1,720,955 research outputs found
Doprinos mišićno-intrinzične toksičnosti ALS-mutiranog FUS-a motornoj neurodegeneraciji u ALS-u
No full textAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons. Most commonly exhibited symptoms include muscular weakness and atrophy. Clinical manifestations begin in adult age and the disease progresses until eventually, death occurs due to respiratory system failure, on average around 3-5 years after clinical onset. The majority of ALS cases are sporadic, with no previously recorded family history of the disease, while a minor proportion of cases are familial. Genes most commonly implicated in ALS are C9orf72, SOD1, FUS and TDP-43. FUS is an RNA/DNA binding protein involved in multiple cellular processes, including transcription regulation, splicing, RNA transport and degradation. Most ALS mutations in FUS are found in the nuclear localization signal, a domain responsible for import of FUS into the nucleus. Mutations in the NLS disrupt FUS import into the nucleus and cause FUS to aggregate within the cytoplasm. ALS is considered to be a distal axonopathy, and the dying-back hypothesis proposes that it originates in the neuromuscular junctions and progresses retrogradely, implicating the involvement of skeletal muscle in disease pathogenesis. The FusΔNLS mutant mice are an adequate model for FUS-ALS as their mutation mimicks those in ALS patients by preventing the transcription of the NLS. The mutation can be fully reversed to wild-type, and its reversal in just the skeletal muscle cells allows the study of non-cell-autonomous contribution of muscle tissue to ALS. FusΔNLS mice exhibit mild but progressive motor deficits, motor axon loss as well as muscular atrophy. Number and area of muscle fibers are slightly reduced, and signs of denervation in motor neurons are also present, as indicated by the reduction in axon numbers. Reversal of the mutation in skeletal muscle partially rescues some phenotypes. The findings suggest that ALS does indeed arise at least in part due to non-cell-autonomous mechanisms of skeletal muscle.Amiotrofična lateralna skleroza (ALS) je progresivna neurodegenerativna bolest karakterizirana gubitkom motornih neurona. Najčešći simptomi uključuju slabost i atrofiju mišića. Kliničke manifestacije započinju u odrasloj dobi i bolest napreduje dok naposljetku ne nastupi smrt uslijed zatajenja respiratornog sustava, u prosjeku 3-5 godina nakon nastupanja kliničkih znakova. Većina slučajeva ALS-a jest sporadično, bez prethodno zabilježene obiteljske povijesti bolesti, s manjim udjelom familijarnih slučajeva. Najčešći geni koji imaju ulogu u ALS-u su C9orf72, SOD1, FUS i TDP-43. FUS je protein koji veže RNA i DNA, i koji je uključen u mnoge stanične procese, poput regulacije transkripcije, „splicinga“, te transporta i razgradnje RNA. Većina ALS mutacija u FUS genu događa se u nuklearnom lokalizacijskom signalu, domeni odgovornoj za unos FUS-a u jezgru. Mutacije u NLS-u ometaju unos FUS-a u jezgru i uzrokuju agregaciju FUS-a unutar citoplazme. ALS se smatra distalnom aksonopatijom, i „dying-back“ hipoteza postulira da bolest započinje u neuromuskularnim spojevima te da napreduje retrogradno, sugerirajući na upletenost skeletnih mišića u patogenezi bolesti. FusΔNLS miševi su prikladan model za FUS-ALS budući da njihova mutacija oponaša mutacije zapažene kod ALS pacijenata time što sprječava transkripciju NLS-a. Mutacija se može u potpunosti poništiti preobraćanjem na divlji genotip, a preobraćanje mutacije samo u stanicama skeletnih mišića omogućava proučavanje ne-stanično-autonomnog doprinosa mišićnog tkiva ALS-u. FusΔNLS miševi iskazuju blage ali progresivne motorne defekte, gubitak motornih aksona, kao i atrofiju mišića. Broj i povšina mišićnih vlakana su blago umanjeni, i znakovi denervacije u motornim neuronima su također prisutni, što je dokazano smanjenjem broja aksona. Preobraćanje mutacije u skeletnim mišićima djelomično spašava neke fenotipe. Ova otkrića sugeriraju da se ALS razvija barem djelomično zbog ne-stanično-autonomnih mehanizama skeletnih mišića
