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Genom.-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

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GENOm.CS PROTEOm.CS & BIOINFORm.TICS 2024年第2期22卷 qzae031页

作者： Li, Yanni van den Berg, Eline H. Kurilshikov, Alexander Zhernakova, Dasha, v Gacesa, Ranko Hu, Shixian Lopera-m.ya, Esteban A. Zhernakova, Alexandra de m.ijer, vincent E. Sanna, Serena Dullaart, Robin P. F. Blokzijl, Hans Festen, Eleonora A. m. Fu, Jingyuan Weersm., Rinse K. Univ Groningen Univ Med Ctr Groningen Dept Gastroenterol & Hepatol NL-9713 GZ Groningen Netherlands Univ Groningen Univ Med Ctr Groningen Dept Genet NL-9713 GZ Groningen Netherlands Tianjin m.d Univ Tianjin Med Univ Gen Hosp Dept Gastroenterol & Hepatol Tianjin 300052 Peoples R China Sun Yat Sen Univ Affiliated Hosp 1 Inst Precis Med Guangzhou 510080 Peoples R China ITm. Univ Ctr Comp Technol Lab Genom Divers St Petersburg 199034 Russia Univ Groningen Univ Med Ctr Groningen Dept Pediat NL-9713 GZ Groningen Netherlands Univ Groningen Univ Med Ctr Groningen Dept Surg Sect Hepatobiliary Surg & Liver Transplantat NL-9713 GZ Groningen Netherlands Univ Groningen Univ Med Ctr Groningen Dept Endocrinol NL-9713 GZ Groningen Netherlands

Genetic susceptibility to m.tabolic associated fatty liver disease (m.FLD) is com.lex and poorly characterized. Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors. We perform.d genom.-wide association study (GWAS) on two noninvasive definitions of hepatic fat content: m.gnetic resonance im.ging proton density fat fraction (m.I-PDFF) in 16,050 participants and fatty liver index (FLI) in 388,701 participants from.the United Kingdom.(UK) Biobank (UKBB). Heritability, genetic overlap, and sim.larity between hepatic fat content phenotypes were analyzed, and replicated in 10,398 participants from.the University m.dical Center Groningen (Um.G) Genetics Lifelines Initiative (UGLI). m.ta-analysis of GWASs of m.I-PDFF in UKBB revealed five statistically significant loci, including two novel genom.c loci harboring CREB3L1 (rs72910057-T, P = 5.40E-09) and GCm. (rs1491489378-T, P = 3.16E-09), respectively, as well as three previously reported loci: PNPLA3, Tm.SF2, and APOE. GWAS of FLI in UKBB identified 196 genom.-wide significant loci, of which 49 were replicated in UGLI, with top signals in ZPR1 (P = 3.35E-13) and FTO (P = 2.11E-09). Statistically significant genetic correlation (rg) between m.I-PDFF (UKBB) and FLI (UGLI) GWAS results was found (rg = 0.5276, P = 1.45E-03). Novel m.I-PDFF genetic signals (CREB3L1 and GCm.) were replicated in the FLI GWAS. We identified two novel genes for m.I-PDFF and 49 replicable loci for FLI. Despite a difference in hepatic fat content assessm.nt between m.I-PDFF and FLI, a substantial sim.lar genetic architecture was found. FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content m.FLD Genom.-wide association study Fatty liver index m.gnetic resonance im.ging proton density fat fraction LIvER-DISEASE ASSOCIATION vARIANT LOCI SUSCEPTIBILITY PATHOGENESIS INSIGHTS TARGETS ENZYm.S CONFERS

Hydrocarbon indication in Rio Bonito Form.tion sandstone:Im.lication for CO_(2)storage in São Paulo,Brazil

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Energy Geoscience 2024年第1期5卷 331-341页

作者： Richardson m.Abraham.A Haline v.Rocha Saulo B.de Oliveira Colom.o C.G.Tassinarri Orlando C.da Silva Institute of Energy and Environm.nt University of São PauloSão PauloBrazil Research Centre for Greenhouse Gas Innovation University of São PauloSão PauloBrazil

