排序方式: 共有97条查询结果,搜索用时 109 毫秒
91.
Christopher L. Baker Pavlina Petkova Michael Walker Petr Flachs Ondrej Mihola Zdenek Trachtulec Petko M. Petkov Kenneth Paigen 《PLoS genetics》2015,11(9)
Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9
+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape. 相似文献
92.
Jihui Ren Coney Pei-Chen Lin Manish C. Pathak Brenda R. S. Temple Aaron H. Nile Carl J. Mousley Mara C. Duncan Debra M. Eckert Thomas J. Leiker Pavlina T. Ivanova David S. Myers Robert C. Murphy H. Alex Brown Jolien Verdaasdonk Kerry S. Bloom Eric A. Ortlund Aaron M. Neiman Vytas A. Bankaitis 《Molecular biology of the cell》2014,25(5):712-727
Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumed during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and phosphoinositide) biology that are invisible to contemporary haploid-centric cell biological, proteomic, and functional genomics approaches. 相似文献
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94.
Stanka Stoeva Pavlina Dolashka Katja Pervanova Nicolay Genov Wolfgang Voelter 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》1997,118(4):927-934
The Rapana thomasiana hemocyanin structural subunit RHSS1 is composed of eight functional dioxygen-binding domains. To determine the multidomain structure, the polypeptide chain of RHSS1 was subjected to limited proteolysis with TPCK-trypsin, elastase and other proteinases. Individual functional units and fragments, containing two or three domains, were isolated and characterized. All domains and fragments were N-terminally sequenced and the order of the dioxygen-binding units in the polypeptide chain of RHSS1 was established. 相似文献
95.
Emily J A Taylor Pavlina Konstantinova Fiona Leigh Jayne A Bates David Lee 《Génome》2004,47(3):519-525
This paper describes the development of S-SAP (sequence-specific amplified polymorphism) using a primer derived from the LTR (long terminal repeat) of the Pyggy retrotransposon isolated from Pyrenophora graminea. Fragments were amplified by S-SAP from different Pyrenophora spp., indicating the presence of Pyggy-like sequences in these genomes. The bands were highly polymorphic between isolates and the number of bands differed by as much as 10-fold between species, demonstrating the potential of this method for genetic analysis in fungi. The phylogenetic relationship among the isolates as deduced using S-SAP data is presented, and shows evidence of genetic exchange between P. graminea and P. teres. 相似文献
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97.
Maksym V. Kopanitsa Kimmo K. Lehtimäki Markku Forsman Ari Suhonen Juho Koponen Tuukka O. Piiponniemi Anna-Mari Kärkkäinen Pavlina Pavlidi Artem Shatillo Patrick J. Sweeney Avia Merenlender-Wagner Joel Kaye Aric Orbach Antti Nurmi 《Genes, Brain & Behavior》2021,20(1):e12663
Cognitive problems frequently accompany neurological manifestations of multiple sclerosis (MS). However, during screening of preclinical candidates, assessments of behaviour in mouse models of MS typically focus on locomotor activity. In the present study, we analysed cognitive behaviour of 9 to 10-week-old female C57Bl/6J mice orally administered with the toxin cuprizone that induces demyelination, a characteristic feature of MS. Animals received 400 mg/kg cuprizone daily for 2 or 4 weeks, and their performance was compared with that of vehicle-treated mice. Cuprizone-treated animals showed multiple deficits in short touchscreen-based operant tasks: they responded more slowly to visual stimuli, rewards and made more errors in a simple rule-learning task. In contextual/cued fear conditioning experiments, cuprizone-treated mice showed significantly lower levels of contextual freezing than vehicle-treated mice. Diffusion tensor imaging showed treatment-dependent changes in fractional anisotropy as well as in axial and mean diffusivities in different white matter areas. Lower values of fractional anisotropy and axial diffusivity in cuprizone-treated mice indicated developing demyelination and/or axonal damage. Several diffusion tensor imaging measurements correlated with learning parameters. Our results show that translational touchscreen operant tests and fear conditioning paradigms can reliably detect cognitive consequences of cuprizone treatment. The suggested experimental approach enables screening novel MS drug candidates in longitudinal experiments for their ability to improve pathological changes in brain structure and reverse cognitive deficits. 相似文献