共查询到20条相似文献,搜索用时 15 毫秒
1.
P. N. Alexandrov M. E. Percy Walter J. Lukiw 《Cellular and molecular neurobiology》2018,38(3):769-774
Down’s syndrome (DS; also known as trisomy 21; T21) is caused by a triplication of all or part of human chromosome 21 (chr21). DS is the most common genetic cause of intellectual disability attributable to a naturally-occurring imbalance in gene dosage. DS incurs huge medical, healthcare, and socioeconomic costs, and there are as yet no effective treatments for this incapacitating human neurogenetic disorder. There is a remarkably wide variability in the ‘phenotypic spectrum’ associated with DS; the progression of symptoms and the age of DS onset fluctuate, and there is further variability in the biophysical nature of the chr21 duplication. Besides the cognitive disruptions and dementia in DS patients other serious health problems such as atherosclerosis, altered lipogenesis, Alzheimer’s disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease), autoimmune disease, various cancers including lymphoma, leukemia, glioma and glioblastoma, status epilepticus, congenital heart disease, hypotonia, manic depression, prostate cancer, Usher syndrome, motor disorders, Hirschsprung disease, and various physical anomalies such as early aging occur at elevated frequencies, and all are part of the DS ‘phenotypic spectrum.’ This communication will review the genetic link between these fore-mentioned diseases and a small group of just five stress-associated microRNAs (miRNAs)—that include let-7c, miRNA-99a, miRNA-125b, miRNA-155, and miRNA-802—encoded and clustered on the long arm of human chr21 and spanning the chr21q21.1-chr21q21.3 region. 相似文献
2.
Grabeklis Andrey R. Skalny Anatoly V. Skalnaya Anastasia A. Zhegalova Irina V. Notova Svetlana V. Mazaletskaya Anna L. Skalnaya Margarita G. Tinkov Alexey A. 《Biological trace element research》2019,187(1):230-242
Biological Trace Element Research - Chronic exposure to lead causes disruption to energy production mechanisms and tissue damage, in particular through its binding to thiol groups and competition... 相似文献
3.
Steffes DM 《Journal of the history of biology》2007,40(2):327-361
Sewall Wright first encountered the complex systems characteristic of gene combinations while a graduate student at Harvard’s
Bussey Institute from 1912 to 1915. In Mendelian breeding experiments, Wright observed a hierarchical dependence of the organism’s
phenotype on dynamic networks of genetic interaction and organization. An animal’s physical traits, and thus its autonomy
from surrounding environmental constraints, depended greatly on how genes behaved in certain combinations. Wright recognized
that while genes are the material determinants of the animal phenotype, operating with great regularity, the special nature
of genetic systems contributes to the animal phenotype a degree of spontaneity and novelty, creating unpredictable trait variations by virtue
of gene interactions. As a result of his experimentation, as well as his keen interest in the philosophical literature of
his day, Wright was inspired to see genetic systems as conscious, living organisms in their own right. Moreover, he decided
that since genetic systems maintain ordered stability and cause unpredictable novelty in their organic wholes (the animal phenotype), it would be necessary for biologists to integrate
techniques for studying causally ordered phenomena (experimental method) and chance phenomena (correlation method). From 1914
to 1921 Wright developed his “method of path coefficient” (or “path analysis”), a new procedure drawing from both laboratory
experimentation and statistical correlation in order to analyze the relative influence of specific genetic interactions on
phenotype variation. In this paper I aim to show how Wright’s philosophy for understanding complex genetic systems (panpsychic
organicism) logically motivated his 1914–1921 design of path analysis. 相似文献
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Abid Oueslati Blaise Lovisa John Perrin Georges Wagnières Hubert van den Bergh Yanik Tardy Hilal A. Lashuel 《PloS one》2015,10(10)
Converging lines of evidence indicate that near-infrared light treatment, also known as photobiomodulation (PBM), may exert beneficial effects and protect against cellular toxicity and degeneration in several animal models of human pathologies, including neurodegenerative disorders. In the present study, we report that chronic PMB treatment mitigates dopaminergic loss induced by unilateral overexpression of human α-synuclein (α-syn) in the substantia nigra of an AAV-based rat genetic model of Parkinson’s disease (PD). In this model, daily exposure of both sides of the rat’s head to 808-nm near-infrared light for 28 consecutive days alleviated α-syn-induced motor impairment, as assessed using the cylinder test. This treatment also significantly reduced dopaminergic neuronal loss in the injected substantia nigra and preserved dopaminergic fibers in the ipsilateral striatum. These beneficial effects were sustained for at least 6 weeks after discontinuing the treatment. Together, our data point to PBM as a possible therapeutic strategy for the treatment of PD and other related synucleinopathies. 相似文献
6.
