排序方式: 共有13条查询结果,搜索用时 15 毫秒
1.
Magda Whitrow 《Annals of science》2013,70(6):585-587
R. P. de Lamanon was trained in theology and philosophy, but he chose the career of a self-taught geologist/naturalist, later adding experimental physics to his skills. Recommended by Condorcet, Secretary to the Académie Royale des Sciences, for the post of ‘Naturaliste’ on La Pérouse's expedition, he carried out delicate measurements at sea requested by the Académie and made two important discoveries: the barometric tide at the equator, and the variation of magnetic intensity with latitude. Killed by natives of Samoa in 1787, his reports were long delayed in publication, inadequately presented, and some even lost. Except for brief recognition by von Humboldt many years later, Lamanon's pioneering measurements have been largely ignored or forgotten. This paper revives his memory. 相似文献
2.
The breast cancer tumor-suppressor gene, BRCA1, encodes a protein with a BRCT domain-a motif that is found in many proteins that are implicated in DNA damage response and in genome stability. Phosphorylation of BRCA1 by the DNA damage-response proteins ATM, ATR and hCds1/Chk2 changes in response to DNA damage and at replication-block checkpoints. Although cells that lack BRCA1 have an abnormal response to DNA damage, the exact role of BRCA1 in this process has remained unclear. Here we show that BRCA1 is essential for activating the Chk1 kinase that regulates DNA damage-induced G2/M arrest. Thus, BRCA1 controls the expression, phosphorylation and cellular localization of Cdc25C and Cdc2/cyclin B kinase-proteins that are crucial for the G2/M transition. We show that BRCA1 regulates the expression of both Wee1 kinase, an inhibitor of Cdc2/cyclin B kinase, and the 14-3-3 family of proteins that sequesters phosphorylated Cdc25C and Cdc2/cyclin B kinase in the cytoplasm. We conclude that BRCA1 regulates key effectors that control the G2/M checkpoint and is therefore involved in regulating the onset of mitosis. 相似文献
3.
Jadwiga Jabłońska Magda Dubińska-Magiera Teresa Jagla Krzysztof Jagla Małgorzata Daczewska 《Cellular and molecular life sciences : CMLS》2018,75(23):4341-4356
The Drosophila Hsp67Bc gene encodes a protein belonging to the small heat-shock protein (sHSP) family, identified as the nearest functional ortholog of human HSPB8. The most prominent activity of sHSPs is preventing the irreversible aggregation of various non-native polypeptides. Moreover, they are involved in processes such as development, aging, maintenance of the cytoskeletal architecture and autophagy. In larval muscles Hsp67Bc localizes to the Z- and A-bands, which suggests its role as part of the conserved chaperone complex required for Z-disk maintenance. In addition, Hsp67Bc is present at neuromuscular junctions (NMJs), which implies its involvement in the maintenance of NMJ structure. Here, we report the effects of muscle-target overexpression of Drosophila Hsp67Bc hot-spot variants Hsp67BcR126E and Hsp67BcR126N mimicking pathogenic variants of human HSPB8. Depending on the substitutions, we observed a different impact on muscle structure and performance. Expression of Hsp67BcR126E affects larval motility, which may be caused by impairment of mitochondrial respiratory function and/or by NMJ abnormalities manifested by a decrease in the number of synaptic boutons. In contrast, Hsp67BcR126N appears to be an aggregate-prone variant, as reflected in excessive accumulation of mutant proteins and the formation of large aggregates with a lesser impact on muscle structure and performance compared to the Hsp67BcR126E variant. 相似文献
4.
Hrecka K Hao C Gierszewska M Swanson SK Kesik-Brodacka M Srivastava S Florens L Washburn MP Skowronski J 《Nature》2011,474(7353):658-661
Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies and linking innate virus detection to antiviral adaptive immune responses. Human immunodeficiency virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to transduce macrophages, due to an as yet uncharacterized mechanism that inhibits infection by interfering with efficient synthesis of viral complementary DNA. In contrast, HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) transduce myeloid cells efficiently owing to their virion-associated Vpx accessory proteins, which counteract the restrictive mechanism. Here we show that the inhibition of HIV-1 infection in macrophages involves the cellular SAM domain HD domain-containing protein 1 (SAMHD1). Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi-Goutières syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection. Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutières syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors. Thus, our findings show that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncover an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens. 相似文献
5.
