Euphorbia transtagana Boiss. (Euphorbiaceae) endemismo ibero-tingitano en España

New spanish record for Euphorbia transtagana Boiss. (Euphorbiaceae) in Huelva (SW of Spain)Palabras clave. Corología, Flora Vascular, Euphorbia transtagana, Huelva, SO España.Key words. Chorology, Vascular Flora, Euphorbia transtagana, Huelva, SW of Spain

Nuevas citas de dos ciperáceas raras en Andalucía

El estudio de materiales del género Carex (Cyperaceae) de los herbarios de E. Sánchez Gullón y P. Weickert nos ha permitido detectar dos importantes novedades corológicas en la comarca natural del Andévalo, en la provincia de Huelva (Andalucía): C. demissa Hornem. y C. helodes Link. Duplicados de estos pliegos han sido depositados en el herbario público UPOS de Sevilla. Con estos hallazgos se continúan los trabajos corológicos anteriores sobre la provincia de Huelva de Sánchez Gullón & Weickert (Lagascalia, 22: 172- 179. 2002) y Sánchez Gullón et al. (Lagascalia, 26: 187-196. 2006). Se cita también C. demissa de Sierra Nevada con base en materiales de otros herbarios (MA y JACA) que habían sido determinados como Carex nevadensis Boiss. & Reuter

Plantas americanas nuevas para la flora adventicia del sur de España

New data about american neophytes for southern Andalusian flora.Palabras clave. Corología, xenófitos americanos, especies invasoras, Andalucía, SO de España.Key words. Chorology, american xenophytes, invasive flora, Andalusía, SW Spain

A new specie of Iridaceae for SW of Spain.

Una nueva especie de Iridaceae para el sudoeste de España.Palabras clave. Flora, corología, Ferraria crispa, Iridaceae, xenófito adventicio naturalizado, Huelva, AndalucíaKey words. Flora, corology, Ferraria crispa, Iridaceae, xenophyte adventitious naturalised, Huelva, Andalusi

Nuevas localidades de especies interesantes en Doñana y la costa de Huelva (Sw España)

New floristic records of species for Doñana and Huelva (SW Spain) Palabras clave. Flora, Doñana, Calystegia soldanella, Herniaria cinerea, Trigonella monspeliaca, Viola lactea, Wolffia arrhiza, especies amenazadas.Key words. Flora, Doñana, Calystegia soldanella, Herniaria cinerea, Trigonella monspeliaca, Viola lactea, Wolffia arrhiza, threatened species

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Characterisation of DNA-protein crosslink repair with the Purification of x-linked Proteins technique

DNA-Protein Crosslinks (DPCs) have emerged as an important source of endogenous and exogenous DNA damage. DPCs arise when proteins get covalently trapped on DNA, what can happen during the action of enzymes that naturally establish covalent intermediates with DNA -such as topoisomerases- but also by the action of reactive compounds. One of these compounds, formaldehyde, is an environmental toxin and a metabolite produced during one-carbon metabolism and methanol detoxification. Formaldehyde is extremely reactive and generates protein-protein crosslinks, RNA-protein crosslinks and DPCs. DPCs are toxic because they can block essential chromatin transactions such as replication or transcription. Their toxicity has been exploited in chemotherapy with the use of different drugs that induce these genomic lesions either specifically, camptothecin (CPT) traps TOP1 or etoposide traps TOP2, or unspecifically, with compounds like cisplatin commonly used in breast cancer treatment. DPC-repair generally involves specialized proteases which mediate the destruction of the protein adduct. In higher eukaryotes, the metalloprotease SPRTN is recruited to the lesion in a process that involves the collision of the replication fork with the adduct. SPRTN is activated by the DNA structure generated by polymerase stalling, cleaves the protein and allows peptide bypass by translesion synthesis (TLS). The study of DPC-repair and the identification of DPCs generated by non-specific crosslinkers has remained elusive due to limited methodology to study these lesions. Previous methods to isolate DPCs, rely on DNA precipitation and are prone to technical biases due to the presence of protein aggregates, giving false positives, or changes in DNA precipitation behaviour due to the variable crosslinked protein nature, giving false negatives. Therefore, I established during my master thesis, and optimized during my PhD, a method for the isolation, identification and monitoring of DPCs, the Purification of x-linked Proteins (PxP). Using PxP in combination with mass spectrometry, I uncovered the identity of DPCs generated by physiologically relevant levels of formaldehyde. Strikingly, formaldehyde-induced DPCs are less complex than anticipated, they mostly consist of crosslinked nucleosomes. Then, we decided to apply PxP for the study of 5-azadC-induced DPCs, which consists mostly of the DNA Methyl Transferase 1 (DNMT1). We observed DNMT1-DPC formation in a dose-dependent manner and could monitor their repair kinetics. We discovered that repair of this crosslinks involved the SUMOylation of the adduct and SUMO-targeted ubiquitylation by the StUbL RNF4, which triggered proteasomal degradation of crosslinked DNMT1. In agreement with biochemical data and previous work, RNF4 knock-out cells displayed 5-azadC sensitivity. Interestingly, we observed a cleaved DNMT1-DPC fragment whose appearance was dependent on the same modifications -SUMO and ubiquitin- but not generated by the proteasome. We identified SPRTN as the enzyme responsible for this cleavage and, through structure function analysis, conclude that the UBZ domain is responsible for the recruitment of SPRTN to DNMT1-DPCs. Strikingly, only the loss of the UBZ domain completely phenocopied the SPRTN-ΔC allele, which is causative for Ruijs-Aalfs syndrome. Our data support a replication-independent role for the metalloprotease SPRTN during DPC-repair and highlight the importance of the UBZ domain during lesion recognition. Given the multiple applications of the PxP for the study of DPC biology, we decided to write an article in which we described the method step by step to facilitate its implementation in other labs. We show that the PxP can be used to isolate also other types of DPCs such as those generated by non-competitive inhibitors (e.g etoposide) and that it can successfully isolate relevant physiological DPCs, like those generated by HMCES after short wavelength ultraviolet light (UVC) exposure. In conclusion, we believe that this manuscript will be a great resource for laboratories which do research on the DNA damage field