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About 219,428 results

A ferroptosis defense mechanism mediated by glycerol-3-phosphate dehydrogenase 2 in mit...
https://doi.org/10.1073/pnas.2121987119
Proceedings of the National Academy of Sciences of the Un... Wu S, Mao C et. al.

Jun 25th, 2022 - Mechanisms of defense against ferroptosis (an iron-dependent form of cell death induced by lipid peroxidation) in cellular organelles remain poorly understood, hindering our ability to target ferroptosis in disease treatment. In this study, metabolomic analyses revealed that treatment of cancer cells with glutathione peroxidase 4 (GPX4) inhibitors results in intracellular glycerol-3-phosphate (...

Structure of human NADK2 reveals atypical assembly and regulation of NAD kinases from a...
https://doi.org/10.1073/pnas.2200923119
Proceedings of the National Academy of Sciences of the Un... Du J, Estrella M et. al.

Jun 24th, 2022 - All kingdoms of life produce essential nicotinamide dinucleotide NADP(H) using NAD kinases (NADKs). A panel of published NADK structures from bacteria, eukaryotic cytosol, and yeast mitochondria revealed similar tetrameric enzymes. Here, we present the 2.8-Å structure of the human mitochondrial kinase NADK2 with a bound substrate, which is an exception to this uniformity, diverging both structu...

Phylogenomic and functional characterization of an evolutionary conserved cytochrome P4...
https://doi.org/10.1073/pnas.2205850119
Proceedings of the National Academy of Sciences of the Un... Haas J, Hayward A et. al.

Jun 24th, 2022 - The regulatory process for assessing the risks of pesticides to bees relies heavily on the use of the honeybee, Apis mellifera, as a model for other bee species. However, the validity of using A. mellifera as a surrogate for other Apis and non-Apis bees in pesticide risk assessment has been questioned. Related to this line of research, recent work on A. mellifera has shown that specific P450 en...

Interaction between S4 and the phosphatase domain mediates electrochemical coupling in ...
https://doi.org/10.1073/pnas.2200364119
Proceedings of the National Academy of Sciences of the Un... Mizutani N, Kawanabe A et. al.

Jun 23rd, 2022 - Voltage-sensing phosphatase (VSP) consists of a voltage sensor domain (VSD) and a cytoplasmic catalytic region (CCR), which is similar to phosphatase and tensin homolog (PTEN). How the VSD regulates the innate enzyme component of VSP remains unclear. Here, we took a combined approach that entailed the use of electrophysiology, fluorometry, and structural modeling to study the electrochemical co...

Regression of EGFR positive established solid tumors in mice with the conditionally act...
https://doi.org/10.1136/jitc-2021-004336
Journal for Immunotherapy of Cancer; Dettling DE, Kwok E et. al.

Jun 22nd, 2022 - Despite clinical success with T cell engagers (TCEs) targeting hematological malignancies, achieving a safe and efficacious dose in patients with solid tumors remains challenging. Due to potency, low levels of target antigen expression on normal tissues may not be tolerated. To overcome this, we engineered a novel conditionally active TCE design called COBRA (Conditional Bispecific Redirected A...

The GALNS p.P77R variant is a probable Gujarati-Indian founder mutation causing Mucopol...
https://doi.org/10.1186/s12864-022-08693-4 10.1016/0006-291X(74)91022-5 10.1006/geno.1994.1132 10.1016/j.ymgme.2018.05.004 10.1016/j.ymgme.2013.04.002 10.1007/s004390050641 10.1002/ajmg.a.20314 10.3390/ijms21030989 10.1002/ajmg.a.32781 10.1186/s13023-019-1105-6 10.1016/0006-291X(91)91244-7 10.1016/j.ymgme.2014.03.004 10.1002/ajmg.a.36735 10.1038/gim.2015.30 10.1002/humu.22751 10.1634/theoncologist.2015-0416 10.1371/journal.pone.0207409 10.1093/hmg/9.9.1283 10.1002/humu.20257 10.1016/j.gene.2019.04.026 10.1086/302946 10.1186/s13023-020-01597-0 10.1371/journal.pone.0039122 10.1093/clinchem/35.7.1472 10.1016/0003-2697(82)90674-1 10.1016/0009-8981(90)90339-T 10.1093/nar/16.3.1215 10.1093/bioinformatics/btu353 10.1101/gr.147686.112 10.1126/science.1227764 10.1093/bioinformatics/btp324 10.1093/bioinformatics/18.6.894
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...