Summary Sister chromatid exchange was studied in lymphocyte and fibroblast cultures. Alcohol caused no disturbance under normal conditions but an acetaldehyde level above 40 M inhibited cell multiplication and elevated SCE considerably. A high acetaldehyde level is thought to elicit the fetal alcohol syndrome, a view supported by clinical and experimental observations. 相似文献
6.
Quesada V Conde L Villamor N Ordóñez GR Jares P Bassaganyas L Ramsay AJ Beà S Pinyol M Martínez-Trillos A López-Guerra M Colomer D Navarro A Baumann T Aymerich M Rozman M Delgado J Giné E Hernández JM González-Díaz M Puente DA Velasco G Freije JM Tubío JM Royo R Gelpí JL Orozco M Pisano DG Zamora J Vázquez M Valencia A Himmelbauer H Bayés M Heath S Gut M Gut I Estivill X López-Guillermo A Puente XS Campo E López-Otín C 《Nature genetics》2012,44(1):47-52
Here we perform whole-exome sequencing of samples from 105 individuals with chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries. We found 1,246 somatic mutations potentially affecting gene function and identified 78 genes with predicted functional alterations in more than one tumor sample. Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals. Further analysis in 279 individuals with CLL showed that SF3B1 mutations were associated with faster disease progression and poor overall survival. This work provides the first comprehensive catalog of somatic mutations in CLL with relevant clinical correlates and defines a large set of new genes that may drive the development of this common form of leukemia. The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies. 相似文献
7.
Human gut microbiome viewed across age and geography 总被引:2,自引:0,他引:2
Yatsunenko T Rey FE Manary MJ Trehan I Dominguez-Bello MG Contreras M Magris M Hidalgo G Baldassano RN Anokhin AP Heath AC Warner B Reeder J Kuczynski J Caporaso JG Lozupone CA Lauber C Clemente JC Knights D Knight R Gordon JI 《Nature》2012,486(7402):222-227
Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization. 相似文献
8.
Magda Dubinska-Magiera Magdalena Zaremba-Czogalla Ryszard Rzepecki 《Cellular and molecular life sciences : CMLS》2013,70(15):2713-2741
The aim of this review article is to evaluate the current knowledge on associations between muscle formation and regeneration and components of the nuclear lamina. Lamins and their partners have become particularly intriguing objects of scientific interest since it has been observed that mutations in genes coding for these proteins lead to a wide range of diseases called laminopathies. For over the last 10 years, various laboratories worldwide have tried to explain the pathogenesis of these rare disorders. Analyses of the distinct aspects of laminopathies resulted in formulation of different hypotheses regarding the mechanisms of the development of these diseases. In the light of recent discoveries, A-type lamins—the main building blocks of the nuclear lamina—together with other key elements, such as emerin, LAP2α and nesprins, seem to be of great importance in the modulation of various signaling pathways responsible for cellular differentiation and proliferation. 相似文献
9.
Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions 总被引:1,自引:0,他引:1
Zhao Z Tavoosidana G Sjölinder M Göndör A Mariano P Wang S Kanduri C Lezcano M Sandhu KS Singh U Pant V Tiwari V Kurukuti S Ohlsson R 《Nature genetics》2006,38(11):1341-1347
10.
Klein C Grudzien M Appaswamy G Germeshausen M Sandrock I Schäffer AA Rathinam C Boztug K Schwinzer B Rezaei N Bohn G Melin M Carlsson G Fadeel B Dahl N Palmblad J Henter JI Zeidler C Grimbacher B Welte K 《Nature genetics》2007,39(1):86-92
Autosomal recessive severe congenital neutropenia (SCN) constitutes a primary immunodeficiency syndrome associated with increased apoptosis in myeloid cells, yet the underlying genetic defect remains unknown. Using a positional cloning approach and candidate gene evaluation, we identified a recurrent homozygous germline mutation in HAX1 in three pedigrees. After further molecular screening of individuals with SCN, we identified 19 additional affected individuals with homozygous HAX1 mutations, including three belonging to the original pedigree described by Kostmann. HAX1 encodes the mitochondrial protein HAX1, which has been assigned functions in signal transduction and cytoskeletal control. Here, we show that HAX1 is critical for maintaining the inner mitochondrial membrane potential and protecting against apoptosis in myeloid cells. Our findings suggest that HAX1 is a major regulator of myeloid homeostasis and underline the significance of genetic control of apoptosis in neutrophil development. 相似文献