A few years into the COVID-19 pandemic, the SARS-CoV-2 Omicron strain rapidly becomes and has remained the predominant strain. To date, Omicron and its subvariants, while more transmittable, appear to cause less severe disease than prior strains. To study the cause of this reduced pathogenicity we compare SARS-CoV-2 ancestral Nsp6 with Nsp6-Omicron, which we have previously identified as one of the most pathogenic viral proteins.
View Article and Find Full Text PDFJ Hand Surg Eur Vol
November 2024
We present a novel surgical technique for avoiding joint surface injury by directly immobilizing the bone mass fracture fragment with K-wires sparing the joint.
View Article and Find Full Text PDFThe multiprotein complexes known as the complex of proteins associated with Set1 (COMPASS) play a crucial role in the methylation of histone 3 lysine 4 (H3K4). In Drosophila, the COMPASS series complexes comprise core subunits Set1, Trx, and Trr, which share several common subunits such as ash2, Dpy30-L1, Rbbp5, and wds, alongside their unique subunits: Wdr82 for Set1/COMPASS, Mnn1 for Trx/COMPASS-like, and Ptip for Trr/COMPASS-like. Our research has shown that flies deficient in any of these common or unique subunits exhibited high lethality at eclosion (the emergence of adult flies from their pupal cases) and significantly shortened lifespans of the few adults that do emerge.
View Article and Find Full Text PDFMitochondria are crucial for cellular ATP production. They are highly dynamic organelles, whose morphology and function are controlled through mitochondrial fusion and fission. The specific roles of mitochondria in podocytes, the highly specialized cells of the kidney glomerulus, remain less understood.
View Article and Find Full Text PDFDiabetes is a metabolic disorder characterized by high blood glucose levels and is a leading cause of kidney disease. Diabetic nephropathy has been attributed to dysfunctional mitochondria. However, many questions remain about the exact mechanism.
View Article and Find Full Text PDFPeople carrying two risk alleles (RA) or are at greater risk of developing HIV-associated nephropathy (HIVAN). Studies in transgenic mice showed that the expression of HIV-1 genes in podocytes, and in particular, led to HIVAN. However, it remains unclear whether APOL1-RA and HIV-1 Nef interact to induce podocyte cell death.
View Article and Find Full Text PDFHighly evolutionarily conserved multiprotein complexes termed Complex of Proteins Associated with Set1 (COMPASS) are required for histone 3 lysine 4 (H3K4) methylation. Set1, Trx, and Trr form the core subunits of these complexes. We show that flies deficient in any of these three subunits demonstrated high lethality at eclosion (emergence of adult flies from their pupal cases) and significantly shortened lifespans for the adults that did emerge.
View Article and Find Full Text PDFPeople of African ancestry who carry the APOL1 risk alleles G1 or G2 are at high risk of developing kidney diseases through not fully understood mechanisms that impair the function of podocytes. It is also not clear whether the APOL1-G1 and APOL1-G2 risk alleles affect these cells through similar mechanisms. Previously, we have developed transgenic Drosophila melanogaster lines expressing either the human APOL1 reference allele (G0) or APOL1-G1 specifically in nephrocytes, the cells homologous to mammalian podocytes.
View Article and Find Full Text PDFBackground: People of Sub-Saharan African ancestry are at higher risk of developing chronic kidney disease (CKD), attributed to the Apolipoprotein L1 (APOL1) gene risk alleles (RA) G1 and G2. The underlying mechanisms by which the APOL1-RA precipitate CKD remain elusive, hindering the development of potential treatments.
Results: Using a Drosophila genetic modifier screen, we found that SNARE proteins (Syx7, Ykt6, and Syb) play an important role in preventing APOL1 cytotoxicity.
W.T. Wang 1980 is an important traditional medicinal plant used for the treatment of cardiac diseases.
View Article and Find Full Text PDFMethyltransferases regulate transcriptome dynamics during development and aging, as well as in disease. Various methyltransferases have been linked to heart disease, through disrupted expression and activity, and genetic variants associated with congenital heart disease. However, in vivo functional data for many of the methyltransferases in the context of the heart are limited.
View Article and Find Full Text PDFJ Cardiovasc Dev Dis
July 2023
Epigenetic marks regulate the transcriptomic landscape by facilitating the structural packing and unwinding of the genome, which is tightly folded inside the nucleus. Lysine-specific histone methylation is one such mark. It plays crucial roles during development, including in cell fate decisions, in tissue patterning, and in regulating cellular metabolic processes.