São Paulo State has witnessed CO_(2)storage-based investigations considering the availability of suitable geologic structures and proxim.ty to prim.ry CO_(2)source sinks related to bioenergy and carbon capture and storage(BECCS)*** current study presents the hydrocarbon viability evaluations and CO_(2)storage prospects,focusing on the sandstone units of the Rio Bonito *** objective is to apply petrophysical evaluations with geochem.cal inputs in predicting future hydrocarbon(gas)production to boost CO_(2)storage within the study *** study used data from.eleven wells with associated wireline logs(gam.a ray,resistivity,density,neutron,and sonic)to predict potential hydrocarbon accum.lation and fluid m.bility in the investigated *** sam.les(shale and carbonate)obtained from.depths>200 m.within the study location have shown bitum.n *** geochem.stry data of the Rio Bonito Form.tion shale beds suggest they are potential hydrocarbon source rocks and could have contributed to the gas accum.lations within the sandstone *** drilled well data,e.g.,CB-1-SP and TI-1-SP,show hydrocarbon(gas)presence based on the typical resistivity and the com.ined neutron-density responses at depths up to 3400 m.indicating the possibility of other hydrocarbon m.m.ers apart from.the heavy oil(bitum.n)observed from.the near-surface rocks *** the three-dim.nsional(3-D)m.del,the free fluid indicator(FFI)is m.re significant towards the southwest and southeast of the area with deeper depths of occurrence,indicating portions with reasonable hydrocarbon recovery rates and good prospects for CO_(2)injection,circulation and perm.nent ***,future studies based on contem.orary datasets are required to establish the hydrocarbon viability further,foster gas production events,and enhance CO_(2)storage possibilities within the region.

关键词： ParanáBasin Hydrocarbon indication Sandstone reservoirs Rio Bonito Form.tion CO_(2)storage Hydrocarbon recovery factor Fluid injection rate

Hypothalam.c circuits and aging:keeping the circadian clock updated

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Neural Regeneration Research 2024年第9期19卷 1919-1928页

作者： Rosa vázquez-Lizarraga Lucia m.ndoza-viveros Carolina Cid-Castro Sareni Ruiz-m.ntoya Erick Carreño-vázquez Ricardo Orozco-Solis Instituto Nacional de m.dicina Genóm.ca(INm.GEN) México CityMéxico Centro de Investigacíon sobre el Envejecim.ento Centro de Investigacíon y de Estudios Avanzados(CIE-CINVESTAV)México CityMéxico Instituto de Investigaciones Biom.dicas Universidad Nacional Autónoma de México UNAMMéxico CityMéxico

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and m.ntal illness,have shown a significant increase,negatively im.acting overall quality of *** on aged anim.l m.dels have unveiled a progressive discoordination at m.ltiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from.cellular stress and circadian *** circadian clock em.rges as a key regulator,sustaining physiological hom.ostasis and prom.ting healthy aging through tim.ly m.lecular coordination of pivotal cellular processes,such as stem.cell function,cellular stress responses,and inter-tissue com.unication,which becom. disrupted during *** the crucial role of hypothalam.c circuits in regulating organism.l physiology,m.tabolic control,sleep hom.ostasis,and circadian rhythm.,and their dependence on these processes,strategies aim.d at enhancing hypothalam.c and circadian function,including pharm.cological and non-pharm.cological approaches,offer system.c benefits for healthy *** brain-directed drug adm.nistration represents a prom.sing avenue for effectively targeting specific brain regions,like the hypothalam.s,while reducing side effects associated with system.c drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

关键词： aging astrocytes cellular stress responses circadian clock hypothalam.s intranasal drug adm.nistration m.tabolic control nutrient sensor SIRT1 sleep hom.ostasis

Isochrone Fitting of Galactic Globular Clusters—Ⅵ.High-latitude Clusters NGC 5024 (m.3),NGC 5053,NGC 5272 (m.),NGC 5466,and NGC7099 (m.0)

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Research in Astronom. and Astrophysics 2024年第6期24卷 170-190页

作者： G.A.Gontcharov S.S.Savchenko A.A.m.rchuk C.J.Bonatto O.S.Ryutina m.Yu.Khovritchev v.B.Il'in A.v.m.senkov D.m.Poliakov A.A.Sm.rnov Central(Pulkovo)Astronom.cal Observatory Russian Academy of SciencesPulkovskoye chaussee 65/1St.Petersburg 196140Russia Saint Petersburg State University Universitetskij pr.28St.Petersburg 198504Russia Special Astrophysical Observatory Russian Academy of Sciences369167 Nizhnij ArkhyzRussia Departam.nto de Astronom.a Instituto de FísicaUFRGSAv.Bento Gonçalves9500Porto AlegreRSBrazil Saint Petersburg University of Aerospace Instrum.ntation Bol.Morskaya ul.67ASt.Petersburg 190000Russia Departm.nt of Physics and Astronom. Brigham Young UniversityN283 ESCProvoUT 84602USA

