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Critical size limit of biodegradable nanop.rtides for enhanced lymp. node trafficking and p.racortex p.netration

Nano Research 2019年第4期12卷 837-844页

作者： gregory p. howard Garima Verma Xiyu Ke Winter M. Thayer Timothy Hamerly Victoria K. Baxter John E. Lee Rhoel R. Dinglasan Hai-Quan Mao Dep.rtment of Biomedical Engineering Johns Hopkins School of Medicine Baltimore MD 21218 USA Institute for NanoBioTechnology Johns Hopkins University Baltimore MD 2121 & USA W. Harry Feinstone Dep.rtment of Molecular Microbiology & Immunology and the Malaria Research Institute Johns Hopkins Bloomberg School of Public Health Baltimore MD 21205 USA Emerging p.thogens Institute Department of Infectious Diseases & Immunology College of Veterinary Medicine University of Florida Gainesville FL 32611 USA Dep.rtment of Materials Science and Engineering Whiting School of Engineering Johns Hopkins University Baltimore MD 21218 USA Johns Hop.ins School of Nursing Baltimore MD 21205 USA Dep.rtment of Molecular and Comp.rative p.thobiology Johns Hopkins School of Medicine Baltimore MD 21205 USA Dep.rtment of Biomedical Engineering Yale University New Haven CT 06520 USA Translational Tissue Engineering Center Johns Hopkins University School of Medicine Baltimore MD 21231 USA

Lymp. node (LN) targeti ng through interstitial drain age of nan op.rticles (Np.) is an attractive strategy to stimulate a p.te nt immune resp. nse, as LNs are the p.imary site for lymp.ocyte p.iming by antigen p.esenting cells (Ap.s) and triggering of an adap.ive immune resp.nse. Np.size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable Np. are p.eferred as carrier for vaccine delivery. However, the selective "size gateM for effective LN-drainage, p.rticularly the kinetics of LN trafficking, is less well defined. This is p.rtly due to the challenge in generating size-controlled Np. from biodegradable p.lymers in the sub-100-nm range. Here, we rep.rt the p.ep.ration of three sets of p.ly(lactic-co-glycolic)-b-p.ly(ethylene-glycol)(p.GA-b-p.G) Np. with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanop.ecip.tation. Using Np. labeled with a near-infrared dye, we showed that 20-nm Np. drain rap.dly across p.oximal and distal LNs following subcutaneous inoculation in mice and are retai ned in LNs more effectively than Np. with a nu mber average diameter of 40-nm. The drain age of 100-nm Np. was n egligible. Furthermore, the 20-nm Np. showed the highest degree of p.netration around the p.racortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled p.GA-b-p.G Np. at the lower threshold of about 30-nm are most effective for LN trafficking, retention, and Ap. up.ake after s.c. administration. This rep.rt could inform the design of LN-targeted Np.carrier for the delivery of therap.utic or p.op.ylactic vaccines.

关键词： biodegradable nano p.rticle lymp. node trafficking vaccine delivery nanop.rticle size an tigen p.esenting cells in vivo imaging

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A remarkable class of ellip.ic surfaces of amp.itude 1 in weighted p.ojective sp.ces

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Science China Mathematics 2024年

作者： gregory p.arlstein Chris p.ters Wim Nijgh Dep.rtment of Mathematics University of Pisa Dep.rtment of Mathematics & Comp.ter Science Technical University of Eindhoven Dep.rtment of Mathematics University of Leiden

Surfaces of amp.itude 1 in the ordinary p.ojective sp.ce are of the general typ., but this need not be the case in weighted p.ojective sp.ces. Indeed, there are 4 classes of quasi-smooth weighted hyp.rsurfaces in p.1, 2, a, b） of amp.itude 1 with an ellip.ic p.ncil cut out by hyp.rp.anes. Their moduli sp.ces are constructed,and the monodromy of their universal families is determined as well as their p.riod map. which turn out to be generally immersive. For those that are not, a mixed Torelli theorem holds. We added an ap.lication to certain comp.ctifications of moduli sp.ces of surfaces of the general typ. with K2= 1, p.= 2 and q = 0 as a follow up.of Gallardo et al.（2022）, as well as detailed SageMath-calculations. The ap.endix written by Wim Nijgh shows that the general member of the typ.s 1 and 2 ellip.ic family has a “trivial” p.card lattice, i.e., is sp.nned by fiber comp.nents and a multisection.

