2,146 research outputs found
Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients
Background: Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic
kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated.
Methods: We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D ,75 nmol/L. Brachial
artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks.
Results: Clinical characteristics of 26 patients were: age 50614 (mean61SD) years, eGFR 41611 ml/min/1.73 m2, males
73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43616
to 84629 nmol/L, p,0.001 and 2.3760.09 to 2.4260.09 mmol/L; p = 0.004, respectively) and parathyroid hormone
decreased (10.868.6 to 7.464.4; p = 0.001). FMD improved from 3.163.3% to 6.163.7%, p = 0.001. Endothelial biomarker
concentrations decreased: E-Selectin from 566662123 to 525662058 pg/mL; p = 0.032, ICAM-1, 3.4560.01 to
3.1061.04 ng/mL; p = 0.038 and VCAM-1, 54633 to 42633 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand
factor and Fibroblast Growth Factor-23, remained unchanged.
Conclusion: This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23.
Trial Registration: ClinicalTrials.gov NCT0200571
Spanish medical students’ attitudes and views towards Mental Health and Psychiatry: a multicentric cross-sectional study.
Objective The aim of this study is to investigate the attitudes
towards mental illness and psychiatry among fifth year
Spanish medical students.
Methods The study included 171 students from three medical
schools located in different areas of Spain: Cádiz; UCA (n=
113), Madrid; San Pablo-CEU (n=22), and Barcelona; UAB
(n=36). They responded, prior to their undergraduate medical
course in psychiatry, to the AMI questionnaire to measure the
attitudes towards mental illness and to Balon’s adapted questionnaire
to investigate their view towards psychiatry.
Results The students (93.4 %) had a positive attitude towards
mental illness (AMI). Attitudes towards psychiatry were fairly
positive with a few negative views, specifically regarding the
role of psychiatrists (items 11 and 13) and the prestige of the
specialty (item 16). There were some statistically significant
differences between the three medical schools in the perception
of psychiatry as a medical discipline. A better attitude
towards mental illness was associated with a better view of the
overall merits of psychiatry.
Conclusions Findings suggest that Spanish medical students
do not have a negative attitude towards mental illness and they
have a good perception of psychiatry, although there are still
some misconceptions about this specialty. These student’s
attitudes could favor an appropriate management of patients
suffering from mental illness
LRRK2 is a negative regulator of <em>Mycobacterium tuberculosis</em> phagosome maturation in macrophages
\ua9 2018 EMBO. Mutations in the leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson\u27s disease, chronic inflammation and mycobacterial infections. Although there is evidence supporting the idea that LRRK2 has an immune function, the cellular function of this kinase is still largely unknown. By using genetic, pharmacological and proteomics approaches, we show that LRRK2 kinase activity negatively regulates phagosome maturation via the recruitment of the Class III phosphatidylinositol-3 kinase complex and Rubicon to the phagosome in macrophages. Moreover, inhibition of LRRK2 kinase activity in mouse and human macrophages enhanced Mycobacterium tuberculosis phagosome maturation and mycobacterial control independently of autophagy. In vivo, LRRK2 deficiency in mice resulted in a significant decrease in M. tuberculosis burdens early during the infection. Collectively, our findings provide a molecular mechanism explaining genetic evidence linking LRRK2 to mycobacterial diseases and establish an LRRK2-dependent cellular pathway that controls M. tuberculosis replication by regulating phagosome maturation
Small RNA Profile in Moso Bamboo Root and Leaf Obtained by High Definition Adapters
Moso bamboo (Phyllostachy heterocycla cv. pubescens L.) is an economically important fast-growing tree. In order to gain better understanding of gene expression regulation in this important species we used next generation sequencing to profile small RNAs in leaf and roots of young seedlings. Since standard kits to produce cDNA of small RNAs are biased for certain small RNAs, we used High Definition adapters that reduce ligation bias. We identified and experimentally validated five new microRNAs and a few other small non-coding RNAs that were not microRNAs. The biological implication of microRNA expression levels and targets of microRNAs are discussed
Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.
