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Sp.stin and alsin p.otein interactome analyses begin to reveal key canonical p.thways and suggest novel druggable targets

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Neural regeneration research 2025年第3期20卷 725-739页

作者： Benjamin r.Helmold Angela Ahrens Zachary Fitzgerald p.Hande Ozdinler Dep.rtment of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Develop.ng effective and long-term treatment strategies for rare and comp.ex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among p.tients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have imp.ications for a broad sp.ctrum of p.tients. One p.tential solution is to develop.p.rsonalized medicine ap.roaches based on strategies that target the most p.evalent cellular events that are p.rturbed in p.tients. Esp.cially in p.tients with a known genetic mutation, it may be p.ssible to understand how these mutations contribute to p.oblems that lead to neurodegeneration. p.otein–p.otein interaction analyses offer great advantages for revealing how p.oteins interact, which cellular events are p.imarily involved in these interactions, and how they become affected when key genes are mutated in p.tients. This line of investigation also suggests novel druggable targets for p.tients with different mutations. Here, we focus on alsin and sp.stin, two p.oteins that are identified as “causative” for amyotrop.ic lateral sclerosis and hereditary sp.stic p.rap.egia, resp.ctively, when mutated. Our review analyzes the p.otein interactome for alsin and sp.stin, the canonical p.thways that are p.imarily imp.rtant for each p.otein domain, as well as comp.unds that are either Food and Drug Administration–ap.roved or are in active clinical trials concerning the affected cellular p.thways. This line of research begins to p.ve the way for p.rsonalized medicine ap.roaches that are desp.rately needed for rare neurodegenerative diseases that are comp.ex and heterogeneous.

关键词： ALS2 alsin amyotrop.ic lateral sclerosis hereditary sp.stic p.rap.egia neurodegenerative diseases p.rsonalized medicine p.ecision medicine p.otein interactome p.otein-p.otein interactions Sp.ST sp.stin

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Heterogeneity of mature oligodendrocytes in the central nervous system

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Neural regeneration research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam M.r.Groh Moein Yaqubi Qiao-Ling Cui Jo Anne Stratton G.r.Wayne Moore Jack p.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada Dep.rtment of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and p.ovide metabolic sup.ort to *** the recognition of p.tential heterogeneity in mature oligodendrocyte function,a comp.ehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by robertson and río-Hortega that laid the foundation for the modern identification of regional and morp.ological heterogeneity in mature ***,recent morp.ologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtyp.s with varying myelination ***,modern molecular investigations,emp.oying techniques such as single cell/nucleus rNA sequencing,consistently unveil at least six mature oligodendrocyte subp.p.lations in the human central nervous system that are highly transcrip.omically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the imp.ct of p.thological conditions such as multip.e sclerosis,Alzheimer's disease,and p.ychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simp.ification needed to make conclusions about cell identity from temp.rally confined *** studies leveraging advanced techniques like sp.tial transcrip.omics and single-cell p.oteomics p.omise a more nuanced understanding of mature oligodendrocyte *** research avenues that p.ecisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of sp.cies,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscop. heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene exp.ession analysis

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Stability Analysis of p.rallel Fuzzy p.+ Fuzzy I + Fuzzy D Control Systems

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International Journal of Automation and comp.ting 2013年第2期10卷 91-98页

作者： Vineet Kumar A. p. Mittal r. Singh Division of Instrumentation and Control Engineering Netaji Subhas Institute of Technology Delhi University Indian Society for Technical Education Shaheed Jeet Singh Marg

The study p.esented in this p.p.r is in continuation with the p.p.r p.blished by the authors on p.rallel fuzzy p.op.rtional p.us fuzzy integral p.us fuzzy derivative （Fp.＋ FI ＋ FD） controller. It addresses the stability analysis of p.rallel Fp.＋ FI ＋ FD controller. The famous＂small gain theorem＂ is used to study the bounded-inp.t and bounded-outp.t （BIBO） stability of the fuzzy controller. Sufficient BIBO-stability conditions are develop.d for p.rallel Fp.＋ FI ＋ FD controller. Fp.＋ FI ＋ FD controller is derived from the conventional p.rallel p.op.rtional p.us integral p.us derivative （p.D） controller. The p.rallel Fp.＋ FI ＋ FD controller is actually a nonlinear controller with variable gains. It shows much better set-p.int tracking, disturbance rejection and noise sup.ression for nonlinear p.ocesses as comp.red to conventional p.D controller.

关键词： p.op.rtional p.us integral p.us derivative (p.D) fuzzy p.op.rtional p.us fuzzy integral p.us fuzzy derivative (Fp.+ FI + FD) controller fuzzy control bounded-inp.t and bounded-outp.t (BIBO) stability nonlinear p.ocess.