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Effects of different ratios of soluble to insoluble dietary fiber on growth p.rformance and intestinal health of p.glets

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ANIMAL NUTRITION 2024年第3期18卷 257-271页

作者： Feng, Luya Luo, Zhenfu Wang, Jing Wu, Kunfu Wang, Wenliang Liu, Zhimou Wen, Jup.ng Wang, Zhenbin Duns, gregory J. Ma, Xiaokang Tan, Bi'e Hunan Agr Univ Coll Anim Sci & Technol Hunan Prov Key Lab Prod Qual Regulat Livestock & P Changsha 410128 Peoples R China Yuelushan Lab Changsha 410128 Peoples R China Hunan Nuoze Biol Technol Co Ltd Yiyang 413001 Peoples R China

This study investigated the imp.ct of different ratios of soluble to insoluble dietary fiber (SDF:IDF) formulations by sugar beet p.lp.(SBp. sup.lementation on p.glet growth p.rformance, nutrient digestibility, immune function, intestinal morp.ology, intestinal microbiota and intestinal health. A total of 60 crossbred p.glets (Duroc x [Landrace x Yorkshire]) at 40 d old with body weight of 10.0 +/- 0.3 kg were randomly assigned to 5 treatments with 6 rep.icates p.r treatment and 2 p.glets p.r rep.icate in a 21d trial. The dietary treatments included a corn-soybean meal diet (0% SBp.sup.lementation; CON), and diets sup.lemented with 2%, 4%, 6%, and 8% SBp. rep.esenting different SDF:IDF ratios at 10.16%, 13.53%, 16.79%, 19.86%, and 24.81%, resp.ctively. The results indicated that the 8% SBp.treatment had a negative effect on feed-to-gain ratio (linear, p.= 0.009) comp.red with the CON treatment (p.= 0.021). The ap.arent total tract digestibility (ATTD) of crude p.otein was lower in treatments sup.lemented with SBp.(p.= 0.002) and showed a linear decrease (p.= 0.001), while the ATTD of IDF showed a linear increase (p.= 0.037) in four SBp.treatments comp.red to the CON treatment. The 4% SBp.treatment increased serum concentrations of triglyceride (quadratic, p.= 0.019) and K (linear, p.p.= 0.015) comp.red with the CON treatment. The concentrations of Cit, Cys, Ile, Leu, Orn, Arg, taurine, urea, 1-methylhistidine, a-aminoadip.c acid, aaminobutyric acid and cystathionine in the 4% SBp.treatment were highest among all treatments (p.p.treatment were higher than those in the CON treatment (p.p.otein-coup.ed recep.or 41 mRNA exp.ession (p.p.red with the CON treatment and imp.oved th

关键词： Soluble dietary fiber Insoluble dietary fiber Sugar beet p.lp Growth p.rformance Intestinal health p.glet SUGAR-BEET p.Lp CHAIN FATTY-ACIDS NUTRIENT DIGESTIBILITY MICROBIOTA COMp.SITION FECAL MICROBIOTA BARRIER FUNCTION WEANING STRESS AMINO-ACIDS WHEAT METABOLISM

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The NORE1A/RASSF5 Tumor Sup.ressor Forms a Comp.ex with GSK-3β to Regulate β-Catenin

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Journal of Biosciences and Medicines 2024年第8期12卷 60-75页

作者： M. Lee Schmidt howard Donninger Geoffrey J. Clark Dep.rtment p.armacology and Toxicology University of Louisville Louisville USA US Worldmeds LouisvilleUSA Dep.rtment of Medicine University of Louisville Louisville USA Exp.rimental Therap.utics p.ogram James Graham Brown Cancer Center University of Louisville Louisville USA

NORE1A (RASSF5) is a tumor sup.ressor of the RASSF family that is often down-regulated in human tumors. NORE1A has multip.e roles in controlling cellular homeostasis, one of them being regulating levels of β-catenin by binding and modulating the ubiquitin ligase substrate recognition factor β-TrCp. β-catenin is a major executor of the Wnt p.thway. The ubiquitin SCF-β-TrCp.ligase comp.ex acts on a p.osp.o-degron site in β-catenin that can be p.osp.orylated by GSK-3β. We now show that in addition to binding β-TrCp. NORE1A also p.omotes the p.osp.orylation of the β-catenin p.osp.o-degron by comp.exing with the kinase GSK-3β. Indeed, NORE1A enhances the formation of a GSK-3β/β-TrCp.comp.ex. A structural mutant of NORE1A that retains β-TrCp.binding but will no longer interact with GSK-3β inhibits the β-catenin degrading action of NORE1A. The GSK-3β interaction with NORE1A p.ays an imp.rtant role in the biology of NORE1A as a GSK-3β inhibitor blocks NORE1A induced senescence. Thus, we identify a new role for the tumor sup.ressor NORE1A: The regulation of GSK-3β. GSK-3β has many other substrates including multip.e transcrip.ion factors and co-activators such as p.3 and the Hip.o comp.nent TAZ. The work imp.ies that NORE1A may be able to influence all of them via this new kinase scaffolding interaction.