Catechol-O-methyltransferase activity in individuals with substance use disorders: a ca...
https://doi.org/10.1186/s12888-022-04068-x 10.1176/appi.ajp.158.11.1783 10.1111/j.1369-1600.2008.00129.x 10.1111/nyas.13977 10.1016/j.bcp.2007.06.043 10.1176/appi.ajp.159.10.1642 10.1016/j.cell.2015.07.046 10.1523/JNEUROSCI.1180-12.2012 10.1080/02791072.2000.10736099 10.2174/187152712800672481 10.1016/S0306-4522(02)00556-0 10.1371/journal.pone.0006507 10.1016/j.biopsych.2011.03.028 10.2174/187152712800672409 10.2478/bjmg-2020-0010 10.3109/10826084.2014.901391 10.1007/s11307-009-0257-5 10.1152/physrev.1998.78.1.189 10.1177/014107689608900711 10.1177/1557988316681339 10.1016/S0924-9338(97)83296-8 10.1016/S0924-9338(97)86748-X 10.3389/fpsyt.2018.00010 10.1159/000259089 10.1037/lhb0000174 10.1016/j.forsciint.2004.03.019 10.1590/s1516-44462006005000020 10.1080/1068316X.2015.1054386 10.1159/000365282 10.1007/s40519-015-0213-0 10.1006/abio.1976.9999 10.1016/s0006-8993(99)01063-x 10.1371/journal.pone.0229876 10.1111/1556-4029.14137 10.1177/0306624X16689833 10.1186/1471-244X-6-33 10.1001/archpsyc.1997.01830130077015 10.1521/pedi.2005.19.4.339 10.1016/j.tics.2015.06.007 10.1016/j.molmed.2006.10.005 10.1186/1747-597X-2-22 10.1007/s00213-020-05599-5
BMC Psychiatry; da Costa Azevedo JN, Carvalho C et. al.

Jun 22nd, 2022 - Impulsivity and substance use disorders (SUD) have been both associated with changes in dopaminergic processes. In this study, we intended to evaluate the dopaminergic function in imprisoned SUD offenders through the determination of s-COMT activity. The study included 46 male individuals from a Portuguese penal institution. The participants were assessed through a battery of standardised instr...

Kinetic model for reversible radical transfer in ribonucleotide reductase.
https://doi.org/10.1073/pnas.2202022119
Proceedings of the National Academy of Sciences of the Un... Reinhardt CR, Konstantinovsky D et. al.

Jun 18th, 2022 - The enzyme ribonucleotide reductase (RNR), which catalyzes the reduction of ribonucleotides to deoxynucleotides, is vital for DNA synthesis, replication, and repair in all living organisms. Its mechanism requires long-range radical translocation over ∼32 Å through two protein subunits and the intervening aqueous interface. Herein, a kinetic model is designed to describe reversible radical trans...

Nuclear speckle integrity and function require TAO2 kinase.
https://doi.org/10.1073/pnas.2206046119
Proceedings of the National Academy of Sciences of the Un... Gao S, Esparza M et. al.

Jun 16th, 2022 - Nuclear speckles are non-membrane-bound organelles known as storage sites for messenger RNA (mRNA) processing and splicing factors. More recently, nuclear speckles have also been implicated in splicing and export of a subset of mRNAs, including the influenza virus M mRNA that encodes proteins required for viral entry, trafficking, and budding. However, little is known about how nuclear speckles...

Naringenin as a potential inhibitor of human cyclin-dependent kinase 6: Molecular and s...
https://doi.org/10.1016/j.ijbiomac.2022.06.013
International Journal of Biological Macromolecules; Yousuf M, Shamsi A et. al.

