96 research outputs found
iSTAR first light: Characterizing astronomy education research dissertations in the iSTAR database
There is widespread interest among discipline-based science education researchers to situate their research in the existing scholarly literature base. Unfortunately, traditional approaches to conducting a thorough literature review are unduly hindered in astronomy education research as the venues in which scholarship is reported are fragmented and widely dispersed across journals of varying disciplines. The international STudies of Astronomy education Research (iSTAR) online repository is the result of a concerted international community effort to collect and categorize existing research from peer-reviewed journal articles, dissertations/theses, and grey literature. In a “first light” survey of over 300 U.S. dissertations, we find: (i) work in AER dates back to 1923; (ii) the number of extant dissertations is far greater than anticipated; (iii) research methods definitions have evolved; and (iv) most work has studied participants’ broad knowledge rather than specific learning targets. The surprisingly wide breadth of rarely cited research motivates us to collect more AER from across international and cross-disciplinary sources
USP49 deubiquitinase regulates the mitotic spindle checkpoint and prevents aneuploidy.
The spindle assembly checkpoint (SAC) is an essential mechanism that ensures the accurate chromosome segregation during mitosis, thus preventing genomic instability. Deubiquitinases have emerged as key regulators of the SAC, mainly by determining the fate of proteins during cell cycle progression. Here, we identify USP49 deubiquitinase as a novel regulator of the spindle checkpoint. We show that loss of USP49 in different cancer cell lines impairs proliferation and increases aneuploidy. In addition, USP49-depleted cells overcome the arrest induced by the SAC in the presence of nocodazole. Finally, we report new binding partners of USP49, including ribophorin 1, USP44, and different centrins.We thank A.P. Ugalde, D. Rodríguez, J.G. Pérez-Silva, Y. Español and F. Rodríguez for
helpful comments and advice. We also thank S.A. Miranda, D. Álvarez-Puente and C.
Garabaya for excellent technical assistance, as well as the staff of the scientific core
facilities from the University of Oviedo (Unidad de Ensayos Biotecnológicos y
Biomédicos, Servicios Científico-Técnicos). This work was supported by the Ministerio
de Ciencia e Innovación (SAF2017-87655-R, PDI2020-118394RB-100 and PGC2018-
097019-B-I00), “la Caixa” Banking Foundation (project code HR17-00247), and the
European Research Council (742067, DeAge). The IUOPA is funded by the Asturian
Government and Fundación Cajastur-Liberbank.S
SME’s perspective on psychosocial risks: From identifying to intervening in four countries
Introduction: Certain aspects of the work design or the organization as well as the social context of work may lead to negative physical, psychological and social outcomes. These aspects are considered psychosocial risks. Portugal, Spain, Italy, and Greece are facing the biggest consequences of the economic crisis with psychosocial risks being exacerbated. In these countries, small and medium enterprises play an important role in the economy. This paper presents the quantitative data from the project, collected in those four countries. The main goal of the survey was to determine the SMEs’ perspective about emergent psychosocial risks, difficulties and concerns related to its prevention as well as to assess their knowledge and existing practices regarding psychosocial risks prevention.info:eu-repo/semantics/publishedVersio
Participative prevention of psychosocial emergent risks in small and medium enterprises Overview of a collaborative project
info:eu-repo/semantics/publishedVersio
GA design of small thin-wire antennas: comparison with Sierpinski-type prefractal antennas
A new set of genetically generated electrically small thin-wire antennas with a better performance than that of several families of Sierpinsky prefractal monopoles of the same electrical size at resonance is presentedPeer Reviewe
Novel approaches for the rapid development of rationally designed arbovirus vaccines
Vector-borne diseases, including those transmitted by mosquitoes, account for more than 17% of infectious diseases worldwide. This number is expected to rise with an increased spread of vector mosquitoes and viruses due to climate change and man-made alterations to ecosystems. Among the most common, medically relevant mosquito-borne infections are those caused by arthropod-borne viruses (arboviruses), especially members of the genera Flavivirus and Alphavirus. Arbovirus infections can cause severe disease in humans, livestock and wildlife. Severe consequences from infections include congenital malformations as well as arthritogenic, haemorrhagic or neuroinvasive disease. Inactivated or live-attenuated vaccines (LAVs) are available for a small number of arboviruses; however there are no licensed vaccines for the majority of these infections. Here we discuss recent developments in pan-arbovirus LAV approaches, from site-directed attenuation strategies targeting conserved determinants of virulence to universal strategies that utilize genome-wide re-coding of viral genomes. In addition to these approaches, we discuss novel strategies targeting mosquito saliva proteins that play an important role in virus transmission and pathogenesis in vertebrate hosts. For rapid pre-clinical evaluations of novel arbovirus vaccine candidates, representative in vitro and in vivo experimental systems are required to assess the desired specific immune responses. Here we discuss promising models to study attenuation of neuroinvasion, neurovirulence and virus transmission, as well as antibody induction and potential for cross-reactivity. Investigating broadly applicable vaccination strategies to target the direct interface of the vertebrate host, the mosquito vector and the viral pathogen is a prime example of a One Health strategy to tackle human and animal diseases.Molecular basis of virus replication, viral pathogenesis and antiviral strategie
A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection
There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways; in this study we took advantage of the SeeSaw Reporter, in which the repair of double-strand breaks by homology-independent or -dependent mechanisms is distinguished by the accumulation of green or red fluorescence, respectively. Using a genome-wide human esiRNA (endoribonuclease- prepared siRNA) library, we isolate genes that control the recombination/endjoining ratio. Here we report that two distinct sets of genes are involved in the control of the balance between NHEJ and HR: those that are required to facilitate recombination and those that favour NHEJ. This last category includes CCAR2/DBC1, which we show inhibits recombination by limiting the initiation and the extent of DNA end resection, thereby acting as an antagonist of CtIP
Selective small molecule induced degradation of the BET bromodomain protein BRD4
The Bromo- and Extra-Terminal (BET)
proteins BRD2, BRD3, and BRD4
play important roles in transcriptional regulation, epigenetics, and
cancer and are the targets of pan-BET selective bromodomain inhibitor
JQ1. However, the lack of intra-BET selectivity limits the scope of
current inhibitors as probes for target validation and could lead
to unwanted side effects or toxicity in a therapeutic setting. We
designed Proteolysis Targeted Chimeras (PROTACs) that tether JQ1 to
a ligand for the E3 ubiquitin ligase VHL, aimed at triggering the
intracellular destruction of BET proteins. Compound MZ1 potently and
rapidly induces reversible, long-lasting, and unexpectedly selective
removal of BRD4 over BRD2 and BRD3. The activity of MZ1 is dependent
on binding to VHL but is achieved at a sufficiently low concentration
not to induce stabilization of HIF-1α. Gene expression profiles
of selected cancer-related genes responsive to JQ1 reveal distinct
and more limited transcriptional responses induced by MZ1, consistent
with selective suppression of BRD4. Our discovery opens up new opportunities
to elucidate the cellular phenotypes and therapeutic implications
associated with selective targeting of BRD4
SARS-CoV-2-specific immune responses converge in kidney disease patients and controls with hybrid immunity
Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.</p
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