Noves possibilitats estructurals per a la condensació dels cromosomes

La cromatina és el material amb què es formen els cromosomes. Generalment s'accepta que el DNA s'empaqueta en els cromosomes durant la mitosi seguint una successió de plegaments de fibres de cromatina. Segons un treball realitzat per investigadors de la UAB, la cromatina, a més de fibres, forma grànuls i plaques. Per tant, poden existir formes prèviament desconegudes d'empaquetament del DNA en els cromosomes.La cromatina es el material con el que se forman los cromosomas. Generalmente se acepta que el DNA se empaqueta en los cromosomas durante la mitosis siguiendo una sucesión de pliegues de fibras de cromatina. Según un trabajo realizado por investigadores de la UAB, la cromatina, además de fibras, forma gránulos y placas. Por tanto, pueden existir formas previamente desconocidas de empaquetamiento del DNA en los cromosomas.Chromosomes are composed of a material named chromatin. Generally it is accepted that DNA is packaged in chromosomes during mitosis following a succession of chromatin fiber folds. According to a study carried out by UAB researchers, in addition to fibers, chromatin forms granules and plates. Therefore, there could be previously unknown ways of DNA packaging in chromosomes

Noves tècniques per estudiar la cromatina

En el nucli de les cèl·lules el DNA no està lliure, es troba associat amb unes proteïnes bàsiques molt abundoses que s'anomenen histones. El complex resultant és la cromatina. Mitjançant una tècnica microscòpica que permet visualitzar les mostres en el seu entorn aquós natural, investigadors de la UAB han trobat que la cromatina en les condicions iòniques corresponents a la interfase del cicle cel·lular és molt més compacta del que es considera actualment en molts altres laboratoris.En el núcleo de las células el ADN no está libre, se encuentra asociado con unas proteínas básicas muy abundantes que se denominan histonas. El complejo resultante es la cromatina. Mediante una técnica microscópica que permite visualizar las muestras en su entorno acuoso natural, investigadores de la UAB han encontrado que la cromatina en las condiciones iónicas correspondientes a la interfase del ciclo celular es mucho más compacta de lo que se considera actualmente en muchos otros laboratorios

Nou model estructural en capes primes per al cromosoma metafàsic

Experiments realitzats fent servir molt diverses tècniques de microscòpia han permès als investigadors del Laboratori de Cromatina de la UAB descobrir que, durant la divisió cel·lular, els cromosomes tenen el DNA empaquetat dins d'unes estructures planes que estan formades de moltes capes molt primes. Aquestes estructures planes estan apilades, omplen tot el volum dels cromosomes i probablement estan orientades perpendicularment respecte a l'eix central de les cromàtides.Experimentos realizados utilizando muy diversas técnicas demicroscopía han permitido a los investigadores del Laboratorio de Cromatina de la UAB descubrir que, durante la división celular, los cromosomas tienen el ADN empaquetado dentro de unas estructuras planas que están formadas de muchas capas muy delgadas. Estas estructuras planas están apiladas, llenan todo el volumen de los cromosomas y probablemente están orientadas perpendicularmente respecto al eje central de las cromátidasExperiments performed using several different microscopy techniques have allowed researchers at the UAB Chromatin Laboratory to discover that, during cell division, chromosome DNA is packaged with in planar structures formed by many extremely thin layers. These planar structuresare stacked, occupy the entire volume of the chromosomes, and are probably oriented perpendicular to the central chromatid axis. The planar geometry of these structures is very well defined, but the nucleosomes inside the successive layers are irregularly oriented

Addition of hyaluronic acid improves tlerance to 7% hypertonic saline solution in bronchiectasis patients.

Background: The excessive retention of sputum in the airways, leading to pulmonary infections, is a common consequence of bronchiectasis. Although inhalation of 7% hypertonic saline (HS) has proven an effective method to help remove the mucus, many patients are intolerant of this treatment. The addition of 0.1% hyaluronic acid to HS (HS+HA) could increase tolerance to HS in these patients. The main objective of this study was to evaluate the tolerability of HS+HA in bronchiectasis patients who are intolerant to HS. Methods: This prospective, observational, open-label study analysed the outcomes of two groups of bronchiectasis patients previously scheduled to start HS therapy. Patients were assessed for tolerance to HS by a questionnaire, spirometry and clinical evaluation. Patients who were intolerant were evaluated for tolerance to HS+HA approximately one week later. All patients were evaluated for their tolerance to HS or HS+HA 4 weeks after the start of their treatment. Patients were also assessed with quality-of-life and adherence questionnaires, and all adverse events were registered. Results: A total of 137 bronchiectasis patients were enrolled in the study (age = 63.0 ± 14.7 years; 63.5% women). Of these, 92 patients (67.1%) were tolerant and 45 patients (32.9%) were intolerant to HS. Of the 45 patients intolerant to HS, 31 patients (68.9%) were tolerant and 14 patients (31.1%) intolerant to HS+HA. Of these 31 tolerant patients, 26 (83.9%) could complete the 4-week treatment with HS+HA. Conclusions: Two-thirds of bronchiectasis patients that presented intolerance to inhaled HS alone are tolerant to inhaled HS+HA, suggesting that HA improves tolerance to HS therapy