Jun 12th, 2022 - Cancer is one of the major causes of global deaths and needs immediate therapeutic development. So far, several strategies have been undertaken to prevent cancer, including kinase targeting by small-molecule inhibitors. Cyclin dependent kinase 6 (CDK6) plays an essential role in cancer progression and development as its overexpression is associated with tumor development and progression. The pr...

Chitin deacetylases are necessary for insect femur muscle attachment and mobility.
https://doi.org/10.1073/pnas.2120853119
Proceedings of the National Academy of Sciences of the Un... Mun S, Noh MY et. al.

Jun 9th, 2022 - Muscle attachment sites (MASs, apodemes) in insects and other arthropods involve specialized epithelial cells, called tendon cells or tenocytes, that adhere to apical extracellular matrices containing chitin. Here, we have uncovered a function for chitin deacetylases (CDAs) in arthropod locomotion and muscle attachment using a double-stranded RNA-mediated gene-silencing approach targeted toward...

WNT/RYK signaling functions as an antiinflammatory modulator in the lung mesenchyme.
https://doi.org/10.1073/pnas.2201707119
Proceedings of the National Academy of Sciences of the Un... Kim HT, Panza P et. al.

Jun 8th, 2022 - A number of inflammatory lung diseases, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and pneumonia, are modulated by WNT/β-catenin signaling. However, the underlying molecular mechanisms remain unclear. Here, starting with a forward genetic screen in mouse, we identify the WNT coreceptor Related to receptor tyrosine kinase (RYK) acting in mesenchymal tissues a...

Myeloid caspase-8 restricts RIPK3-dependent proinflammatory IL-1β production and CD4 T ...
https://doi.org/10.1073/pnas.2117636119
Proceedings of the National Academy of Sciences of the Un... Kim S, Lu HC et. al.

Jun 8th, 2022 - Caspase-8 functions at the crossroad of programmed cell death and inflammation. Here, using genetic approaches and the experimental autoimmune encephalomyelitis model of inflammatory demyelination, we identified a negative regulatory pathway for caspase-8 in infiltrated macrophages whereby it functions to restrain interleukin (IL)-1β-driven autoimmune inflammation. Caspase-8 is partially activa...

Pyruvate Kinase M2 Protects Heart from Pressure Overload-Induced Heart Failure by Phosp...
https://doi.org/10.1161/JAHA.121.024854
Journal of the American Heart Association; Ni L, Lin B et. al.

Jun 4th, 2022 - Background Heart failure, caused by sustained pressure overload, remains a major public health problem. PKM (pyruvate kinase M) acts as a rate-limiting enzyme of glycolysis. PKM2 (pyruvate kinase M2), an alternative splicing product of PKM, plays complex roles in various biological processes and diseases. However, the role of PKM2 in the development of heart failure remains unknown. Methods and...

Cell proliferation effects of S-allyl-L-cysteine are associated with phosphorylation of...
https://doi.org/10.1016/j.ejphar.2022.175067
European Journal of Pharmacology; Moteki H, Ogihara M et. al.

Jun 3rd, 2022 - The cell proliferation effect of S-allyl-L-cysteine (SAC) and its mechanisms were examined in primary cultures of adult rat hepatocytes. In serum-free cultivation, SAC (10-6 M)-stimulated hepatocytes showed significant proliferation compared to control at 5-h culture; the effect was dependent on the culture time and the dose of SAC (EC50 value 8.58 × 10-8 M). In addition, SAC-stimulated hepatoc...

