1,721,152 research outputs found
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
Basis of Neurofilament light chain trajectories in body fluids in Alzheimer’s disease and normal aging
No full textDie Dissertation ist gesperrt bis zum 26. November 2026 !As life expectancy increases, the prevalence of age-related health problems is expected to rise. Neurodegeneration and associated cognitive impairments are of particular importance because of their significant impact on health span and quality of life. Although several risk factors are associated with neurodegeneration, aging itself has by far the greatest impact. Alzheimer’s disease (AD) is the most common neurodegenerative disorder associated with aging. Neurofilament light chain (NfL) has gained increasing attention as a potential biomarker for neurodegeneration. Therefore, the aim of this work was to better understand NfL changes in both AD and normal aging. The first part of this thesis aimed at deciphering the mechanism behind NfL increases in AD using APPPS1 transgenic mice, a widely used mouse model of cerebral β-amyloidosis. In these mice, we found increased levels of NfL in the cerebrospinal fluid (CSF) with progressive amyloid-β (Aβ) pathology, overall strikingly similar to the NfL changes in humans with autosomal dominant AD. APPPS1 mice do not develop neurofibrillary Tau tangles, but we could demonstrate increased phosphorylated Tau species (pTau181 and pTau217) in the CSF. To investigate whether Aβ aggregation is sufficient to induce CSF-NfL increases in APPPS1 transgenic mice or whether (p)Tau changes are the driver of the NfL increase in this rodent model, we generated APPPS1 mice with reduced (APPPS1,Tau+/-) or absent (APPPS1,Tau-/-) Tau and compared them to normal (APPPS1,Tau+/+) littermates. Using histological, biochemical and proteomic tools, our results suggest that regardless of Tau reduction or deletion, APPPS1 transgenic mice show an increase in CSF-NfL, indicating that Tau is not required for amyloid-induced neurodegeneration and may even be neuroprotective. In the second part of this thesis, NfL changes in blood were examined in the context of normal aging. We found similar trajectories of plasma-NfL with increasing age in human and mouse (C57BL/6J) cohorts. Further analyses in human centenarians revealed a strong association between plasma-NfL and mortality. In addition, we found an attenuated increase in plasma-NfL in diet-restricted mice, which was accompanied by an increase in lifespan. These observations suggest that age-related mortality may be influenced by declining nervous system function. To investigate the underlying mechanisms and the prognostic value of plasma-NfL as a biomarker of mortality (remaining healthy lifespan), we developed strategies and initiated a comprehensive longitudinal study, assessing plasma-NfL and mortality in aging mice. While the study is still ongoing, preliminary data from 20- and 21-month-old mice revealed a shorter median lifespan of mice with plasma-NfL levels in the highest quartile. This was even more pronounced when the rate of NfL change was used rather than single NfL levels. Furthermore, our preliminary data suggest that frailty and weight loss between 20 and 21 months of age are more strongly associated with mortality than plasma-NfL at this age. Ongoing analyses of later time points and two additional batches of aging mice, as well as comparative analyses of epigenetic changes in blood and faecal microbiome, will increase the validity and complement these initial results. In conclusion, NfL has become a widely used fluid biomarker to assess neurodegeneration in AD and to predict healthy lifespan in humans. The present results add to our mechanistic understanding of NfL changes in AD pathogenesis and NfL as a biomarker of the healthy lifespan in the context of other established biomarkers
Microglia network homeostasis in health and disease
No full textDie Dissertation ist gesperrt bis zum 02. Mai 2026 !Microglia are the resident immune cells of the brain and play an important role in regulating brain function in health and disease. They are organized in a brain-wide network, with each cell having its own territory. It is generally recognized that microglia are long-lived cells, and individual cortical microglia can survive for a lifetime in a laboratory mouse. How the microglial network is maintained and how aging and disease affect the homeostasis of the network is not yet fully understood.
To investigate the homeostasis of the microglial network, I pursued two approaches. First, I describe my efforts to develop a new mouse model to study the response of the microglial network after ablation of individual microglia in vivo. The mouse model co-expresses the diphtheria toxin receptor (iDTR) and tdTomato dependent on Cre-recombination in a small percentage of microglial cells, rendering tdTomato-positive microglia susceptible to diphtheria toxin-induced cell death. Unfortunately, Cre-recombination of tdTomato and iDTR rarely, if ever, occurred in the same cell. Most likely, differences in length between the two loxP sites flanking the STOP cassette hampered success of this in vivo approach.