Angiogenesis has been proposed to play a role in the inflammation observed in Sjögren’s Syndrome (SS). However, no studies have validated the degree of angiogenesis in salivary glands with SS. Therefore, the goal of this study was to determine the presence and localization of angiogenesis and lymphangiogenesis in salivary glands with SS. We used frozen tissue sections from human minor salivary glands (hMSG) with and without SS in our analyses. To investigate signs of angiogenesis, hMSG tissue lysates were used to detect levels of the pro-angiogenic protein vascular endothelial growth factor (VEGF) by western blot analyses. Additionally, we labeled blood vessels using antibodies specific to platelet endothelial cell adhesion molecule-1 (PECAM-1) and von Willebrand Factor (vWF) to determine blood vessel organization and volume fraction using fluorescence microscopy. Lymphatic vessel organization and volume fraction were determined using antibodies specific to lymphatic vessel endothelial hyaluronan receptor (LYVE-1). Our results suggest that expression levels of VEGF are decreased in hMSG with SS as compared with controls. Interestingly, there were no significant differences in blood or lymphatic vessel organization or volume fraction between hMSG with and without SS, suggesting that angiogenesis and lymphangiogenesis have little impact on the progression of SS. 相似文献
7.
Herbert J. Harwick George M. Kalmanson Lucien B. Guze 《The Western journal of medicine》1972,116(5):1-7
The mycoplasmas (formerly called pleuropneumonia-like organisms, or pplo) are a group of pleomorphic micro-organisms characterized by lack of cell wall and ability to form colonies on agar resembling tiny fried eggs. They have been recognized as pathogens of lower mammals since 1898. Of the more than 40 known veterinary species, many are pathogens, commonly causing pneumonia, arthritis or arteritis. Of the mycoplasmas found in man, Mycoplasma pneumoniae is the only well established human pathogen. It is responsible for a variety of respiratory syndromes, of which the most frequently recognized is cold agglutinin-positive atypical pneumonia. Hematologic, neurologic and dermatologic complications of this infection have been noted. M. hominis has been implicated as a causative factor in various febrile complications of pregnancy, such as septic abortion and amnionitis. T-strain mycoplasmas are ubiquitous in the human genitourinary tract, but attempts to link their presence to disease have thus far been unsuccessful. Mycoplasmas also have been associated with neoplastic disease and with rheumatoid arthritis. The validity of these latter findings is unclear, and additional study is needed. 相似文献
9.
Uspenskaya N. Y. Akopov S. B. Snezhkov E. V. Sverdlov E. D. 《Russian Journal of Genetics》2019,55(5):523-534
Russian Journal of Genetics - The emergence of genetic diseases and evolutionary processes are associated with the flow of genetic information from one generation to another, in which genetic... 相似文献
10.
《Endocrine practice》2005,11(6):382-384
ObjectiveTo report a case of ganglioneuroma masquerading as an incidental adrenal mass in an adult patient with Turner’s syndrome.MethodsWe present the clinical, laboratory, radiologic, and pathologic findings in this patient.ResultsA 31-year-old woman with Turner’s syndrome who had previously been treated with growth hormone replacement had an incidentally discovered mass, apparently arising from the left adrenal gland. The mass was “silent” clinically and biochemically, but imaging characteristics were not reassuring for a benign cortical adenoma. Because of uncertainty regarding the nature of the mass, it was removed laparoscopically; during this procedure, it was noted to be intimately associated with, but anatomically distinct from, the left adrenal gland. The pathology report confirmed the presence of a benign ganglioneuroma.Conclusion: Although ganglioneuroma has previously been noted to be associated with Turner’s syndrome (especially in pediatric patients), to the best of our knowledge this is the first report of a ganglioneuroma manifesting as an incidental adrenal mass in an adult patient with Turner’s syndrome. (Endocr Pract. 2005;11:382-384) 相似文献
11.
