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1.
J. Benitez E. Fernandez P. Garcia Ruiz M. Robledo C. Ramos J. Yebenes 《Human genetics》1994,94(5):563-564
Huntington's disease (HD) is a neurodegenerative and hereditary disease characterized by progressive movement disorders and mental and behavioral abnormalities. The HD gene is an expanding and unstable trinucleotide repeat (CAG repeat sequences). We studied 77 individuals from 38 families with HD in an attempt to obtain information for genetic counselling and differential diagnosis. Our results indicate that individuals with more than 40 repeats will be affected by the disease, whereas those with fewer than 30 will be healthy. There can be some overlap between 30 and 40 repeats, and one should be careful when interpreting these results. 相似文献
2.
Roberto de la Herrán Miguel Hermida Juan Andres Rubiolo Jèssica Gómez-Garrido Fernando Cruz Francisca Robles Rafael Navajas-Pérez Andres Blanco Paula Rodriguez Villamayor Dorinda Torres Pablo Sánchez-Quinteiro Daniel Ramirez Maria Esther Rodríguez Alberto Arias-Pérez Ismael Cross Neil Duncan Teresa Martínez-Peña Ana Riaza Adrian Millán M. Cristina De Rosa Davide Pirolli Marta Gut Carmen Bouza Diego Robledo Laureana Rebordinos Tyler Alioto Carmelo Ruíz-Rejón Paulino Martínez 《Molecular ecology resources》2023,23(4):886-904
Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC-FISH. Whole genome resequencing of six males and six females enabled the identification of 41 single nucleotide polymorphism variants in the follicle stimulating hormone receptor (fshr) consistent with an XX/XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. The fshr gene displayed differential expression between male and female gonads from 86 days post-fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y-linked fshr allele, which included 24 nonsynonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X-linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testis. 相似文献
3.
In situ pancreatic DNaseI digestions were used as probes to study the structural organization of facultative and constitutive heterochromatin during both mitotic and meiotic divisions. Three different types of heterochromatic regions from three insect species were chosen for this study. These regions had been previously characterized by in situ treatments with restriction endonucleases (AT and GC rich DNA sequences). Progressive increase in DNaseI concentration (from 10 to 200 ng/ml) or in incubation time (from 5 to 30 min) revealed a specific pattern of sequential digestion of the constitutive heterochromatic regions, the centromeric ones (AT-rich DNA) being the most resistant to DNaseI action. The interstitial C-bands (with AT or GC-rich DNA) were more sensitive to DNaseI, and the band 4.4 from Baetica ustalata was the most resistant of the non-centromeric bands. Similar results were obtained during meiosis, but increased accessibility to DNAseI was observed compared to mitosis. DNA methylation in the non-centromeric band 4.4 of B. ustulata could be responsible for its differential digestion with respect to the remaining intercalar heterochromatin. Facultatively heterochromatic regions (X chromosomes) were found to exhibit a differential response to DNaseI attack from mitosis to meiosis. While they behaved as cuchromatin during mitosis, they were the most resistant together with centromeric heterochromatin regions, during metaphase I and II. The different responses to digestion of the X chromosome and X-derived regions between somatic and meiotic divisions are probably a consequence of the changes in the organization of this chromosome during the facultative heterochromatinization process. 相似文献
4.
Ana B. Fagundo Rafael de la Torre Susana Jiménez-Murcia Zaida Agüera Antoni Pastor Felipe F. Casanueva Roser Granero Rosa Ba?os Cristina Botella Amparo del Pino-Gutierrez Jose M. Fernández-Real Jose C. Fernández-García Gema Frühbeck Javier Gómez-Ambrosi José M. Menchón Inés Moragrega Roser Rodríguez Salomé Tárrega Francisco J. Tinahones Fernando Fernández-Aranda 《PloS one》2013,8(6)
Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches. 相似文献
5.
