UBE2QL1 is Disrupted by a Constitutional Translocation Associated with Renal Tumor Predisposition and is a Novel Candidate Renal Tumor Suppressor Gene

Investigation of rare familial forms of renal cell carcinoma (RCC) has led to the identification of genes such as VHL and MET that are also implicated in the pathogenesis of sporadic RCC. In order to identify a novel candidate renal tumor suppressor gene, we characterized the breakpoints of a constitutional balanced translocation, t(5;19)(p15.3;q12), associated with familial RCC and found that a previously uncharacterized gene UBE2QL1 was disrupted by the chromosome 5 breakpoint. UBE2QL1 mRNA expression was downregulated in 78.6% of sporadic RCC and, although no intragenic mutations were detected, gene deletions and promoter region hypermethylation were detected in 17.3% and 20.3%, respectively, of sporadic RCC. Reexpression of UBE2QL1 in a deficient RCC cell line suppressed anchorage-independent growth. UBE2QL1 shows homology to the E2 class of ubiquitin conjugating enzymes and we found that (1) UBE2QL1 possesses an active-site cysteine (C88) that is monoubiquitinated in vivo, and (2) UBE2QL1 interacts with FBXW7 (an F box protein providing substrate recognition to the SCF E3 ubiquitin ligase) and facilitates the degradation of the known FBXW7 targets, CCNE1 and mTOR. These findings suggest UBE2QL1 as a novel candidate renal tumor suppressor gen

Effects of regulating the European Internal Market on the integration of variable renewable energy

ABSTRACT: The new proposal for regulating the European Internal Market for Electricity (EIME) can motivate the harmonization of the various National markets. The process of harmonizing the day-ahead markets (DAMs) is at an advanced stage, with an efficiency in the use of interconnectors of 86%. However, the harmonization of both intraday (IDMs) and balancing markets (BMs) is still in its infancy, with an efficiency in the use of interconnectors of 50 and 19%, respectively. The new proposal brings new targets to DAMs, and European countries should make efforts to comply with them. The same is true for IDMs and BMs, but involving more ambitious targets, requiring higher efforts to be accomplished. Both the analysis of the various National markets (according to their compliance with the new proposal for regulating the EIME) and the advantages of the new proposal for key market participants (particularly, consumers, variable renewable generation, and conventional generation) are presented. The analysis indicates that the proposal contributes to a potential increase of the general welfare of market participants. However, some aspects of the proposal can negatively affect the revenue obtained from the National markets, notably for variable renewable generation and conventional generation. This article is categorized under: Wind Power > Systems and Infrastructure Energy Policy and Planning > Economics and Policy Energy Systems Analysis > Economics and Policy Energy and Development > Economics and Policyinfo:eu-repo/semantics/publishedVersio

Self-Affirmation and Identity-Driven Political Behavior

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this recordData availability: The data, code, and any additional materials required to replicate all analyses in this article are available at the Journal of Experimental Political Science Dataverse within the Harvard Dataverse Network, at: doi:10.7910/DVN/HUJZMOPsychological attachment to political parties can bias people’s attitudes, beliefs, and group evaluations. Studies from psychology suggest that self-affirmation theory may ameliorate this problem in the domain of politics on a variety of outcome measures. We report a series of studies conducted by separate research teams that examine whether a self-affirmation intervention affects a variety of outcomes, including political or policy attitudes, factual beliefs, conspiracy beliefs, affective polarization, and evaluations of news sources. The different research teams use a variety of self-affirmation interventions, research designs, and outcomes. Despite these differences, the research teams consistently find that self-affirmation treatments have little effect. These findings suggest considerable caution is warranted for researchers who wish to apply the self-affirmation framework to studies that investigate political attitudes and beliefs. By presenting the “null results” of separate research teams, we hope to spark a discussion about whether and how the self-affirmation paradigm should be applied to political topics.European Union Horizon 2020NASAEnergy FoundationUniversity of MinnesotaNational Science Foundation (NSF

