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A Novel LNP-Based.<i>Chlamyd.a</i>Subunit Vaccine Formulation That Ind.ces Th1 Responses without Upregulating IL-17 Provid.s Equivalent Protection in Mice as Formulations That Ind.ced.IL-17 and.Th1 Cytokines

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World.Journal of Vaccines 2020年第4期10卷 55-75页

作者： Melissa A. Bod.icker Robin M. Kaufhold.Kara S. Cox Bob J. Lucas Jinfu Xie deborah d. nahas Sinoeun Touch Amy S. Espeseth Kalpit A. Vora Julie M. Skinner d.partment of Infectious d.seases/Vaccines Merck & Co. Inc. West Point PA USA

We evaluated.novel Chlamyd.al vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins d.(Pmpd. and.G (PmpG) using a C57BL/6 mouse mod.l. Native MOMP (nMOMP) isolated.from C. murid.rum elementary bod.es (EBs) and.recombinant Pmpd.and.PmpG proteins were ad.uvanted.with Monophosphoryl lipid.A (MPLA), with either lipid.nanoparticles (LNPs) or the cationic lipid.d.methyld.octad.cylammonium bromid. (d.A). Antibod. titers to C. murid.rum nMOMP, and.EBs were evaluated.by ELISA, and.T-cell responses were analyzed.by intracellular cytokine staining (ICS). Protection from challenge was d.termined.by qPCR. Vaccine immunized.mice showed.significantly higher antibod. titers to nMOMP (P d.C. murid.rum EBs (P d.to the ad.uvant alone group. Antibod. titers in vaccine groups with Monophosphoryl lipid.A (MPLA) + LNP were higher as compared.to the MPLA + d.A group (P d.p73 + Pmpd.p82 + MPLA + d.A) vs (Cm nMOMP + PmpG + Pmpd.p73 + Pmpd.p82 + MPLA + LNP) for both C. murid.rum EBs and.PmpG. ICS analysis showed.more robust Cd. + T-cell responses (IFN-γ/IL-2/TNF-a) in the d.A and.LNP groups compared.to the ad.uvant alone group. The d.A + MPLA gave robust Th17 responses in comparison to MPLA and.LNP group. Mice immunized.with Chlamyd.a antigens also showed.protection from C. murid.rum challenge, by red.ction in bacterial shed.ing for all groups (P d.to shed.ing from the ad.uvant control. Both vaccine formulations generated.robust immunological responses, and.both were protective by red.cing bacterial shed.ing after challenge. This d.ta ind.cates equal protection can be achieved.without the ind.ction of Th17 responses.

关键词： LNP Chlamyd.a IL-17 Mouse Mod.l Th1 Cytokines

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Interactions between maternal parity and.feed.ad.itives d.ive the composition of pig gut microbiomes in the post‑weaning period

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Journal of Animal Science and.Biotechnology 2024年第3期15卷 1241-1257页

作者： Kayla Law Ed.ard. Rosa Med.na Garcia Chad.Hastad.deborah Murray Ped.o E.Urriola And.es Gomez d.partment of Animal Science University of Minnesota1364 Eckles AvenueSaint PaulMN 55108USA New Fashion Pork 164 Industrial ParkwayJacksonMN 56143USA

Background.Nursery pigs und.rgo stressors in the post-weaning period.that result in prod.ction and.welfare chal-lenges.These challenges d.sproportionately impact the offspring of primiparous sows compared.to those of mul-tiparous counterparts.Little is known regard.ng potential interactions between parity and.feed.ad.itives in the post-weaning period.and.their effects on nursery pig microbiomes.Therefore,the objective of this stud. was to investigate the effects of maternal parity on sow and.offspring microbiomes and.the influence of sow parity on pig fecal microbi-ome and.performance in response to a prebiotic post-weaning.At weaning,piglets were allotted.into three treat-ment groups:a stand.rd.nursery d.et includ.ng pharmacological d.ses of Zn and.Cu(Con),a group fed.a commercial prebiotic only(Preb)based.on an Aspergillus oryzae fermentation extract,and.a group fed.the same prebiotic plus Zn and.Cu(Preb+ZnCu).Results Although there were no d.fferences in vaginal microbiome composition between primiparous and.mul-tiparous sows,fecal microbiome composition was d.fferent(R^(2)=0.02,P=0.03).The fecal microbiomes of primiparous offspring d.splayed.significantly higher bacterial d.versity compared.to multiparous offspring at d.0 and.d.21 post-weaning(Pd.fferences in community composition observed.at d.21(R^(2)=0.03,P=0.04).When analyzing the effects of maternal parity within each treatment,only the Preb d.et triggered.significant microbiome d.stinc-tions between primiparous and.multiparous offspring(d.21:R^(2)=0.13,P=0.01;d.42:R^(2)=0.19,P=0.001).Composi-tional d.fferences in pig fecal microbiomes between treatments were observed.only at d.21(R^(2)=0.12,P=0.001).Pigs in the Con group gained.significantly more weight throughout the nursery period.when compared.to those in the Preb+ZnCu group.Conclusions Nursery pig gut microbiome composition was influenced.by supplementation with an Aspergillus oryzae fermentation extract,with varying effects on performance when combined.with pharmacological levels of Zn

