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About 24,193 results

A kinase-independent function of cyclin-dependent kinase 6 promotes outer radial glia e...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499540
Proceedings of the National Academy of Sciences of the Un... Wang L, Park JY et. al.

Sep 13th, 2022 - The neocortex, the center for higher brain function, first emerged in mammals and has become massively expanded and folded in humans, constituting almost half the volume of the human brain. Primary microcephaly, a developmental disorder in which the brain is smaller than normal at birth, results mainly from there being fewer neurons in the neocortex because of defects in neural progenitor cells...

A partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436381
Proceedings of the National Academy of Sciences of the Un... Guillén-Samander A, Wu Y et. al.

Aug 23rd, 2022 - Chorea-acanthocytosis (ChAc) and McLeod syndrome are diseases with shared clinical manifestations caused by mutations in VPS13A and XK, respectively. Key features of these conditions are the degeneration of caudate neurons and the presence of abnormally shaped erythrocytes. XK belongs to a family of plasma membrane (PM) lipid scramblases whose action results in exposure of PtdSer at the cell su...

Colistin-degrading proteases confer collective resistance to microbial communities duri...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389796
Microbiome Lee DH, Cha JH et. al.

Aug 19th, 2022 - The increasing prevalence of resistance against the last-resort antibiotic colistin is a significant threat to global public health. Here, we discovered a novel colistin resistance mechanism via enzymatic inactivation of the drug and proposed its clinical importance in microbial communities during polymicrobial infections. A bacterial strain of the Gram-negative opportunistic pathogen Stenotrop...

Structures of the mannose-6-phosphate pathway enzyme, GlcNAc-1-phosphotransferase.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388126
Proceedings of the National Academy of Sciences of the Un... Gorelik A, Illes K et. al.

Aug 9th, 2022 - The mannose-6-phosphate (M6P) pathway is responsible for the transport of hydrolytic enzymes to lysosomes. N-acetylglucosamine-1-phosphotransferase (GNPT) catalyzes the first step of tagging these hydrolases with M6P, which when recognized by receptors in the Golgi diverts them to lysosomes. Genetic defects in the GNPT subunits, GNPTAB and GNPTG, cause the lysosomal storage diseases mucolipidos...

Restoration of atypical protein kinase C ζ function in autosomal dominant polycystic ki...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335328
Proceedings of the National Academy of Sciences of the Un... Akbari M, West JD et. al.

Jul 23rd, 2022 - Autosomal dominant polycystic kidney disease (ADPKD) affects more than 500,000 individuals in the United States alone. In most cases, ADPKD is caused by a loss-of-function mutation in the PKD1 gene, which encodes polycystin-1 (PC1). Previous studies reported that PC1 interacts with atypical protein kinase C (aPKC). Here we show that PC1 binds to the ζ isoform of aPKC (PKCζ) and identify two PKC...

A versatile fluorescence-quenched substrate for quantitative measurement of glucocerebr...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304032
Proceedings of the National Academy of Sciences of the Un... Deen MC, Zhu Y et. al.

Jul 21st, 2022 - Loss of activity of the lysosomal glycosidase β-glucocerebrosidase (GCase) causes the lysosomal storage disease Gaucher disease (GD) and has emerged as the greatest genetic risk factor for the development of both Parkinson disease (PD) and dementia with Lewy bodies. There is significant interest into how GCase dysfunction contributes to these diseases, however, progress toward a full understand...

Tropism of SARS-CoV-2 for human cortical astrocytes.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335272
Proceedings of the National Academy of Sciences of the Un... Andrews MG, Mukhtar T et. al.

Jul 21st, 2022 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, accompany as many as one-third of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortica...

Recurrent PTPN14 Mutations in Trichilemmoma: Evidence for Distinct Pathways of Molecula...
https://doi.org/10.1097/DAD.0000000000002015
The American Journal of Dermatopathology; Russell-Goldman E, Dong F et. al.

Jul 14th, 2022 - Trichilemmoma is a benign cutaneous neoplasm that recapitulates the outer root sheath of the hair follicle. Trichilemmomas may occur sporadically or in association with Cowden syndrome, which is characterized by germline mutations in the lipid phosphatase PTEN (phosphatase and tensin homolog on chromosome 10). Interestingly, most sporadic trichilemmomas do not show PTEN aberrations, but rather ...

A male steroid controls female sexual behaviour in the malaria mosquito.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352575
Nature Peng D, Kakani EG et. al.

Jul 7th, 2022 - Insects, unlike vertebrates, are widely believed to lack male-biased sex steroid hormones1. In the malaria mosquito Anopheles gambiae, the ecdysteroid 20-hydroxyecdysone (20E) appears to have evolved to both control egg development when synthesized by females2 and to induce mating refractoriness when sexually transferred by males3. Because egg development and mating are essential reproductive t...

Clinical features of superficial esophagus squamous cell carcinoma according to alcohol...
https://doi.org/10.1007/s00535-022-01892-6
Journal of Gastroenterology; Tajiri A, Ishihara R et. al.

Jul 6th, 2022 - Inactivated alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are related to esophageal carcinogenesis. We aimed to clarify the clinical features associated with the alcohol-degrading enzyme genotypes, ADH1B and ALDH2. We also investigated the risk factors for metachronous esophageal squamous cell carcinoma (ESCC) and head and neck SCC (HNSCC). We conducted a single-center, retrospe...

Pattern of Recurrence of Glioblastoma Versus Grade 4 IDH-Mutant Astrocytoma Following C...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247382
Technology in Cancer Research & Treatment; Stewart J, Sahgal A et. al.

