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排序方式: 共有546条查询结果,搜索用时 31 毫秒
411.
Molecular mechanisms of desiccation tolerance in the resurrection glacial relic Haberlea rhodopensis
Tsanko S. Gechev Maria Benina Toshihiro Obata Takayuki Tohge Neerakkal Sujeeth Ivan Minkov Jacques Hille Mohamed-Ramzi Temanni Andrew S. Marriott Ed Bergström Jane Thomas-Oates Carla Antonio Bernd Mueller-Roeber Jos H. M. Schippers Alisdair R. Fernie Valentina Toneva 《Cellular and molecular life sciences : CMLS》2013,70(4):689-709
412.
EL Heinzen KJ Swoboda Y Hitomi F Gurrieri S Nicole B de Vries FD Tiziano B Fontaine NM Walley S Heavin E Panagiotakaki;European Alternating Hemiplegia of Childhood 《Nature genetics》2012,44(9):1030-1034
Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation in a case of familial AHC. Notably, most AHC cases are caused by one of seven recurrent ATP1A3 mutations, one of which was observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3. 相似文献
413.
Laurie CC Laurie CA Rice K Doheny KF Zelnick LR McHugh CP Ling H Hetrick KN Pugh EW Amos C Wei Q Wang LE Lee JE Barnes KC Hansel NN Mathias R Daley D Beaty TH Scott AF Ruczinski I Scharpf RB Bierut LJ Hartz SM Landi MT Freedman ND Goldin LR Ginsburg D Li J Desch KC Strom SS Blot WJ Signorello LB Ingles SA Chanock SJ Berndt SI Le Marchand L Henderson BE Monroe KR Heit JA de Andrade M Armasu SM Regnier C Lowe WL Hayes MG Marazita ML Feingold E Murray JC Melbye M Feenstra B Kang JH Wiggs JL 《Nature genetics》2012,44(6):642-650
We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18). 相似文献
414.
The cerebrospinal fluid (CSF) has attracted renewed interest as an active signaling milieu that regulates brain development, homeostasis, and disease. Advances in proteomics research have enabled an improved characterization of the CSF from development through adulthood, and key neurogenic signaling pathways that are transmitted via the CSF are now being elucidated. Due to its immediate contact with neural stem cells in the developing and adult brain, the CSF's ability to swiftly distribute signals across vast distances in the central nervous system is opening avenues to novel and exciting therapeutic approaches. In this review, we will discuss the development of the choroid plexus-CSF system, and review the current literature on how the CSF actively regulates mammalian brain development, behavior, and responses to traumatic brain injury. 相似文献
415.
Abreu-Blanco MT Watts JJ Verboon JM Parkhurst SM 《Cellular and molecular life sciences : CMLS》2012,69(15):2469-2483
Wound repair on the cellular and multicellular levels is essential to the survival of complex organisms. In order to avoid further damage, prevent infection, and restore normal function, cells and tissues must rapidly seal and remodel the wounded area. The cytoskeleton is an important component of wound repair in that it is needed for actomyosin contraction, recruitment of repair machineries, and cell migration. Recent use of model systems and high-resolution microscopy has provided new insight into molecular aspects of the cytoskeletal response during wound repair. Here we discuss the role of the cytoskeleton in single-cell, embryonic, and adult repair, as well as the striking resemblance of these processes to normal developmental events and many diseases. 相似文献
416.
417.
Functional interplay between tetraspanins and proteases 总被引:1,自引:1,他引:0
Yáñez-Mó M Gutiérrez-López MD Cabañas C 《Cellular and molecular life sciences : CMLS》2011,68(20):3323-3335
Several recent publications have described examples of physical and functional interations between tetraspanins and specific
membrane proteases belonging to the TM-MMP and α-(ADAMs) and γ-secretases families. Collectively, these examples constitute
an emerging body of evidence supporting the notion that tetraspanin-enriched microdomains (TEMs) represent functional platforms
for the regulation of key cellular processes including the release of surface protein ectodomains ("shedding"), regulated
intramembrane proteolysis ("RIPing") and matrix degradation and assembly. These cellular processes in turn play a crucial
role in an array of physiological and pathological phenomena. Thus, TEMs may represent new therapeutical targets that may
simultaneously affect the proteolytic activity of different enzymes and their substrates. Agonistic or antagonistic antibodies
and blocking soluble peptides corresponding to tetraspanin functional regions may offer new opportunities in the treatment
of pathologies such as chronic inflammation, cancer, or Alzheimer's disease. In this review article, we will discuss all these
aspects of functional regulation of protease activities by tetraspanins. 相似文献
418.