Long-term research challenges in wind energy – a research agenda by the European Academy of Wind Energy

The European Academy of Wind Energy (eawe), representing universities and institutes with a significant wind energy programme in 14 countries, has discussed the long-term research challenges in wind energy. In contrast to research agendas addressing short- to medium-term research activities, this eawe document takes a longer-term perspective, addressing the scientific knowledge base that is required to develop wind energy beyond the applications of today and tomorrow. In other words, this long-term research agenda is driven by problems and curiosity, addressing basic research and fundamental knowledge in 11 research areas, ranging from physics and design to environmental and societal aspects. Because of the very nature of this initiative, this document does not intend to be permanent or complete. It shows the vision of the experts of the eawe, but other views may be possible. We sincerely hope that it will spur an even more intensive discussion worldwide within the wind energy community

MiDAS 4: A global catalogue of full-length 16S rRNA gene sequences and taxonomy for studies of bacterial communities in wastewater treatment plants

Microbial communities are responsible for biological wastewater treatment, but our knowledge of their diversity and function is still poor. Here, we sequence more than 5 million high-quality, full-length 16S rRNA gene sequences from 740 wastewater treatment plants (WWTPs) across the world and use the sequences to construct the ‘MiDAS 4’ database. MiDAS 4 is an amplicon sequence variant resolved, full-length 16S rRNA gene reference database with a comprehensive taxonomy from domain to species level for all sequences. We use an independent dataset (269 WWTPs) to show that MiDAS 4, compared to commonly used universal reference databases, provides a better coverage for WWTP bacteria and an improved rate of genus and species level classification. Taking advantage of MiDAS 4, we carry out an amplicon-based, global-scale microbial community profiling of activated sludge plants using two common sets of primers targeting regions of the 16S rRNA gene, revealing how environmental conditions and biogeography shape the activated sludge microbiota. We also identify core and conditionally rare or abundant taxa, encompassing 966 genera and 1530 species that represent approximately 80% and 50% of the accumulated read abundance, respectively. Finally, we show that for well-studied functional guilds, such as nitrifiers or polyphosphate-accumulating organisms, the same genera are prevalent worldwide, with only a few abundant species in each genus.Fil: Dueholm, Morten Kam Dahl. Aalborg University; DinamarcaFil: Nierychlo, Marta. Aalborg University; DinamarcaFil: Andersen, Kasper Skytte. Aalborg University; DinamarcaFil: Rudkjøbing, Vibeke. Aalborg University; DinamarcaFil: Knutsson, Simon. Aalborg University; DinamarcaFil: Arriaga, Sonia. Instituto Potosino de Investigación Científica y Tecnológica; MéxicoFil: Bakke, Rune. University College of Southeast Norway; NoruegaFil: Boon, Nico. University of Ghent; BélgicaFil: Bux, Faizal. Durban University of Technology; SudáfricaFil: Christensson, Magnus. Veolia Water Technologies Ab; SueciaFil: Chua, Adeline Seak May. University Malaya; MalasiaFil: Curtis, Thomas P.. University of Newcastle; Reino UnidoFil: Cytryn, Eddie. Agricultural Research Organization Of Israel; IsraelFil: Erijman, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires; ArgentinaFil: Etchebehere, Claudia. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Fatta Kassinos, Despo. University of Cyprus; ChipreFil: Frigon, Dominic. McGill University; CanadáFil: Garcia Chaves, Maria Carolina. Universidad de Antioquia; ColombiaFil: Gu, April Z.. Cornell University; Estados UnidosFil: Horn, Harald. Karlsruher Institut Für Technologie; AlemaniaFil: Jenkins, David. David Jenkins & Associates Inc; Estados UnidosFil: Kreuzinger, Norbert. Tu Wien; AustriaFil: Kumari, Sheena. Durban University of Technology; SudáfricaFil: Lanham, Ana. University of Bath; Reino UnidoFil: Law, Yingyu. Singapore Centre For Environmental Life Sciences Engineering; SingapurFil: Leiknes, TorOve. King Abdullah University of Science and Technology; Arabia SauditaFil: Morgenroth, Eberhard. Eth Zürich; SuizaFil: Muszyński, Adam. Politechnika Warszawska; PoloniaFil: Petrovski, Steve. La Trobe University; AustraliaFil: Pijuan, Maite. Catalan Institute For Water Research; EspañaFil: Pillai, Suraj Babu. Va Tech Wabag Ltd; IndiaFil: Reis, Maria A. M.. Universidade Nova de Lisboa; PortugalFil: Rong, Qi. Chinese Academy of Sciences; ChinaFil: Rossetti, Simona. Istituto Di Ricerca Sulle Acque (irsa) ; Consiglio Nazionale Delle Ricerche;Fil: Seviour, Robert. La Trobe University; AustraliaFil: Tooker, Nick. University of Massachussets; Estados UnidosFil: Vainio, Pirjo. Espoo R&D Center; FinlandiaFil: van Loosdrecht, Mark. Delft University of Technology; Países BajosFil: Vikraman, R.. VA Tech Wabag, Philippines Inc; FilipinasFil: Wanner, Jiří. University of Chemistry And Technology; República ChecaFil: Weissbrodt, David. Delft University of Technology; Países BajosFil: Wen, Xianghua. Tsinghua University; ChinaFil: Zhang, Tong. The University of Hong Kong; Hong KongFil: Nielsen, Per H.. Aalborg University; DinamarcaFil: Albertsen, Mads. Aalborg University; DinamarcaFil: Nielsen, Per Halkjær. Aalborg University; Dinamarc

