Royal Economic Society Women’s Committee Survey on the Gender and Ethnic Balance of Academic Economics 2010

This report describes the data from the eighth, 2010, survey of gender and ethnic balance amongst academic economists in CHUDE membership departments in UK universities.gender ethnic economics Women's Committee

Mitophagy: a selective form of autophagy that participates in hemopoyetic cell homeostasis

Fil: Kornblihtt, Laura Inés.Fil: Cavaliere, Victoria.Fil: Blanco, Guillermo Armando C.

Targeting Mitophagy in Combined Therapies of Haematological Malignancies

Mitophagy is a selective form of autophagy that eliminates mitochondria and is part of a larger network of mitochondrial quality control processes that respond to mitochondrial damage. Treatment of haematological malignancies often involves drugs that ultimately cause cell death by mitochondrial injury and initiation of apoptosis. Thus, mitophagy is a potential cause of resistance to anticancer drugs that target the mitochondria (mitocans). Since mitophagy is integrated to mitochondrial biogenesis, mitochondrial fission and fusion, the bioenergetics profile and metabolic reprogramming of tumour cells, the blockage of mitophagy may not be sufficient to overcome resistance. In addition, the mitochondrial unfolded protein response and the outer mitochondrial membrane-associated degradation have extensive crosstalk with mitophagy, and advanced forms of neoplasms will require targeting both systems. Proteasome inhibitors and vinca alkaloids target many of the critical steps involved in resistance to mitocans, while inducers of mitochondrial turnover (biogenesis and mitophagy) like valproic acid have a variable effect depending on metabolic reprograming and the activity of oxidative phosphorylation of tumour cells. Here we discuss the mechanisms of mitophagy and its associated mechanisms, and discuss its application to the rationale of targeted combined therapies of low- and high-grade B-cell neoplasms

Climate-sensitive hydrological drought insurance for irrigated agriculture under deep uncertainty. Insightful results from the Cega River Basin in Spain

This paper assesses the feasibility and robustness of an index-based insurance scheme against hydrological droughts under climate change. To this end, we develop a grand ensemble that samples both modeling and scenario uncertainty in the estimation of the insurance risk premium, so to reveal potential unfavorable surprises and minimize regret in the design of the proposed insurance scheme. The grand ensemble combines four microeconomic models and seven GAMLSS models, which are run for three alternative climate change scenarios: stationary climate/no climate change, RCP 2.6, and RCP 8.5. Methods are illustrated with an application to the Cega River Sub-basin (CRS) in central Spain. Results indicate that for a conventional deductible of 30%, the proposed index-based insurance scheme would be actuarially feasible and affordable under all models for the stationary climate scenario (i.e., robust). For climate change scenarios RCP 2.6 and 8.5 and a 30% deductible, the suggested index-based insurance would be actuarially feasible under most models, albeit some outliers point towards potential unfavorable surprises. Lower deductibles decrease feasibility, particularly for deductibles <10%

Switching from a protease inhibitor-based regimen to a dolutegravir-based regimen : a randomized clinical trial to determine the effect on peripheral blood and ileum biopsies from antiretroviral therapy-suppressed human immunodeficiency virus-infected individuals

Background: Optimization of combination antiretroviral therapy (cART) can impact the human immunodeficiency virus (HIV) reservoir. We evaluated the effect on the HIV reservoir in peripheral blood and ileum biopsies in patients switching from boosted protease inhibitor (PI/r)-based therapy to dolutegravir (DTG)-based therapy. Methods: Impact of Integrase-inhibitor DOlutegravir On the viral Reservoir (INDOOR) is a phase 4 open-label clinical trial that randomly included 42 HIV type 1-infected individuals on effective cART: 20 who switched from PI/r-based to DTG-based cART (switch group), and 22 who remained in PI/r-based regimens (control group). We analyzed blood and ileum biopsies to quantify episomal, total, and integrated HIV DNA, cell-associated HIV RNA, residual plasma viremia, T-cell subsets, cell activation, and inflammation markers. Results: There were no related adverse events or treatment discontinuations due to drug intolerance. The HIV reservoir was consistently larger in ileal than in peripheral CD4(+) T cells in both groups (P <.01). Residual viremia in plasma decreased in the switch group (P =.03). However, we did not observe significant longitudinal changes in low-level viral replication, total and integrated HIV reservoir, HIV transcription, T-cell maturation subsets, immunoactivation markers, inflammatory soluble proteins, or cellular markers of latently infected cells. Conclusions: The INDOOR study is the first evaluation of changes in HIV reservoir size in ileum biopsies and in peripheral blood in individuals switched from PI/r- to DTG-based cART. Although this switch was safe and well tolerated, it had no impact on a large array of immunological and inflammatory markers or on HIV reservoir markers in peripheral or in ileal CD4(+) T cells

Identification of two proteins that interact with the Erp virulence factor from Mycobacterium tuberculosis by using the bacterial two-hybrid system