View Article and Find Full Text PDFhas a long-standing history of use in traditional medicine for the treatment of tuberculosis diseases. However, the plant's therapeutic potential extends beyond this specific ailment. The present study aimed to investigate the antioxidant properties of and lay the groundwork for further research on its potential therapeutic applications.
View Article and Find Full Text PDFSARS-CoV-2 infection causes COVID-19, a severe acute respiratory disease associated with cardiovascular complications including long-term outcomes. The presence of virus in cardiac tissue of patients with COVID-19 suggests this is a direct, rather than secondary, effect of infection. Here, by expressing individual SARS-CoV-2 proteins in the Drosophila heart, we demonstrate interaction of virus Nsp6 with host proteins of the MGA/MAX complex (MGA, PCGF6 and TFDP1).
View Article and Find Full Text PDFMammalian KMT2C, KMT2D, and HCFC1 are expressed during heart development and have been associated with congenital heart disease, but their roles in heart development remain elusive. We found that the Drosophila Lpt and trr genes encode the N-terminal and C-terminal homologs, respectively, of mammalian KMT2C or KMT2D. Lpt and trr mutant embryos showed reduced cardiac progenitor cells.
View Article and Find Full Text PDFOncogenic Ras mutations are highly prevalent in hematopoietic malignancies. However, it is difficult to directly target oncogenic RAS proteins for therapeutic intervention. We have developed a Drosophila acute myeloid leukemia model induced by human KRASG12V, which exhibits a dramatic increase in myeloid-like leukemia cells.
View Article and Find Full Text PDFHistone acetylations are important epigenetic markers for transcriptional activation in response to metabolic changes and various stresses. Using the high-throughput SEquencing-Based Yeast replicative Lifespan screen method and the yeast knockout collection, we demonstrate that the HDA complex, a class-II histone deacetylase (HDAC), regulates aging through its target of acetylated H3K18 at storage carbohydrate genes. We find that, in addition to longer lifespan, disruption of HDA results in resistance to DNA damage and osmotic stresses.
View Article and Find Full Text PDFBackground: SARS-CoV-2 causes COVID-19 with a widely diverse disease profile that affects many different tissues. The mechanisms underlying its pathogenicity in host organisms remain unclear. Animal models for studying the pathogenicity of SARS-CoV-2 proteins are lacking.
View Article and Find Full Text PDFBackground: Continuous cropping of ginseng (Panax ginseng Meyer) cultivated in farmland for an extended period gives rise to soil-borne disease. The change in soil microbial composition is a major cause of soil-borne diseases and an obstacle to continuous cropping. The impact of cultivation modes and ages on the diversity and composition of the P.
View Article and Find Full Text PDFBackground: Studies have linked mutations in genes encoding the eight-protein exocyst protein complex to kidney disease, but the underlying mechanism is unclear. Because nephrocytes share molecular and structural features with mammalian podocytes, they provide an efficient model for studying this issue.
Methods: We silenced genes encoding exocyst complex proteins specifically in nephrocytes and studied the effects on protein reabsorption by lacuna channels and filtration by the slit diaphragm.
Background: Studies have identified mutations in >50 genes that can lead to monogenic steroid-resistant nephrotic syndrome (SRNS). The gene, which encodes one of the protein components of the nuclear pore complex nucleoporin 160 kD (Nup160), is expressed in both human and mouse kidney cells. Knockdown of impairs mouse podocytes in cell culture.
View Article and Find Full Text PDFObjective: To compare the clinical efficacy of minimally invasive percutaneous plate osteosynthesis(MIPPO)and open reduction and internal fixation (ORIF) in treating senile NEER IIproximal humerus fractures.
Methods: From March 2014 to March 2016, 46 elderly patients with Neer II proximal humerus fractures were retrospectively reviewed. Among them, 20 patients in MIPPO group included 9 males and 11 females with an average age of (70.
Key Points: Sensory information processing in hippocampal circuits is critical for numerous hippocampus-dependent functions, but the underlying synaptic mechanism remains elusive. We performed whole-cell recording in vivo to examine visually evoked synaptic activity in hippocampal CA1 pyramidal cells (PCs). We first found that at resting potentials, ∼30% of CA1 PCs showed synaptic responses to a flash of visual stimulation.
View Article and Find Full Text PDF