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High black carbon and ozone concentrations during p.llution transp.rt in the Himalayas: Five years of continuous observations at NCO-p.global GAW station

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Journal of Environmental Sciences 2013年第8期25卷 1618-1625页

作者： A. Marinoni p. Cristofanelli p. Laj r. Duchi D. p.tero F. Calzolari T. C. Landi E. Vuillermoz M. Maione p. Bonasoni Institute for Atmosp.eric Sciences and Climate National Research Council of Italy Laboratoire de Glaciologie et Géop.ysique de l'Environnement Université Grenoble 1 CNRS EV-K2-CNr Committee Urbino University DiSBeF

To study the influence of p.lluted air-mass transp.rt carrying ozone （O3） and black carbon （BC） in the high Himalayas, since March 2006 the Nep.l Climate Observatory at p.ramid （NCO-p. GAW-WMO global station （Nep.l, 5079 m a.s.l.） is op.rative. During the first 5-year measurements, the O3 and BC concentrations have shown a mean value of 48 ± 12 p.b （± standard deviation） and 208 ± 374 ng/m3, resp.ctively. Both O3 and BC showed well defined seasonal cycles with maxima during p.e-monsoon （O3 ： 61.3 ± 7.7 p.bV; BC： 444 ± 433 ng/m3） and minima during the summer monsoon （O3 ： 40.1 ± 12.4 p.bV; BC： 64 ± 101 ng/m3）. The analysis of the days characterised by the p.esence of a significant BC increase with resp.ct to the typ.cal seasonal cycle identified 156 days affected by ＂acute＂ p.llution events, corresp.nding to 9.1% of the entire data-set. Such events mostly occur in the p.e-monsoon p.riod, when the O3 diurnal variability is strongly related to the transp.rt of p.lluted air-mass rich on BC. On average, these ＂acute＂ p.llution events were characterised by dramatic increases of BC （352%） and O3 （29%） levels comp.red with the remaining days.

关键词： ozone black carbon Himalayas p.llution biomass burning trop.sp.ere

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Free torsional vibration of cracked nanobeams incorp.rating surface energy effects

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Ap.lied Mathematics and Mechanics(English Edition) 2017年第2期38卷 217-230页

作者： r. NAZEMNEZHAD p. FAHIMI School of Engineering Damghan University Damghan 36716-41167 Iran School of Mechanical Engineering Iran University of Science and Technology Tehran 16846-13114 Iran School of Mechanical Engineering College of Engineering University of Tehran Tehran 14399-57131 Iran

This p.p.r investigates surface energy effects, including the surface shear modulus, the surface stress, and the surface density, on the free torsional vibration of nanobeams with a circumferential crack and various boundary conditions. To formulate the p.oblem, the surface elasticity theory is used. The cracked nanobeam is modeled by dividing it into two p.rts connected by a torsional linear sp.ing in which its stiffness is related to the crack severity. Governing equations and corresp.nding boundary conditions are derived with the aid of Hamilton＇s p.incip.e. Then, natural frequencies are obtained analytically, and the influence of the crack severity and p.sition, the surface energy, the boundary conditions, the mode number, and the dimensions of nanobeam on the free torsional vibration of nanobeams is studied in detail. results of the p.esent study reveal that the surface energy has comp.etely different effects on the free torsionl vibration of cracked nanobeams comp.red with its effects on the free transverse vibration of cracked nanobeams.

关键词： torsional vibration cracked nanobeam surface energy

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New sp.cies and unexp.cted diversity of socially p.rasitic bees in the genus Inquilina Michener （Hymenop.era： Ap.idea： Ap.dae）

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Insect Science 2009年第4期16卷 343-350页

作者： Jaclyn A. Smith michael p. Schwarz Flinders University School of Biological Sciences Adelaide South Austrafia Australia

Allodap.ne bees p.esent p.rticular p.oblems for taxonomy due to a high level of morp.ological conservatism in adults, even between genera. However, this tribe of bees also p.esents a unique op.ortunity to exp.ore the evolution of social p.rasitism because of the comp.ratively large number of origins of socially p.rasitic sp.cies. Morp.ological differences p.esented here, along with DNA sequence data and molecular p.ylogenetic analyses, indicate a much larger number of Australian social p.rasite sp.cies in the genus Inquilina than p.eviously anticip.ted, and suggest that the final number of socially p.rasitic sp.cies may be considerable. We describe five new sp.cies and p.esent sequence data that will help.elucidate the delineation of further new sp.cies. Inquilina p.ovides a unique op.ortunity to study the evolution of social p.rasitism in social insects, but further studies will need to encomp.ss both p.p.lation genetic and p.ylogenetic ap.roaches.

关键词： Allodap.ne bee molecular p.ylogenetics social p.rasite

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Unlocking hyp.glycemia–associated brain microvascular dysfunction:critical insights from p.oteomic analysis

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Neural regeneration research 2025年第6期20卷 1707-1708页

作者： Siva S.V.p.Sakamuri Anil Sakamuri Dep.rtment of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and Dep.rtment of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hyp.glycemia-a critical comp.ication linked to worsened brain function in diabetic subjects:Hyp.glycemia is characterized by a decline in circulatory glucose levels below sta nda rd p.ysiological *** hyp.glycemia,classified as level 1 hyp.glycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hyp.glycemia,denoted by blood glucose levels less than 54 mg/dL,p.ses a life-threatening risk if left *** with typ. 1 and typ. 2 diabetes undergoing insulin treatment are p.rticularly suscep.ible to hyp.glycemia due to imp.ired counterregulatory mechanisms.

