MATERIAL ELÉTRICO

Internationalization is a worldwide phenomenon that is changing the way of management control systems should be conducted so that businesses can be competitive and meet the needs of the global economy. The intention of this work is to address the following questions: What are the characteristics of the management control systems in internationalized Brazilian companies? What kind of management control systems internationalized companies adopt in order to face the new reality of a competitive international environment? To answer these questions, a case study was done whose approach meant to capture the true essence of the internationalization characteristics in the company studied. The case study chosen is of a company in the energy sector. Primary and secondary data were collected. The Primary data were collected from a questionnaire directed to people who are involved in the decision-making process of the company. Subsequently, these data were analyzed to investigate the degree of proximity or remoteness that the managerial control of the company studied has in relation to the literature considered on the characteristics of managerial control systems in internationalized companies. There are few matching points between what is presented in the literature and what was identified in the company studied. Probably due to the lack of an adequate system of management control in the company during the process of internationalization and also out of it, even winning the of Latin American international market, the company failed to maintain its position after the loss of the partnership contract.A internacionalização é um fenômeno mundial que está mudando a forma como os sistemas de controle gerencial devem ser conduzidos, a fim de que as empresas possam ser competitivas e atendam às necessidades da economia global. A intenção deste estudo é abordar as seguintes questões: Quais as características do sistema de controle gerencial em empresas brasileiras internacionalizadas? Que tipo de controle gerencial as empresas internacionalizadas adotam face à nova realidade de um ambiente internacional competitivo? Para responder a estas perguntas foi realizado um estudo de caso em que a abordagem foi feita com o intuito de captar a essência das características da internacionalização na empresa estudada. O estudo de caso escolhido é de uma empresa do setor elétrico. Foram coletados dados primários e secundários. Dados primários foram retirados de um questionário direcionado às pessoas envolvidas no processo de tomada de decisão da empresa. Posteriormente estes dados foram analisados para investigar o grau de afastamento ou proximidade que o controle gerencial da empresa estudada tem em relação à literatura trabalhada acerca das características dos sistemas de controle gerencial em empresas internacionalizadas. Há poucos pontos coincidentes entre aquilo que é apresentado na literatura e o que foi identificado na empresa estudada. Provavelmente pela falta de um sistema de controle gerencial adequado na empresa durante o processo de internacionalização e também fora dele, é que, mesmo tendo conquistado o mercado internacional da América Latina, a empresa não conseguiu manter a sua posição após a perda do contrato de parceria

Dangerous liaisons? The role of inflammation and comorbidities in HIV and SARS-CoV-2 infection

In people living with HIV (PLWH), immune activation and inflammation levels are high even when viral suppression is maintained, potentially contributing to several comorbidities, and hampering the immune response to infections such as the recent SARS-CoV-2 disease 2019 (COVID-19)

Histone H3 lysine 9 trimethylation is required for suppressing the expression of an embryonically activated retrotransposon in Xenopus laevis.

Transposable elements in the genome are generally silenced in differentiated somatic cells. However, increasing evidence indicates that some of them are actively transcribed in early embryos and the proper regulation of retrotransposon expression is essential for normal development. Although their developmentally regulated expression has been shown, the mechanisms controlling retrotransposon expression in early embryos are still not well understood. Here, we observe a dynamic expression pattern of retrotransposons with three out of ten examined retrotransposons (1a11, λ-olt 2-1 and xretpos(L)) being transcribed solely during early embryonic development. We also identified a transcript that contains the long terminal repeat (LTR) of λ-olt 2-1 and shows a similar expression pattern to λ-olt 2-1 in early Xenopus embryos. All three retrotransposons are transcribed by RNA polymerase II. Although their expression levels decline during development, the LTRs are marked by histone H3 lysine 4 trimethylation. Furthermore, retrotransposons, especially λ-olt 2-1, are enriched with histone H3 lysine 9 trimethylation (H3K9me3) when their expression is repressed. Overexpression of lysine-specific demethylase 4d removes H3K9me3 marks from Xenopus embryos and inhibits the repression of λ-olt 2-1 after gastrulation. Thus, our study shows that H3K9me3 is important for silencing the developmentally regulated retrotransposon in Xenopus laevis.Gurdon laboratory is supported by grants from the Wellcome Trust (RG69899) and MRC to J.B.GThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep1423

G-quadruplex DNA structures in human stem cells and differentiation.

