Faculty Opinions recommendation of Somatic LINE-1 retrotransposition in cortical neurons and non-brain tissues of Rett patients and healthy individuals.

2020 ◽  
Author(s):  
Anuj Kumar
Keyword(s):  
Cortical Neurons ◽  
Healthy Individuals ◽  
Brain Tissues

scholarly journals Somatic LINE-1 retrotransposition in cortical neurons and non-brain tissues of Rett patients and healthy individuals

PLoS Genetics ◽  
2019 ◽  
Vol 15 (4) ◽  
pp. e1008043 ◽  
Author(s):  
Boxun Zhao ◽  
Qixi Wu ◽  
Adam Yongxin Ye ◽  
Jing Guo ◽  
Xianing Zheng ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Healthy Individuals ◽  
Brain Tissues

scholarly journals Somatic LINE-1 retrotransposition in cortical neurons and non-brain tissues of Rett patients and healthy individuals

2018 ◽  
Author(s):  
Boxun Zhao ◽  
Qixi Wu ◽  
Adam Yongxin Ye ◽  
Jing Guo ◽  
Xianing Zheng ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Genomic Diversity ◽  
Healthy Controls ◽  
Genome Wide ◽  
Retrotransposon Family ◽  
Somatic Tissues ◽  
The Brain ◽  
Specific Line ◽  
Human Specific ◽  
Brain Tissues

AbstractMounting evidence supports that LINE-1 (L1) retrotransposition can occur postzygotically in healthy and diseased human tissues, contributing to genomic mosaicism in the brain and other somatic tissues of an individual. However, the genomic distribution of somatic L1Hs (Human-specific LINE-1) insertions and their potential impact on carrier cells remain unclear. Here, using a PCR-based targeted bulk sequencing approach, we profiled 9,181 somatic insertions from 20 postmortem tissues from five Rett patients and their matched healthy controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues. In Rett patients, somatic insertions were significantly depleted in exons—mainly contributed by long genes—than healthy controls, implying that cells carrying MECP2 mutations might be defenseless against a second exonic L1Hs insertion. We observed a significant increase of somatic L1Hs insertions in the brain compared with non-brain tissues from the same individual. Compared to germline insertions, somatic insertions were less sense-depleted to transcripts, indicating that they underwent weaker selective pressure on the orientation of insertion. Our observations demonstrate that somatic L1Hs insertions contribute to genomic diversity and MECP2 dysfunction alters their genomic patterns in Rett patients.Author SummaryHuman-specific LINE-1 (L1Hs) is the most active autonomous retrotransposon family in the human genome. Mounting evidence supports that L1Hs retrotransposition occurs postzygotically in the human brain cells, contributing to neuronal genomic diversity, but the extent of L1Hs-driven mosaicism in the brain is debated. In this study, we profiled genome-wide L1Hs insertions among 20 postmortem tissues from Rett patients and matched controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues, with a higher jumping activity in the brain. We further found that MECP2 dysfunction might alter the genomic pattern of somatic L1Hs in Rett patients.

scholarly journals Capping Protein Regulator and Myosin 1 Linker 3 (CARMIL3) as a Molecular Signature of Ischemic Neurons in the DWI-T2 Mismatch Areas After Stroke

2021 ◽  
Vol 14 ◽  
Author(s):  
Shin-Joe Yeh ◽  
Pang-Hung Hsu ◽  
Ti-Yen Yeh ◽  
Wei-Kang Yang ◽  
Ko-Ping Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Human Brain ◽  
Cortical Neurons ◽  
Cell Model ◽  
Expression Profiles ◽  
Molecular Signature ◽  
Sulfonylurea Receptor ◽  
Sprague Dawley ◽  
Capping Protein ◽  
Brain Tissues

Ischemic stroke with a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) or T2-weighted images indicates onset within 4.5 h, but the pathological substrates in the DWI-T2 mismatch and T2(+) areas remain elusive. In this study, proteomics was used to explore (1) the protein expression profiles in the T2(+), mismatch, and contralateral areas, and (2) the protein with the highest expression in the T2(+) area in the brains of male Sprague-Dawley rats within 4.5 h after middle cerebral artery occlusion (MCAO). The expression of the candidate protein was further validated in (1) rat brain subjected to MCAO, (2) rat primary cortical neuronal culture with oxygen-glucose deprivation (OGD), and (3) infarcted human brain tissues. This study showed that apoptosis was observed in the T2(+) and mismatch regions and necroptosis in the T2(+) region of rat brains after MCAO. We identified capping protein regulator and myosin 1 linker 3 (CARMIL3) as the candidate molecule in the T2(+) and mismatch areas, exclusively in neurons, predominantly in the cytoplasm, and most abundant in the mismatch area. The CARMIL3(+) neurons and neurites in the mismatch and T2(+) areas were larger than those in the control area, and associated with (1) increased expression of sulfonylurea receptor 1 (SUR1), indicating edema, (2) accumulation of p62, indicating impaired autophagy, and (3) increase in 8-hydroxy-2′-deoxyguanosine (8-OHdG), indicating oxidative stress. The increased expression of CARMIL3 was validated in a cell model of cortical neurons after OGD and in infarcted human brain tissues. In conclusion, this study shows that the mismatch and T2(+) areas within 4.5 h after ischemia are characterized by upregulated expression of CARMIL3 in neurons, particularly the mismatch area, which is associated with neuronal edema, impaired autophagy, and oxidative stress, indicating that CARMIL3 serves as a molecular signature of brain ischemia.