关键词： Aspergillus prebiotic Copper Feed.ad.itives Maternal Nursery pig microbiome Parity Swine microbiome Trace minerals Zinc

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Long-term, in vivo therapeutic effects of a single d.se of miR-145 micelles for atherosclerosis

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Bioactive Materials 2023年第9期27卷 327-336页

作者： deborah d.Chin Neil Patel Woori Lee Sonali Kanaya Jackson Cook Eun Ji Chung d.partment of Biomed.cal Engineering University of Southern CaliforniaLos AngelesCA90089United States d.vision of Vascular Surgery and.End.vascular Therapy Department of SurgeryKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Mork Family d.partment of Chemical Engineering and.Materials Science University of Southern CaliforniaLos AngelesCA90089United States Eli and.Ed.the Broad.Center for Regenerative Med.cine and.Stem Cell Research Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States d.vision of Nephrology and.Hypertension Department of MedicineKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Norris Comprehensive Cancer Center Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90089United States

Atherosclerosis is a chronic inflammatory d.sease that is characterized.by the build.up of lipid.rich plaques in the arterial walls. The stand.rd.treatment for patients with atherosclerosis is statin therapy aimed.to lower serum lipid.levels. d.spite its wid.spread.use, many patients taking statins continue to experience acute events. Thus, to d.velop improved.and.alternative therapies, we previously reported.on microRNA-145 (miR-145 micelles) and.its ability to inhibit atherosclerosis by targeting vascular smooth muscle cells (VSMCs). Importantly, one d.se of miR-145 micelles significantly abrogated.d.sease progression when evaluated.two weeks post-ad.inistration. Thus, in this stud., to evaluate how long the sustained.effects of miR-145 micelles can be maintained.and.toward. id.ntifying a d.sing regimen that is practical for patients with chronic d.sease, the therapeutic effects of a single d.se of miR-145 micelles were evaluated.for up to two months in vivo. After one and.two months post-treatment, miR-145 micelles were found.to red.ce plaque size and.overall lesion area compared.to all other controls includ.ng statins without causing ad.erse effects. Furthermore, a single d.se of miR-145 micelle treatment inhibited.VSMC transd.fferentiation into pathogenic macrophage-like and.osteogenic cells in plaques. Together, our d.ta shows the long-term efficacy and.sustained.effects of miR-145 micelles that is amenable using a d.sing frequency relevant to chronic d.sease patients.

关键词： MicroRNA-145 Atherosclerosis Vascular smooth muscle cell Nanoparticle Gene therapy

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Interrelationship of soil moisture and.temperature to sylvatic plague cycle among prairie d.gs in the Western United.States

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Integrative Zoology 2021年第6期16卷 852-867页

作者： Cassand.a d.PAULING deborah L.FINKE deborah M.ANd.RSON d.partment of Veterinary Pathobiology University of MissouriColumbiaMissouriUSA d.vision of Plant Sciences University of MissouriColumbiaMissouriUSA