New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved
The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice
<p>Abstract</p> <p>Background</p> <p>Ets transcription factors have been widely implicated in the control of tumorigenesis, with most studies suggesting tumor-promoting roles. However, few studies have examined Ets tumorigenesis-modifying functions <it>in vivo </it>using model genetic systems.</p> <p>Methods</p> <p>Using mice expressing a previously characterized Ets dominant repressor transgene in the intestinal epithelium (Villin-En/Erm), we examined the consequences of blocking endogenous Ets-mediated transcriptional activation on tumorigenesis in the Apc<sup>Min </sup>model of intestinal carcinoma.</p> <p>Results</p> <p>En/Erm expression in the intestine, at levels not associated with overt crypt-villus dysmorphogenesis, results in a marked increase in tumor number in Apc<sup>Min </sup>animals. Moreover, when examined histologically, tumors from En/Erm-expressing animals show a trend toward greater stromal invasiveness. Detailed analysis of crypt-villus homeostasis in these En/Erm transgenic animals suggests increased epithelial turnover as one possible mechanism for the enhanced tumorigenesis.</p> <p>Conclusion</p> <p>Our findings provide <it>in vivo </it>evidence for a tumor-restricting function of endogenous Ets factors in the intestinal epithelium.</p
Sexually dimorphic gene expression in bovine conceptuses at the initiation of implantation
In cattle, maternal recognition of pregnancy occurs on Day 16 via secretion of interferon tau (IFNT) by the conceptus. The endometrium can distinguish between embryos with different developmental competencies. In eutherian mammals, X-chromosome inactivation (XCI) is required to ensure an equal transcriptional level of most X-linked genes for both male and female embryos in adult tissues, but this process is markedly different in cattle than mice. We examined how sexual dimorphism affected conceptus transcript abundance and amino acid composition as well as the endometrial transcriptome during the peri-implantation period of pregnancy. Of the 5132 genes that were differentially expressed on Day 19 in male compared to female conceptuses, 2.7% were located on the X-chromosome. Concentrations of specific amino acids were higher in the uterine luminal fluid with male compared to female conceptuses, while female conceptuses had higher transcript abundance of specific amino acid transporters (SLC6A19 and SLC1A35). Of note, the endometrial transcriptome was not different in cattle gestating a male or a female conceptus. These data support the hypothesis that, far from being a blastocyst specific phenomenon, XCI is incomplete before and during implantation in cattle. Despite differences in transcript abundance and amino acid utilization in male versus female conceptuses, the sex of the conceptus itself does not elicit a different transcriptomic response in the endometrium
The Genomic Signature of Crop-Wild Introgression in Maize
The evolutionary significance of hybridization and subsequent introgression
has long been appreciated, but evaluation of the genome-wide effects of these
phenomena has only recently become possible. Crop-wild study systems represent
ideal opportunities to examine evolution through hybridization. For example,
maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter,
mexicana) are known to hybridize in the fields of highland Mexico. Despite
widespread evidence of gene flow, maize and mexicana maintain distinct
morphologies and have done so in sympatry for thousands of years. Neither the
genomic extent nor the evolutionary importance of introgression between these
taxa is understood. In this study we assessed patterns of genome-wide
introgression based on 39,029 single nucleotide polymorphisms genotyped in 189
individuals from nine sympatric maize-mexicana populations and reference
allopatric populations. While portions of the maize and mexicana genomes were
particularly resistant to introgression (notably near known
cross-incompatibility and domestication loci), we detected widespread evidence
for introgression in both directions of gene flow. Through further
characterization of these regions and preliminary growth chamber experiments,
we found evidence suggestive of the incorporation of adaptive mexicana alleles
into maize during its expansion to the highlands of central Mexico. In
contrast, very little evidence was found for adaptive introgression from maize
to mexicana. The methods we have applied here can be replicated widely, and
such analyses have the potential to greatly informing our understanding of
evolution through introgressive hybridization. Crop species, due to their
exceptional genomic resources and frequent histories of spread into sympatry
with relatives, should be particularly influential in these studies
Effect of promoter architecture on the cell-to-cell variability in gene expression
According to recent experimental evidence, the architecture of a promoter,
defined as the number, strength and regulatory role of the operators that
control the promoter, plays a major role in determining the level of
cell-to-cell variability in gene expression. These quantitative experiments
call for a corresponding modeling effort that addresses the question of how
changes in promoter architecture affect noise in gene expression in a
systematic rather than case-by-case fashion. In this article, we make such a
systematic investigation, based on a simple microscopic model of gene
regulation that incorporates stochastic effects. In particular, we show how
operator strength and operator multiplicity affect this variability. We examine
different modes of transcription factor binding to complex promoters
(cooperative, independent, simultaneous) and how each of these affects the
level of variability in transcription product from cell-to-cell. We propose
that direct comparison between in vivo single-cell experiments and theoretical
predictions for the moments of the probability distribution of mRNA number per
cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte
Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK
The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin
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