检索结果-南通市图书馆

Restoring expression of Stathmin-2:a novel strategy to treat TDP-43 proteinopathies

在线全文

学校读者我要写书评

暂无评论

Signal Transduction and Targeted Therapy 2023年第8期8卷 3553-3554页

作者： sonja menge Lorena Decker Axel Freischmidt Department of Neurology Ulm University89081 UlmGermany

In a recent study published in Science,Baughn et *** that TDP-43 acts as a steric block in STMN2 pre-mRNA processing preventing inclusion of a deleterious cryptic exon,and present strategies for substituting this function to compensate for the loss of nuclear TDP-43 in a variety of neurodegenerative diseases(NDs)including amyotrophic lateral sclerosis(ALS).1 Stathmin-2(STMN2)is a microtubule-associated protein speci-fically expressed in neurons and required for axon outgrowth and maintenance,as well as for axon regeneration after injury in vitro.

关键词： Stathmin diseases

Can DyeCycling break the photobleaching limit in single-molecule FRET?

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Nano Research 2022年第11期15卷 9818-9830页

作者： Benjamin Vermeer sonja Schmid NanoDynamicsLab Laboratory of BiophysicsWageningen UniversityStippeneng 46708WE WageningenThe Netherlands

Biomolecular systems,such as proteins,crucially rely on dynamic processes at the *** biomolecular nanodynamics is therefore key to obtaining a mechanistic understanding of the energies and molecular driving forces that controlbiomolecular ***-molecule fluorescence resonance energy transfer(smFRET)is a powerful technique to observe inreal-time how a single biomolecule proceeds through its functional cycle involving a sequence of distinct structural ***,this technique is fundamentally limited by irreversible photobleaching,causing the untimely end of the experiment andthus,a narrow temporal bandwidth of≤3 orders of ***,we introduce“DyeCycling”,a measurement scheme withwhich we aim to break the photobleaching limit in *** introduce the concept of spontaneous dye replacement bysimulations,and as an experimental proof-of-concept,we demonstrate the intermittent observation of a single biomolecule forone hour with a time resolution of ***,DyeCycling can provide>100-fold more information per singlemolecule than conventional *** discuss the experimental implementation of DyeCycling,its current and fundamentallimitations,and specific biological use *** its general simplicity and versatility,DyeCycling has the potential torevolutionize the field of time-resolved smFRET,where it may serve to unravel a wealth of biomolecular dynamics by bridgingfrom milliseconds to the hour range.

关键词： biomolecular dynamics single-molecule fluorescence resonance energy transfer(smFRET) photobleaching conformational changes single-molecule kinetics

Optogenetic neuroregeneration

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2022年第7期17卷 1468-1470页

作者： Harald Janovjak sonja Kleinlogel EMBL Australia Australian Regenerative Medicine InstituteFaculty of MedicineNursing and Health SciencesMonash UniversityClayton/MelbourneAustralia Institute of Physiology University of BernBernSwitzerland

Optogenetics is a powerful technology that employs light and genetics to manipulate physiology and behavior with unprecedented *** high acuity of light stimulation permits fine control both in space(e.g.,to target just one tissue in an animal)and in time(e.g.,to interfere with a specific disease stage),whilst genetic targeting restricts manipulation to a functionally-relevant cell population(Figure 1A).

关键词： stimulation manipulation Figure

Egocentric social network correlates of physical activity

在线全文

学校读者我要写书评

暂无评论

Journal of Sport and Health Science 2020年第4期9卷 339-344页

作者： sonja Motteli Simone Dohle Department of Health Sciences and Technology(D-HEST) ETH Z€urichZ€urich 8092Switzerland Department of Psychology University of CologneCologne 08215Germany

Background:The social environment might play an important role in explaining people’s physical activity(PA)***,little is known regarding whether personal networks differ between physically active and physically inactive *** study aimed to examine the relationship between personal network characteristics and adults’physical(in)***:An egocentric social network study was conducted in a random sample in Switzerland(n=529,mean age of 53 years,54%females).Individual and personal network measures were compared between regular exercisers and *** extent of these factors’association with PA levels was also ***:Non-exercisers(n=183)had 70%non-exercising individuals in their personal networks,indicating homogeneity,whereas regular exercisers(n=346)had 57%regularly exercising individuals in their networks,meaning more heterogeneous personal ***,having more regular exercisers in personal networks was associated with higher PA levels,over and above individual *** with an entirely active personal network reported,on average,1 day of PA more per week than respondents who had a completely inactive personal *** personal network characteristics,such as network size or gender composition,were not associated with ***:Non-exercisers seem to be clustered in inactive networks that provide fewer opportunities and resources,as well as less social support,for *** effectively promote PA,both individuals and personal networks need to be addressed,particularly the networks of inactive people(e.g.,by promoting group activities).