Jun 29th, 2022 - Background and Purpose: To quantitatively compare the recurrence patterns of glioblastoma (isocitrate dehydrogenase-wild type) versus grade 4 isocitrate dehydrogenase-mutant astrocytoma (wild type isocitrate dehydrogenase and mutant isocitrate dehydrogenase, respectively) following primary chemoradiation. Materials and Methods: A retrospective matched cohort of 22 wild type isocitrate dehydroge...

Characterization of a thermostable Cas13 enzyme for one-pot detection of SARS-CoV-2.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282225
Proceedings of the National Academy of Sciences of the Un... Mahas A, Marsic T et. al.

Jun 29th, 2022 - Type VI CRISPR-Cas systems have been repurposed for various applications such as gene knockdown, viral interference, and diagnostics. However, the identification and characterization of thermophilic orthologs will expand and unlock the potential of diverse biotechnological applications. Herein, we identified and characterized a thermostable ortholog of the Cas13a family from the thermophilic or...

Crystal Structures of Flavivirus NS5 Guanylyltransferase Reveal a GMP-Arginine Adduct.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327709
Journal of Virology; Jia H, Zhong Y et. al.

Jun 28th, 2022 - The positive-sense flavivirus RNA genome bears a cap 1 structure essential for RNA stability and viral protein translation, and the formation of cap 1 requires the virally encoded nonstructural protein NS5 harboring guanylyltransferase (GTase), cap guanine N7 methyltransferase (N7 MTase), and 5'-nucleotide ribose 2'-O MTase activities in its single-domain MTase module. Despite numerous MTase-co...

Fazirsiran for Liver Disease Associated with Alpha1-Antitrypsin Deficiency.
https://doi.org/10.1056/NEJMoa2205416
The New England Journal of Medicine; Strnad P, Mandorfer M et. al.

Jun 25th, 2022 - Alpha1-antitrypsin (AAT) deficiency results from carriage of a homozygous SERPINA1 "Z" mutation (proteinase inhibitor [PI] ZZ). The Z allele produces a mutant AAT protein called Z-AAT, which accumulates in hepatocytes and can lead to progressive liver disease and fibrosis. This open-label, phase 2 trial investigated the safety and efficacy of fazirsiran, an RNA interference therapeutic, in pati...

The GALNS p.P77R variant is a probable Gujarati-Indian founder mutation causing Mucopol...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210747
BMC Genomics; Sheth H, Naik P et. al.

Jun 22nd, 2022 - Mucopolysaccharidosis IVA (Morquio syndrome A, MPS IVA) is an autosomal recessive lysosomal storage disorder caused due to biallelic variants in the N-acetylgalactoseamine-6-sulfate sulfatase (GALNS) gene. The mutation spectrum in this condition is determined amongst sub-populations belonging to the north, south and east India geography, however, sub-populations of west Indian origin, especiall...

Relation between endothelial nitric oxide synthase genetic polymorphisms and pulmonary ...
https://doi.org/10.1080/10641963.2022.2085736
Clinical and Experimental Hypertension (New York, N.Y. : ... Lin QF, Rao JH et. al.

Jun 15th, 2022 - To investigate whether endothelial nitric oxide synthase (eNOS) rs1799983, rs2070744, and rs61722009 gene polymorphisms are associated with pulmonary arterial hypertension (PAH) in South Fujian newborns with congenital heart disease (CHD). Genotyping for the eNOS rs1799983, rs2070744, and rs61722009 polymorphisms was performed using Sanger sequencing in 50 newborns with PAH secondary to CHD [CH...

Hepatitis B Virus X Protein Is Stabilized by the Deubiquitinating Enzyme VCPIP1 in a Ub...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278118
Journal of Virology; Wu Q, Zhang L et. al.

Jun 14th, 2022 - Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, and the viral X protein (HBx) is an etiological factor in HCC development. HBx is a high-turnover protein, but knowledge of the role of deubiquitinating enzymes (DUBs) in maintaining HBx homeostasis is very limited. We used a 74-DUB library-based yeast two-hybrid assay and determined that a...

Discovery of novel SARS-CoV-2 inhibitors targeting the main protease Mpro by virtual sc...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172283
Antiviral Research; Mercorelli B, Desantis J et. al.

Jun 11th, 2022 - Two years after its emergence, SARS-CoV-2 still represents a serious and global threat to human health. Antiviral drug development usually takes a long time and, to increase the chances of success, chemical variability of hit compounds represents a valuable source for the discovery of new antivirals. In this work, we applied a platform of variably oriented virtual screening campaigns to seek fo...

Secretory Cells Are the Primary Source of pIgR in Small Airways.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9447142
American Journal of Respiratory Cell and Molecular Biology; Blackburn JB, Schaff JA et. al.

Jun 11th, 2022 - Loss of secretory IgA (SIgA) is common in chronic obstructive pulmonary disease (COPD) small airways and likely contributes to disease progression. We hypothesized that loss of SIgA results from reduced expression of pIgR (polymeric immunoglobulin receptor), a chaperone protein needed for SIgA transcytosis, in the COPD small airway epithelium. pIgR-expressing cells were defined and quantified a...

Serological evaluation of the schistosome's secretory enzyme phytochelatin synthase and...
https://doi.org/10.1007/s00436-022-07568-7
Parasitology Research; Angeles JMM, Goto Y et. al.

Jun 8th, 2022 - Secretory enzymes from Schistosoma japonicum are promising candidate antigens in the diagnosis of schistosomiasis. Our previous studies have proven that thioredoxin peroxidase-1 (SjTPx-1) is useful for the detection of this parasitic disease in humans, water buffaloes, and dogs. In this study, we evaluated two more secretory enzymes namely phosphoglycerate mutase (SjPGM) and phytochelatin synth...