Funder: Herchel Smith FundsThe establishment of cell identity during embryonic development involves the activation of specific gene expression programmes and is underpinned by epigenetic factors including DNA methylation and histone post-translational modifications. G-quadruplexes are four-stranded DNA secondary structures (G4s) that have been implicated in transcriptional regulation and cancer. Here, we show that G4s are key genomic structural features linked to cellular differentiation. We find that G4s are highly abundant in human embryonic stem cells and are lost during lineage specification. G4s are prevalent in enhancers and promoters. G4s that are found in common between embryonic and downstream lineages are tightly linked to transcriptional stabilisation of genes involved in essential cellular functions as well as transitions in the histone post-translational modification landscape. Furthermore, the application of small molecules that stabilise G4s causes a delay in stem cell differentiation, keeping cells in a more pluripotent-like state. Collectively, our data highlight G4s as important epigenetic features that are coupled to stem cell pluripotency and differentiation

Castanea sativa Ancient Trees Across Europe: Genetic Diversity And Conservation Strategy

Long-living trees are witnesses of environmental changes and human interventions; these extraordinary organisms not only represent a historical, landscape and environmental heritage of inestimable value, but they also are a reserve of genetic variability which can considered as a great resource for management programs of forest species. This is the first genetic study on Italian ancient chestnut trees (Castanea sativa Mill.). Ninety-nine ancient trees including the oldest known chestnut in Europe, named ‘Cento Cavalli’, which is believed to be to be between 3,000 and 4,000 years old, were collected. For each tree, more than one sample from canopy and root suckers was collected to test for the genetic integrity of the individuals The samples were genotyped using nine nuclear microsatellite markers (nSSRs) and two chloroplast markers (cpDNA). Genetic variability indices were evaluated using GeneAlEx 6.5, GenoDive 3.0 and HP-rare software. We identified a total of 106 unique genetic profiles within the analyzed individuals. A Bayesian analysis was performed using the software STRUCTURE to unveil the genetic relationships existing between the genotyped individuals. We were able to identify a geographic pattern of genetic diversity among the old chestnut trees. In addition, the genetic similarity among the ancient trees and the close chestnut populations to was studied. A phylogeographic structure of plastid diversity was also established. Our results contribute to evaluate the European chestnut genetic resources, gave insights to its domestication history and to define the best conservation and management strategies

Monumental chestnut trees: source of genetic diversity, cultural and landscape value

The monumental trees are unique individuals of venerable age and considerable size, which represent a heritage of inestimable historical, cultural, landscape, and scientific value for the territtory. They also constitute a source of genetic diversity which confers them longevity and ability to adapt to climate and environmental changes. In this context, studies on centennial trees can be useful for interpretatiton of species history as migration events, selection and anthropogenic actiton. The aim of this research was to evaluate the genetic variability of ancient Castanea sativa trees and relate them to actual natural/naturalized populatitons and varieties in order to enhance our knowledge about the demography, cultivatiton processes and the impact of these giant trees on the genetic diversity of the species. We selected a total of 182 ancient trees from Spain and Central - Southern Italy. For each tree, more than one sample was collected to test for genetic integrity and grafing. The samples were genotyped by means of nuclear microsatellite markers and the variability of plastid DNA regitons (trnH-psbA and trnK/matK) was also tested. Using the sofware GeneALex and HPrare, we evaluated observed (Hto) and expected (He) heterozygosity, allelic richness (Ar) private allelic richness (pAr). A Bayesian analysis was performed using the sofware STRUCTURE to identify the different gene pools and gentotypes. The obtained genetic data were compared with those of natural populations and cultivars collected in the same geographic areas. Higher values of allelic richness were observed in the ancient chestnut trees, a genetic similarity of these individual trees to the natural populations was highlighted. A phylogetographic structure of plastid diversity was alsto established. Eleven genotypes were coincident with 11 cultivars in the EU database. Based on the putative age of giant trees we can hyptothesize that the grafing practice occurred in the Iberian peninsula in the 15th century and in the 17th century in Italy. This work provides new knowledge about the history and domesticatiton tof European chestnut, the results are relevant for the conservatiton and management of Castanea sativa genetic resources

The Expression of TALEN before Fertilization Provides a Rapid Knock-Out Phenotype in Xenopus laevis Founder Embryos.

Recent advances in genome editing using programmable nucleases have revolutionized gene targeting in various organisms. Successful gene knock-out has been shown in Xenopus, a widely used model organism, although a system enabling less mosaic knock-out in founder embryos (F0) needs to be explored in order to judge phenotypes in the F0 generation. Here, we injected modified highly active transcription activator-like effector nuclease (TALEN) mRNA to oocytes at the germinal vesicle (GV) stage, followed by in vitro maturation and intracytoplasmic sperm injection, to achieve a full knock-out in F0 embryos. Unlike conventional injection methods to fertilized embryos, the injection of TALEN mRNA into GV oocytes allows expression of nucleases before fertilization, enabling them to work from an earlier stage. Using this procedure, most of developed embryos showed full knock-out phenotypes of the pigmentation gene tyrosinase and/or embryonic lethal gene pax6 in the founder generation. In addition, our method permitted a large 1 kb deletion. Thus, we describe nearly complete gene knock-out phenotypes in Xenopus laevis F0 embryos. The presented method will help to accelerate the production of knock-out frogs since we can bypass an extra generation of about 1 year in Xenopus laevis. Meantime, our method provides a unique opportunity to rapidly test the developmental effects of disrupting those genes that do not permit growth to an adult able to reproduce. In addition, the protocol shown here is considerably less invasive than the previously used host transfer since our protocol does not require surgery. The experimental scheme presented is potentially applicable to other organisms such as mammals and fish to resolve common issues of mosaicism in founders.K.M. was a Research Fellow at Wolfson College and was supported by the Herchel Smith Postdoctoral Fellowship.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014294

