1,720,963 research outputs found
"Investigation on the role of Cl- homeostasis and GABAergic transmission in sleep disorders of Down syndrome and in Prader Willi syndrome: a possible contributor to cognitive impairment"
No full textGABA is the main inhibitory neurotransmitter of the central nervous system (CNS). Recently,
GABAergic transmission has been reported to be depolarizing and possibly excitatory rather than
inhibitory in a number of neurodevelopmental disorders both in patients and mouse models.
In particular, the Ts65Dn mouse model of Down syndrome (DS) exhibits depolarizing GABA due to
upregulation of the Cl- importer NKCC1 both in the hippocampus and in the cortex. Moreover,
NKCC1 inhibition by the FDA-approved diuretic bumetanide is able to rescue inhibitory GABAergic
transmission, synaptic plasticity and cognitive functions in Ts65Dn mice.
Beside cognitive impairment, DS mice and people with DS show sleep disturbaces. Since sleep
pattern is regulated by GABAergc transmission, we reasoned that the alteration of GABAergic
transmission due to upregulation of NKCC1 might be underlying at least some of the sleep
disturbances in DS mice. So, we characterized sleep in Ts65Dn mice and investigated the effects of
a chronic treatment with bumetanide. We found that bumetanide ameliorates the quality of sleep
in NREM and REM sleep phases before and after sleep deprivation and decreases abnormal
wakefulness during light phase at baseline in Ts65Dn mice. Moreover, we also found abnormalities
in other parameters, which could contribute to sleep abnormalities of Ts65Dn mice: an increase of
food intake and activity (partially rescued by bumetanide) with a reduction of body temperature
during dark phase.
Because of the association of altered GABAergic signaling by dysregulation of the expression of
NKCC1 (but also of the Cl- exporter KCC2) in many neurodevelopmental disorders characterized by
cognitive or social impairment, and sleep disorders, we extended our studies to Prader Willi
syndrome (PWS). PWS is a neurodevelopmental disorder, caused by defects of genomic imprinting
and characterized by cognitive, social and sleep abnormalities. Here, we observed that the Snord116
5
mutant mouse model of PWS, PWScrm+/p− show an increased expression of NKCC1, specifically in the
hippocampus in comparison to their wild-type mice. Moreover, we report that PWS mice have
altered cognition and the circadian period in free-running conditions. In particular, mutant mice
present defects of long-term memory and a reduced shortening of their circadian period together
with an increase of alpha activity in dark-dark (DD). Moreover, they also show alteration of pain
sensitivity, that could be linked to defects in the thermoregulation. Interestingly, in constrast with
PWS people, Snord116 mutant mice showed no alterations of anxiety, repetivive, obsessive and
social behaviors.
In an effort to rescue cognition and the circadian phenotype by rescuing NKCC1 inhibition, we
treated Snord116 mutant mice with bumetanide. Remarkably, bumetanide treatment resulted in a
complete rescue of the cognitive defects and circadian alteration in DD, with no effects in controls.
Our results suggest an important link between GABA transmission and the regulation of cognition
and the circadian clock in PWS. In addition, the current study extends the repertoire of disorders in
which NKCC1 inhibition attenuates behavioural deficits and proposes a new potential mechanism
for the investigation of PWS
Inherent Safe and Sustainable Process Design applied to Polyhydroxyalkanoates Bioproduction from Wastes
No full textNowadays, the environmental impact deriving from plastic waste represents a global challenge due to its persistence in natural ecosystems, directly associated to its difficulty in disposal. These issues heightened the urgency to find sustainable alternatives to conventional plastics. Polyhydroxyalkanoates offer a promising solution as biodegradable biopolymers, but their large-scale introduction is hindered by high production costs, primarily due to the use of food-based carbon sources such as glucose, which account for around 50% of the total expenses. This issue can be addressed through the use of alternative carbon substrates like agro-food wastes, which are able to lower the overall production costs and reduce the waste accumulation, becoming powerful resources and introducing polyhydroxyalkanoates production within the biorefinery concept.
With these regards, the present work focused on the development of an inherent safe and economically sustainable design of polyhydroxyalkanoates, basing on preliminary results obtained at a laboratory scale. Indeed, during the first step of this research, the polyhydroxyalkanoates bioproduction in Cupriavidus necator DSM 545, through the use of spent coffee grounds oil as alternative carbon substrate, was investigated. Sequential spent coffee grounds pre-treatments were initially performed demonstrating the potential of this residue, allowing, at the same time, the extraction of oil and the recovery of commercially valuable compounds like caffeine and polyphenols, addressed to several applications, including food and pharmaceuticals sectors. The obtained results, along with those achieved for the spent coffee grounds powder characterization in terms of flammability and explosivity properties, allowed to perform an early-stage inherent safety design and economic analysis of the process. Even if conventional carbon substrates like fructose represent inherently safer solutions than biomass wastes since they do not comprise additional pre-treatment steps, the latter present the potentialities to obtain both appreciable polyhydroxyalkanoates yields and high-added value subproducts, minimizing the overall biopolymer production costs. Furthermore, considering a trade-off between technical feasibility, safety, and economical sustainability at the basis of the technological transfer of a chemical process, the economic viability of the polyhydroxyalkanoates production in the case spent coffee grounds were used as carbon substrate was verified.
In summary, the topics addressed by this thesis work are organized and subdivided into the following chapters:
Chapter 1 – State of the art. This section was dedicated to a literature review about the main existing inherent safety tools and methodologies, with a focus on the index-based approaches. A second part was dedicated to review the main polyhydroxyalkanoates production processes and conditions starting from wastes as carbon substrates.
Chapter 2 – Polyhydroxyalkanoates production from spent coffee grounds: an experimental study. This section focused on an experimental feasibility study concerning the polyhydroxyalkanoates production from spent coffee grounds, properly pre-treated by sequential extraction steps.
Chapter 3 – Study of the flammability and explosiveness properties of spent coffee grounds. This section concerned the flammability and explosiveness characterization of spent coffee grounds powders, both as such and pre-treated by sequential extraction steps.
Chapter 4 – Inherent safety development applied to polyhydroxyalkanoates production from spent coffee grounds. This section was addressed to an inherent safety design of each polyhydroxyalkanoates production step: bacterium and carbon source selection, pre-treatment of the carbon source, and downstream processing.
Chapter 5 – Polyhydroxyalkanoates production from spent coffee grounds and glucose: an economic comparison. This section focused on an economic comparison between two polyhydroxyalkanoates process routes options, based on the use of spent coffee grounds or glucose as carbon feedstocks
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
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