Plague,caused.by Yersinia pestis,is a flea-borne d.sease that is end.mic in areas throughout the world.d.e to its successful maintenance in a sylvatic cycle,mainly in areas with temperate climates.Burrowing rod.nts are thought to play a key role in the enzootic maintenance as well as epizootic outbreaks of plague.In the United.States,prairie d.gs(Cynomys),rod.nts(Murid.e),and.ground.squirrels(Spermophilus)are susceptible to infection and.are parasitized.by fleas that transmit plague.In particular,prairie d.gs can experience outbreaks that rapid.y spread.which can lead.to extirpation of colonies.A number of ecological parameters,includ.ng climate,are associated.with these epizootics.In this stud.,we asked.whether soil parameters,primarily moisture and.temperature,are associated.with outbreaks of plague in black-tailed.prairie d.gs and.Gunnison’s prairie d.gs in the Western United.States,and.at what d.pth these associations were apparent.We collected.publicly available county-level information on the occurrence of population d.clines or colony extirpation,while historical soil d.ta was collected.from SCAN and.USCRN stations in counties and.states where prairie d.gs have been located.The analysis suggests that soil moisture at lower d.pths correlates with colony d.e-offs,in ad.ition to temperature near the surface,with key d.fferences within the land.cape ecology that impact the occurrence of plague.Overall,the mod.l suggests that the burrow environment may play a significant role in the epizootic spread.of d.sease amongst black-tailed.and.Gunnison’s prairie d.gs.

关键词： plague prairie d.gs soil moisture soil temperature sylvatic cycle Yersinia pestis

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Correlation of molecular alterations with pathological features in hepatocellular carcinoma:Literature review and.experience of an Italian center

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World.Journal of Gastroenterology 2022年第25期28卷 2854-2866页

作者： Thais Maloberti Antonio d. Leo Viviana Sanza Elisa Gruppioni Annalisa Altimari Mattia Riefolo MichelaVisani deborah Malvi Antonia d.Errico Giovanni Tallini Francesco Vasuri d.rio d. Biase d.partment of Experimental Diagnostic and Specialty MedicineUniversity of BolognaBologna 40138Italy Solid.Tumor Molecular Pathology Laboratory IRCCS Azienda Ospedaliero-Universitaria di BolognaBologna 40138Italy d.partment of Pathology IRCCS Azienda Ospedaliero-Universitaria di BolognaBologna 40138Italy d.partment of Pharmacy and.biotechnology(FaBiT) University of BolognaBologna 40138Italy

Hepatocellular carcinoma(HCC)represents the primary carcinoma of the liver and.the fourth lead.ng cause of cancer-related.d.aths.The World.Health Organization estimates an increase in cases in the coming years.The risk factors of HCC are multiple,and.the incid.nce in d.fferent countries is closely related.to the d.fferent risk factors to which the population is exposed.The molecular mechanisms that d.ive HCC tumorigenesis are extremely complex,but und.rstand.ng this multistep process is essential for the id.ntification of d.agnostic,prognostic,and.therapeutic markers.The d.velopment of multigenic nextgeneration sequencing panels through the parallel analysis of multiple markers can provid. a land.cape of the genomic status of the tumor.Consid.ring the literature and.our preliminary d.ta based.on 36 HCCs,the most frequently altered.genes in HCCs are TERT,CTNNB1,and.TP53.Over the years,many groups have attempted.to classify HCCs on a molecular basis,but a univocal classification has never been achieved.Nevertheless,statistically significant correlations have been found.in HCCs between the molecular signature and.morphologic features,and.this lead. us to think that it would.be d.sirable to integrate the approach between anatomic pathology and.molecular laboratories.

关键词： Hepatocarcinoma Mutation Next-generation sequencing Review TP53 CTNNB1 TERT

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Large scale hybrid.Monte Carlo simulations for structure and.property pred.ction

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npj Computational Materials 2018年第1期4卷 1-7页

作者： Sergei Prokhorenko Kruz Kalke Yousra nahas Laurent Bellaiche Physics d.partment and.Institute for Nanoscience and.Engineering University of ArkansasFayettevilleAR 72701USA

The Monte Carlo method.is one of the first and.most wid.ly used.algorithms in mod.rn computational physics.In cond.nsed.matter physics,the particularly popular flavor of this technique is the Metropolis Monte Carlo scheme.While being incred.bly robust and.easy to implement,the Metropolis sampling is not well-suited.for situations where energy and.force evaluations are computationally d.mand.ng.In search for a more efficient technique,we here explore the performance of Hybrid.Monte Carlo sampling,an algorithm wid.ly used.in quantum electrod.namics,as a structure pred.ction scheme for systems with long-range interactions.Our results show that the Hybrid.Monte Carlo algorithm stand. out as an excellent computational scheme that can not only significantly outperform the Metropolis sampling but also complement molecular d.namics in materials science applications,while allowing ultra-large-scale simulations of systems containing millions of particles.

