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41.
Khateeb S Flusser H Ofir R Shelef I Narkis G Vardi G Shorer Z Levy R Galil A Elbedour K Birk OS 《American journal of human genetics》2006,79(5):942-948
Infantile neuroaxonal dystrophy (INAD) is an autosomal recessive progressive neurodegenerative disease that presents within the first 2 years of life and culminates in death by age 10 years. Affected individuals from two unrelated Bedouin Israeli kindreds were studied. Brain imaging demonstrated diffuse cerebellar atrophy and abnormal iron deposition in the medial and lateral globus pallidum. Progressive white-matter disease and reduction of the N-acetyl aspartate : chromium ratio were evident on magnetic resonance spectroscopy, suggesting loss of myelination. The clinical and radiological diagnosis of INAD was verified by sural nerve biopsy. The disease gene was mapped to a 1.17-Mb locus on chromosome 22q13.1 (LOD score 4.7 at recombination fraction 0 for SNP rs139897), and an underlying mutation common to both affected families was identified in PLA2G6, the gene encoding phospholipase A2 group VI (cytosolic, calcium-independent). These findings highlight a role of phospholipase in neurodegenerative disorders. 相似文献
42.
Nora Stern Ayala Hochman Naty Zemach Nir Weizman Ilan Hammel Yosef Shiloh Galit Rotman Ari Barzilai 《The Journal of biological chemistry》2002,277(1):602-608
Ataxia-telangiectasia (A-T) is a human genetic disorder caused by mutational inactivation of the ATM gene. A-T patients display a pleiotropic phenotype, in which a major neurological feature is progressive ataxia due to degeneration of cerebellar Purkinje and granule neurons. Disruption of the mouse Atm locus creates a murine model of A-T that exhibits most of the clinical and cellular features of the human disease, but the neurological phenotype is barely expressed. We present evidence for the accumulation of DNA strand breaks in the brains of Atm(-/-), supporting the notion that ATM plays a major role in maintaining genomic stability. We also show a perturbation of the steady state levels of pyridine nucleotides. There is a significant decrease in both the reduced and the oxidized forms of NAD and in the total levels of NADP(T) and NADP(+) in the brains of Atm(-/-) mice. The changes in NAD(T), NADH, NAD(+), NADP(T), and NADP(+) were progressive and observed primarily in the cerebellum of 4-month-old Atm(-/-) mice. Higher rates of mitochondrial respiration were also recorded in 4-month-old Atm(-/-) cerebella. Taken together, our findings support the hypothesis that absence of functional ATM results in continuous stress, which may be an important cause of the degeneration of cerebellar neurons in A-T. 相似文献
43.
We discover and examine within a wide phylogenetic perspective spatial neophobia, avoidance of untrodden terrain, in fruit flies, in an experimental setup that reduces the gap between the field and the laboratory. In our setup, fruit flies use a natal fruit as their origin, freely exploring for days their surroundings, which consists of a mixture of trodden and untrodden terrain. The interface between trodden and untrodden is, however, reduced in our setup to a wide doorway, opened within a surrounding wall. Crossing this doorway, characterized by a sharp contrast interface between trodden and untrodden, generates a behavior whose dynamics betrays the flies'' space neophobia. The moment-by-moment dynamics of crossing is remarkably similar to that reported in mouse models of anxiety. This means that neophobic behavior is either homologous across arthropods and vertebrates or, not less interesting, convergent, whereby the same behavior is mediated in the two phyla by two completely different schemata. 相似文献
44.
We quantify the ‘permanent’ socio-economic impacts of the Great Hanshin-Awaji (Kobe) earthquake in 1995 by employing a large-scale panel dataset of 1,719 cities, towns, and wards from Japan over three decades. In order to estimate the counterfactual—i.e., the Kobe economy without the earthquake—we use the synthetic control method. Three important empirical patterns emerge: First, the population size and especially the average income level in Kobe have been lower than the counterfactual level without the earthquake for over fifteen years, indicating a permanent negative effect of the earthquake. Such a negative impact can be found especially in the central areas which are closer to the epicenter. Second, the surrounding areas experienced some positive permanent impacts in spite of short-run negative effects of the earthquake. Much of this is associated with movement of people to East Kobe, and consequent movement of jobs to the metropolitan center of Osaka, that is located immediately to the East of Kobe. Third, the furthest areas in the vicinity of Kobe seem to have been insulated from the large direct and indirect impacts of the earthquake. 相似文献
45.
