Circumnuclear structure and kinematics in the active galaxy NGC 6951

A study is presented of the central structure and kinematics of the galaxy NGC 6951, by means of broad band B'IJK images and high resolution high dispersion longslit spectroscopy, together with archival HST WFPC2 V and NICMOS2 J and H images. We find that there is evidence of two modes of star formation, in bursts and continuously. The equivalent width of the CaII triplet absorption lines show that, in the metal rich central region, the continuum is dominated by a population of red supergiants. The gaseous and stellar kinematics along three slit position angles, suggest the existence of a hierarchy of disks within disks, whose dynamics are decoupled at the two ILRs, that we find at 180 pc and at 1100 pc. This is supported by the structure seen in the high resolution HST images. The nucleus is spatially resolved within a radius of 1.5 arcsec, just inside the innermost ILR. Outside the iILR, the stellar CaT velocity profile is resolved into two components, associated with the bar and the disk. Several results indicate that this is a dynamically old system. It is thus possible that a nuclear bar has existed in NGC 6951 that drove the gas towards the nucleus, as in the bars within bars scenario, but that this bar has already dissolved by the gas accumulated within the circumnuclear region. We discuss the possibility that the kinematical component inside the iILR could be due to a nuclear outflow produced by the combined effects of SN and SN remnants, or to a nuclear disk, as in the disk within disk scenario that we propose for the fueling of the AGN in NGC 6951.Comment: 14 pages, 16 figures. Accepted for publication in Astronomy and Astrophysics. High resolution images in http://www.iaa.es/~eperez/research/degas.htm

Heterocellular Contacts with Mouse Brain Endothelial Cells Via Laminin and alpha 6 beta 1 Integrin Sustain Subventricular Zone (SVZ) Stem/Progenitor Cells Properties

Neurogenesis in the subventricular zone (SVZ) is regulated by diffusible factors and cell-cell contacts. In vivo, SVZ stem cells are associated with the abluminal surface of blood vessels and such interactions are thought to regulate their neurogenic capacity. SVZ neural stem cells (NSCs) have been described to contact endothelial-derived laminin via (01 integrin. To elucidate whether heterocellular contacts with brain endothelial cells (BEG) regulate SVZ cells neurogenic capacities, cocultures of SVZ neurospheres and primary BEG, both obtained from C57BL/6 mice, were performed. The involvement of laminin integrin interactions in SVZ homeostasis was tested in three ways. Firstly, SVZ cells were analyzed following incubation of BEC with the protein synthesis inhibitor cycloheximide (GHX) prior to coculture, a treatment expected to decrease membrane proteins. Secondly, SVZ cells were cocultured with BEG in the presence of an anti-alpha 6 integrin neutralizing antibody. Thirdly, BEC were cultured with beta 1(-/-) SVZ cells. We showed that contact with BEC supports, at least in part, proliferation and stemness of SVZ cells, as evaluated by the number of BrdU positive (+) and Sox2+ cells in contact with BEG. These effects are dependent on BEG-derived laminin binding to alpha 6 beta 1 integrin and are decreased in cocultures incubated with anti-alpha 6 integrin neutralizing antibody and in cocultures with SVZ beta 1(-/-) cells. Moreover, BEG-derived laminin sustains sternness in SVZ cell cultures via activation of the Notch and mTOR signaling pathways. Our results show that BEC/SVZ interactions involving alpha 6 beta 1 integrin binding to laminin, contribute to SVZ cell proliferation and stemness

Criação em larga escala de Biomphalaria tenagophila

An efficient method for breeding Biomphalaria tenagophila (Taim lineage/RS) was developed over a 5-year-period (2005-2010). Special facilities were provided which consisted of four cement tanks (9.4 x 0.6 x 0.22 m), with their bottom covered with a layer of sterilized red earth and calcium carbonate. Standard measures were adopted, as follows: each tank should contain an average of 3000 specimens, and would be provided with a daily ration of 35,000 mg complemented with lettuce. A green-house effect heating system was developed which constituted of movable dark canvas covers, which allowed the temperature to be controlled between 20 - 24 ºC. This system was essential, especially during the coldest months of the year. Approximately 27,000 specimens with a diameter of 12 mm or more were produced during a 14-month-period. The mortality rates of the newly-hatched and adult snails were 77% and 37%, respectively. The follow-up of the development system related to 310 specimens of B. tenagophila demonstrated that 70-day-old snails reached an average of 17.0 ± 0.9 mm diameter. The mortality rates and the development performance of B. tenagophila snails can be considered as highly satisfactory, when compared with other results in literature related to works carried out with different species of the genus Biomphalaria, under controlled laboratory conditions.Foi desenvolvido um método eficiente de criação em larga escala de Biomphalaria tenagophila (linhagem Taim/RS) durante o período de 2005-2010. Foi concebida uma instalação que consiste de quatro tanques de alvenaria (9,4 x 0,6 x 0,22) com fundos recobertos por uma mistura constituída de terra vermelha esterilizada e carbonato de cálcio. Foi padronizado que cada tanque de criação conteria em média 3.000 exemplares e receberia diariamente 35.000 mg de ração e alface como complemento. O desenvolvimento de um sistema de aquecimento por efeito estufa constituído de lonas escuras móveis permitiu controlar a temperatura entre 20 a 24 ºC, sistema essencial principalmente nos meses mais frios. Durante o período de 14 meses foram produzidos aproximadamente 27.000 exemplares com diâmetros superiores a 12 mm. As taxas de mortalidade dos caramujos recém-eclodidos e adultos foram de 77% e 37%, respectivamente. O acompanhamento do ritmo de crescimento de 310 B. tenagophila demonstrou que caramujos com 70 dias de idade alcançaram em média 17,0 ± 0,9 mm de diâmetro. As taxas de mortalidade e o desempenho de crescimento de caramujos do gênero B. tenagophila podem ser considerados altamente satisfatórios, comparando-se com os resultados da literatura realizados com espécies do gênero Biomphalaria em condições controladas de laboratório

Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations and clinical impact

Recent evidence suggests that complex karyotype (CK) defined by the presence of 653 chromosomal aberrations (structural and/or numerical) identified by chromosome banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges towards routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with 655 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcome, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and or TP53 mutations, TP53abs) and the expression of somatically hypermutated (M-CLL) or unmutated (U-CLL) immunoglobulin heavy variable genes (IGHV). Thus, they contrasted CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs and IGHV gene somatic hypermutation status, we propose a novel hierarchical model where patients with high-CK exhibit the worst prognosis, while M-CLL lacking CK or TP53abs as well as CK with +12,+19 show the longest overall survival. In conclusion, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with 655 chromosomal aberrations emerges as prognostically adverse, independently of other biomarkers. Prospective clinical validation is warranted before finally incorporating high-CK in risk stratification of CLL

Identification of Piecemeal Degranulation and Vesicular Transport of MBP-1 in Liver-Infiltrating Mouse Eosinophils During Acute Experimental Schistosoma mansoni Infection

Eosinophils have been long associated with helminthic infections, although their functions in these diseases remain unclear. During schistosomiasis caused by the trematode Schistosoma mansoni, eosinophils are specifically recruited and migrate to sites of granulomatous responses where they degranulate. However, little is known about the mechanisms of eosinophil secretion during this disease. Here, we investigated the degranulation patterns, including the cellular mechanisms of major basic protein-1 (MBP-1) release, from inflammatory eosinophils in a mouse model of S. mansoni infection (acute phase). Fragments of the liver, a major target organ of this disease, were processed for histologic analyses (whole slide imaging), conventional transmission electron microscopy (TEM), and immunonanogold EM using a pre-embedding approach for precise localization of major basic protein 1 (MBP-1), a typical cationic protein stored pre-synthesized in eosinophil secretory (specific) granules. A well-characterized granulomatous inflammatory response with a high number of infiltrating eosinophils surrounding S. mansoni eggs was observed in the livers of infected mice. Moreover, significant elevations in the levels of plasma Th2 cytokines (IL-4, IL-13, and IL-10) and serum enzymes (alanine aminotransferase and aspartate aminotransferase) reflecting altered liver function were detected in response to the infection. TEM quantitative analyses revealed that while 19.1% of eosinophils were intact, most of them showed distinct degranulation processes: cytolysis (13.0%), classical and/or compound exocytosis identified by granule fusions (1.5%), and mainly piecemeal degranulation (PMD) (66.4%), which is mediated by vesicular trafficking. Immunonanogold EM showed a consistent labeling for MBP-1 associated with secretory granules. Most MBP-1-positive granules had PMD features (79.0 ± 4.8%). MBP-1 was also present extracellularly and on vesicles distributed in the cytoplasm and attached to/surrounding the surface of emptying granules. Our data demonstrated that liver-infiltrating mouse eosinophils are able to degranulate through different secretory processes during acute experimental S. mansoni infections with PMD being the predominant mechanism of eosinophil secretion. This means that a selective secretion of MBP-1 is occurring. Moreover, our study demonstrates, for the first time, a vesicular trafficking of MBP-1 within mouse eosinophils elicited by a helminth infection. Vesicle-mediated secretion of MBP-1 may be relevant for the rapid release of small concentrations of MBP-1 under cell activation

Health care for irregular migrants: pragmatism across Europe. A qualitative study

<p>Abstract</p> <p>Background</p> <p>Health services in Europe face the challenge of delivering care to a heterogeneous group of irregular migrants (IM). There is little empirical evidence on how health professionals cope with this challenge. This study explores the experiences of health professionals providing care to IM in three types of health care service across 16 European countries.</p> <p>Results</p> <p>Semi-structured interviews were conducted with health professionals in 144 primary care services, 48 mental health services, and 48 Accident & Emergency departments (total n = 240). Although legal health care entitlement for IM varies across countries, health professionals reported facing similar issues when caring for IM. These issues include access problems, limited communication, and associated legal complications. Differences in the experiences with IM across the three types of services were also explored. Respondents from Accident & Emergency departments reported less of a difference between the care for IM patients and patients in a regular situation than did respondents from primary care and mental health services. Primary care services and mental health services were more concerned with language barriers than Accident & Emergency departments. Notifying the authorities was an uncommon practice, even in countries where health professionals are required to do this.</p> <p>Conclusions</p> <p>The needs of IM patients and the values of the staff appear to be as important as the national legal framework, with staff in different European countries adopting a similar pragmatic approach to delivering health care to IM. While legislation might help to improve health care for IM, more appropriate organisation and local flexibility are equally important, especially for improving access and care pathways.</p

