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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-mañé laia just-borràs.m.rta balanyà-segura Aleksandra Polishchuk Laura Nadal marta Tomàs Carolina silvera-simón manel m.santafé maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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severe dystrophy in DiGeorge syndrome

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World Journal of Gastroenterology 2009年第11期15卷 1391-1393页

作者： Barnabás Rózsai kos Kiss Gyrgyi Csábi márta Czakó Tamás Decsi Department of Pediatrics University of PécsPécs H-7623 Hungary Department of medical Genetics and Child Development University of PécsPécs H-7623Hungary

We present the case history of a 3-year-old girl who was examined because of severe *** the background,cow’s milk allergy was found,but her body weight was unchanged after eliminating milk from her *** types of malabsorption were *** on nasal regurgitation and facial dysmorphisms,the possibility of DiGeorge syndrome was suspected and was confirmed by fluorescence in situ *** authors suggest a new feature associated with DiGeorge syndrome.

关键词： DiGeorge syndrome Dystrophy Cow's milkallergy Nasal regurgitation Hypoparathyroidism

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Triboelectric nanogenerator based on electrodeposited Ag octahedral nano-assemblies

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Journal of Energy Chemistry 2023年第8期83卷 478-495,I0012页

作者： m.Edith Navarro-segura margarita sanchez-Dominguez Ana Arizmendi-morquecho J.Alvarez-Quintana Group of Colloidal and Interfacial Chemistry Applied to Nanomaterials and Nanoformulations Centro de Investigacion en Materiales Avanzados S.C Unidad MonterreyAlianza Norte#202Autopista Monterrey-Aeropuerto Km.10.C.P.66628 ApodacaNuevo LeonMexico GENEs-Group of Embedded Nanomaterials for Energy scavenging Centro de Investigacion en Materiales Avanzados S.C.Unidad MonterreyAlianza Norte#202Autopista Monterrey-Aeropuerto Km.10.C.P.66628 ApodacaNuevo LeonMexico

The tremendous potential of triboelectric generators-TENGs for converting mechanical energy into electrical energy places them as one of the most promising energy harvesting technologies. In this work, the fabrication of enhanced performance TENGs using Ag octahedron nano-assemblies on ITO as electrodes significantly increases the electric charge collection of the induced tribocharges. Thereby, nanostructured electrical contacts coated with Ag macroscale nano-assemblies with octahedral features were obtained by the electrodeposition technique on flexible PET/ITO substrates. Consequently, the nanostructured triboelectric generator-TENG exhibited 65 times more maximum output power, and almost 10 times more open circuit output voltage than that of a TENG with non-nanostructured contacts passing from μW to m W capabilities, which was attributed to the increment of intrinsic interface states due to a higher effective contact area in the former. Likewise, output performances of TENGs also displayed an asymptotic behavior on the output voltage as the operating frequency of the mechanical oscillations increased, which is attributed to a decrement in the internal impedance of the device with frequency. Furthermore, it is shown that the resulting electrical output power can successfully drive low power consumption electronic devices. On that account, the present research establishes a promising platform which contributes in an original way to the development of the TENGs technology.

关键词： Triboelectric generator Nanostructured electrodeposited electrodes Ag octahedral nanoassemblies Electrode surface structure

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On the role of endogenous neurotoxins and neuroprotection in Parkinson's disease

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Neural Regeneration Research 2017年第6期12卷 897-901页

作者： Juan segura-Aguilar molecular and Clinical Pharmacology ICBM Faculty of Medicine University of Chile