关键词： Egocentric network Exercise Inactivity Personal network Physical activity Questionnaire Similarity/homogeneity

Freedom of Indifference: Its Metaphysical Credentials According to Crusius

在线全文

学校读者我要写书评

暂无评论

Fudan Journal of the Humanities and Social Sciences 2019年第3期12卷 385-405页

作者： sonja Schierbaum Philosophisches Seminar Universitat Hamburg Uberseering 35#4 Postfach 22297 Hamburg Germany

In the history of philosophy, voluntarists-that is, philosophers committed to some version of the freedom of indifference-have worried about its metaphysical credentials, but only a few, at least to my knowledge, have attempted to argue for more than its mere existence. Freedom of indifference is the option to choose between opposites in a given situation. In this paper, I present the ambitious attempt of the German pre-Kantian philosopher Christian August Crusius (1715-1775) to argue for the claim that we have freedom of indifference as a matter of hypothetical necessity. The point is that, in his view, there can be no actual world without freedom of indifference. This is not a logical but a metaphysical truth. I argue that a possible (motivational) reason for CrusiusJs choice to tread this slippery path is that he attempts to bestow some metaphysical dignity on the freedom of indifference. As a consequence, this metaphysical value of freedom of indifference shapes the relation between the divine and free, rational agents in a way that is completely different from a rationalist’s conception such as Leibniz’s. In this paper, I give a plausible interpretation of a metaphysical argument that has been neglected in the relevant literature.

关键词： Freedom of indifference Voluntarism Hypothetical necessity Crusius Leibniz

Induction of ultra-morphological features of apoptosis in mature and immature sperm

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Asian Journal of Andrology 2017年第5期19卷 533-537页

作者： sonja Grunewald Guenther Fitzl Christopher Springsguth Department of Dermatology Venerology and Allergology University Hospital Leipzig Leipzig Germany Institute of Anatomy University of Leipzig Leipzig Germany

There is a fundamental body of evidence suggesting that activated apoptosis signaling in ejaculated human sperm negatively influences their fertilization potential. However, it is still controversial whether this apoptotic signaling is a relic of an abortive apoptosis related to spermatogenesis or if it should be regarded as a functional preformed pathway in mature sperm leading to stereotypical morphological changes reflecting nuclear disassembly. To address this question, apoptosis was induced using betulinic acid in mature and immature ejaculated human sperm enriched by density gradient centrifugation. Execution of apoptosis was monitored by observing ultra-morphological changes via transmission electron microscopy. Typical morphological signs of apoptosis in somatic cells include plasma membrane blebbing with the formation of apoptotic bodies, impaired mitochondrial integrity, defects of the nuclear envelope, and nuclear fragmentation; these morphologies have also been observed in human sperm. In addition, these apoptotic characteristics were more frequent in immature sperm compared to mature sperm. Following betulinic acid treatment, apoptosis-related morphological changes were induced in mature sperm from healthy donors. This effect was much less pronounced in immature sperm. Moreover, in both fractions, the betulinic acid treatment increased the percentage of acrosome-reacted sperm. The results of our ultra-morphological study prove the functional competence of apoptosis in mature ejaculated human sperm. The theory of a sole abortive process may be valid only for immature sperm. The induction of the acrosome reaction by stimulating apoptosis might shed light on the biological relevance of sperm apoptosis.

关键词： apoptosis electron microscopy human morphology sperm

River Water Quality Assessment in Selected Yangtze Tributaries: Background and Method Development

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Earth Science 2010年第6期21卷 876-881页

作者： sonja C Jhnig 蔡庆华 Department of Limnology and Conservation Senckenberg Research Institute and Natural History Museum Gelnhausen Germany Biodiversity and Climate Research Centre (BiK-F) State Key Laboratory of Freshwater Ecology and Biotechnology Institute of Hydrobiology Chinese Academy of Sciences

Water pollution is among the most severe environmental problems in China, particularly in the vicinity of residential and urban areas. In almost all Asian countries, river monitoring is predominantly based on the analysis of chemical data. However, biological data are a worthwhile addition for the determination of the long-term ecological status of rivers and are particularly well-suited in case of steep pollution and disturbance gradients. A tool for river water quality assessment using benthic invertebrates has been developed for selected tributaries of the middle reach of the Yangtze River. Site selection was supported by a preclassification considering physico-chemical and hydromorphological conditions. Following a stratified sampling design, 34 samples were taken in small and large streams in the subtropical mountainous area of western Hubei （湖北）（China） covering a pollution gradient, accompanied by an extensive field protocol on stream characteristics and （physico-） chemical water analyses. The proposed assessment system is computed as an average score per taxon. The challenge to further consider the additional impact from global change into the development of such tools is discussed.