Discovery of non-squalene triterpenes.
https://doi.org/10.1038/s41586-022-04773-3 10.1039/b616857b 10.1016/j.phytochem.2009.07.030 10.1039/C8NP00026C 10.3389/fpls.2019.01166 10.1039/b515312n 10.1039/C4NP00075G 10.1146/annurev-arplant-050312-120229 10.1016/S0021-9258(19)44269-5 10.1039/b108995c 10.1016/j.pbi.2006.03.004 10.1021/acs.chemrev.7b00287 10.1002/anie.201403648 10.1039/C5NP00102A 10.1080/09168451.2015.1065172 10.1074/jbc.M110.147991 10.1021/bi001311p 10.3390/md15090285 10.1002/cbic.201700445 10.1021/acs.accounts.1c00296 10.1073/pnas.2023247118 10.1016/j.jbiotec.2015.12.017 10.1186/1471-2164-13-493 10.1073/pnas.0608426104 10.1021/ol303408a 10.1002/anie.201809954 10.1002/anie.201612439 10.1002/anie.201803800 10.1021/acs.orglett.9b00725 10.1002/anie.201800385 10.1101/gr.849004 10.1021/bi00803a010 10.1021/jo00014a008 10.1002/anie.201507615 10.1002/anie.201812216 10.1021/acschembio.5b00960 10.1021/bi00202a004 10.1038/s41467-021-23589-9 10.2144/04375RV01 10.1021/jz1002007 10.1016/j.sbi.2016.05.010 10.1021/acs.biochem.7b00137 10.1038/s41586-021-03819-2 10.1371/journal.pone.0061777 10.1002/anie.202110842 10.1021/acs.orglett.8b00366 10.1093/molbev/msw054 10.1073/pnas.1705586114 10.1016/j.pep.2015.08.019 10.1107/S0907444909047337 10.1107/S0907444913000061 10.1107/S0021889807021206 10.1107/S0907444909052925 10.1107/S0907444904019158 10.1107/S0907444912001308 10.1107/S0907444904011679 10.1016/j.jsb.2015.11.003 10.7554/eLife.42166 10.1002/jcc.20084
Nature Tao H, Lauterbach L et. al.

Jun 2nd, 2022 - All known triterpenes are generated by triterpene synthases (TrTSs) from squalene or oxidosqualene1. This approach is fundamentally different from the biosynthesis of short-chain (C10-C25) terpenes that are formed from polyisoprenyl diphosphates2-4. In this study, two fungal chimeric class I TrTSs, Talaromyces verruculosus talaropentaene synthase (TvTS) and Macrophomina phaseolina macrophomene ...

Plasma lipoprotein-associated phospholipase A2 is associated with acute ischemic stroke...
https://doi.org/10.1016/j.jocn.2022.05.018
Journal of Clinical Neuroscience : Official Journal of Th... Wang Q

Jun 1st, 2022 - To investigate the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and the incidence of acute ischemic stroke (AIS) in patients with atrial fibrillation (AF). A total of 257 patients admitted to the Kaifeng Central Hospital were enrolled in this study. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression analysis were us...

Role of Stress Granules in Suppressing Viral Replication by the Infectious Bronchitis V...
https://doi.org/10.1128/jvi.00686-22
Journal of Virology; Zhao J, Feng D et. al.

Jun 1st, 2022 - Infectious bronchitis virus (IBV), a γ-coronavirus, causes the economically important poultry disease infectious bronchitis. Cellular stress response is an effective antiviral strategy that leads to stress granule (SG) formation. Previous studies suggested that SGs were involved in the antiviral activity of host cells to limit viral propagation. Here, we aimed to delineate the molecular mechani...

Adenosine kinase (ADK) inhibition with ABT-702 induces ADK protein degradation and a di...
https://doi.org/10.1016/j.ejphar.2022.175050
European Journal of Pharmacology; Wölkart G, Stessel H et. al.

May 27th, 2022 - Pharmacological inhibition of adenosine kinase (ADK), the major route of myocardial adenosine metabolism, can elicit acute cardioprotection against ischemia-reperfusion (IR) by increasing adenosine signaling. Here, we identified a novel, extended effect of the ADK inhibitor, ABT-702, on cardiac ADK protein longevity and investigated its impact on sustained adenosinergic cardioprotection. We fou...

The impact of ALDH7A1 variants in oral cancer development and prognosis.
https://doi.org/10.18632/aging.204099
Aging Lu HJ, Chuang CY et. al.

May 26th, 2022 - The gene encoding aldehyde dehydrogenase 7 family member A1 (ALDH7A1) has been associated with the development and prognosis in multiple cancers; however, the role of ALDH7A1 polymorphisms in oral cancer remains unknown. For this purpose, the influences of ALDH7A1 rs13182402 and rs12659017 on oral cancer development and prognosis were analyzed. Our resulted showed that ALDH7A1 rs13182402 genoty...