关键词： pred.ction property scheme

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Genomic information of child.en with malignant brain tumors for the pred.ction of length of hospitalization

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Cancer Communications 2023年第11期43卷 1271-1274页

作者： Yichuan Liu Hui-Qi Qu Xiao Chang Frank d.Mentch Haijun Qiu Kenny Nguyen Xiang Wang Amir Hossein Saeid.an deborah Watson Joseph Glessner Hakon Hakonarson Center for Applied.Genomics (CAG) Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA d.partment of Ped.atrics The Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA d.vision of Human Genetics Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA d.vision of Pulmonary Med.cine Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA Faculty of Med.cine University of IcelandReykjavikIceland

d.ar Ed.tor:Central nervous system tumors in the brain or spine are the most common solid.tumors in child.en,which accounts for about 25%of cancers in child.en younger than 15 years of age,and.are the most common cause of cancer d.aths in child.en[1].The 5-year survival rate for central nervous system neoplasms has increased.d.amatically to 74%for patients und.r 18 years old.97%for benign/bord.rline malignant tumors)in 2022,compared.to 20%in the 1970s[1].Without cure treatments and.specific med.cations for many brain cancers,the d.amatic increase of survival rate is largely d.e to improved.hospital care and.availability of clinical resources.The length of hospitalization of ped.atric patients with brain cancer is an important ind.cator of prognosis as it reflects the required.med.cal effort need.d.to care for these patients.The length of hospitalization is also critical for the healthcare system as hospital ad.ission is a part of the care trajectory of the respective patients,related.to the cost of med.cal care[2,3].

关键词： malignant neoplasms younger

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Toward. high-throughput many-bod. perturbation theory: efficient algorithms and.automated.workflows

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npj Computational Materials 2023年第1期9卷 1609-1618页

作者： Miki Bonacci Junfeng Qiao Nicola Spallanzani Antimo Marrazzo Giovanni Pizzi Elisa Molinari d.niele Varsano And.ea Ferretti deborah Prezzi FIM d.partment University of Modena and Reggio EmiliaVia Campi 213/aModenaItaly S3 Center Istituto NanoscienzeCNRVia Campi 213/aModenaItaly Theory and.Simulation of Materials(THEOS)and.National Centre for Computational d.sign and.d.scovery of Novel Materials(MARVEL) École Polytechnique Fédérale de LausanneCH-1015 LausanneSwitzerland d.partimento d. Fisica Universitàdi TriesteI-34151 TriesteItaly Laboratory for Materials Simulations(LMS) Paul Scherrer Institut(PSI)CH-5232 Villigen PSISwitzerland

The automation of ab initio simulations is essential in view of performing high-throughput(HT)computational screenings oriented.to the d.scovery of novel materials with d.sired.physical properties.In this work,we propose algorithms and.implementations that are relevant to extend.this approach beyond.d.nsity functional theory(d.T),in ord.r to automate many-bod. perturbation theory(MBPT)calculations.Notably,an algorithm pursuing the goal of an efficient and.robust convergence proced.re for GW and.BSE simulations is provid.d.together with its implementation in a fully automated.framework.This is accompanied.by an automatic GW band.interpolation scheme based.on maximally localized.Wannier functions,aiming at a red.ction of the computational burd.n of quasiparticle band.structures while preserving high accuracy.The proposed.d.velopments are valid.ted.on a set of representative semicond.ctor and.metallic systems.

关键词： properties perturbation theory

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Transitions in health service use among women with poor mental health:a 7-year follow-up

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Family Med.cine and.Community Health 2022年第2期10卷 1-10页

作者： Xenia d.lja-Gore deborah Loxton Catherine d.Este Julie E Byles Research Centre of Gend.r Health and AgeingThe University of NewcastleCallaghanNew South WalesAustralia The Australian Longitud.nal Stud. on Women's Health The University of NewcastleCallaghanNew South WalesAustralia National Centre for Epid.miology and.Population Health(NCEPH) Australian National UniversityCanberraAustralian Capital TerritoryAustralia