For 50 years ago was introduced L-3,4-dihydroxyphenylalanine（L-dopa） in Parkinson＇s disease treatment and during this significant advances has been done but what trigger the degeneration of the nigrostriatal system remain unknown. There is a general agreement in the scientific community that mitochondrial dysfunction, protein degradation dysfunction, alpha-synuclein aggregation to neurotoxic oligomers, neuroinflammation, oxidative and endoplasmic reticulum stress are involved in the loss of dopaminergic neurons containing neuromelanin in Parkinson＇s disease. The question is what triggers these mechanisms. The age of normal onset in idiopathic Parkinson＇s disease suggests that environmental factors such as metals, pollutants or genetic mutations cannot be involved because these factors are related to early onset of Parkinsonism. Therefore, we have to search for endogenous neurotoxins and neuroprotection in order to understand what trigger the loss of dopaminergic neurons. One important feature of Parkinson＇s disease is the rate of the degenerative process before the motor symptoms are evident and during the disease progression. The extremely slow rate of Parkinson＇s disease suggests that the neurotoxins and the neuroprotection have to be related to dopamine metabolism. Possible candidates for endogenous neurotoxins are alpha-synuclein neurotoxic oligomers, 4-dihydroxyphenylacetaldehyde and ortho-quinones formed during dopamine oxidation to neuromelanin. Vesicular monoamine transporter-2, DT-diaphorase and glutathione transferase m2-2 seems to be the most important neuroprotective mechanism to prevent neurotoxic mechanism during dopamine oxidation.

关键词： dopamine endogenous endoplasmic degeneration reticulum extremely glutathione Dopamine transporter metabolism

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single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

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Neural Regeneration Research 2024年第3期19卷 529-535页

作者： sandro Huenchuguala Juan segura-Aguilar Escuela de Tecnología médica Facultad de SaludUniversidad Santo TomásLos CarrerasOsornoChile molecular&Clinical Pharmacology Instituto de Ciencias Biomedicas(ICBM)Faculty of medicineUniversity of ChileIndependenciaSantiagoChile

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal *** preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical ***,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic *** lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big *** our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic *** exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic *** endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in t

关键词： 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 6-hydroxydopamine aminochrome dopaminergic neurons DT-diaphorase exogenous neurotoxins glutathione transferase m2-2

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Unexpected ecotone dynamics of a sand dune vegetation complex following water table decline

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Journal of Plant Ecology 2016年第1期9卷 40-50页

作者： Csaba Tölgyesi márta Zalatnai LászlóErdős Zoltán Bátori Nicole Rosemary Hupp LászlóKörmöczi Department of Ecology University of SzegedSzeged H-6726Hungary Wildlife Biology Program College of Forestry and ConservationUniversity of Montana32 Campus DriveMissoulaMontanaMT 59812USA

Aims Central Hungarian inland dune ranges harbor heterogeneous grassland vegetation with an extensive network of ecotones,arranged perpendicular to topography-driven hydrologic *** area suffers from severe aridification due to climate change and local anthropogenic factors,which have led to a dramatic decline of the water *** a result,groundwater is no longer reachable for lowlying plant communities;thus,we expect they are bound to undergo profound *** study investigates how the plant communities respond to this changing environment over time by monitoring ecotones,since they are frequently the hotspots of ecosystem *** monitored five ecotones along permanent belt transects for 15 years to characterize their dynamic response,and to identify the internal structural changes of the plant communities the ecotones *** Ecotones were delineated with the split moving window *** dynamics of two ecotone parameters,location and contrast,were analyzed with linear regression models incorporating two independent variables:study year as a measure of time since the loss of groundwater,and precipitation as a possible driver of interannual *** internal changes of the patches separated by the ecotones were analyzed using plant functional *** Findings Precipitation had no detectable effect on the ecotone descriptors,but study year influenced ecotones in an unusual *** position of the ecotones appeared to be very stable in time;their dynamics are stationary,not directional as we *** contrasts had clear tendencies;two ecotones disappeared,one new one was formed and two ecotones showed no *** internal changes of the patches over time were dramatic,showing a shift toward more xeric and more open plant assemblages in most stretches of the ***,the dynamic response of the vegetation was not patch expansion ***,but fusion ***,which profoundly restructured the vegetati

关键词： groundwater decline plant functional group sand dune vegetation split moving window stationary ecotone

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The story of the Century

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英语学习 1995年第8期 34-35页

作者： mrta Tikkanen

玛尔塔·蒂坎恩是芬兰本世纪七十至八十年代女权主义运动中著名作家和诗人。她的散文诗《本世纪的故事》严肃地反映了妇女婚姻家庭矛盾,诗中那位妇女发出"Love me less,respect me more"的心声,不难读出作者及那个时代的芬兰女性已渐鲜... 详细信息