In the second part of the thesis, I describe the subsequent development of a novel hippocampal slice culture model as a simplified in vitro model to study microglia network homeostasis. In this model, the endogenous murine microglia were replaced by human induced pluripotent stem cells (iPSC)-derived microglia (iMics), facilitating the discovery of human microglial network changes. iMics in these chimeric hippocampal slice cultures differentiated and matured into microglia with a highly ramified morphology, transcriptional profile and network organization reminiscent of human microglia. In response to lipopolysaccharide stimulation or focal laser injury, iMics secrete pro-inflammatory cytokines or shield the injury site with their processes, respectively. Surprisingly, human colony-stimulating factor 1 (CSF1) was not required for iMic differentiation and survival in these chimeric hippocampal slice cultures, which contrasts with existing xenotransplantation models that express human CSF1. The observation that loss-of-function CSF1 receptor mutations diminish the integration of iMics into mouse brain slices suggests that cross-species ligand-receptor interactions of mouse CSF1 or interleukin 34 are sufficient for the differentiation and survival of iMics in the mouse brain slices.
To investigate how proteopathic lesions affect the homeostasis of this microglial network, chimeric slice cultures were combined with a recently developed -synucleinopathy hippocampal slice culture seeding model. Similar to what has been observed in mouse models of -synucleinopathy, also iMics in chimeric slice cultures develop -synuclein inclusions that accumulate over time and show a transcriptional response associated with neurodegeneration such as upregulation of the inflammatory response and increased phagocytosis.
While the investigation of in vivo microglial network homeostasis will require further adjustments of the mouse model for targeted ablation of individual microglia, the here developed chimeric slice cultures provide an easily accessible and scalable platform for in vitro study of human microglia under both homeostatic as well as diseased conditions
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
Cerebral amyloid angiopathy : new insights from transgenic mice
Full text linkCerebral amyloid angiopathy (CAA) is characterized by the deposition of congophilic material
within the walls of small to medium-sized blood vessels of the brain and leptomeninges. The
incidence of CAA increases with aging, and in its most severe stages, the vascular amyloid
causes a breakdown of the blood vessel wall which results in spontaneous, often recurrent, lobar
intracerebral hemorrhage. CAA is estimated to account for four to twenty percent of all
nontraumatic intracerebral hemorrhages. Besides this major complication, extensive CAA has
been associated with ischemic white matter damage with progressive dementia, perivascular
inflammation, and secondary vasculitis. CAA occurs as a sporadic disorder in the elderly and in
association with Alzheimer's disease (AD) with virtually all AD patients showing some degree of
vascular amyloid in addition to parenchymal plaques. There are also familial forms of CAA such
as hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). The vascular
amyloid in these disorders mainly consists of β -amyloid peptide (Aβ ) that is produced by
proteolytic cleavage from its precursor, which is the β -amyloid precursor protein (APP). The
major Aβ species that is deposited in the vasculature is Aβ 40, while parenchymal amyloid is
mainly composed of Aβ 42. One major difficulty in studying CAA is that it can be definitely
diagnosed only postmortem. Moreover, spontaneous CAA occurs only in old primates and dogs,
both of which are not practical models to study the pathogenesis and therapy of CAA. Rodents
do not spontaneously develop CAA.
The purpose of this thesis was to provide useful model systems to study the pathomechanism of
vascular amyloid formation and associated pathology. To this end we generated and used mice
that are transgenic for human genes bearing mutations that are well known to cause either
hereditary Aβ -CAA or classical familial AD. In a first study we analyzed CAA and CAA-associated
pathological changes in APP23 transgenic mice. These mice overexpress human APP bearing the
Swedish K670N/M671L double mutation, a typical early-onset AD-causing mutation, under the
control of the neuron-specific Thy-1 promoter. In addition to parenchymal amyloid plaques,
APP23 mice show consistent amyloid within leptomeningeal, neocortical, hippocampal, and
thalamic vessel walls. Both CAA frequency and severity significantly increase with aging,
demonstrating that not only more vessels are affected, but also that the amyloid burden of
individual vessels increases with the progression of amyloid deposition. Cerebrovascular amyloid
causes degeneration of vascular smooth muscle cells (SMCs). In severely affected vessels, SMCs
are completely replaced by the amyloid. Similar to humans, amyloid depositing APP23 mice
develop spontaneous hemorrhages, some of them being recurrent. The bleedings are associated
with amyloid-laden vessels and therefore, their anatomical distribution appears very similar to
that of CAA. In aged mice, a quantitative analysis revealed a positive correlation between
hemorrhages and CAA. Interestingly, no significant relationship between hemorrhages and total
amyloid load was observed. Occasionally, CAA-associated vasculitis is seen in animals with
extensive vascular amyloid.