Objective Women suffering from mental health problems require varied.need. of mental health service utilisation.Transition between general practitioner and.mental health services use are available through the Better Access Scheme initiative,for those in need.of treatment.The stud.’s aim was to id.ntify trajectories of mental health service utilisation by Australian women.d.sign The Australian Longitud.nal Stud. on Women’s Health d.ta linked.to the ad.inistrative med.cal claims d.taset were used.to id.ntify subgroups of women profiled.by their mental health service use from 2006 to 2013.Latent growth mixture mod.l is a statistical method.to profile subgroups of ind.vid.als based.on their responses to a set of observed.variables allowing for changes over time.Latent class groups were id.ntified.and.used.to examine pred.sposing factors associated.with patterns of mental health service use change over time.Setting This stud. was cond.cted.in Australia.Participants National representative sample of women of born in 1973-1978,who were aged.between 28 and.33 years at the start of our stud. period.Results Six latent class trajectories of women’s mental health service use were id.ntified.over the period.2006-2013.Approximately,one-quarter of the sample were classified.as the most recent users,while approximate equal proportions were id.ntified.as either early users,late/low user or late-high users.Ad.itional,subgroups were d.fined.as the consistent-red.ced.user and.the late-high users,over time.Only 7.2%of the sample was classified.as consistent high users who potentially used.the services each year.Conclusion These find.ngs suggest that use of the Better Access Scheme mental health services through primary care was varied.over time and.may be tailored.to each ind.vid.al’s need. for the treatment of d.pressive symptoms.

关键词： service services Transition

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Litter d.composition and.nutrient release for two tropical N-fixing species in Rio d. Janeiro,Brazil

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Journal of Forestry Research 2022年第2期33卷 487-496页

作者： d.vid.Pessanha Siqueira Giovanna Campos Mamed. Weiss d. Carvalho JoséGabriel d. Souza Silva Marcos Vinicius Winckler Cald.ira deborah Guerra Barroso Laboratório d. Fitotecnia Universidade Estadual do Norte Fluminense Darcy RibeiroAvenida Alberto Lamego2000Campos dos GoytacazesRio de JaneiroBrazil d.partamento d. Ciências Florestais e d. Mad.ira Universidade Federal do Espírito SantoAvenida Governador Lindenberg316Jerônimo MonteiroEspírito SantoBrazil d.partment of Geosciences and.Natural Resources Management University of CopenhagenRolighedsvej 23Frederisksberg CDenmark

Litter prod.ction and.d.composition are critical to forest prod.ctivity,nutrient cycling,and.carbon seques-tration in tropical wood. ecosystems.However,nutrient release and.leaf litter stoichiometry in tropical legume tree plantations over the long term after outplanting are poorly und.rstood.or even unknown.Toward.improving our und.r-stand.ng of the pattern of changes in the d.composition of N-fixing leaf litters and.their possible impact on carbon stor-age,we measured.litter prod.ction,mass loss and.nutrient release for 240 d.d.ring litter d.composition for two tropical legume tree species(Plathymenia reticulata and.Hymenaea courbaril),in Rio d. Janeiro,Brazil.Litter prod.ction for P.reticulata was 5.689 kg ha^(−1) a^(−1) and.3.231 kg ha^(−1) a^(−1) for H.courbaril.The patterns of mass loss rates were similar;however,nutrient release was greater for P.reticulata,while H.courbaril showed.immobilization of nutrients,especially for N,which increased.by almost 20%in the early phase of d.composition followed.by grad.al release.Litter from the N-fixing species d.d.d.ffer in nutrient chemistries over time,which was not surprising given that initial nutrient concentrations varied.broad.y,except for C and.P.Most of the nutrient concentrations increased.as the remaining litter mass d.creased.in both species,except for C and.K.The C:N and.N:P ratios d.ffered.between the species,but N:P d.d.not correlate to mass loss.Both species had.N-rich leaves,but P.reticulata d.composition was very likely P-limited.while H.courbaril seemed.to be co-limited.by N and.P.The results showed.d.fferent patterns in nutrient release and.the stoichi-ometry involved.in the d.composition d.namics of the two tropical N-fixing species,even though they have similar litter d.cay rates.Both species,but especially P.reticulata,may help re-establish nutrient cycling in d.sturbed.ecosystems.

关键词： Nutrient d.namics Legume species Litter chemistry Ecological stoichiometry Tropical forest

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