玛尔塔·蒂坎恩是芬兰本世纪七十至八十年代女权主义运动中著名作家和诗人。她的散文诗《本世纪的故事》严肃地反映了妇女婚姻家庭矛盾,诗中那位妇女发出"Love me less,respect me more"的心声,不难读出作者及那个时代的芬兰女性已渐鲜明的自我意识。

关键词：女权主义家庭矛盾散文诗 The story of the Century 玛尔塔自我意识

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No association of the cytotoxic T-lymphocyte associated gene CTLA4 +49A/G polymorphisms with Crohn's disease and ulcerative colitis in Hungarian population samples

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World Journal of Gastroenterology 2007年第15期13卷 2205-2208页

作者： Lili magyari Bernadett Faragó Judit Bene Katalin Horvatovich Lilla Lakner márta Varga mária Figler Beáta Gasztonyi Gyula mózsik Béla melegh Department of medical Genetics and Child Development University of Pécs PécsHungary mTA PTE Clinical Genetics Research Group of the Hungarian Academy of sciences at the University of Pécs Pécs Hungary markusovszky Hospital Department of medicine and Gastroenterology SzombathelyHungary Réthy Pál Hospital 3rd Department of medicine and Gastroenterology BékéscsabaHungary Department of medicine school of medicine University of PécsPécsHungary Department of Gastroenterology Zala County Hospital ZalaegerszegHungary

AIm： The goal of the current work was to analyse the prevalence of the ＋49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene （CTLA4） in Hungarian patients with Crohn＇s disease （CD） and ulcerative colitis （UC）. mETHODs： A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism （sNP）. The genotypes were determined by using PCR/RFLP test. REsULTs： The G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively. CONCLUsION： The results of the current study show that carriage of the ＋49G sNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.

关键词： Cytotoxic T-lymphocyte antigen 4 Crohn's disease Ulcerative colitis Inflammatory bowel disease

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Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn’s disease patients

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World Journal of Gastroenterology 2010年第2期16卷 176-183页

作者： Veronika Csngei Luca Járomi Eniksáfrány Csilla sipeky Lili magyari Bernadett Faragó Judit Bene Noémi Polgár Lilla Lakner Patrícia sarlós.m.rta Varga Béla melegh Department of medical Genetics University of Pécs Department of medicine and Gastroenterology Markusovszky Hospital 3rd Department of Internal medicine University of Pécs 3rd Department of medicine and Gastroenterology Réthy Pál Hospital

AIm:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn's disease(CD) patients. mETHODs:A total of 315 unrelated subjects with CD and 314 healthy controls were *** and specific genotype combinations of a total of eight variants were *** variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. REsULTs:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;Ps2201841 CC).Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD)loci indicated that IL23R,ATG16L1,CARD15 and IBD5(IGR2198a_1)contribute independently to disease *** also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk *** almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one *** highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(PsION:The present study suggests a cumulative effect of individual IBD susceptibility loci.

关键词： Gene interaction Interleukin-23 receptor Autophagy-related 16-like 1 IBD5 Caspase recruitment domain-containing protein 15 Crohn’s disease Inflammatory bowel disease

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Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity

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World Journal of Diabetes 2016年第20期7卷 572-598页

作者： Ananthi Anandhakrishnan márta Korbonits Centre for Endocrinology William Harvey Research InstituteBarts and the London School of Medicine and DentistryQueen Mary University of London

Though the pathophysiology of clinical obesity is un-doubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1(GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity. As reductions in functional GLP-1 signalling seem to play a role in clinical obesity, the pharmacological replenishment seems a promising target for the medical management of obesity in clinical practice. GLP-1 analogue liraglutide at a high dose(3 mg/d) has shown promising results in achieving and maintaining greater weight loss in obese individuals compared to placebo control, and currently licensed antiobesity medications. Generally well tolerated, provided that longer-term data in clinical practice supports the currently available evidence of superior short- and longterm weight loss efficacy, GLP-1 analogues provide promise towards achieving the successful, sustainable medical management of obesity that remains as yet, an unmet clinical need.

关键词： Obesity pathophysiology Glucagon-like peptide 1 analogues Glucagon-like peptide 1 Clinical obesity

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