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BioRxiv : the Preprint Server For... Jan 2024Male germ cells, which are responsible for producing millions of genetically diverse sperm through meiosis in the testis, rely on lactate as their central energy...
Male germ cells, which are responsible for producing millions of genetically diverse sperm through meiosis in the testis, rely on lactate as their central energy metabolite. Recent study has revealed that lactate induces epigenetic modification in cells through histone lactylation, a post-translational modification involving the addition of lactyl groups to lysine residues on histones. Here we report dynamic histone lactylation at histone H4-lysine 5 (K5), -K8, and -K12 during meiosis prophase I in mouse spermatogenesis. By profiling genome-wide occupancy of histone H4-K8 lactylation (H4K8la), which peaks at zygotene, our data show that H4K8la mark is observed at the promoters of genes exhibiting active expression with Gene Ontology (GO) functions enriched for meiosis. Notably, our data also demonstrate that H4K8la is closely associated with recombination hotspots, where machinery involved in the processing DNA double-stranded breaks (DSBs), such as SPO11, DMC1, RAD51, and RPA2, is engaged. In addition, H4K8la was also detected at the meiosis-specific cohesion sites (marked by RAD21L and REC8) flanking the recombination hotspots. Collectively, our findings suggest that histone lactylation serves as a novel mechanism through which lactate regulates germ cell meiosis.
PubMed: 38328171
DOI: 10.1101/2024.01.25.576681 -
ACG Case Reports Journal Jan 2021Cholestatic hepatitis is a rare presentation of thyrotoxicosis potentially confused as an adverse effect of antithyroid therapy. We report a 37-year-old man with...
Cholestatic hepatitis is a rare presentation of thyrotoxicosis potentially confused as an adverse effect of antithyroid therapy. We report a 37-year-old man with cholestatic hepatitis as an initial presentation of Graves' disease. Diagnostic evaluation demonstrated (i) elevated transaminases and alkaline phosphatase (R-factor value: 2.6), and marked cholestasis (total bilirubin: 17.3 mg/dL, direct bilirubin: 9.4 mg/dL); (ii) negative hepatitis, viral, and autoimmune serologies; (iii) normal magnetic resonance cholangiopancreatography; (iv) liver biopsy with marked cholestasis and no fibrosis; (v) thyroid-stimulating hormone <0.01, fT4 (free thyroxine): 1.5, fT4 (free triiodothyronine): 4.3 and positive thyroid-stimulating immunoglobulins. Radioiodine uptake scan confirmed Graves' disease. Clinical resolution was achieved with propranolol, prednisone, methimazole, and thyroidectomy.
PubMed: 33490298
DOI: 10.14309/crj.0000000000000526 -
Communications Medicine Dec 2023Single-cell multiplex imaging data have provided new insights into disease subtypes and prognoses recently. However, quantitative models that explicitly capture...
BACKGROUND
Single-cell multiplex imaging data have provided new insights into disease subtypes and prognoses recently. However, quantitative models that explicitly capture single-cell resolution cell-cell interaction features to predict patient survival at a population scale are currently missing.
METHODS
We quantified hundreds of single-cell resolution cell-cell interaction features through neighborhood calculation, in addition to cellular phenotypes. We applied these features to a neural-network-based Cox-nnet survival model to identify survival-associated features. We used non-negative matrix factorization (NMF) to identify patient survival subtypes. We identified atypical subpopulations of triple-negative breast cancer (TNBC) patients with moderate prognosis and Luminal A patients with poor prognosis and validated these subpopulations by label transferring using the UNION-COM method.
RESULTS
The neural-network-based Cox-nnet survival model using all cellular phenotype and cell-cell interaction features is highly predictive of patient survival in the test data (Concordance Index > 0.8). We identify seven survival subtypes using the top survival features, presenting distinct profiles of epithelial, immune, and fibroblast cells and their interactions. We reveal atypical subpopulations of TNBC patients with moderate prognosis (marked by GATA3 over-expression) and Luminal A patients with poor prognosis (marked by KRT6 and ACTA2 over-expression and CDH1 under-expression). These atypical subpopulations are validated in TCGA-BRCA and METABRIC datasets.