关键词： benthic invertebrate biological assessment ecological quality organic pollution Hubei climate change.

Targeting the EGF receptor family in non-small cell lung cancerincreased complexity and future perspectives

在线全文

学校读者我要写书评

暂无评论

Cancer Biology & Medicine 2022年第11期19卷 1543-1564页

作者： Tobias Boch Jens Kohler Melanie Janning sonja Loges DKFZ-Hector Cancer Institute at the University Medical Center Mannheim Mannheim 68135Germany Division of Personalized Medical Oncology(A420) German Cancer Research Center(DKFZ)Heidelberg 69120Germany Department of Personalized Oncology University Medical Center MannheimMedical Faculty MannheimHeidelberg UniversityMannheim 68135Germany

Lung cancer remains the leading cause of cancer-associated mortality worldwide,but with the emergence of oncogene targeted therapies,treatment options have tremendously *** to their biological relevance,members of the ERBB receptor family,including the EGF receptor(EGFR),HER2,HER3 and HER4,are among the best studied oncogenic *** EGFR mutations are frequently observed in non-small cell lung cancer(NSCLC),and small molecule tyrosine kinase inhibitors(TKIs)are the established first line treatment option for patients whose tumors bear"typical/classical"EGFR mutations(exon 19 deletions,L858R point mutations).Additionally,new TKIs are rapidly evolving with better efficacy to overcome primary and secondary treatment resistance(e.g.,that due to T790M or C797S resistance mutations).Some atypical EGFR mutations,such as the most frequent exon 20 insertions,exhibit relative resistance to earlier generation TKIs through steric *** this subgroup,newer TKIs,such as mobocertinib and the bi-specific antibody amivantamab have recently been approved,whereas less frequent atypical EGFR mutations remain *** contrast to EGFR,HER2 has long remained a challenging target,but better structural understanding has led to the development of newer generations of *** recent FDA approval of the antibody-drug conjugate trastuzumab-deruxtecan for pretreated patients with HER2 mutant NSCLC has been an important therapeutic ***3 and HER4 also exert oncogenic potential,and targeted treatment approaches are being developed,particularly for ***,strategies to inhibit the oncogenic function of ERBB receptors in NSCLC are currently evolving at an unprecedented pace;therefore,this review summarizes current treatment standards and discusses the outlook for future developments.

关键词： Oncology NSCLC EGFR HER2 HER3 HER4

Morphodynamics of sandy beaches under the influence of storm sequences:Current research status and future needs

在线全文

学校读者我要写书评

暂无评论

Water Science and Engineering 2019年第3期12卷 221-234页

作者： sonja Eichentopf Harshinie Karunarathna Jose M.Alsina Department of Civil and Environmental Engineering Imperial College London South Kensington Campus London SW7 2AZ UK College of Engineering Swansea University Bay Campus Swansea SA1 8EN UK Laboratori d'Enginyeria Marítima Universitat Politecnica de Catalunya Barcelona 08034 Spain

This paper reviews and discusses the current research status, trends, and future needs in the field of beach morphodynamics under the influence of storm *** paper reviews how the three main research methods, field investigations, numerical modelling, and physical modelling, have been used to study beach morphodynamics during storm *** quantitative definitions of storm sequences at different sites are presented and *** is shown that the definition of storm sequences is site-specific and requires knowledge of the storm climate, beach characteristics, and the temporal scale of beach ***, the paper brings together currently available approaches aimed at describing the effect of storm sequences on beach erosion in a general *** importance of storm chronology and the effects of an extreme storm within a sequence of storms are *** that, the more poorly studied aspect of beach recovery in between storms within a sequence is *** indicators for defining beach recovery, namely the shoreline location, sediment volumes, and the beach state, are identified and ***, important research needs, including the need for detailed physical modelling, are identified.

关键词： Storm sequences Beach morphodynamics Beach erosion Extreme storms Return period Beach recovery