Occupational exposure to pesticides and endometrial cancer in the Screenwide case-control study

Background: Endometrial cancer is the most common gynaecological tumour in developed countries and disease burden is expected to increase over the years. Identifying modifiable risk factors may help developing strategies to reduce the expected increasing incidence of these neoplasms. Objective: This study evaluates the association between occupational exposure to pesticides and endometrial cancer using data from a recent case-control study in Spain. Methods: The analyses included data from 174 consecutive incident endometrial cancer cases and 216 hospital controls frequency-matched by age. Data were collected through structured epidemiological questionnaires and exposure to pesticides was assessed using a Spanish job-exposure matrix (MatEmESp). Results: Overall, 12% of controls and 18% of cases were occupationally exposed to pesticides. We observed a positive association between occupational exposure to pesticides and endometrial cancer (OR = 2.08; 95% CI = 1.13-3.88 compared to non-exposed). In general, exposures that occurred farther in the past were significantly associated with endometrial cancer. Exposure to insecticides, fungicides and herbicides were positively associated with endometrial cancer (OR = 2.08; 95% CI = 1.13-3.88, OR = 4.40; 95% CI = 1.65-13.33, and OR = 5.25; 95% CI = 1.84-17.67, respectively). The agricultural, poultry and livestock activities scenario was associated with endometrial cancer (OR = 4.16; 95% CI = 1.59-12.32), while the cleaning exposure scenario was not (OR = 1.22; 95% CI = 0.55-2.67). Conclusions: Assessment of occupational exposure to pesticides assessed using a Spanish job-exposure matrix revealed a positive association with endometrial cancer. The elucidation of the role of pesticide compounds on endometrial cancer should shed a light on the aetiology of this tumour

Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer

Background The incidence of endometrial cancer is increasing worldwide. While delays in diagnosis reduce survival, case molecular misclassification might be associated with under- and over-treatment. The objective of this study was to evaluate genetic alterations to detect and molecularly classify cases of endometrial cancer using non-invasive samples. Methods Consecutive patients with incident endometrial cancer (N = 139) and controls (N = 107) from a recent Spanish case–control study were included in this analysis. Overall, 339 cervicovaginal samples (out of which 228 were clinician-collected and 111 were self-collected) were analysed using a test based on next-generation sequencing (NGS), which targets 47 genes. Immunohistochemical markers were evaluated in 133 tumour samples. A total of 159 samples were used to train the detection algorithm and 180 samples were used for validation. Findings Overall, 73% (N = 94 out of 129 clinician-collected samples, and N = 66 out of 90 self-collected samples) of endometrial cancer cases had detectable mutations in clinician-collected and self-collected samples, while the specificity was 80% (79/99) for clinician-collected samples and 90% (19/21) for self-collected samples. The molecular classifications obtained using tumour samples and non-invasive gynaecologic samples in our study showed moderate-to-good agreement. The molecular classification of cases of endometrial cancer into four groups using NGS of both clinician-collected and self-collected cervicovaginal samples yielded significant differences in disease-free survival. The cases with mutations in POLE had an excellent prognosis, whereas the cases with TP53 mutations had the poorest clinical outcome, which is consistent with the data on tumour samples. Interpretation This study classified endometrial cancer cases into four molecular groups based on the analysis of cervicovaginal samples that showed significant differences in disease-free survival. The molecular classification of endometrial cancer in non-invasive samples may improve patient care and survival by indicating the early need for aggressive surgery, as well as reducing referrals to highly specialized hospitals in cancers with good prognosis. Validation in independent sets will confirm the potential for molecular classification in non-invasive samples. Funding This study was funded by a competitive grant from Instituto de Salud Carlos III through the projects PI19/01835, PI23/00790, and FI20/00031, CIBERESP CB06/02/0073 and CIBERONC CB16/12/00231, CB16/12/00234 (Co-funded by European Regional Development Fund. ERDF: A way to build Europe). Samples and data were provided by Biobank HUB-ICO-IDIBELL, integrated into the Spanish Biobank Network, and funded by the Instituto de Salud Carlos III (PT20/00171) and by Xarxa de Bancs de Tumors de Catalunya (XBTC) sponsored by Pla Director d’Oncologia de Catalunya. This work was supported in part by the AECC, Grupos estables (GCTRA18014MATI). It also counts with the support of the Secretariat for Universities and Research of the Department of Business and Knowledge of the Generalitat de Catalunya, and grants to support the activities of research groups 2021SGR01354 and 2021SGR1112