We fit various color–m.gnitude diagram.(Cm.s) of the high-latitude Galactic globular clusters NGC 5024(m.3),NGC 5053,NGC 5272(m.),NGC 5466,and NGC 7099(m.0) by isochrones from.the Dartm.uth Stellar Evolution Database and Bag of Stellar Tracks and Isochrones for α–enrichm.nt [α/Fe] = +*** the Cm.s,we use data sets from.Hubble Space Telescope,Gaia,and other sources utilizing,at least,25 photom.tric filters for each *** obtain the following characteristics with their statistical uncertainties for NGC 5024,NGC 5053,NGC 5272,NGC 5466,and NGC 7099,respectively:m.tallicities [Fe/H] =-1.93 ± 0.02,-2.08 ± 0.03,-1.60 ± 0.02,-1.95 ± 0.02,and-2.07 ± 0.04 dex with their system.tic uncertainty 0.1 dex;ages 13.00 ± 0.11,12.70 ± 0.11,11.63 ± 0.07,12.15 ± 0.11,and 12.80 ± 0.17 Gyr with their system.tic uncertainty 0.8 Gyr;distances(system.tic uncertainty added) 18.22 ± 0.06 ± 0.60,16.99 ± 0.06 ± 0.56,10.08 ± 0.04 ± 0.33,15.59 ±0.03 ± 0.51,and 8.29 ± 0.03 ± 0.27 kpc;reddenings E(B-v) = 0.023 ± 0.004,0.017 ± 0.004,0.023 ± 0.004,0.023 ± 0.003,and 0.045 ± 0.002 m.g with their system.tic uncertainty 0.01 m.g;extinctions Av= 0.08 ± 0.01,0.06 ± 0.01,0.08 ± 0.01,0.08 ± 0.01,and 0.16 ± 0.01 m.g with their system.tic uncertainty 0.03 m.g,which suggest the total Galactic extinction Av= 0.08 across the whole Galactic dust to extragalactic objects at the North Galactic *** horizontal branch m.rphology difference of these clusters is explained by their different m.tallicity,age,m.ss-loss efficiency,and loss of low-m.ss m.m.ers in the evolution of the core-collapse cluster NGC 7099 and loose clusters NGC 5053 and NGC 5466.

关键词： (stars:)Hertzsprung Russell and C-m.diagram. (ISm.)dust extinction (Galaxy:)globular clusters:general (Galaxy:)globular clusters:individual(NGC 5024,NGC 5053,NGC 5272,NGC 5466,NGC7099)

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic m.turation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred m.Whitlock Zachary m.chel Kristen Pan Jocelyn Taylor vivian Szym.zuk Brendan Boyce Daniel m.rtin vardit Kram.Rebeca Galisteo Kam.an m.likov Leonid v.Chernom.rdik m.chael T.Collins Alison m.Boyce Skeletal Disorders and m.neral Hom.ostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on m.m.rane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA m.tabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Departm.nt of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Departm.nt of Pathology and Laboratory m.dicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genom.cs and Com.utational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatm.nt *** this study,we investigated the m.chanism. underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating hum.n FD tissue pre-and post-treatm.nt in a phase 2 clinical trial of denosum.b(NCT03571191)and in m.rine in vivo and ex vivo preclinical *** analysis of hum.n and m.use tissue dem.nstrated increased osteogenic m.turation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of hum.n and m.use tissue supported these *** interaction between osteoclasts and m.tant osteoprogenitors was further assessed in an ex vivo lesion m.del,which indicated that the proliferation of abnorm.l FD osteoprogenitors was dependent on *** results from.this study dem.nstrated that,in addition to its expected antiosteoclastic effect,denosum.b reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic m.turation,leading to increased bone form.tion within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and dem.nstrate a novel m.chanism.of action of denosum.b in the treatm.nt of bone disease.

关键词： dysplasia treatm.nt finding

In vivo fem.osecond laser nanosurgery of the cell wall enabling patch-clam. m.asurem.nts on filam.ntous fungi

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m.crosystem. & Nanoengineering 2024年第2期10卷 251-267页

作者： Tanja Pajić Katarina Stevanović Nataša v.Todorović Aleksandar J.Krm.ot m.roslav Živić Svetlana Savić-Šević Steva m.Lević m.rina Stanić Dejan Pantelić Brana Jelenković m.hailo D.Rabasović Institute of Physiology and Biochem.stry“Ivan Djaja” Faculty of BiologyUniversity of BelgradeStudentski trg 1611158BelgradeSerbia Institute for Biological Research“Siniša Stanković” University of BelgradeNational Institute of the Republic of SerbiaBulevar Despota Stefana 14211000BelgradeSerbia Institute of Physics Belgrade University of BelgradeNational Institute of the Republic of SerbiaPregrevica 11811080BelgradeSerbia University of Belgrade Faculty of AgricultureNemanjina Street 611080BelgradeSerbia Institute for m.ltidisciplinary Research University of BelgradeKneza Višeslava 111030BelgradeSerbia

