The RC protein, a translational repressor that coordinates carbon metabolism in pseudomonas

Comunicaciones a congreso

Contaminations contaminate common databases

The polymerase chain reaction (PCR) is a very powerful method to detect and identify pathogens. The high sensitivity of the method, however, comes with a cost; any of the millions of artificial DNA copies generated by PCR can serve as a template in a following experiment. If not identified as contaminations, these may result in erroneous conclusions on the occurrence of the pathogen, thereby inflating estimates of host range and geographic distribution. In the present paper, we evaluate whether several published records of avian haemosporidian parasites, in either unusual host species or geographical regions, might stem from PCR contaminations rather than novel biological findings. The detailed descriptions of these cases are shedding light upon the steps in the work process that might lead to PCR contaminations. By increasing the awareness of this problem, it will aid in developing procedures that keep these to a minimum. The examples in the present paper are from haemosporidians of birds, however the problem of contaminations and suggested actions should apply generally to all kinds of PCR‐based identifications, not just of parasites and pathogens

Transcription factor NFE2L2/NRF2 is a regulator of macroautophagy genes

Autophagy is a highly coordinated process that is controlled at several levels including transcriptional regulation. Here, we identify the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) as a regulator of autophagy gene expression and its relevance in a mouse model of Alzheimer disease (AD) that reproduces impaired APP (amyloid β precursor protein) and human (Hs)MAPT/TAU processing, clearance and aggregation. We screened the chromatin immunoprecipitation database ENCODE for 2 proteins, MAFK and BACH1, that bind the NFE2L2-regulated enhancer antioxidant response element (ARE). Using a script generated from the JASPAR's consensus ARE sequence, we identified 27 putative AREs in 16 autophagy-related genes. Twelve of these sequences were validated as NFE2L2 regulated AREs in 9 autophagy genes by additional ChIP assays and quantitative RT-PCR on human and mouse cells after NFE2L2 activation with sulforaphane. Mouse embryo fibroblasts of nfe2l2-knockout mice exhibited reduced expression of autophagy genes, which was rescued by an NFE2L2 expressing lentivirus, and impaired autophagy flux when exposed to hydrogen peroxide. NFE2L2-deficient mice co-expressing HsAPP(V717I) and HsMAPT(P301L), exhibited more intracellular aggregates of these proteins and reduced neuronal levels of SQSTM1/p62, CALCOCO2/NDP52, ULK1, ATG5 and GABARAPL1. Also, colocalization of HsAPP(V717I) and HsMAPT(P301L) with the NFE2L2-regulated autophagy marker SQSTM1/p62 was reduced in the absence of NFE2L2. In AD patients, neurons expressing high levels of APP or MAPT also expressed SQSTM1/p62 and nuclear NFE2L2, suggesting their attempt to degrade intraneuronal aggregates through autophagy. This study shows that NFE2L2 modulates autophagy gene expression and suggests a new strategy to combat proteinopathies

Human–landscape interactions in the Conquezuela–Ambrona Valley (Soria, continental Iberia): From the early Neolithic land use to the origin of the current oak woodland

The sedimentological, geochemical and palynological analyses performed in the Conquezuela palaeolake (41°11′N; 2°33′W; 1124 m a.s.l.) provide a detailed, multiproxy palaeoenvironmental reconstruction in one of the key areas of inner Iberian Neolithic colonization. Combined with archaeobotanical and archaeological data from well-dated settlements along the Conquezuela–Ambrona Valley we investigate how environmental conditions may affect both socio-economic adaptations and livelihood strategies of prehistoric communities. The first evidences of early Neolithic occupation in the valley ca. 7250–6450 cal yr BP (5300–4500 BC) coincided with the onset of a period (7540–6200 cal yr BP, 5590–4250 BC) with higher water availability and warmer climate as alluvial environments were substituted by carbonate-wetland environments in the basin. The Conquezuela record supports an early Neolithic colonization of the inner regions of Iberia favored by warmer and humid climate features and with preferential settlement patterns associated to lakes. The maximum human occupation of the valley occurred during the mid–late Neolithic and Chalcolithic (6200–3200 cal yr BP, 4250–1250 BC) as evidenced by the high number of archaeological sites. Although a number of hydrological oscillations have been detected during this period, the intense landscape transformation at basin-scale, leading to a deforested landscape, was largely a consequence of widespread farming and pastoral practices. Socio-economic activities during Bronze, Iron and Roman times modified this inherited landscape, but the second largest ecosystem transformation only occurred during Mediaeval times when a new agrarian landscape developed with the expansion of stockbreeding transhumance. The current vegetation cover characterized by patches of holm and marcescent oaks and fields reflects an intense human management combining both extensive herding with agrarian activities in order to transform the previous forested landscape into a dehesa-like system.The funding for the present study derives from DINAMO2 (CGL-BOS 2012-33063) and AGRIWESTMED (ERC Grant Agreement #230561) projects, provided by the Spanish Inter-Ministry Commission of Science and Technology (CICYT) and the European Research Council under the European Union's Seventh Framework Programme (FP7/2007–2013). XRF data were obtained at the XRF Core Scanner Laboratory (CRG Marine Geosciences, University of Barcelona). Josu Aranbarri acknowledges the predoctoral funding provided by the Basque Country Government (ref: FI-2010-5). Graciela Gil-Romera hold a post-doctoral contract funded by “Juan de la Cierva” (ref: JCI2009-04345) program. Eduardo García-Prieto and Maria Leunda are supported by predoctoral FPI grants BES-2010-038593 and BES-2013-063753, respectively. We also thank Elena Royo for her help with the lab procedures and the two anonymous referees for their valuable suggestions.Peer reviewe

GEICAM Guidelines for the Management of Patients with Breast Cancer During the COVID-19 Pandemic in Spain

Breast cancer (BC) is the most common cancer in women in Spain. During the COVID-19 pandemic caused by the SARSCoV-2 virus, patients with BC still require timely treatment and follow-up; however, hospitals are overwhelmed with infected patients and, if exposed, patients with BC are at higher risk for infection and serious complications if infected. Thus, health care providers need to evaluate each BC treatment and in-hospital visit to minimize pandemic-associated risks while maintaining adequate treatment efficacy. Here we present a set of guidelines regarding available options for BC patient management and treatment by BC subtype in the context of the COVID-19 pandemic. Owing to the lack of evidence about COVID-19 infection, these recommendations are mainly based on expert opinion, medical organizations’ and societies’ recommendations, and some published evidence. We consider this a useful tool to facilitate medical decision making in this health crisis situation we are facing

What to consider when pseudohypoparathyroidism is ruled out: IPPSD and differential diagnosis

Background: Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright''s hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. Methods: We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. Results: A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. Conclusions: This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

A search for point sources of EeV photons

Measurements of air showers made using the hybrid technique developed with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for point sources of EeV photons anywhere in the exposed sky. A multivariate analysis reduces the background of hadronic cosmic rays. The search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been detected. An upper limit on the photon flux has been derived for every direction. The mean value of the energy flux limit that results from this, assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in which EeV cosmic ray protons are emitted by non-transient sources in the Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical Journa

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201