Jos Antonio Solis Ilan Perrot Rosenberg Jorge Olivares Benjamin Tudela Gabriel Veillon Gabriel Lazcano 《Reports of Practical Oncology and Radiotherapy》2021,26(3):360
BackgroundThe treatment of early stage cervical cancer has different therapeutic options. Adjuvant external beam radiotherapy for surgically treated intermediate risk cervical cancer patients has shown acceptable oncological outcomes with a low incidence of toxicity. The aim of this study was to analyze the oncological outcomes and safety of adjuvant small pelvic field radiotherapy in surgically treated stage IB1-2 cervical cancer patients who met the Sedlis intermediate-risk criteria.Materials and methodsA retrospective cohort study was carried out with 28 patients treated from 2007 to November 2019 with biopsy proven intermediate risk stage IB1–2 cervical cancer previously treated with radical hysterectomy and bilateral lymphadenectomy who received adjuvant small pelvic field radiotherapy. The primary endpoints were local and distant control and overall survival. Secondary endpoints were acute and late gastrointestinal and genitourinary toxicity. Survival curves were analyzed using the Kaplan-Meier method.ResultsAfter a median follow up period of 41.5 (27.5–80.5) months, adjuvant small pelvic field radiotherapy showed a 100% overall survival rate, 81.82% disease free survival and 86.36% local recurrence-free survival with no incidence of grade 3 or 4 acute or late toxicity. Three patients suffered from relapse, 1 in the vaginal cuff, 1 in the retrovesical area and 1 patient in the retroperitoneal area.ConclusionsAdjuvant small pelvic field radiotherapy is an efficient and safe treatment option that offers excellent oncological outcomes to surgically treated intermediate-risk stage IB1–2 cervical cancer patients with an excellent toxicity profile. 相似文献
46.
Ilan Hammel Tanya Shoichetman Dina Amihai Stephen J. Galli Ehud Skutelsky 《Cell and tissue research》2010,339(3):561-570
We used the egg avidin gold complex as a polycationic probe for the localization of negatively charged sites in the secretory
granules of mouse mast cells. We compared the binding of this reagent to mast cell granules in wild-type mice and in congenic
brachymorphic mice in which mast cell secretory granules contained undersulfated proteoglycans. We localized anionic sites
by post-embedding labeling of thin sections of mouse skin and tongue tissues fixed in Karnovsky’s fixative and OsO4 and embedded in Araldite. Transmission electron microscopy revealed that the mast cell granules of bm/bm mice had a lower optical density than those of wild-type mice (P<0.001) and a lower avidin gold binding density (by approximately 50%, P<0.001). The latter result provided additional evidence that the contents of mast cell granules in bm/bm mice were less highly sulfated than in those of wild-type mice. In both wild-type and bm/bm mast cells, the distribution of granule equivalent volumes was multimodal, but the unit granule volume was approximately
19% lower in bm/bm cells than in wild-type cells (P<0.05). Thus, bm/bm mast cells develop secretory granules that differ from those of wild-type mice in exhibiting a lower optical density and
slightly smaller unit granules, however the processes that contribute to granule maturation and granule-granule fusion in
mast cells are operative in bm/bm cells. 相似文献
47.
Sea squirts are simple invertebrate chordates. In this issue of Developmental Cell, Takatori et?al. show nuclear migration within ascidian mesendodermal cells enables polarized localization of Not mRNA, which encodes a homeobox protein that distinguishes mesoderm from endoderm fates. The link between nuclear migration and mRNA localization suggests exciting parallels with protostomes. 相似文献
48.
Assaf Zaritsky Doron Kaplan Inbal Hecht Sari Natan Lior Wolf Nir S. Gov Eshel Ben-Jacob Ilan Tsarfaty 《PLoS computational biology》2014,10(7)
The ability of cells to coordinately migrate in groups is crucial to enable them to travel long distances during embryonic development, wound healing and tumorigenesis, but the fundamental mechanisms underlying intercellular coordination during collective cell migration remain elusive despite considerable research efforts. A novel analytical framework is introduced here to explicitly detect and quantify cell clusters that move coordinately in a monolayer. The analysis combines and associates vast amount of spatiotemporal data across multiple experiments into transparent quantitative measures to report the emergence of new modes of organized behavior during collective migration of tumor and epithelial cells in wound healing assays. First, we discovered the emergence of a wave of coordinated migration propagating backward from the wound front, which reflects formation of clusters of coordinately migrating cells that are generated further away from the wound edge and disintegrate close to the advancing front. This wave emerges in both normal and tumor cells, and is amplified by Met activation with hepatocyte growth factor/scatter factor. Second, Met activation was found to induce coinciding waves of cellular acceleration and stretching, which in turn trigger the emergence of a backward propagating wave of directional migration with about an hour phase lag. Assessments of the relations between the waves revealed that amplified coordinated migration is associated with the emergence of directional migration. Taken together, our data and simplified modeling-based assessments suggest that increased velocity leads to enhanced coordination: higher motility arises due to acceleration and stretching that seems to increase directionality by temporarily diminishing the velocity components orthogonal to the direction defined by the monolayer geometry. Spatial and temporal accumulation of directionality thus defines coordination. The findings offer new insight and suggest a basic cellular mechanism for long-term cell guidance and intercellular communication during collective cell migration. 相似文献
49.
PECAM-1: old friend, new partners 总被引:15,自引:0,他引:15
50.