Cintia Roodveldt Adahir Labrador-Garrido Elena Gonzalez-Rey Christian C. Lachaud Tim Guilliams Rafael Fernandez-Montesinos Alicia Benitez-Rondan Gema Robledo Abdelkrim Hmadcha Mario Delgado Christopher M. Dobson David Pozo 《PloS one》2013,8(11)
In recent years, it has become accepted that α-synuclein (αSyn) has a key role in the microglia-mediated neuroinflammation, which accompanies the development of Parkinson’s disease and other related disorders, such as Dementia with Lewy Bodies and Alzheimer’s disease. Nevertheless, the cellular and molecular mechanisms underlying its pathological actions, especially in the sporadic forms of the diseases, are not completely understood. Intriguingly, several epidemiological and animal model studies have revealed a link between certain microbial infections and the onset or progression of sporadic forms of these neurodegenerative disorders. In this work, we have characterized the effect of toll-like receptor (TLR) stimulation on primary murine microglial cultures and analysed the impact of priming cells with extracellular wild-type (Wt) αSyn on the subsequent TLR stimulation of cells with a set of TLR ligands. By assaying key interleukins and chemokines we report that specific stimuli, in particular Pam3Csk4 (Pam3) and single-stranded RNA40 (ssRNA), can differentially affect the TLR2/1- and TLR7-mediated responses of microglia when pre-conditioned with αSyn by augmenting IL-6, MCP-1/CCL2 or IP-10/CXCL10 secretion levels. Furthermore, we report a skewing of αSyn-primed microglia stimulated with ssRNA (TLR7) or Pam3 (TLR2/1) towards intermediate but at the same time differential, M1/M2 phenotypes. Finally, we show that the levels and intracellular location of activated caspase-3 protein change significantly in αSyn-primed microglia after stimulation with these particular TLR agonists. Overall, we report a remarkable impact of non-aggregated αSyn pre-sensitization of microglia on TLR-mediated immunity, a phenomenon that could contribute to triggering the onset of sporadic α-synuclein-related neuropathologies. 相似文献
6.
Abdul Malik S. A. Bazire A. Gamboa-Muñoz A. Bedoux G. Robledo D. García-Maldonado J. Q. Bourgougnon N. 《Microbiology》2020,89(6):778-788
Microbiology - Macroalgae host a dense bacterial epibiome forming surface biofilms, which act as a biological defense by protecting the surface from macrofoulers. During experimental cultivation of... 相似文献
7.
Borja L. Holgado Laura Martínez-Muñoz Juan Antonio Sánchez-Alcañiz Pilar Lucas Vicente Pérez-García Gema Pérez José Miguel Rodríguez-Frade Marta Nieto Óscar Marín Yolanda R. Carrasco Ana C. Carrera Manuel Álvarez-Dolado Mario Mellado 《Molecular neurobiology》2013,48(1):217-231
The migratory route of neural progenitor/precursor cells (NPC) has a central role in central nervous system development. Although the role of the chemokine CXCL12 in NPC migration has been described, the intracellular signaling cascade involved remains largely unclear. Here we studied the molecular mechanisms that promote murine NPC migration in response to CXCL12, in vitro and ex vivo. Migration was highly dependent on signaling by the CXCL12 receptor, CXCR4. Although the JAK/STAT pathway was activated following CXCL12 stimulation of NPC, JAK activity was not necessary for NPC migration in vitro. Whereas CXCL12 activated the PI3K catalytic subunits p110α and p110β in NPC, only p110β participated in CXCL12-mediated NPC migration. Ex vivo experiments using organotypic slice cultures showed that p110β blockade impaired NPC exit from the medial ganglionic eminence. In vivo experiments using in utero electroporation nonetheless showed that p110β is dispensable for radial migration of pyramidal neurons. We conclude that PI3K p110β is activated in NPC in response to CXCL12, and its activity is necessary for immature interneuron migration to the cerebral cortex. 相似文献
8.