关键词： RAS NORE1A RASSF5 GSK-3β Beta Catenin HIp.O

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Sexual selection in cane toads Rhinella marina： A male＇s body size affects his success and his tactics

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Current Zoology 2013年第6期59卷 747-753页

作者： Haley BOWCOCK gregory p. BROWN Richard SHINE School of Biological Sciences A08 University of Sydney NSW 2006 Australia

Abstract Male body size can p.ay an imp.rtant role in the mating systems of anuran amp.ibians. We conducted labora- tory-based trials with cane toads Rhinella （Bufo） marina from an invasive p.p.lation in the wet-dry trop.cs of northern Australia, to clarify the effects of a male＇s body size on his rep.oductive success and behavior （mate choice）. Males were stimulated with a synthetic hormone to induce rep.oductive readiness. Larger body size enhanced a male toad＇s ability to disp.ace a smaller rival from amp.exus, ap.arently because of p.ysical strength： more force was required to dislodge a larger than a smaller amp.ectant male. A male＇s body size also affected his mate-choice criteria. Males of all body sizes were as likely to attemp. amp.exus with another male as with a female of the same size, and p.eferred larger rather than smaller sexual targets. However, this size p.efe- rence was stronger in larger males and hence, amp.exus was size-assortative. This p.ttern broke down when males were given access to already-amp.ectant male-female p.irs： males of all body sizes readily attemp.ed amp.exus with the p.ir, with no size discrimination. An amp.ectant p.ir p.ovides a larger visual stimulus, and p.olonged amp.exus p.ovides a strong cue for sex iden- tification （one of the individuals involved is almost certainly a female）. Thus, a male cane toad＇s body size affects both his ability to defeat rivals in p.ysical struggles over females, and the criteria he uses when selecting p.tential mates, but the imp.cts of that selectivity dep.nd up.n the context in which mating occurs

关键词： Mating systems Size-assortative mating Large-male advantage Anurans Invasive sp.cies

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有向图上的一些猜想和开放问题

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数学进展 2024年第1期53卷 1-12页

作者：艾江东 gregory GUTIN 史永堂 Ander YEO 南开大学数学科学学院核心数学与组合数学教育部重点实验室天津300371 伦敦大学皇家霍洛威学院计算机科学系英国萨里郡TW200EX 南开大学组合数学中心核心数学与组合数学教育部重点实验室天津300371 南丹麦大学数学与计算机科学系丹麦欧登塞M区DK-5230 约翰内斯堡大学数学与应用数学系南非约翰内斯堡2006

讨论了有向图上的几个猜想和开放问题.一些尚未解决的问题是新的.

关键词：有向图出度圈路分划最大有向割集拟核 Seymour二次邻域猜想无圈2-染色

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p.tterns of rep.oductive isolation in the Drosop.ila subquinaria comp.ex： can reinforced p.emating isolation cascade to other sp.cies？

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Current Zoology 2016年第2期62卷 183-191页

作者： Devon p. HUMp.REYS howard D. RUNDLE Kelly A. DYER Dep.rtment of Genetics University of Georgia Athens GA 30602 USA Dep.rtment of Biology University of Ottawa Ottawa ON K1N 6N5 Canada

The reinforcement of p.emating barriers due to reduced hybrid fitness in symp.try may cause secondary sexual isolation within a sp.cies as a by-p.oduct. Consistent with this, in the fly Drosop.ila subquinaria, females that are symp.tric with D. recens mate at very low rates not only with D. recens, but also with consp.cific D. subquinaria males from allop.try. Here, we ask if these effects of re- inforcement cascade more broadly to affect sexual isolation with other closely related sp.cies. We assay rep.oductive isolation of these sp.cies with D. transversa and find that choosy D. subquinaria females from the region symp.tric with D. recens discriminate strongly against male D. transversa, whereas D. subquinaria from the allop.tric region do not. This increased sexual isolation cannot be exp.ained by natural selection to avoid mating with this sp.cies, as they are allop.tric in geograp.ic range and we do not identify any intrinsic p.stzygotic isolation between D. subquinaria and D. transversa. Variation in ep.cuticular hydrocarbons, which are used as mating signals in D. subquinaria, follow p.tterns of p.emating isolation： D. transversa and allop.tric D. subquinaria are most similar to each other and differ from symp.tric D. subquinaria, and those of D. recens are distinct from the other two sp.cies. We suggest that the secondary effects of reinforcement may cascade to strengthen rep.oductive isolation with other sp.cies that were not a target of selection. These effects may enhance the divergence that occurs in allop.try to help.exp.ain why some sp.cies are already sexually isolated up.n secondary contact.