<p>Abstract</p> <p>Background</p> <p>The exported repetitive protein (<it>erp</it>) gene encodes a secreted 36-kDa protein with a central domain containing several proline-glycine-leucine-threonine-serine (PGLTS) repeats. It has been demonstrated that <it>erp </it>is a virulence-associated factor since the disruption of this gene impairs the growth of <it>Mycobacterium bovis </it>and <it>Mycobacterium tuberculosis </it>in mice.</p> <p>Results</p> <p>In order to elucidate the function of Erp we searched for Erp-binding proteins from <it>M. tuberculosis </it>by using a bacterial two-hybrid system. Our results indicate that Erp interacts specifically with two putative membrane proteins, Rv1417 and Rv2617c. Further analysis revealed that the latter two interact with each other, indicating that Rv1417, Rv2617c and Erp are connected through multiple interactions. While Rv1417 is disseminated in several <it>Actinomycetales </it>genera, orthologues of Rv2617c are exclusively present in members of the <it>M. tuberculosis </it>complex (MTC). The central and amino-terminal regions of Erp were determined to be involved in the interaction with Rv1417 and Rv2627c. Erp forms from <it>Mycobacterium smegmatis </it>and <it>Mycobacterium leprae </it>were not able to interact with Rv2617c in two-hybrid assays. Immunolocalization experiments showed that Rv1417 and Rv2617c are found on the cell membrane and Erp on the bacterial cell wall. Finally, comparative genomics and expression studies revealed a possible role of Rv1417 in riboflavin metabolism.</p> <p>Conclusion</p> <p>We identified interactive partners of Erp, an <it>M. tuberculosis </it>protein involved in virulence, which will be the focus of future investigation to decipher the function of the Erp family protein.</p

Study of the role of Mce3R on the transcription of mce genes of Mycobacterium tuberculosis

<p>Abstract</p> <p>Background</p> <p><it>mce3 </it>is one of the four virulence-related <it>mce </it>operons of <it>Mycobacterium tuberculosis</it>. In a previous work we showed that the overexpression of Mce3R in <it>Mycobacterium smegmatis </it>and <it>M. tuberculosis </it>abolishes the expression of <it>lacZ </it>fused to the <it>mce3 </it>promoter, indicating that Mce3R represses <it>mce3 </it>transcription.</p> <p>Results</p> <p>We obtained a knockout mutant strain of <it>M. tuberculosis </it>H37Rv by inserting a hygromycin cassette into the <it>mce3R </it>gene. The mutation results in a significant increase in the expression of <it>mce3 </it>genes either <it>in vitro </it>or in a murine cell macrophages line as it was determined using promoter-<it>lacZ </it>fusions in <it>M. tuberculosis</it>. The abundance of <it>mce1</it>, <it>mce2 </it>and <it>mce4 </it>mRNAs was not affected by this mutation as it was demonstrated by quantitative RT-PCR. The <it>mce3R </it>promoter activity in the presence of Mce3R was significantly reduced compared with that in the absence of the regulator, during the <it>in vitro </it>culture of <it>M. tuberculosis</it>.</p> <p>Conclusion</p> <p>Mce3R repress the transcription of <it>mce3 </it>operon and self regulates its own expression but does not affect the transcription of <it>mce1</it>, <it>mce2 </it>and <it>mce4 </it>operons of <it>M. tuberculosis</it>.</p

Sleep State Modulates Resting-State Functional Connectivity in Neonates.

The spontaneous cerebral activity that gives rise to resting-state networks (RSNs) has been extensively studied in infants in recent years. However, the influence of sleep state on the presence of observable RSNs has yet to be formally investigated in the infant population, despite evidence that sleep modulates resting-state functional connectivity in adults. This effect could be extremely important, as most infant neuroimaging studies rely on the neonate to remain asleep throughout data acquisition. In this study, we combine functional near-infrared spectroscopy with electroencephalography to simultaneously monitor sleep state and investigate RSNs in a cohort of healthy term born neonates. During active sleep (AS) and quiet sleep (QS) our newborn neonates show functional connectivity patterns spatially consistent with previously reported RSN structures. Our three independent functional connectivity analyses revealed stronger interhemispheric connectivity during AS than during QS. In turn, within hemisphere short-range functional connectivity seems to be enhanced during QS. These findings underline the importance of sleep state monitoring in the investigation of RSNs

Constructing a small modular stellarator in Latin America

https://www.scopus.com/inward/record.url?eid=2-s2.0-84938118149&partnerID=40&md5=1d385f1e177901beaf6f30228abdd67bThis paper aims at briefly describing the design and construction issues of the stellarator of Costa Rica 1 (SCR-1). The SCR-1 is a small modular stellarator for magnetic confinement of plasma developed by the Plasma Laboratory for Fusion Energy and Applications of the Instituto Tecnológico de Costa Rica (ITCR). SCR-1 will be a 2-field period small modular stellarator with an aspect ratio > 4.4; low shear configuration with core and edge rotational transform equal to 0.32 and 0.28; it will hold plasma in a 6061-T6 aluminum torus shaped vacuum vessel with an minor plasma radius 54.11 mm, a volume of 13.76 liters (0.01 m3), and major radius R = 238 mm. Plasma will be confined in the volume by on axis magnetic field 43.8 mT generated by 12 modular coils with 6 turns each, carrying a current of 767.8 A per turn providing a total toroidal field (TF) current of 4.6 kA-turn per coil. The coils will be supplied by a bank of cell batteries of 120 V. Typical length of the plasma pulse will be between 4 s to 10 s. The SCR-1 plasmas will be heated by ECH second harmonic at 2.45 GHz with a plasma density cut-off value of 7.45 × 1016 m-3. Two magnetrons with a maximum output power of 2 kW and 3 kW will be used. © Published under licence by IOP Publishing Ltd.Ad Astra Rocket Company,Instituto Tecnologico de Costa Rica,International Atomic Energy Agency (IAEA),Universidad Nacional de Costa Ric