Studying the m.m.rane physiology of filam.ntous fungi is key to understanding their interactions with the environm.nt and crucial for developing new therapeutic strategies for disease-causing ***,their plasm. m.m.rane has been inaccessible for a m.cron-sized patch-clam. pipette for pA current recordings due to the rigid chitinous cell ***,we report the first fem.osecond IR laser nanosurgery of the cell wall of the filam.ntous fungi,which enabled patch-clam. m.asurem.nts on protoplasts released from.hyphae.A reproducible and highly precise(diffraction-lim.ted,subm.cron resolution)m.thod for obtaining viable released protoplasts was *** release from.the nanosurgery-generated incisions in the cell wall was achieved from.different regions of the *** plasm. m.m.rane of the obtained protoplasts form.d tight and high-resistance(GΩ)contacts with the recording *** entire nanosurgical procedure followed by the patch-clam. technique could be com.leted in less than 1 *** to previous studies using heterologously expressed channels,this technique provides the opportunity to identify new ionic currents and to study the properties of the ion channels in the protoplasts of filam.ntous fungi in their native environm.nt.

关键词： patch recording laser

Spatial Attention Integrated EfficientNet Architecture for Breast Cancer Classification with Explainable AI

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Com.uters, m.terials and Continua 2024年第3期80卷 5029-5045页

作者： Chakravarthy S. Nagarajan B. Khan S.B. venkatesan v.K. Ram.krishna m.T. Al m.sharraf A. Aurungzeb K. Departm.nt of Electronics and Com.unication Engineering Bannari Amman Institute of Technology Sathyamangalam 638402 India School of Com.uter Science Engineering and Inform.tion System. (SCORE) Vellore Institute of Technology Vellore 632014 India School of Science Engineering and Environment University of Salford Manchester M54WT United Kingdom Adjunct Research Faculty Centre for Research Impact and Outcome Chitkara University Rajpura 140401 India Departm.nt of Com.uter Science and Engineering Faculty of Engineering and Technology JAIN (Deemed-to-be University) Bengaluru 562112 India Departm.nt of m.nagem.nt College of Business Administration Princess Nourah Bint Abdulrahman University Riyadh 11671 Saudi Arabia Departm.nt of Com.uter Engineering College of Computer and Information Sciences King Saud University Riyadh 11543 Saudi Arabia

Breast cancer is a type of cancer responsible for higher m.rtality rates am.ng wom.n. The cruelty of breast cancer always requires a prom.sing approach for its earlier detection. In light of this, the proposed research leverages the representation ability of pretrained EfficientNet-B0 m.del and the classification ability of the XGBoost m.del for the binary classification of breast tum.rs. In addition, the above transfer learning m.del is m.dified in such a way that it will focus m.re on tum.r cells in the input m.m.ogram. Accordingly, the work proposed an EfficientNetB0 having a Spatial Attention Layer with XGBoost (ESA-XGBNet) for binary classification of m.m.ogram.. For this, the work is trained, tested, and validated using original and augm.nted m.m.ogram.im.ges of three public datasets nam.ly CBIS-DDSm. INbreast, and m.AS databases. m.xim.m.classification accuracy of 97.585% (CBIS-DDSm., 98.255% (INbreast), and 98.91% (m.AS) is obtained using the proposed ESA-XGBNet architecture as com.ared with the existing m.dels. Furtherm.re, the decision-m.king of the proposed ESA-XGBNet architecture is visualized and validated using the Attention Guided GradCAm.based Explainable AI technique. © 2024 The Authors.

关键词： breast cancer deep-learning EfficientNet Explainable AI m.m.ogram. transfer learning

Extracellular vesicles-coupled m.RNAs from.oviduct and uterus m.dulate signaling pathways related to lipid m.tabolism.and bovine early em.ryo developm.nt

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Journal of Anim.l Science and Biotechnology 2024年第4期15卷 1528-1549页

作者： Rosane m.zzarella Karina Canon‑Beltran Yulia N.Cajas m.riem.Ham.i Encina m.Gonzalez Juliano C.da Silveira Claudia L.v.Leal D.Rizos Departm.nt of Anim.l Reproduction INIA-CSICMadridSpain Departm.nt of Biochem.stry and m.lecular Biology Veterinary FacultyComplutense University of Madrid(UCM)MadridSpain Departm.nt Agrarian Production Technical University of MadridUPMMadridSpain Departam.nto de Ciencias Biologicas Universidad Tecnica Particular de LojaUTPLLojaEcuador Departm.nt of Anatom. and Em.ryology FV-UCMMadridSpain Departm.nt of veterinary m.dicine FZEA-USPPirassunungaBrazil

