The new face of monkeypox virus : an emerging global emergency

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Sce3, a suppressor of the Schizosaccharomyces pombe septation mutant cdc11, encodes a putative RNA-binding protein

In the fission yeast Schizosaccharomyces pombe, the cdc11 gene is required for the initiation of septum formation at the end of mitosis. The sce3 gene was cloned as a multi-copy suppressor of the heat-sensitive mutant cdc11-136. When over-expressed, it rescues all mutants of cdc11 and also a heat-sensitive allele of cdc14, but not the cdc14 null mutant. Deletion shows that sce3 is not essential for cell proliferation. It encodes a putative RNA-binding protein which shows homology to human eIF4B. Immunolocalisation indicates that Sce3p is located predominantly in the cytoplasm. Elevated expression of sce3 increases the steady-state level of cdc14 mRNA. Possible mechanisms of its action are discusse

Centrosomal MPF triggers the mitotic and morphogenetic switches of fission yeast

PMCID: PMC3549529.-- et al.Activation of mitosis-promoting factor (MPF) drives mitotic commitment. In human cells active MPF appears first on centrosomes. We show that local activation of MPF on the equivalent organelle of fission yeast, the spindle pole body (SPB), promotes Polo kinase activity at the SPBs long before global MPF activation drives mitotic commitment. Artificially promoting MPF or Polo activity at various locations revealed that this local control of Plo1 activity on G2 phase SPBs dictates the timing of mitotic commitment. Cytokinesis of the rod-shaped fission yeast cell generates a naive, new, cell end. Growth is restricted to the experienced old end until a point in G2 phase called new end take off (NETO) when bipolar growth is triggered. NETO coincided with MPF activation of Plo1 on G2 phase SPBs (ref. 4). Both MPF and Polo activities were required for NETO and both induced NETO when ectopically activated at interphase SPBs. NETO promotion by MPF required polo. Thus, local MPF activation on G2 SPBs directs polo kinase to control at least two distinct and temporally separated, cell-cycle transitions at remote locations.This work was supported by Cancer Research UK (CRUK) grant number C147/A6058. V.S. and A.K. were supported by the Swiss National Science Foundation and EPFL.Peer reviewe

Extending the Schizosaccharomyces pombe molecular genetic toolbox

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Targeted alteration of the genome lies at the heart of the exploitation of S. pombe as a model system. The rate of analysis is often determined by the efficiency with which a target locus can be manipulated. For most loci this is not a problem, however for some loci, such as fin1+, rates of gene targeting below 5% can limit the scope and scale of manipulations that are feasible within a reasonable time frame. We now describe a simple modification of transformation procedure for directing integration of genomic sequences that leads to a 5-fold increase in the transformation efficiency when antibiotic based dominant selection markers are used. We also show that removal of the pku70+ and pku80+ genes, which encode DNA end binding proteins required for the non-homologous end joining DNA repair pathway, increases the efficiency of gene targeting at fin1+ to around 75-80% (a 16-fold increase). We describe how a natMX6/rpl42+ cassette can be used for positive and negative selection for integration at a targeted locus. To facilitate the evaluation of the impact of a series of mutations on the function of a gene of interest we have generated three vector series that rely upon different selectable markers to direct the expression of tagged/untagged molecules from distinct genomic integration sites. pINTL and pINTK vectors use ura4+ selection to direct disruptive integration of leu1+ and lys1+ respectively, while pINTH vectors exploit nourseothricin resistance to detect the targeted disruption of a hygromycin B resistance conferring hphMX6 cassette that has been integrated on chromosome III. Finally, we have generated a series of multi-copy expression vectors that use resistance to nourseothricin or kanamycin/G418 to select for propagation in prototrophic hosts. Collectively these protocol modifications and vectors extend the versatility of this key model system.Swiss National Science Foundation (www.snf.ch). École polytechnique fédérale de Lausanne (www.epfl.ch). Cancer Research UK [CRUK] C147/A6058.Peer Reviewe

Concentration and dispersion of primary care physicians and implications for access to care in Cook County, Illinois: 2000-2008

The health care system in the United States has experienced drastic changes in the recent past. Continuously growing pressures to control health care costs and the increasing corporatization of health care are changing physician decisions about how and where to provide medical care. Physicians are increasingly drawn to medical office complexes, group practices, and hospital-owned practices, resulting in a shifting landscape of physician services. The goal of this research is to analyze the changing spatial distribution and clustering of primary care physicians in Cook County, Illinois from 2000 to 2008. Using data from the American Medical Association's Physicians Master File for 2000 and 2008, primary care physician locations are geocoded, mapped, and analyzed to evaluate change over time. Spatial analysis methods such as kernel density mapping and the L-function are used to analyze changes in the spatial clustering and dispersion of primary care physician locations. Geographically weighted regression models are then used to compare primary care physician supply to the socioeconomic demographics of census tracts in Cook County. Results indicate that spatial clustering of primary care physicians increased over the eight year period. Linear regression analyses show positive relationships between primary care physician-to-population ratios and median income and percentage of the work force employed. However, geographically weighted regression shows that these relationships vary throughout the county. Implications for access to care and possible policy changes to increase primary care physician spatial accessibility are discussed

Performance of contrast-enhanced ultrasound in thyroid nodules : Review of current state and future perspectives