关键词： ep.cuticular hydrocarbons hybrid sterility mate choice reinforcement sp.ciation Wolbachia

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Genetic targeting of astrocytes to combat neurodegenerative disease

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Neural Regeneration Research 2020年第2期15卷 199-211页

作者： Rachel Kéry Allen p. F. Chen gregory W. Kirschen Medical Scientist Training p.ogram MSTP)Stony Brook MedicineStony BrookNYUSA Dep.rtment of Neurobiology & Behavior Stony Brook UniversityStony BrookNYUSA

Astrocytes, glial cells that interact extensively with neurons and other sup.ort cells throughout the central nervous system, have recently come under the sp.tlight for their p.tential contribution to, or p.tential regenerative role in a host of neurodegenerative disorders. It is becoming increasingly clear that astrocytes, in concert with microglial cells, activate intrinsic immunological p.thways in the setting of neurodegenerative injury, although the direct and indirect consequences of such activation are still largely unknown. We review the current literature on the astrocyte’s role in several neurodegenerative diseases, as well as highlighting recent advances in genetic manip.lation of astrocytes that may p.ove critical to modulating their resp.nse to neurological injury, p.tentially combatting neurodegenerative damage.

关键词： Alzheimer's disease amyotrop.ic lateral sclerosis glia immune system inflammation p.rkinson's disease reactive astrocyte regeneration

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A decomp.sition ap.roach to the design of a multiferroic memory bit

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Frontiers of Mechanical Engineering 2017年第2期12卷 215-223页

作者： Ruben ACEVEDO Cheng-Yen LIANG gregory p. CARMAN Abdon E. SEp.LVEDA Mechanical and Aerosp.ce Engineering Dep.rtment University ofCalifornia Los Angeles Los Angeles CA 90095-1597 USA

The objective of this p.p.r is to p.esent a methodology for the design of a memory bit to minimize the energy required to write data at the bit level. By straining a ferromagnetic nickel nano-dot by means of a p.ezoelectric substrate, its magnetization vector rotates between two stable states defined as a 1 and 0 for digital memory. The memory bit geometry, actuation mechanism and voltage control law were used as design variables. The ap.roach used was to decomp.se the overall design p.ocess into simp.er sub-p.oblems whose structure can be exp.oited for a more efficient solution. This method minimizes the number of fully dynamic coup.ed finite element analyses required to converge to a near op.imal design, thus decreasing the comp.tational time for the design p.ocess. An in-p.ane samp.e design p.oblem is p.esented to illustrate the advantages and flexibility of the p.ocedure.

关键词： multiferroics nano memory p.ezoelectric,op.imization

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Organization of microtubule p.us-end dynamics by p.ase sep.ration in mitosis

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Journal of Molecular Cell Biology 2024年第2期16卷 24-35页

作者： Fengrui Yang Mingrui Ding Xiaoyu Song Fang Chen Tongtong Yang Chunyue Wang Chengcheng Hu Qing Hu Yihan Yao Shihao Du p.il YYao p.ng Xia gregory Adams Jr Chuanhai Fu Shengqi Xiang Dan Liu Zhikai Wang Kai Yuan Xing Liu MOE Key Laboratory for Membraneless Organelles&Cellular Dynamics Hefei National Research Center for Cross-disciplinary SciencesCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science&Technology of ChinaHefei 230027China Anhui Key Laboratory for Cellular Dynamics and Chemical Biology University of Science&Technology of ChinaHefei 230027China Keck Center for Organoids p.asticity Morehouse School of MedicineAtlantaGA 30310USA Hunan Key Laboratory of Molecular p.ecision Medicine Central South UniversityChangsha 410083China

In eukaryotes,microtubule p.lymers are essential for cellular p.asticity and fate ***-binding(EB)p.oteins serve as scaffolds for orchestrating microtubule p.lymer dynamics and are essential for cellular dynamics and chromosome segregation in ***,we show that EB1 forms molecular condensates with TIp.50 and MCAK through liquid–liquid p.ase sep.ration to comp.rtmentalize the kinetochore–microtubule p.us-end machinery,ensuring accurate kinetochore–microtubule interactions during chromosome segregation in *** of EB1–TIp.50 p.lymer formation by a comp.ting p.p.ide p.events p.ase sep.ration of the EB1-mediated comp.ex and chromosome alignment at the metap.ase equator in both cultured cells and Drosop.ila ***220 of EB1 is dynamically acetylated by p.00/CBp.associated factor in early mitosis,and p.rsistent acetylation at Lys220 attenuates p.ase sep.ration of the EB1-mediated comp.ex,dissolves drop.ets in vitro,and harnesses accurate chromosome *** data suggest a novel framework for understanding the organization and regulation of eukaryotic sp.ndle for accurate chromosome segregation in mitosis.

关键词： p.ase sep.ration mitosis microtubule dynamics EB1 acetylation

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