Frontotemporal dementia and its subtypes: a genome-wide association study

SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with {FTD} and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with {FTD} and 4308 controls), we did separate association analyses for each {FTD} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and {FTD} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p&lt;5 × 10−8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p&lt;5 × 10−8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, \{HLA\} locus (immune system), for rs9268877 (p=1·05 × 10−8; odds ratio=1·204 95% \{CI\} 1·11–1·30), rs9268856 (p=5·51 × 10−9; 0·809 0·76–0·86) and rs1980493 (p value=1·57 × 10−8, 0·775 0·69–0·86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural \{FTD\} subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10−7; 0·814 0·71–0·92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center

Current state of cannabis use, policies, and research across sixteen countries : cross-country comparisons and international perspectives

INTRODUCTION : Varying public views on cannabis use across countries may explain the variation in the prevalence of use, policies, and research in individual countries, and global regulation of cannabis. This paper aims to describe the current state of cannabis use, policies, and research across sixteen countries. METHODS : PubMed and Google Scholar were searched for studies published from 2010 to 2020. Searches were conducted using the relevant country of interest as a search term (e.g., “Iran”), as well as relevant predefined keywords such as “cannabis,” “marijuana,” “hashish,” “bhang “dual diagnosis,” “use,” “addiction,” “prevalence,” “co-morbidity,” “substance use disorder,” “legalization” or “policy” (in English and non-English languages). These keywords were used in multiple combinations to create the search string for studies’ titles and abstracts. Official websites of respective governments and international organizations were also searched in English and non-English languages (using countries national languages) to identify the current state of cannabis use, policies, and research in each of those countries. RESULTS : The main findings were inconsistent and heterogeneous reporting of cannabis use, variation in policies (e.g., legalization), and variation in intervention strategies across the countries reviewed. European countries dominate the cannabis research output indexed on PubMed, in contrast to Asian countries (Thailand, Malaysia, India, Iran, and Nepal). CONCLUSIONS : Although global cannabis regulation is ongoing, the existing heterogeneities across countries in terms of policies and epidemiology can increase the burden of cannabis use disorders disproportionately and unpredictably. There is an urgent need to develop global strategies to address these cross-country barriers to improve early detection, prevention, and interventions for cannabis use and related disorders.The Indian Council of Medical Research.https://www.scielo.br/j/trendsam2023Family Medicin

Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia: findings from the GENetic Frontotemporal dementia Initiative (GENFI) cohort

Abstract Biomarkers that can predict disease progression in individuals with genetic frontotemporal dementia are urgently needed. We aimed to identify whether baseline MRI-based grey and white matter abnormalities are associated with different clinical progression profiles in presymptomatic mutation carriers in the GENetic Frontotemporal dementia Initiative. 387 mutation carriers were included (160 GRN, 160 C9orf72, 67 MAPT), together with 240 non-carrier cognitively normal controls. Cortical and subcortical grey matter volumes were generated using automated parcellation methods on volumetric 3 T T1-weighted MRI scans, while white matter characteristics were estimated using diffusion tensor imaging. Mutation carriers were divided into two disease stages based on their global CDR®+NACC-FTLD score: presymptomatic (0 or 0.5) and fully symptomatic (1 or greater). W-scores in each grey matter volumes and white matter diffusion measures were computed to quantify the degree of abnormality compared to controls for each presymptomatic carrier, adjusting for their age, sex, total intracranial volume, and scanner type. Presymptomatic carriers were classified as “normal” or “abnormal” based on whether their grey matter volume and white matter diffusion measure w-scores were above or below the cut point corresponding to the 10th percentile of the controls. We then compared the change in disease severity between baseline and one year later in both the “normal” and “abnormal” groups within each genetic subtype, as measured by the CDR®+NACC-FTLD sum-of-boxes score and revised Cambridge Behavioural Inventory total score. Overall, presymptomatic carriers with normal regional w-scores at baseline did not progress clinically as much as those with abnormal regional w-scores. Having abnormal grey or white matter measures at baseline was associated with a statistically significant increase in the CDR®+NACC-FTLD of up to 4 points in C9orf72 expansion carriers, and 5 points in the GRN group as well as a statistically significant increase in the revised Cambridge Behavioural Inventory of up to 11 points in MAPT, 10 points in GRN, and 8 points in C9orf72 mutation carriers. Baseline regional brain abnormalities on MRI in presymptomatic mutation carriers are associated with different profiles of clinical progression over time. These results may be helpful to inform stratification of participants in future trials