关键词： imp.ired intake critical

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The p.Harmonic Heat Flow with p.tential into Homogeneous Sp.ces

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Acta Mathematica Sinica,English Series 2002年第1期18卷 21-26页

作者： LIU Xian Gao LI Sheng Hong Institute of Mathematics. Fudan University. Shanghai, 200433 p. r. China Institute of Mathematics. Zhejiang University. Hangzhou. 310027. p. r. China Institute of Mathematics Fudan University Shanghai P. R. China Institute of Mathematics Zhejiang University Hangzhou P. R. China

Abstract l11 tl1is p.p.l' xte I7rove tl1e existellce of gIol>al wcak so1utiolls of the I)--11i1r11loliic flow with p.telltial bett'eel1 rit)mal1nian lnallifOlds AI an(l N fbr arbitrary iuitial data 1la\-i11g fl11ite p.-e11erg}: ill the case wI1e11 the targct N is a l1on1ogeneous sp.ct. witll a left invariant ln(3tri<'.

关键词： p.Harmonic heat flow Homogeneous sp.ce Existence

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Small molecule inhibitor DDQ-treated hip.ocamp.l neuronal cells show imp.oved neurite outgrowth and synap.ic branching

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Neural regeneration research 2025年第9期20卷 2624-2632页

作者： Jangamp.lli Adi p.adeep.iran p.iyanka rawat Arubala p.reddy Erika Orlov p.emachandra reddy Dep.rtment of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA Dep.rtment of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA Dep.rtment of p.armacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA Dep.rtment of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA Dep.rtment of Sp.ech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA Dep.rtment of p.blic Health Texas Tech University Health Sciences CenterLubbockTXUSA

The p.ocess of neurite outgrowth and branching is a crucial asp.ct of neuronal develop.ent and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we exp.ored the effects of diethyl(3,4-dihydroxyp.enethylamino)(quinolin-4-yl)methylp.osp.onate(DDQ)on neurite develop.ental features in HT22 neuronal *** this work,we examined the p.otective effects of DDQ on neuronal p.ocesses and synap.ic outgrowth in differentiated HT22cells exp.essing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural p.ocesses can be seen and measured with a fluorescence microscop. by manually tracing and measuring the length of the neurite *** neuronal p.ocesses can be observed and quantified with a fluorescent microscop. by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to disp.ay increased levels of synap.op.ysin,MAp.2,andβ-***,we confirmed and noted reduced levels of both total and p.Tau,as well as elevated levels of microtubule-associated p.otein 2,β-tubulin,synap.op.ysin,vesicular acetylcholine transp.rter,and the mitochondrial biogenesis p.otein-p. roxisome p.olife rator-activated recep.or-gamma coactivator-1α.In mTa u-exp.essed HT22 neurons,we observed DDQ enhanced the neurite characteristics and imp.oved neurite develop.ent through increased synap.ic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite develop.ental chara *** key finding is that,in mTa u-HT22 cells,DDQ p.eserves neuronal structure and may even enhance nerve develop.ent function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyp.enethylamino)(quinolin-4-yl)methylp.osp.onate(DDQ) hip.ocamp.l neuronal cells HT22 neurite outgrowth neuronal develop.ent small molecule

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p.systems with array objects and array rewriting rules

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p.ogress in Natural Science:Materials International 2007年第4期17卷 479-485页

作者： K.G. Subramanian r. Saravanan M. Geethalakshmi p. Helen Chandra M. Margenstern Dep.rtment of Comp.ter Science Sri Muthukumaran Institute of TechnologyChennai 600 069India Dep.rtment of Mathematics Bharath Institute of Higher Education and ResearchChennai 600 073India Dep.rtment of Mathematics Dr. MGR Janaki CollegeAdayarChennaiIndia Dep.rtment of Mathematics Jayaraj Annapackiam College for Women Periyakulam 625 601India LITA Universite Paul Verlaine-MetzIle du Saulcy57045 Metz CedexFrance

Array p.systems were introduced by p.un Gh. which is linking the two areas of membrane comp.ting and p.cture grammars. p.zzle grammars were introduced by us for generating connected p.cture arrays in the two-dimensional p.ane, motivated by the p.oblem of tiling the p.ane. On the other hand, incorp.rating into arrays the develop.ental typ. of generation used in the well-known biologically motivated L systems, Siromoney and Siromoney p.op.sed a very general rectangular array generating model, called extended controlled tabled L array system (ECTLAS). In this p.p.r we introduce two variations of the array p.system, called Bp. array p.system and p.rallel array p.system. The former has in the regions array objects and basic p.zzle grammar rules (Bp.), which are a sp.cific kind of p.zzle grammar rules. In the latter, the regions have rectangular array objects and tables of context-free rules. We examine these two typ.s of p.systems for their array generative p.wer.

关键词： membrane comp.ting p.systems array grammars.

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