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1.
Science ; 376(6599): eabh3104, 2022 06 17.
Article in English | MEDLINE | ID: mdl-35549308

ABSTRACT

A hallmark of meiosis is chromosomal pairing, which requires telomere tethering and rotation on the nuclear envelope through microtubules, driving chromosome homology searches. Telomere pulling toward the centrosome forms the "zygotene chromosomal bouquet." Here, we identified the "zygotene cilium" in oocytes. This cilium provides a cable system for the bouquet machinery and extends throughout the germline cyst. Using zebrafish mutants and live manipulations, we demonstrate that the cilium anchors the centrosome to counterbalance telomere pulling. The cilium is essential for bouquet and synaptonemal complex formation, oogenesis, ovarian development, and fertility. Thus, a cilium represents a conserved player in zebrafish and mouse meiosis, which sheds light on reproductive aspects in ciliopathies and suggests that cilia can control chromosomal dynamics.


Subject(s)
Chromosome Pairing , Cilia , Oocytes , Oogenesis , Ovary , Animals , Centromere/genetics , Centromere/physiology , Chromosome Pairing/genetics , Chromosome Pairing/physiology , Cilia/physiology , Female , Fertility/physiology , Mice , Morphogenesis , Oocytes/growth & development , Oogenesis/genetics , Oogenesis/physiology , Ovary/growth & development , Telomere/genetics , Telomere/physiology , Zebrafish/genetics , Zebrafish/physiology
2.
Neuropathol Appl Neurobiol ; 42(4): 366-76, 2016 06.
Article in English | MEDLINE | ID: mdl-25967384

ABSTRACT

AIMS: Complex visual hallucinations occur in 70% of dementia with Lewy bodies (DLB) cases and significantly affect patient well-being. Visuo-cortical and retinal abnormalities have been recorded in DLB and may play a role in visual hallucinations. The present study aimed to investigate the lateral geniculate nucleus (LGN), a visual relay centre between the retina and visual cortex, to see if changes to this structure underlie visual hallucinations in DLB. METHODS: Fifty-one [17 probable DLB, 19 control and 15 probable Alzheimer's disease (AD)] cases were recruited for a functional magnetic resonance imaging study, in which patients' response to a flashing checkerboard stimulus was detected and measured in the LGN, before comparison across experimental groups. Additionally, post mortem LGN tissue was acquired for a cross-sectional study using 20 (six DLB, seven control and seven AD) cases and analysed using stereology. α-Synuclein, phosphorylated tau and amyloid-ß pathology was also assessed in all cases. RESULTS: DLB cases did not significantly differ from controls on neuroimaging, morphometry or pathology. However, a significant increase in amyloid-ß pathology, a reduction in number of parvocellular neurones and magnocellular gliosis was found in AD cases compared with control and DLB cases. CONCLUSIONS: These findings suggest that the early visual system is relatively spared in DLB, which implies that upstream visual structures may be largely responsible for the generation of hallucinatory percepts. The significance of the degeneration of the LGN in AD cases is uncertain.


Subject(s)
Alzheimer Disease/pathology , Alzheimer Disease/physiopathology , Geniculate Bodies/pathology , Geniculate Bodies/physiopathology , Lewy Body Disease/pathology , Lewy Body Disease/physiopathology , Aged , Aged, 80 and over , Brain Mapping , Cross-Sectional Studies , Female , Humans , Magnetic Resonance Imaging , Male , Photic Stimulation
3.
Psychiatry Res ; 194(2): 184-9, 2011 Nov 30.
Article in English | MEDLINE | ID: mdl-21924875

ABSTRACT

Previous imaging and morphometric studies have identified volumetric and cellular abnormalities in prefrontal areas in late-life depression. This study aimed to examine cellular morphology using stereological methodology in the supragenual region of the anterior cingulate cortex in late-life depressed patients compared with age-matched controls. Post-mortem tissue was acquired from nine patients with depression and 11 control patients and analyzed using the optical disector and nucleator methods. No changes were found in glial, non-pyramidal and pyramidal cell density, or in non-pyramidal or pyramidal cell volume within individual layers (2-5) or the supragenual anterior cortex as a whole. This study, therefore, does not provide further evidence for cellular abnormalities in late-life depression.


Subject(s)
Depression/pathology , Gyrus Cinguli/pathology , Neuroglia/pathology , Neurons/pathology , Aged , Aged, 80 and over , Cell Count , Female , Gyrus Cinguli/cytology , Humans , Male , Postmortem Changes , Stereotaxic Techniques
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