An Integrated Approach for the Early Detection of Endometrial and Ovarian Cancers (Screenwide Study): Rationale, Study Design and Pilot Study

Screenwide is a case-control study (2017-2021) including women with incident endometrial and ovarian cancers (EC and OC), BRCA1/2 and MMR pathogenic variant carriers, and age-matched controls from three centers in Spain. Participants completed a personal interview on their sociodemographic factors, occupational exposure, medication, lifestyle, and medical history. We collected biological specimens, including blood samples, self-collected vaginal specimens, cervical pap-brush samples, uterine specimens, and, when available, tumor samples. The planned analyses included evaluation of the potential risk factors for EC/OC; evaluation of molecular biomarkers in minimally invasive samples; evaluation of the cost-effectiveness of molecular tests; and the generation of predictive scores to integrate different epidemiologic, clinical, and molecular factors. Overall, 182 EC, 69 OC, 98 BRCA pathogenic variant carriers, 104 MMR pathogenic variant carriers, and 385 controls were enrolled. The overall participation rate was 85.7%. The pilot study using 61 samples from nine EC cases and four controls showed that genetic variants at the variant allele fraction > 5% found in tumors (n = 61 variants across the nine tumors) were detected in paired endometrial aspirates, clinician-collected cervical samples, and vaginal self-samples with detection rates of 90% (55/61), 79% (48/61), and 72% (44/61) by duplex sequencing, respectively. Among the controls, only one somatic mutation was detected in a cervical sample. We enrolled more than 800 women to evaluate new early detection strategies. The preliminary data suggest that our methodological approach could be useful for the early detection of gynecological cancers

Obstetric outcomes of sars-cov-2 infection in asymptomatic pregnant women

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13-3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms

The GenTree Platform: growth traits and tree-level environmental data in 12 European forest tree species

Background: Progress in the field of evolutionary forest ecology has been hampered by the huge challenge of phenotyping trees across their ranges in their natural environments, and the limitation in high-resolution environmental information. Findings: The GenTree Platform contains phenotypic and environmental data from 4,959 trees from 12 ecologically and economically important European forest tree species: Abies alba Mill. (silver fir), Betula pendula Roth. (silver birch), Fagus sylvatica L. (European beech), Picea abies (L.) H. Karst (Norway spruce), Pinus cembra L. (Swiss stone pine), Pinus halepensis Mill. (Aleppo pine), Pinus nigra Arnold (European black pine), Pinus pinaster Aiton (maritime pine), Pinus sylvestris L. (Scots pine), Populus nigra L. (European black poplar), Taxus baccata L. (English yew), and Quercus petraea (Matt.) Liebl. (sessile oak). Phenotypic (height, diameter at breast height, crown size, bark thickness, biomass, straightness, forking, branch angle, fructification), regeneration, environmental in situ measurements (soil depth, vegetation cover, competition indices), and environmental modeling data extracted by using bilinear interpolation accounting for surrounding conditions of each tree (precipitation, temperature, insolation, drought indices) were obtained from trees in 194 sites covering the species’ geographic ranges and reflecting local environmental gradients. Conclusion: The GenTree Platform is a new resource for investigating ecological and evolutionary processes in forest trees. The coherent phenotyping and environmental characterization across 12 species in their European ranges allow for a wide range of analyses from forest ecologists, conservationists, and macro-ecologists. Also, the data here presented can be linked to the GenTree Dendroecological collection, the GenTree Leaf Trait collection, and the GenTree Genomic collection presented elsewhere, which together build the largest evolutionary forest ecology data collection available

Between but not within species variation in the distribution of fitness effects

New mutations provide the raw material for evolution and adaptation. The distribution of fitness effects (DFE) describes the spectrum of effects of new mutations that can occur along a genome, and is therefore of vital interest in evolutionary biology. Recent work has uncovered striking similarities in the DFE between closely related species, prompting us to ask whether there is variation in the DFE among populations of the same species, or among species with different degrees of divergence, i.e., whether there is variation in the DFE at different levels of evolution. Using exome capture data from six tree species sampled across Europe we characterised the DFE for multiple species, and for each species, multiple populations, and investigated the factors potentially influencing the DFE, such as demography, population divergence and genetic background. We find statistical support for there being variation in the DFE at the species level, even among relatively closely related species. However, we find very little difference at the population level, suggesting that differences in the DFE are primarily driven by deep features of species biology, and that evolutionarily recent events, such as demographic changes and local adaptation, have little impact