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Ultrasound has been established as a baseline imaging technique for thyroid nodules. The main advantage of adding CEUS is the ability to assess the sequence and intensity of vascular perfusion and hemodynamics in the thyroid nodule, thus providing real-time characterization of nodule features, considered a valuable new approach in the determination of benign vs. malignant nod-ules. Original studies, reviews and six meta-analyses were included in this article. A total of 624 studies were retrieved, and 107 were included in the study. As recognized for thyroid nodule malignancy risk stratification by US, for acceptable accuracy in malignancy a combination of several CEUS parameters should be applied: hypo-enhancement, heterogeneous, peripheral irregular enhancement in combination with internal enhancement patterns, and slow wash-in and wash-out curve lower than in normal thyroid tissue. In contrast, homogeneous, intense enhancement with smooth rim enhancement and “fast-in and slow-out” are indicative of the benignity of the thyroid nodule. Even though overlapping features require standardization, with further research, CEUS may achieve reliable performance in detecting or excluding thyroid cancer. It can also play an op-erative role in guiding ablation procedures of benign and malignant thyroid nodules and metastatic lymph nodes, and providing accurate follow-up imaging to assess treatment efficacy.publishersversionPeer reviewe

Retour aux sources : refaire des stratégies BoP un enjeu Business

Il y a dix ans, lorsque des spécialistes de la gestion ont présenté le concept de « bas de la pyramide » (Bottom of the Pyramid, BoP) au monde des affaires, l’idée semblait révolutionnaire. Cette notion transformait les pauvres du monde entier, bénéficiaires de l'aumône des gouvernements et des organisations à but non lucratif, en consommateurs d'un marché colossal encore inexploité, désirant ardemment acquérir les produits des grandes sociétés. Les actes ont très vite suivi les débats. Des s..

Dma1-dependent degradation of SIN proteins during meiosis in Schizosaccharomyces pombe

The Schizosaccharomyces pombe septation initiation network (SIN) is required for cytokinesis during vegetative growth and for spore formation during meiosis. Regulation of the SIN during mitosis has been studied extensively, but less is known about its meiotic regulation. Here, we show that several aspects of SIN regulation differ between mitosis and meiosis. First, the presence of GTP-bound Spg1p is not the main determinant of the timing of Cdc7p and Sid1p association with the spindle pole body (SPB) during meiosis. Second, the localisation dependencies of SIN proteins differ from those in mitotic cells, suggesting a modified functional organisation of the SIN during meiosis. Third, there is stage-specific degradation of SIN components in meiosis; Byr4p is degraded after meiosis I, whereas the degradation of Cdc7p, Cdc11p and Sid4p occurs after the second meiotic division and depends upon the ubiquitin ligase Dma1p. Finally, Dma1p-dependent degradation is not restricted to the SIN, as we show that Dma1p is needed for the degradation of Mcp6p (also known as Hrs1p) during meiosis I. Taken together, these data suggest that stage-specific targeted proteolysis plays an important role in regulating meiotic progression

Back to Business Fundamentals: Making “Bottom of the Pyramid” Relevant to Core Business

Over the last half-decade, corporate interest in Bottom of the Pyramid (BOP) — strategies for profitably serving the world’s lowest income consumers—has dropped precipitously or migrated to the CSR (i.e., philanthropic) side of the business. We contend that these trends stem from a fundamental misalignment generated when BOP is framed and managed as a market-based solution to poverty alleviation rather than an internally competitive investment opportunity. Examining macro, meso, and micro dimensions of a company’s core operations, we argue that if corporations are to make BOP part of their investment portfolios, there needs to be four changes to management practice which ensure business fundamentals guide decision-making. First, proponents need to drop the development-infused term “Bottom of the Pyramid” and communicate in terms familiar to and used by the majority of business managers in emerging market country offices. Second, in framing the business case, managers need to leave behind exaggerated, emotionally-tinged claims in favor of concrete, bounded opportunities that address the objectives and investment parameters of a specific unit in the company. Third, at the field level, managers need to reorient their focus from co-creation and community engagement strategies to the business economic drivers of business unit profitability. Finally, to evaluate projects and investments, managers need to measure outputs that link directly to business performance and curtail the growing overemphasis on ”impact assessments.

Difference in markers of microbial translocation and cell apoptosis in HIV monoinfected and HIV/HCV coinfected patients

Funding Information: The authors thank Valentina Sondore, MD. This study was supported by National Research Programme “Biomedicine for Public Health” (BIOMEDICINE) and by corporation “Latvijas Gâze”. Publisher Copyright: © 2019 Monta Madelane et al., published by Sciendo 2019.Immune activation in human immunodeficiency virus (HIV) infection is driven by microbial translocation and in HIV patients is one of the contributors to faster progression of liver disease along with increased cell apoptosis. The aim of the study was to compare microbial translocation and apoptosis markers in HIV monoinfected and HIV/hepatitis C virus (HCV) coinfected patients, depending on HIV immune status and antiretroviral treatment (ART). We analysed data for 78 HIV monoinfected and 105 HIV/HCV coinfected patients from the Rīga East University Hospital. Lipopolysaccharide (LPS), endotoxin core antibodies (EndoCAb), cytokeratin 18 (CK18) and cyto-chrome c (Cyt-c) levels were measured. No significant difference in LPS, EndoCAb, Cyt-c levels between HIV and HIV/HCV patients was found. The CK18 level was higher in the HIV/HCV group. Correlation between CD4+ cell count and EndoCAb antibodies was found in HCV positive patients. There was a significant effect of ART on markers for EndoCAb IgA and EndoCAb IgM antibodies in the HIV monoinfected group. Correlation between CD4+ cell count and EndoCAb antibodies and LPS was found in HIV/HCV patients on ART. Coinfection with HCV can lead to more pronounced response in EndoCAb antibody production and higher levels of cell apoptosis markers, despite similar LPS levels. ART has a positive effect on immune activation.publishersversionPeer reviewe