Nerea Rebolleda Ignacio Losada-Fernandez Gema Perez-Chacon Raquel Castejon Silvia Rosado Marta Morado Maria Teresa Vallejo-Cremades Andrea Martinez Juan A. Vargas-Nu?ez Paloma Perez-Aciego 《PloS one》2016,11(4)
B-cell chronic lymphocytic leukemia (CLL) remains an incurable disease, and despite the improvement achieved by therapeutic regimes developed over the last years still a subset of patients face a rather poor prognosis and will eventually relapse and become refractory to therapy. The natural rotenoid deguelin has been shown to induce apoptosis in several cancer cells and cell lines, including primary human CLL cells, and to act as a chemopreventive agent in animal models of induced carcinogenesis. In this work, we show that deguelin induces apoptosis in vitro in primary human CLL cells and in CLL-like cells from the New Zealand Black (NZB) mouse strain. In both of them, deguelin dowregulates AKT, NFκB and several downstream antiapoptotic proteins (XIAP, cIAP, BCL2, BCL-XL and survivin), activating the mitochondrial pathway of apoptosis. Moreover, deguelin inhibits stromal cell-mediated c-Myc upregulation and resistance to fludarabine, increasing fludarabine induced DNA damage. We further show that deguelin has activity in vivo against NZB CLL-like cells in an experimental model of CLL in young NZB mice transplanted with spleen cells from aged NZB mice with lymphoproliferation. Moreover, the combination of deguelin and fludarabine in this model prolonged the survival of transplanted mice at doses of both compounds that were ineffective when administered individually. These results suggest deguelin could have potential for the treatment of human CLL. 相似文献
9.
Pedro Lax Gema Esquiva Lorena Fuentes-Broto Francisco Segura Ana Sánchez-Cano Nicolás Cuenca 《Chronobiology international》2016,33(4):374-391
The melanopsin system consists of intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (mRGCs). These mRGCs mediate several non-image-forming visual functions, including light entrainment of circadian rhythms. Here we evaluate age-related alterations of the melanopsin system and circadian rhythms in P23H line 1 (P23H-1) rats, a rodent model of retinitis pigmentosa (RP). In homozygous P23H-1 rats and wild-type control rats from the same genetic background (Sprague–Dawley), body temperature and locomotor activity were continuously monitored at 10-min intervals for 7 days, once every 4–5 weeks, between 2 and 24 months of age, using a telemetry transmitter. The distribution and number of mRGCs were assessed in control rats at 12, 18, and 24 months of age and in P23H-1 rats aged 12, 18, 24, and 30 months by immunostaining whole-mount retinas with antibodies against melanopsin. The mean density of mRGCs in control rats showed no significant variations when evaluated at 12 and 18 months of age, and fell by approximately 56% between 18 and 24 months of age. Meanwhile, a significant decrease in the mean number of mRGCs was found in 18-month-old P23H-1 rats as compared to 18-month-old control rats (81% decrease). Parametric and non-parametric analyses of the records showed a gradual age-dependent weakening of body temperature and locomotor activity circadian rhythms robustness in both control and P23H-1 rats from 2 to 24 months of age. However, body temperature and locomotor activity circadian patterns were less robust throughout the experiment in P23H-1 as compared to control rats, with lower amplitude, weaker coupling strength to environmental zeitgebers and higher fragmentation of the rhythms. The present study shows that the degeneration of photoreceptors and inner retinal neurons, characteristic of RP, has age-related degenerative effects on the melanopsin system and is associated with weaker circadian patterns. 相似文献
10.
Juan Antonio Surez‐Cuenca Rogelio Robledo‐Nolasco Marco Antonio Alcntara‐Melndez Luis Javier Díaz Hernndez Eduardo Vera‐Gmez Alejandro Hernndez‐Patricio Karla Susana Snchez‐Díaz Juan Ariel Buendía‐Gutirrez Alejandra Contreras‐Ramos Atzin Su Ruíz‐Hernndez Rebeca Prez‐Cabeza de Vaca Paul Mondragn‐Tern 《Journal of cellular and molecular medicine》2019,23(7):4844-4849