CONCLUSIONS
This work provides an approach to bridge single-cell level information toward population-level survival prediction.
PubMed: 38114659
DOI: 10.1038/s43856-023-00414-6 -
JIMD Reports 2015Adult Refsum disease is an autosomal recessive peroxisomal disorder characterized by phytanic acid storage. Clinical symptoms usually begin in late childhood before the...
Adult Refsum disease is an autosomal recessive peroxisomal disorder characterized by phytanic acid storage. Clinical symptoms usually begin in late childhood before the age of 20. Typical clinical presentation includes nyctalopia caused by retinitis pigmentosa, and anosmia. After 10-15 years, deafness, cerebellar ataxia, polyneuropathy, ichthyosis, and cardiac arrhythmia can occur.We report the case of a very late-onset adult Refsum disease presenting with marked cognitive decline and severe leukoencephalopathy, without peripheral nervous system involvement. Brain MRI showed a leukoencephalopathy involving the periventricular white matter, subcortical area, and the brainstem with relative sparing of juxtacortical U fibers. This was associated with severe cortical and subcortical atrophy with ventricle dilatation. MR spectroscopy showed a marked increase in the choline/NAA ratio. Elevated plasma phytanic acid level was found, whereas plasma levels of pristanic and very long chain fatty acids were normal. The patient is homozygous for a previously undescribed PHYH frameshift mutation. Whether the very unusual phenotype is related to this peculiar mutation remains unclear.
PubMed: 25604618
DOI: 10.1007/8904_2014_355 -
Journal of Veterinary Diagnostic... Jul 2019is a small subshrub that is distributed throughout Brazil and is responsible for lysosomal storage disease and occasional reproductive problems in cattle, goats,...
is a small subshrub that is distributed throughout Brazil and is responsible for lysosomal storage disease and occasional reproductive problems in cattle, goats, equids, sheep, and deer. We describe herein the clinical, epidemiologic, and pathologic features of hydrallantois in 3 cows naturally poisoned by in Rio Grande do Sul State, Brazil. Clinically, all cows had marked abdominal distension and mild ataxia. After natural death or euthanasia, autopsies revealed that the abdominal distension in all 3 cases was caused by severe enlargement of the uterus, which contained 100-120 L of translucent fluid within the allantois, in addition to adventitial placentation. Microscopic evaluation of the placenta revealed marked diffuse edema, sometimes with a myxomatous appearance. Neurons in the cerebellum and obex were swollen, with mild-to-moderate cytoplasmic granular vacuolation. Histochemical examination with lectins ConA, WGA, and sWGA revealed mild-to-marked staining in the cytoplasm of neurons of the cerebellum and medulla at the level of the obex, indicating the occurrence of α-mannosidosis.
Topics: Allantois; Animals; Brain Diseases; Brazil; Cattle; Cattle Diseases; Female; Malvaceae; Plant Poisoning
PubMed: 31122163
DOI: 10.1177/1040638719850610 -
AMA Journal of Ethics Dec 2020Why is the transition from "living" to "dying" not socially marked in the same way that death is marked? This question is addressed using classical anthropological...
Why is the transition from "living" to "dying" not socially marked in the same way that death is marked? This question is addressed using classical anthropological theory, which highlights the significance of liminality, the transitional period during a rite of passage. Seriously ill and dying patients are subject to social vulnerabilities as they approach the end of life. Clinicians' awareness of these factors may improve their patients' care.
Topics: Attitude to Death; Hospitals; Humans; Terminal Care
PubMed: 33419508
DOI: 10.1001/amajethics.2020.1062 -
Frontiers in Sociology 2023The article employs ethnomethodological conversation analysis (CA) and experimental video analysis to scrutinize the gaze behavior of urban passersby. We operationalize...