The aberrant epigenetic landscape of a cancer cell is characterized by global genomic hypomethylation, CpG island promoter
hypermethylation of tumor suppressor genes, and changes in histone modification patterns, as well as altered expression profiles
of chromatin-modifying enzymes. Recent advances in the field of epigenetics have revealed that microRNAs’ expression is also
under epigenetic regulation and that certain microRNAs control elements of the epigenetic machinery. The reversibility of
epigenetic marks catalyzed the development of epigenetic-altering drugs. However, a better understanding of the intertwined
relationship between genetics, epigenetics and microRNAs is necessary in order to resolve how gene expression aberrations
that contribute to tumorigenesis can be therapeutically corrected. 相似文献
419.
Xu B Roos JL Dexheimer P Boone B Plummer B Levy S Gogos JA Karayiorgou M 《Nature genetics》2011,43(9):864-868
Despite its high heritability, a large fraction of individuals with schizophrenia do not have a family history of the disease (sporadic cases). Here we examined the possibility that rare de novo protein-altering mutations contribute to the genetic component of schizophrenia by sequencing the exomes of 53 sporadic cases, 22 unaffected controls and their parents. We identified 40 de novo mutations in 27 cases affecting 40 genes, including a potentially disruptive mutation in DGCR2, a gene located in the schizophrenia-predisposing 22q11.2 microdeletion region. A comparison to rare inherited variants indicated that the identified de novo mutations show a large excess of non-synonymous changes in schizophrenia cases, as well as a greater potential to affect protein structure and function. Our analyses suggest a major role for de novo mutations in schizophrenia as well as a large mutational target, which together provide a plausible explanation for the high global incidence and persistence of the disease. 相似文献
420.
Rafnar T Gudbjartsson DF Sulem P Jonasdottir A Sigurdsson A Jonasdottir A Besenbacher S Lundin P Stacey SN Gudmundsson J Magnusson OT le Roux L Orlygsdottir G Helgadottir HT Johannsdottir H Gylfason A Tryggvadottir L Jonasson JG de Juan A Ortega E Ramon-Cajal JM García-Prats MD Mayordomo C Panadero A Rivera F Aben KK van Altena AM Massuger LF Aavikko M Kujala PM Staff S Aaltonen LA Olafsdottir K Bjornsson J Kong A Salvarsdottir A Saemundsson H Olafsson K Benediktsdottir KR Gulcher J Masson G 《Nature genetics》2011,43(11):1104-1107
Ovarian cancer causes more deaths than any other gynecologic malignancy in developed countries. Sixteen million sequence variants, identified through whole-genome sequencing of 457 Icelanders, were imputed to 41,675 Icelanders genotyped using SNP chips, as well as to their relatives. Sequence variants were tested for association with ovarian cancer (N of affected individuals = 656). We discovered a rare (0.41% allelic frequency) frameshift mutation, c.2040_2041insTT, in the BRIP1 (FANCJ) gene that confers an increase in ovarian cancer risk (odds ratio (OR) = 8.13, P = 2.8 × 10(-14)). The mutation was also associated with increased risk of cancer in general and reduced lifespan by 3.6 years. In a Spanish population, another frameshift mutation in BRIP1, c.1702_1703del, was seen in 2 out of 144 subjects with ovarian cancer and 1 out of 1,780 control subjects (P = 0.016). This allele was also associated with breast cancer (seen in 6/927 cases; P = 0.0079). Ovarian tumors from heterozygous carriers of the Icelandic mutation show loss of the wild-type allele, indicating that BRIP1 behaves like a classical tumor suppressor gene in ovarian cancer. 相似文献