BRCAness Profile of Sporadic Ovarian Cancer Predicts Disease Recurrence

BACKGROUND:The consequences of defective homologous recombination (HR) are not understood in sporadic ovarian cancer, nor have the potential role of HR proteins other than BRCA1 and BRCA2 been clearly defined. However, it is clear that defects in HR and other DNA repair pathways are important to the effectiveness of current therapies. We hypothesize that a subset of sporadic ovarian carcinomas may harbor anomalies in HR pathways, and that a BRCAness profile (defects in HR or other DNA repair pathways) could influence response rate and survival after treatment with platinum drugs. Clinical availability of a BRCAness profile in patients and/or tumors should improve treatment outcomes. OBJECTIVE:To define the BRCAness profile of sporadic ovarian carcinoma and determine whether BRCA1, PARP, FANCD2, PTEN, H2AX, ATM, and P53 protein expression correlates with response to treatment, disease recurrence, and recurrence-free survival. MATERIALS AND METHODS:Protein microarray analysis of ovarian cancer tissue was used to determine protein expression levels for defined DNA repair proteins. Correlation with clinical and pathologic parameters in 186 patients with advanced stage III-IV and grade 3 ovarian cancer was analyzed using Chi square, Kaplan-Meier method, Cox proportional hazard model, and cumulative incidence function. RESULTS:High PARP, FANCD2 and BRCA1 expressions were significantly correlated with each other; however, elevated p53 expression was associated only with high PARP and FANCD2. Of all patients, 9% recurred within the first year. Among early recurring patients, 41% had high levels of PARP, FANCD2 and P53, compared to 19.5% of patients without early recurrence (p = 0.04). Women with high levels of PARP, FANCD2 and/or P53 had first year cumulative cancer incidence of 17% compared with 7% for the other groups (P = 0.03). CONCLUSIONS:Patients with concomitantly high levels of PARP, FANCD2 and P53 protein expression are at increased risk of early ovarian cancer recurrence and platinum resistance

Cancer risks associated with germline PALB2 pathogenic variants: An international study of 524 families

PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers