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Talia Herman Keren Rosenberg-Katz Yael Jacob Eitan Auriel Tanya Gurevich Nir Giladi Jeffrey M. Hausdorff 《PloS one》2013,8(1)
Background
Brain white matter hyperintensities (WMHs) commonly observed on brain imaging of older adults are associated with balance and gait impairment and have also been linked to cognitive deficits. Parkinson’s disease (PD) is traditionally sub-classified into the postural instability gait difficulty (PIGD) sub-type, and the tremor dominant (TD) sub-type. Considering the known association between WMHs and axial symptoms like gait disturbances and postural instability, one can hypothesize that WMHs might contribute to the disparate clinical sub-types of patients with PD.Methods
110 patients with PD underwent a clinical evaluation and a 3T MRI exam. Based on the Unified Parkinson Disease Rating Scale, the patients were classified into motor sub-types, i.e., TD or PIGD, and scores reflecting PIGD and TD symptoms were computed. We compared white matter burden using three previously validated methods: one using a semi-quantitative visual rating scale in specific brain regions and two automated methods.Results
Overall, MRI data were obtained in 104 patients. The mean WMHs scores and the percent of subjects with lesions in specific brain regions were similar in the two subtypes, p = 0.678. The PIGD and the TD scores did not differ even when comparing patients with a relatively high burden of WMHs to patients with a relatively low burden. Across most of the brain regions, mild to moderate correlations between WMHs and age were found (r = 0.23 to 0.41; p<0.021). Conversely, no significant correlations were found between WMHs and the PIGD score or disease duration. In addition, depressive symptoms and cerebro-vascular risk factors were similar among the two subtypes.Conclusions
In contrast to what has been reported previously among older adults, the present study could not demonstrate any association between WMHs and the PIGD or TD motor sub-types in patients with PD. 相似文献84.
Amjad Horani Steven L. Brody Thomas W. Ferkol David Shoseyov Mollie G. Wasserman Asaf Ta-shma Kate S. Wilson Philip V. Bayly Israel Amirav Malena Cohen-Cymberknoh Susan K. Dutcher Orly Elpeleg Eitan Kerem 《PloS one》2013,8(8)
Background
Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by impaired ciliary function, leading to chronic sinopulmonary disease. The genetic causes of PCD are still evolving, while the diagnosis is often dependent on finding a ciliary ultrastructural abnormality and immotile cilia. Here we report a novel gene associated with PCD but without ciliary ultrastructural abnormalities evident by transmission electron microscopy, but with dyskinetic cilia beating.Methods
Genetic linkage analysis was performed in a family with a PCD subject. Gene expression was studied in Chlamydomonas reinhardtii and human airway epithelial cells, using RNA assays and immunostaining. The phenotypic effects of candidate gene mutations were determined in primary culture human tracheobronchial epithelial cells transduced with gene targeted shRNA sequences. Video-microscopy was used to evaluate cilia motion.Results
A single novel mutation in CCDC65, which created a termination codon at position 293, was identified in a subject with typical clinical features of PCD. CCDC65, an orthologue of the Chlamydomonas nexin-dynein regulatory complex protein DRC2, was localized to the cilia of normal nasal epithelial cells but was absent in those from the proband. CCDC65 expression was up-regulated during ciliogenesis in cultured airway epithelial cells, as was DRC2 in C. reinhardtii following deflagellation. Nasal epithelial cells from the affected individual and CCDC65-specific shRNA transduced normal airway epithelial cells had stiff and dyskinetic cilia beating patterns compared to control cells. Moreover, Gas8, a nexin-dynein regulatory complex component previously identified to associate with CCDC65, was absent in airway cells from the PCD subject and CCDC65-silenced cells.Conclusion
Mutation in CCDC65, a nexin-dynein regulatory complex member, resulted in a frameshift mutation and PCD. The affected individual had altered cilia beating patterns, and no detectable ultrastructural defects of the ciliary axoneme, emphasizing the role of the nexin-dynein regulatory complex and the limitations of certain methods for PCD diagnosis. 相似文献85.
86.