The article employs ethnomethodological conversation analysis (CA) and experimental video analysis to scrutinize the gaze behavior of urban passersby. We operationalize Goffman's concept of civil inattention to make it an empirical research object with defined boundaries. Video analysis enabled measurement of gaze lengths to establish measures for "normal" gazes within civil inattention and to account for their breaches. We also studied the dependence of gazing behavior on the recipient's social appearance by comparing the unmarked condition, the experimenter wearing casual, indistinctive clothes, to marked conditions, the experimenter wearing either a distinct sunhat or an abaya and niqab. The breaches of civil inattention toward marked gaze recipients were 10-fold compared to unmarked recipients. Furthermore, the analysis points out the commonality of hitherto unknown micro gazes and multiple gazes. Together the findings suggest the existence of subconscious monitoring beneath the public social order, which pre-structures interaction order, and indicates that stigmatization is a source for relational segregation.
PubMed: 37731909
DOI: 10.3389/fsoc.2023.1212090 -
Nature Biomedical Engineering Dec 2021In cardiovascular tissues, changes in the mechanical properties of the extracellular matrix are associated with cellular de-differentiation and with subsequent...
In cardiovascular tissues, changes in the mechanical properties of the extracellular matrix are associated with cellular de-differentiation and with subsequent functional declines. However, the underlying mechanoreceptive mechanisms are largely unclear. Here, by generating high-resolution, full-field strain maps of cardiomyocyte nuclei during contraction in vitro, complemented with evidence from tissues from patients with cardiomyopathy and from mice with reduced cardiac performance, we show that cardiomyocytes establish a distinct nuclear organization during maturation, characterized by the reorganization of H3K9me3-marked chromatin towards the nuclear border. Specifically, we show that intranuclear tension is spatially correlated with H3K9me3-marked chromatin, that reductions in nuclear deformation (through environmental stiffening or through the disruption of complexes of the linker of nucleoskeleton and cytoskeleton) abrogate chromatin reorganization and lead to the dissociation of H3K9me3-marked chromatin from the nuclear periphery, and that the suppression of H3K9 methylation induces chromatin reorganization and reduces the expression of cardiac developmental genes. Overall, our findings indicate that, by integrating environmental mechanical cues, the nuclei of cardiomyocytes guide and stabilize the fate of cells through the reorganization of epigenetically marked chromatin.
Topics: Animals; Cell Nucleus; Chromatin; Cytoskeleton; Humans; Mice; Myocytes, Cardiac
PubMed: 34857921
DOI: 10.1038/s41551-021-00823-9 -
Oncotarget Aug 2015
PubMed: 26317653
DOI: 10.18632/oncotarget.5178 -
Interventional Neuroradiology : Journal... Jun 2020Diploic arteriovenous fistulas are rare arteriovenous shunts involving the skull, which often drain antegradely into the internal or external jugular veins. Diploic... (Review)
Review
Diploic arteriovenous fistulas are rare arteriovenous shunts involving the skull, which often drain antegradely into the internal or external jugular veins. Diploic arteriovenous fistulas with marked cortical venous reflux are extremely rare. Here, we present the case of a patient with diploic arteriovenous fistulas with marked cortical venous reflux and a literature review. A 73-year-old woman presented with headache. Magnetic resonance angiography revealed abnormal signal intensity in the diploic layer of the left frontal bone. Digital subtraction angiography demonstrated a diploic arteriovenous fistulas located in the left frontal bone. The arteriovenous fistulas were fed by multiple branches of the left external carotid artery, mainly from the middle meningeal artery, branches of the ophthalmic artery, and the inferolateral trunk. The fistulas drained into the cerebral cortical veins surrounding the frontal lobe via an emissary vein of the frontal bone. With the femoral arterial approach, transarterial catheterization into the shunted diploic vein was performed with a small tapered microcatheter, and the arteriovenous fistulas were completely embolized with N-butyl-2-cyanoacrylate. The patient was discharged without complications. No recurrent arteriovenous fistulas were observed during the 12-month follow-up period. Endovascular treatment is an effective technique for the curative treatment of diploic arteriovenous fistulas.
Topics: Aged; Angiography, Digital Subtraction; Arteriovenous Fistula; Cerebral Angiography; Diagnosis, Differential; Embolization, Therapeutic; Enbucrilate; Female; Humans; Intracranial Arteriovenous Malformations; Magnetic Resonance Angiography
PubMed: 31856646
DOI: 10.1177/1591019919894496