Human cells typically consist of 23 pairs of chromosomes. Telomeres are repetitive sequences of DNA located at the ends of chromosomes. During cell replication, a number of basepairs are lost from the end of the chromosome and this shortening restricts the number of divisions that a cell can complete before it becomes senescent, or non-replicative. In this paper, we use Monte Carlo simulations to form a stochastic model of telomere shortening to investigate how telomere shortening affects normal aging. Using this model, we study various hypotheses for the way in which shortening occurs by comparing their impact on aging at the chromosome and cell levels. We consider different types of length-dependent loss and replication probabilities to describe these processes. After analyzing a simple model for a population of independent chromosomes, we simulate a population of cells in which each cell has 46 chromosomes and the shortest telomere governs the replicative potential of the cell. We generalize these simulations to Werner’s syndrome, a condition in which large sections of DNA are removed during cell division and, amongst other conditions, results in rapid aging. Since the mechanisms governing the loss of additional basepairs are not known, we use our model to simulate a variety of possible forms for the rate at which additional telomeres are lost per replication and several expressions for how the probability of cell division depends on telomere length. As well as the evolution of the mean telomere length, we consider the standard deviation and the shape of the distribution. We compare our results with a variety of data from the literature, covering both experimental data and previous models. We find good agreement for the evolution of telomere length when plotted against population doubling. 相似文献
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Although it is an essential aspect of one of the most common forms of entertainment, psychologists know almost nothing about how children understand the act of portraying a character in a realistic manner—realistic acting. Do children possess the sort of meta-theory of acting that adults possess? In two studies we find that, unlike adults, children between the ages of 3–5 do not think that a realistic actor is better at portraying a characteristic than a nonrealistic actor, nor do they prefer one to the other. As they develop, they come to understand that realistic acting is different from nonrealistic acting, but unlike adults, children think that a nonrealistic, pretense-like portrayal is more difficult to achieve than a realistic representation of an emotional or physical state. These findings show that children’s metarepresentational understanding of acting is relatively immature at age 5, and that their understanding of this specific domain of pretense lags behind their understanding of pretense in general. 相似文献
14.
《Cell cycle (Georgetown, Tex.)》2013,12(4):268-272
Patients with Bloom’s syndrome (BS) show a strong genetic instability and a predisposition to all types of cancer. Here, we report that the Bloom’s syndrome protein (BLM) is cleaved in response to hydroxyurea (HU)- or UVC-induced apoptosis. The appearance and solubility of BLM proteolytic products differed according to whether proteolysis occurred in response to HU or UVC. One BS cell line homozygous for a null mutation in BLM was resistant to both UVC- and HU-induced apoptosis, while another one expressing a mutated BLM protein was resistant to HU-induced apoptosis but displayed normal sensitivity to UVC. Thus, UVC and HU appear to induce apoptosis through distinct pathways. Key Words:Bloom’s syndrome, Apoptosis, Hydroxyurea, Ultraviolet C radiation, RecQ helicase 相似文献
15.
Two fatty acid binding proteins, MvFABPa and MvFABPb were identified in the parasite Mesocestoides vogae (Platyhelmithes, Cestoda). Fatty acid binding proteins are small intracellular proteins whose members exhibit great diversity. Proteins of this family have been identified in many organisms, of which Platyhelminthes are among the most primitive. These proteins have particular relevance in flatworms since de novo synthesis of fatty acids is absent. Fatty acids should be captured from the media needing an efficient transport system to uptake and distribute these molecules. While HLBPs could be involved in the shuttle of fatty acids to the surrounding host tissues and convey them into the parasite, FABPs could be responsible for the intracellular trafficking. In an effort to understand the role of MvFABPs in fatty acid transport of M. vogae larvae, we analysed the intracellular localization of both MvFABPs and the co-localization with in vivo uptake of fatty acid analogue BODIPY FL C16. Immunohistochemical studies on larvae sections using specific antibodies, showed a diffuse cytoplasmic distribution of each protein with some expression in nuclei and mitochondria. MvFABPs distribution was confirmed by mass spectrometry identification from 2D-electrophoresis of larvae subcellular fractions. This work is the first report showing intracellular distribution of MvFABPs as well as the co-localization of these proteins with the BODIPY FL C16 incorporated from the media. Our results suggest that fatty acid binding proteins could target fatty acids to cellular compartments including nuclei. In this sense, M. vogae FABPs could participate in several cellular processes fulfilling most of the functions attributed to vertebrate’s counterparts. 相似文献
16.
Catherine Labbé Kotaro Ogaki Oswaldo Lorenzo-Betancor Minerva M. Carrasquillo Michael G. Heckman Allan McCarthy Alexandra I. Soto-Ortolaza Ronald L. Walton Timothy Lynch Joanna Siuda Grzegorz Opala Anna Krygowska-Wajs Maria Barcikowska Krzysztof Czyzewski Dennis W. Dickson Ryan J. Uitti Zbigniew K. Wszolek Owen A. Ross 《PloS one》2015,10(6)
Genome-wide association studies (GWAS) in Parkinson’s disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11–1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD. 相似文献
17.