Doprinos mišićno-intrinzične toksičnosti ALS-mutiranog FUS-a motornoj neurodegeneraciji u ALS-u
No full textAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons. Most commonly exhibited symptoms include muscular weakness and atrophy. Clinical manifestations begin in adult age and the disease progresses until eventually, death occurs due to respiratory system failure, on average around 3-5 years after clinical onset. The majority of ALS cases are sporadic, with no previously recorded family history of the disease, while a minor proportion of cases are familial. Genes most commonly implicated in ALS are C9orf72, SOD1, FUS and TDP-43. FUS is an RNA/DNA binding protein involved in multiple cellular processes, including transcription regulation, splicing, RNA transport and degradation. Most ALS mutations in FUS are found in the nuclear localization signal, a domain responsible for import of FUS into the nucleus. Mutations in the NLS disrupt FUS import into the nucleus and cause FUS to aggregate within the cytoplasm. ALS is considered to be a distal axonopathy, and the dying-back hypothesis proposes that it originates in the neuromuscular junctions and progresses retrogradely, implicating the involvement of skeletal muscle in disease pathogenesis. The FusΔNLS mutant mice are an adequate model for FUS-ALS as their mutation mimicks those in ALS patients by preventing the transcription of the NLS. The mutation can be fully reversed to wild-type, and its reversal in just the skeletal muscle cells allows the study of non-cell-autonomous contribution of muscle tissue to ALS. FusΔNLS mice exhibit mild but progressive motor deficits, motor axon loss as well as muscular atrophy. Number and area of muscle fibers are slightly reduced, and signs of denervation in motor neurons are also present, as indicated by the reduction in axon numbers. Reversal of the mutation in skeletal muscle partially rescues some phenotypes. The findings suggest that ALS does indeed arise at least in part due to non-cell-autonomous mechanisms of skeletal muscle.Amiotrofična lateralna skleroza (ALS) je progresivna neurodegenerativna bolest karakterizirana gubitkom motornih neurona. Najčešći simptomi uključuju slabost i atrofiju mišića. Kliničke manifestacije započinju u odrasloj dobi i bolest napreduje dok naposljetku ne nastupi smrt uslijed zatajenja respiratornog sustava, u prosjeku 3-5 godina nakon nastupanja kliničkih znakova. Većina slučajeva ALS-a jest sporadično, bez prethodno zabilježene obiteljske povijesti bolesti, s manjim udjelom familijarnih slučajeva. Najčešći geni koji imaju ulogu u ALS-u su C9orf72, SOD1, FUS i TDP-43. FUS je protein koji veže RNA i DNA, i koji je uključen u mnoge stanične procese, poput regulacije transkripcije, „splicinga“, te transporta i razgradnje RNA. Većina ALS mutacija u FUS genu događa se u nuklearnom lokalizacijskom signalu, domeni odgovornoj za unos FUS-a u jezgru. Mutacije u NLS-u ometaju unos FUS-a u jezgru i uzrokuju agregaciju FUS-a unutar citoplazme. ALS se smatra distalnom aksonopatijom, i „dying-back“ hipoteza postulira da bolest započinje u neuromuskularnim spojevima te da napreduje retrogradno, sugerirajući na upletenost skeletnih mišića u patogenezi bolesti. FusΔNLS miševi su prikladan model za FUS-ALS budući da njihova mutacija oponaša mutacije zapažene kod ALS pacijenata time što sprječava transkripciju NLS-a. Mutacija se može u potpunosti poništiti preobraćanjem na divlji genotip, a preobraćanje mutacije samo u stanicama skeletnih mišića omogućava proučavanje ne-stanično-autonomnog doprinosa mišićnog tkiva ALS-u. FusΔNLS miševi iskazuju blage ali progresivne motorne defekte, gubitak motornih aksona, kao i atrofiju mišića. Broj i povšina mišićnih vlakana su blago umanjeni, i znakovi denervacije u motornim neuronima su također prisutni, što je dokazano smanjenjem broja aksona. Preobraćanje mutacije u skeletnim mišićima djelomično spašava neke fenotipe. Ova otkrića sugeriraju da se ALS razvija barem djelomično zbog ne-stanično-autonomnih mehanizama skeletnih mišića