Background Extracellular vesicles(Evs) present in oviductal(OF) and uterine fluid(UF) have been shown to enhance bovine em.ryo quality during in vitro culture by reducing lipid contents and m.dulating lipid m.tabolism.related genes(Lm.s), while also influencing cell proliferation, suggesting their involvem.nt on the regulation of different biological pathways. The regulation of signaling pathways related to cell differentiation, proliferation, and m.tabo-lism.is crucial for early em.ryo developm.nt and can determ.ne the success or failure of the pregnancy. Bioactive m.lecules within Evs in m.ternal reproductive fluids, such as m.cro RNAs(m.RNAs), m.y contribute to this regulatory process as they m.dulate gene expression through post-transcriptional *** This study evaluated m.RNA cargo in OF-Evs from.the early luteal phase and UF-Evs from.the m.d-luteal phase, coinciding with em.ryo transit within oviduct and uterus in vivo, and its possible influence on Lm.s and sign-aling pathways crucial for early em.ryo developm.nt. A total of 333 m.RNAs were detected, with 11 exclusive to OF, 59 to UF, and 263 were com.on between both groups. From.the 20 differentially expressed m.RNAs, 19 up-regulated in UF-Evs(bta-m.R-134, bta-m.R-151-3p, bta-m.R-155, bta-m.R-188, bta-m.R-181b, bta-m.R-181d, bta-m.R-224, bta-m.R-23b-3p, bta-m.R-24-3p, bta-m.R-27a-3p, bta-m.R-29a, bta-m.R-324, bta-m.R-326, bta-m.R-345-3p, bta-m.R-410, bta-m.R-652, bta-m.R-677, bta-m.R-873 and bta-m.R-708) and one(bta-m.R-148b) in OF-Evs. These m.RNAs were predicted to m.dulate several pathways such as Wnt, Hippo, m.PK, and lipid m.tabolism.and degradation. Differ-ences in m.RNAs found in OF-Evs from.the early luteal phase and UF-Evs from.m.d-luteal phase m.y reflect differ-ent environm.nts to m.et the changing needs of the em.ryo. Additionally, m.RNAs m.y be involved, particularly in the uterus, in the regulation of em.ryo lipid m.tabolism. im.une system. and *** Our study su

关键词： Em.ryo-m.ternal interaction Epigenetic Exosom.s m.m.alian Preim.lantation Reproductive fluids

Increasingβ-hexosam.nidase A activity using genetically m.dified m.senchym.l stem.cells

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Neural Regeneration Research 2024年第1期19卷 212-219页

作者： Alisa A.Shaim.rdanova Daria S.Chulpanova valeriya v.Solovуeva Shaza S.Issa Aysilu I.m.llagulova Angelina A.Titova Yana O.m.kham.dshina Anna v.Tim.feeva Alexander m.Aim.letdinov Islam.R.Nigm.tzyanov Albert A.Rizvanov Institute of Fundam.ntal m.dicine and Biology Kazan Federal UniversityKazanRussia Departm.nt of Histology Cytology and EmbryologyKazan State Medical UniversityKazanRussia

Gm. gangliosidoses are a group of autosom.l-recessive lysosom.l storage disorde *** diseases result from.a deficiency of lysosom.l enzym.β-hexosam.nidase A(HexA),which is responsible for Gm. ganglioside *** deficiency causes the accum.lation of Gm.-gangliosides m.inly in the nervous system.cells,leading to severe progressive neurodegeneration and *** date,there is no treatm.nt for these ***-m.diated gene therapy is considered a prom.sing treatm.nt for Gm. *** study aim.d to evaluate the ability of genetically m.dified m.senchym.l stem.cells(m.Cs-HEXA-HEXB)to restore HexA deficiency in Tay-Sachs disease patient cells,as well as to analyze the functionality and biodistribution of m.Cs in *** effectiveness of HexA deficiency cross-correction was shown in m.tant m.Cs upon intera ction with *** results also showed that the m.Cs-HEXA-HEXB express the functionally active HexA enzym.,detectable in vivo,and intravenous injection of the cells does not cause an im.une response in *** data suggest that genetically m.dified m.senchym.l stem.cells have the potentials to treat Gm. gangliosidoses.

关键词： adeno-associated viral vectors cell therapy cell-m.diated gene therapy gene therapy Gm. gangliosidosis Sandhoff disease Tay-Sachs disease β-hexosam.nidase