《PloS one》2016,11(4)
We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1. Six deletions with plausible cis-regulatory effects were identified: five that were 3ʹ (telomeric) to PAX6 and one within a gene desert 5ʹ (telomeric) to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p.Leu101Pro). No intragenic mutations were detected in PITX2. FISH mapping in an individual with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed disruption of a gene at each breakpoint: ARHGAP6 on the X chromosome and PHF21A on chromosome 11. In the other individuals with Gillespie syndrome no mutations were identified in either of these genes, or in HCCS which lies close to the Xp breakpoint. Disruption of PHF21A has previously been implicated in the causation of intellectual disability (but not aniridia). Plausibly causative mutations were identified in 15 out of 42 individuals (12/32 aniridia; 3/11 Gillespie syndrome). Fourteen of these mutations presented in the known aniridia genes; PAX6, FOXC1 and PITX2. The large number of individuals in the cohort with no mutation identified suggests greater locus heterogeneity may exist in both isolated and syndromic aniridia than was previously appreciated. 相似文献
18.
Species often exhibit different levels of genetic structuring correlated to their environment. However, understanding how environmental heterogeneity influences genetic variation is difficult because the effects of gene flow, drift and selection are confounded. We investigated the genetic variation and its ecological correlates in an endemic and critically endangered stream breeding mountain newt, Neurergus kaiseri, within its entire range in southwestern Iran. We identified two geographic regions based on phylogenetic relationships using Bayesian inference and maximum likelihood of 779 bp mtDNA (D-loop) in 111 individuals from ten of twelve known breeding populations. This analysis revealed a clear divergence between northern populations, located in more humid habitats at higher elevation, and southern populations, from drier habitats at lower elevations regions. From seven haplotypes found in these populations none was shared between the two regions. Analysis of molecular variance (AMOVA) of N. kaiseri indicates that 94.03% of sequence variation is distributed among newt populations and 5.97% within them. Moreover, a high degree of genetic subdivision, mainly attributable to the existence of significant variance among the two regions is shown (θCT = 0.94, P = 0.002). The positive and significant correlation between geographic and genetic distances (r = 0.61, P = 0.002) following controlling for environmental distance suggests an important influence of geographic divergence of the sites in shaping the genetic variation and may provide tools for a possible conservation based prioritization policy for the endangered species. 相似文献
19.
Yih-Ru Wu Kuo-Hsuan Chang Wen-Teng Chang Ya-Chin Hsiao Hsuan-Chu Hsu Pei-Ru Jiang Yi-Chun Chen Chih-Ying Chao Yi-Chung Chang Bo-Hsun Lee Fen-Ju Hu Wan-Ling Chen Guey-Jen Lee-Chen Chiung-Mei Chen 《PloS one》2013,8(12)
Genetic variants of leucine-rich repeat kinase 2 (LRRK2) were reported to alter the risk for Parkinson’s disease (PD). However, the genetic spectrum of LRRK2 variants has not been clearly disclosed yet in Taiwanese population. Herein, we sequenced LRRK2 coding region in 70 Taiwanese early onset PD patients (age at onset ≤ 50), and found six amino acid-changing single nucleotide polymorphisms (SNPs, N551K, R1398H, R1628P, S1647T, G2385R and M2397T), one reported (R1441H) and 2 novel missense (R767H and S885N) mutations. We examined the frequency of identified LRRK2 variants by genotyping 573 Taiwanese patients with PD and 503 age-matched control subjects. The results showed that PD patients demonstrated a higher frequency of G2385R A allele (4.6%) than control subjects (2.1%; odds ratio = 2.27, 95% confidence interval: 1.38–3.88, P = 0.0017). Fewer PD patients (27.7%) carried the 1647T-2397T haplotype as compared with the control subjects (33.0%; odds ratio = 0.80, 95% confidence interval: 0.65–0.97, P = 0.0215). However, the frequency of 1647T-2385R-2397T haplotype (4.3%) in PD patients was still higher than in control subjects (1.9%, odds ratio: 2.15, 95% confidence interval: 1.27–3.78, P = 0.0058). While no additional subject was found to carry R767H and R1441H, one more patient was observed to carry the S885N variant. Our results indicate a robust risk association regarding G2385R and a new possible protective haplotype (1647T-2397T). Gene-environmental interaction and a larger cohort study are warranted to validate our findings. Additionally, two new missense mutations (R767H and S885N) regarding LRRK2 in PD patients were identified. Functional studies are needed to elucidate the effects of these LRRK2 variants on protein function. 相似文献
20.
Erin N Smith Kristen Jepsen Angelo D Arias Peter J Shepard Christina D Chambers Kelly A Frazer 《Genome biology》2014,15(2):1-7