Doprinos mišićno-intrinzične toksičnosti ALS-mutiranog FUS-a motornoj neurodegeneraciji u ALS-u
No full textAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons. Most commonly exhibited symptoms include muscular weakness and atrophy. Clinical manifestations begin in adult age and the disease progresses until eventually, death occurs due to respiratory system failure, on average around 3-5 years after clinical onset. The majority of ALS cases are sporadic, with no previously recorded family history of the disease, while a minor proportion of cases are familial. Genes most commonly implicated in ALS are C9orf72, SOD1, FUS and TDP-43. FUS is an RNA/DNA binding protein involved in multiple cellular processes, including transcription regulation, splicing, RNA transport and degradation. Most ALS mutations in FUS are found in the nuclear localization signal, a domain responsible for import of FUS into the nucleus. Mutations in the NLS disrupt FUS import into the nucleus and cause FUS to aggregate within the cytoplasm. ALS is considered to be a distal axonopathy, and the dying-back hypothesis proposes that it originates in the neuromuscular junctions and progresses retrogradely, implicating the involvement of skeletal muscle in disease pathogenesis. The FusΔNLS mutant mice are an adequate model for FUS-ALS as their mutation mimicks those in ALS patients by preventing the transcription of the NLS. The mutation can be fully reversed to wild-type, and its reversal in just the skeletal muscle cells allows the study of non-cell-autonomous contribution of muscle tissue to ALS. FusΔNLS mice exhibit mild but progressive motor deficits, motor axon loss as well as muscular atrophy. Number and area of muscle fibers are slightly reduced, and signs of denervation in motor neurons are also present, as indicated by the reduction in axon numbers. Reversal of the mutation in skeletal muscle partially rescues some phenotypes. The findings suggest that ALS does indeed arise at least in part due to non-cell-autonomous mechanisms of skeletal muscle.Amiotrofična lateralna skleroza (ALS) je progresivna neurodegenerativna bolest karakterizirana gubitkom motornih neurona. Najčešći simptomi uključuju slabost i atrofiju mišića. Kliničke manifestacije započinju u odrasloj dobi i bolest napreduje dok naposljetku ne nastupi smrt uslijed zatajenja respiratornog sustava, u prosjeku 3-5 godina nakon nastupanja kliničkih znakova. Većina slučajeva ALS-a jest sporadično, bez prethodno zabilježene obiteljske povijesti bolesti, s manjim udjelom familijarnih slučajeva. Najčešći geni koji imaju ulogu u ALS-u su C9orf72, SOD1, FUS i TDP-43. FUS je protein koji veže RNA i DNA, i koji je uključen u mnoge stanične procese, poput regulacije transkripcije, „splicinga“, te transporta i razgradnje RNA. Većina ALS mutacija u FUS genu događa se u nuklearnom lokalizacijskom signalu, domeni odgovornoj za unos FUS-a u jezgru. Mutacije u NLS-u ometaju unos FUS-a u jezgru i uzrokuju agregaciju FUS-a unutar citoplazme. ALS se smatra distalnom aksonopatijom, i „dying-back“ hipoteza postulira da bolest započinje u neuromuskularnim spojevima te da napreduje retrogradno, sugerirajući na upletenost skeletnih mišića u patogenezi bolesti. FusΔNLS miševi su prikladan model za FUS-ALS budući da njihova mutacija oponaša mutacije zapažene kod ALS pacijenata time što sprječava transkripciju NLS-a. Mutacija se može u potpunosti poništiti preobraćanjem na divlji genotip, a preobraćanje mutacije samo u stanicama skeletnih mišića omogućava proučavanje ne-stanično-autonomnog doprinosa mišićnog tkiva ALS-u. FusΔNLS miševi iskazuju blage ali progresivne motorne defekte, gubitak motornih aksona, kao i atrofiju mišića. Broj i povšina mišićnih vlakana su blago umanjeni, i znakovi denervacije u motornim neuronima su također prisutni, što je dokazano smanjenjem broja aksona. Preobraćanje mutacije u skeletnim mišićima djelomično spašava neke fenotipe. Ova otkrića sugeriraju da se ALS razvija barem djelomično zbog ne-stanično-autonomnih mehanizama skeletnih mišića
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
- …