Justin B. Lack Amir Yassin Quentin D. Sprengelmeyer Evan J. Johanning Jean R. David John E. Pool 《Ecology and evolution》2016,6(16):5893-5906
Understanding the physiological and genetic basis of growth and body size variation has wide‐ranging implications, from cancer and metabolic disease to the genetics of complex traits. We examined the evolution of body and wing size in high‐altitude Drosophila melanogaster from Ethiopia, flies with larger size than any previously known population. Specifically, we sought to identify life history characteristics and cellular mechanisms that may have facilitated size evolution. We found that the large‐bodied Ethiopian flies laid significantly fewer but larger eggs relative to lowland, smaller‐bodied Zambian flies. The highland flies were found to achieve larger size in a similar developmental period, potentially aided by a reproductive strategy favoring greater provisioning of fewer offspring. At the cellular level, cell proliferation was a strong contributor to wing size evolution, but both thorax and wing size increases involved important changes in cell size. Nuclear size measurements were consistent with elevated somatic ploidy as an important mechanism of body size evolution. We discuss the significance of these results for the genetic basis of evolutionary changes in body and wing size in Ethiopian D. melanogaster. 相似文献
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Ecosystem Services of Woody Crop Production Systems 总被引:1,自引:0,他引:1
Ronald S. ZalesnyJr John A. Stanturf Emile S. Gardiner James H. Perdue Timothy M. Young David R. Coyle William L. Headlee Gary S. Bañuelos Amir Hass 《Bioenergy Research》2016,9(2):465-491
Short-rotation woody crops are an integral component of regional and national energy portfolios, as well as providing essential ecosystem services such as biomass supplies, carbon sinks, clean water, and healthy soils. We review recent USDA Forest Service Research and Development efforts from the USDA Biomass Research Centers on the provisioning of these ecosystem services from woody crop production systems. For biomass, we highlight productivity and yield potential, pest susceptibility, and bioenergy siting applications. We describe carbon storage in aboveground woody biomass and studies assessing the provision of clean and plentiful water. Soil protection and wildlife habitat are also mentioned, in the context of converting lands from traditional row-crop agriculture to woody production systems. 相似文献
89.
The ε-amino group of lysine residues may be mono-, di- or tri-methylated by protein lysine methyltransferases. In the past few years it has been highly considered that methylation of both histone and non-histone proteins has fundamental role in development and progression of various human diseases. Thus, the establishment of tools to study lysine methylation that will distinguish between the different states of methylation is required to elucidate their cellular functions. The 3X malignant brain tumor domain (3XMBT) repeats of the Lethal(3)malignant brain tumor-like protein 1 (L3MBTL1) have been utilized in the past as an affinity reagent for the identification of mono- and di-methylated lysine residues on individual proteins and on a proteomic scale. Here, we have utilized the 3XMBT domain to develop an enzyme-linked immunosorbent assay (ELISA) that allows the high-throughput detection of 3XMBT binding to methylated lysines. We demonstrated that this system allows the detection of methylated peptides, methylated proteins and PKMT activity on both peptides and proteins. We also optimized the assay to detect 3XMBT binding in crude E. coli lysates which facilitated the high throughput screening of 3XMBT mutant libraries. We have utilized protein engineering tools and generated a double site saturation 3XMBT library of residues 361 and 411 that were shown before to be important for binding mono and di-methylated substrates and identified variants that can exclusively recognize only di-methylated peptides. Together, our results demonstrate a powerful new approach that will contribute to deeper understanding of lysine methylation biology and that can be utilized for the engineering of domains for specific binders of other post-translational modifications. 相似文献
90.
Yedael Y. Waldman Arjun Biddanda Natalie R. Davidson Paul Billing-Ross Maya Dubrovsky Christopher L. Campbell Carole Oddoux Eitan Friedman Gil Atzmon Eran Halperin Harry Ostrer Alon Keinan 《PloS one》2016,11(3)
The Bene Israel Jewish community from West India is a unique population whose history before the 18th century remains largely unknown. Bene Israel members consider themselves as descendants of Jews, yet the identity of Jewish ancestors and their arrival time to India are unknown, with speculations on arrival time varying between the 8th century BCE and the 6th century CE. Here, we characterize the genetic history of Bene Israel by collecting and genotyping 18 Bene Israel individuals. Combining with 486 individuals from 41 other Jewish, Indian and Pakistani populations, and additional individuals from worldwide populations, we conducted comprehensive genome-wide analyses based on FST, principal component analysis, ADMIXTURE, identity-by-descent sharing, admixture linkage disequilibrium decay, haplotype sharing and allele sharing autocorrelation decay, as well as contrasted patterns between the X chromosome and the autosomes. The genetics of Bene Israel individuals resemble local Indian populations, while at the same time constituting a clearly separated and unique population in India. They are unique among Indian and Pakistani populations we analyzed in sharing considerable genetic ancestry with other Jewish populations. Putting together the results from all analyses point to Bene Israel being an admixed population with both Jewish and Indian ancestry, with the genetic contribution of each of these ancestral populations being substantial. The admixture took place in the last millennium, about 19–33 generations ago. It involved Middle-Eastern Jews and was sex-biased, with more male Jewish and local female contribution. It was followed by a population bottleneck and high endogamy, which can lead to increased prevalence of recessive diseases in this population. This study provides an example of how genetic analysis advances our knowledge of human history in cases where other disciplines lack the relevant data to do so. 相似文献