scholarly journals The functional role of hemojuvelin in acute ischemic stroke

2019 ◽  
Vol 40 (6) ◽  
pp. 1316-1327 ◽  
Author(s):  
Guang-Huar Young ◽  
Sung-Chun Tang ◽  
Vin-Cent Wu ◽  
Kuo-Chuan Wang ◽  
Jing-Yi Nong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cortical Neurons ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Small Interfering Rnas ◽  
Basic Part ◽  
Post Stroke ◽  
Brain Tissues

Our study aimed to establish the role of hemojuvelin (HJV) in acute ischemic stroke (AIS). We performed immunohistochemistry for HJV expression in human brain tissues from 10 AIS and 2 non-stroke autopsy subjects. Plasma HJV was measured in 112 AIS patients within 48 h after stroke. The results showed significantly increased HJV expression in brain tissues from AIS patients compare to non-stroke subjects. After adjusting for clinical variables, plasma levels of HJV within 48 h after stroke were an independent predictor of poor functional outcome three months post-stroke (OR:1.78, 95% CI: 1.03–3.07; P = 0.038). In basic part, Western blotting showed that HJV expression in mice brains was apparent at 3 h after middle cerebral artery occlusion (MCAO), and increased significantly at 72 h. In cultured cortical neurons, expression of HJV protein increased remarkably 24 h after oxygen glucose deprivation (OGD), and small interfering RNAs (siHJV) transfected OGD neurons had a lower apoptotic rate. Importantly, 72 h post-MCAO, HJV knockout mice had significantly smaller infarcts and less expression of cleaved caspase-3 protein compared with wild-type mice. In summary, HJV participates in the mechanisms of post-stroke neuronal injury, and that plasma HJV levels can be a potential early outcome indicator for AIS patients.

Diazepam potentiation of purinergie depression of central neurons

1979 ◽  
Vol 57 (4) ◽  
pp. 432-435 ◽  
Author(s):  
J. W. Phillis
Keyword(s):  
Cortical Neurons ◽  
Spontaneous Firing ◽  
Central Neurons ◽  
Depressant Action ◽  
Cerebral Cortical Neurons ◽  
Brain Tissues

Intravenously or iontophoretically applied diazepam potentiated the depressant action of iontophoretically applied 5′-AMP on the spontaneous firing of rat cerebral cortical neurons. This potentiation of purinergic depression may be a result of the previously reported inhibition by diazepam of uptake of adenosine into brain tissues.

Morphological and elemental analysis of isolated incubated frog retina-choroid

1984 ◽  
Vol 42 ◽  
pp. 298-299
Author(s):  
B. J. Panessa-Warren ◽  
J. B. Warren ◽  
H. W. Kraner
Keyword(s):  
Elemental Analysis ◽  
Pigment Epithelium ◽  
Human Retina ◽  
Healthy Individuals ◽  
Anterior Portion ◽  
Pathological Conditions ◽  
Frog Retina ◽  
Isolated Retina ◽  
Vertebrate Eye ◽  
Retina Pigment Epithelium

Our previous studies have demonstrated that abnormally high amounts of calcium (Ca) and zinc (Zn) can be accumulated in human retina-choroid under pathological conditions and that barium (Ba), which was not detected in the eyes of healthy individuals, is deposited in the retina pigment epithelium (RPE), and to a lesser extent in the sensory retina and iris. In an attempt to understand how these cations can be accumulated in the vertebrate eye, a morphological and microanalytical study of the uptake and loss of specific cations (K, Ca,Ba,Zn) was undertaken with incubated Rana catesbiana isolated retina and RPE preparations. Large frogs (650-800 gms) were dark adapted, guillotined and their eyes enucleated in deep ruby light. The eyes were hemisected behind the ora serrata and the anterior portion of the eye removed. The eyecup was bisected along the plane of the optic disc and the two segments of retina peeled away from the RPE and incubated.

Qualitative and quantitative assessment of nailfold capillaries by capillaroscopy in healthy volunteers

VASA ◽  
2012 ◽  
Vol 41 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Hoerth ◽  
Kundi ◽  
Katzenschlager ◽  
Hirschl
Keyword(s):  
Scoring System ◽  
Morphological Changes ◽  
Connective Tissue Diseases ◽  
Capillary Density ◽  
Diagnostic Value ◽  
Healthy Individuals ◽  
Extreme Position ◽  
Qualitative And Quantitative ◽  
Diffuse Loss ◽  
Density Results

Background: Nailfold capillaroscopy (NVC) is a diagnostic tool particularly useful in the differential diagnosis of rheumatic and connective tissue diseases. Although successfully applied since many years, little is known about prevalence and distribution of NVC changes in healthy individuals. Probands and methods: NVC was performed in 120 individuals (57 men and 63 women; age 18 to 70 years) randomly selected according to predefined age and sex strata. Diseases associated with NVC changes were excluded. The nailfolds of eight fingers were assessed according to standardized procedures. A scoring system was developed based on the distribution of the number of morphologically deviating capillaries, microhaemorrhages, and capillary density. Results: Only 18 individuals (15 %) had no deviation in morphology, haemorrhages, or capillary density on any finger. Overall 67 % had morphological changes, 48 % had microhaemorrhages, and 40 % of volunteers below 40 years of age and 18 % above age 40 had less than 8 capillaries/mm. Among morphological changes tortous (43 %), ramified (47 %), and bushy capillaries (27 %) were the most frequently altered capillary types. A semiquantitative scoring system was developed in such a way that a score above 1 indicates an extreme position (above the 90th percentile) in the distribution of scores among healthy individuals. Conclusions: Altered capillaries occur frequently among healthy individuals and should be interpreted as normal unless a suspicious increase in their frequency is determined by reference to the scoring system. Megacapillaries and diffuse loss of capillaries were not found and seem to be of specific diagnostic value.

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