In a second study, we generated transgenic mice that express human APP E693Q under the
control of the same neuron-specific Thy-1 promoter (APPDutch mice) that has been used in
APP23 mice. In HCHWA-D patients, the APP E693Q Dutch mutation causes severe CAA with
recurrent cerebral hemorrhagic strokes often leading to death early in their fifties, or to
dementia in patients that survive the strokes. In contrast to AD patients that show parenchymal
amyloid plaques, HCHWA-D patients exhibit few parenchymal amyloid deposits. Similar to
HCHWA-D, aged APPDutch mice show extensive Aβ deposits mainly within the walls of
leptomeningeal vessels followed by cortical vessels. Parenchymal Aβ deposits are mostly absent.
In severely affected vessels, the SMCs are completely displaced by the amyloid. In regions with
CAA, fresh and old hemorrhages are observed, and activated perivascular microglia and reactive
astrocytes are found. To examine the mechanism that leads to the almost exclusive vascular
amyloid formation in APPDutch mice, we compared the mice with transgenic mice
overexpressing wild-type (wt) human APP using the same neuronal promoter (APPwt mice). As
they age, APPwt mice develop parenchymal plaques with limited vascular amyloid deposits. A
biochemical analysis of Aβ 40 and Aβ 42 levels revealed significant higher Aβ 40:42 ratios in
amyloid depositing and pre-depositing APPDutch mice compared to APPwt mice. To
demonstrate that the high Aβ 40:42 ratio in APPDutch mice is linked to the almost exclusive
vascular amyloid deposition, we crossed APPDutch mice with mice that overexpress human
presenilin-1 bearing the G384A mutation (PS45 mice) that is known to dramatically increase the
production of Aβ 42. Strikingly, young APPDutch/PS45 double-transgenic mice develop massive
diffuse and compact parenchymal amyloid with only very little CAA. Thus, shifting the Aβ 40:42
ratio towards Aβ 42 is sufficient to redistribute the amyloid pathology from the vasculature to the
parenchyma.
A third series of experiments using neurografting techniques was performed to investigate the
mechanisms involved in the initiation of cerebral amyloidosis in vivo . Cell suspensions of
transgenic APP23 and wild-type B6 embryonic brain tissue were injected into the neocortex and
hippocampus of both APP23 and B6 mice, respectively. In wild-type hosts, APP23 grafts did not
show amyloid deposits up to 20 months after grafting. Interestingly, transgenic and wild-type
grafts in young APP23 hosts develop amyloid plaques as early as three months after grafting.
Although the majority of the amyloid is of the diffuse type, some compact and congophilic
amyloid plaques are observed in the wild-type grafts. These congophilic amyloid lesions are
surrounded by neuritic changes and gliosis, comparable to the amyloid-associated pathology
that has previously been described in APP23 mice. These results support the importance of
neuronally secreted Aβ for the development of cerebral amyloidosis which can be initiated
distant from the site of Aβ production, a finding that supports the observation of the above
mentioned APPDutch mouse model.
In summary, we demonstrate that APP23 and APPDutch mice recapitulate CAA and CAAassociated
pathology observed in humans and thus are valuable models for studying the human
disease. Our results stress the importance of neuronally secreted Aβ for the development of CAA
and emphasize the Aβ 40:42 ratio as an important factor in determining parenchymal versus
vascular amyloid deposition. The understanding that different Aβ species can drive amyloid
pathology in different cerebral compartments not only provides insights into the
pathomechanism of sporadic and familial CAA but also has implications for current anti-amyloid
therapeutic strategies
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
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