Promoter G-quadruplex folding precedes transcription and is controlled by chromatin

Funder: Herchel Smith FundsAbstract: Background: Four-stranded G-quadruplexes (G4s) are DNA secondary structures in the human genome that are primarily found in active promoters associated with elevated transcription. Here, we explore the relationship between the folding of promoter G4s, transcription and chromatin state. Results: Transcriptional inhibition by DRB or by triptolide reveals that promoter G4 formation, as assessed by G4 ChIP-seq, does not depend on transcriptional activity. We then show that chromatin compaction can lead to loss of promoter G4s and is accompanied by a corresponding loss of RNA polymerase II (Pol II), thus establishing a link between G4 formation and chromatin accessibility. Furthermore, pre-treatment of cells with a G4-stabilising ligand mitigates the loss of Pol II at promoters induced by chromatin compaction. Conclusions: Overall, our findings show that G4 folding is coupled to the establishment of accessible chromatin and does not require active transcription

Sperm is epigenetically programmed to regulate gene transcription in embryos.

For a long time, it has been assumed that the only role of sperm at fertilization is to introduce the male genome into the egg. Recently, ideas have emerged that the epigenetic state of the sperm nucleus could influence transcription in the embryo. However, conflicting reports have challenged the existence of epigenetic marks on sperm genes, and there are no functional tests supporting the role of sperm epigenetic marking on embryonic gene expression. Here, we show that sperm is epigenetically programmed to regulate embryonic gene expression. By comparing the development of sperm- and spermatid-derived frog embryos, we show that the programming of sperm for successful development relates to its ability to regulate transcription of a set of developmentally important genes. During spermatid maturation into sperm, these genes lose H3K4me2/3 and retain H3K27me3 marks. Experimental removal of these epigenetic marks at fertilization de-regulates gene expression in the resulting embryos in a paternal chromatin-dependent manner. This demonstrates that epigenetic instructions delivered by the sperm at fertilization are required for correct regulation of gene expression in the future embryos. The epigenetic mechanisms of developmental programming revealed here are likely to relate to the mechanisms involved in transgenerational transmission of acquired traits. Understanding how parental experience can influence development of the progeny has broad potential for improving human health.We thank: T. Jenuwein and N. Shukeir for anti-H3K27me3 antibody; A. Bannister, J. Ahringer and E. Miska for comments on the manuscript; Gurdon group members for reading the manuscript; The International Xenopus laevis Genome Project Consortium (the Harland, Rokhsar, Taira labs and others) for providing unpublished genome and gene annotation information. M.T. is supported by WT089613 and by MR/K011022/1. V.G. and P.Z. are funded by AICR 10-0908. A.S. is supported by MR/K011022/1. K.M. is a Research Fellow at Wolfson College and is supported by the Herchel Smith Postdoctoral Fellowship. E.M.M. is supported by National Institutes of Health, National Science Foundation, Cancer Prevention Research Institute of Texas, and the Welch Foundation (F1515). J.J. and J.B.G. are supported by WT101050/Z/13/Z. S.E. acknowledges Boehringer Ingelheim Fond fellowship. A.H.F.M.P. is supported by the Swiss National Science Foundation (31003A_125386) and the Novartis Research Foundation. All members of the Gurdon Institute acknowledge the core support provided by CRUK C6946/A14492 and WT092096.This is the final version of the article. It first appeared from Cold Spring Harbor Laboratory Press via https://doi.org/10.1101/gr.201541.11

Landscape of G-quadruplex DNA structural regions in breast cancer.

Response and resistance to anticancer therapies vary due to intertumor and intratumor heterogeneity1. Here, we map differentially enriched G-quadruplex (G4) DNA structure-forming regions (∆G4Rs) in 22 breast cancer patient-derived tumor xenograft (PDTX) models. ∆G4Rs are associated with the promoters of highly amplified genes showing high expression, and with somatic single-nucleotide variants. Differences in ΔG4R landscapes reveal seven transcription factor programs across PDTXs. ∆G4R abundance and locations stratify PDTXs into at least three G4-based subtypes. ∆G4Rs in most PDTXs (14 of 22) were found to associate with more than one breast cancer subtype, which we also call an integrative cluster (IC)2. This suggests the frequent coexistence of multiple breast cancer states within a PDTX model, the majority of which display aggressive triple-negative IC10 gene activity. Short-term cultures of PDTX models with increased ∆G4R levels are more sensitive to small molecules targeting G4 DNA. Thus, G4 landscapes reveal additional IC-related intratumor heterogeneity in PDTX biopsies, improving breast cancer stratification and potentially identifying new treatment strategies.The Caldas and Balasubramanian laboratories are supported by core funding from Cancer Research UK (C14303/A17197). The Balasubramanian laboratory is supported by Program grant funding from Cancer Research UK (C9681/A18618 and C9681/A29214) and a Wellcome Trust Investigator Award (209441/z/17/z). Prior to the revision of this study work by Dr. Robert Hänsel-Hertsch was supported by the Balasubramanian group, afterwards additionally supported by core funding of the Center for Molecular Medicine Cologne (CMMC)