1,238 research outputs found
The role of Isocitrate Lyase (ICL1) in the metabolic adaptation of Candida albicans biofilms
Background
A major characteristic of Candida biofilm cells that differentiates them from free-floating cells is their high tolerance to antifungal drugs. This high resistance is attributed to particular biofilm properties, including the accumulation of extrapolymeric substances, morphogenetic switching, and metabolic flexibility.
Objectives
This study evaluated the roles of metabolic processes (in particular the glyoxylate cycle) on biofilm formation, antifungal drug resistance, morphology, and cell wall components.
Methods
Growth, adhesion, biofilm formation, and cell wall carbohydrate composition were quantified for isogenic Candida albicans ICL1/ICL1, ICL1/icl1, and icl1/icl1 strains. The morphology and topography of these strains were compared by light microscopy and scanning electron microscopy. FKS1 (glucan synthase), ERG11 (14-α-demethylase), and CDR2 (efflux pump) mRNA levels were quantified using qRT-PCR.
Results
The ICL1/icl1 and icl1/icl1 strains formed similar biofilms and exhibited analogous drug-tolerance levels to the control ICL1/ICL1 strains. Furthermore, the drug sequestration ability of β-1, 3-glucan, a major carbohydrate component of the extracellular matrix, was not impaired. However, the inactivation of ICL1 did impair morphogenesis. ICL1 deletion also had a considerable effect on the expression of the FKS1, ERG11, and CDR2 genes. FKS1 and ERG11 were upregulated in ICL1/icl1 and icl1/icl1 cells throughout the biofilm developmental stages, and CDR2 was upregulated at the early phase. However, their expression was downregulated compared to the control ICL1/ICL1 strain.
Conclusions
We conclude that the glyoxylate cycle is not a specific determinant of biofilm drug resistance
k is the Magic Number -- Inferring the Number of Clusters Through Nonparametric Concentration Inequalities
Most convex and nonconvex clustering algorithms come with one crucial
parameter: the in -means. To this day, there is not one generally
accepted way to accurately determine this parameter. Popular methods are simple
yet theoretically unfounded, such as searching for an elbow in the curve of a
given cost measure. In contrast, statistically founded methods often make
strict assumptions over the data distribution or come with their own
optimization scheme for the clustering objective. This limits either the set of
applicable datasets or clustering algorithms. In this paper, we strive to
determine the number of clusters by answering a simple question: given two
clusters, is it likely that they jointly stem from a single distribution? To
this end, we propose a bound on the probability that two clusters originate
from the distribution of the unified cluster, specified only by the sample mean
and variance. Our method is applicable as a simple wrapper to the result of any
clustering method minimizing the objective of -means, which includes
Gaussian mixtures and Spectral Clustering. We focus in our experimental
evaluation on an application for nonconvex clustering and demonstrate the
suitability of our theoretical results. Our \textsc{SpecialK} clustering
algorithm automatically determines the appropriate value for , without
requiring any data transformation or projection, and without assumptions on the
data distribution. Additionally, it is capable to decide that the data consists
of only a single cluster, which many existing algorithms cannot
Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours
Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions
Impaired decisional impulsivity in pathological videogamers
Abstract
Background
Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort.
Methods
Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment.
Results
In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time.
Conclusions
We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management
Colored Resonant Signals at the LHC: Largest Rate and Simplest Topology
We study the colored resonance production at the LHC in a most general
approach. We classify the possible colored resonances based on group theory
decomposition, and construct their effective interactions with light partons.
The production cross section from annihilation of valence quarks or gluons may
be on the order of 400 - 1000 pb at LHC energies for a mass of 1 TeV with
nominal couplings, leading to the largest production rates for new physics at
the TeV scale, and simplest event topology with dijet final states. We apply
the new dijet data from the LHC experiments to put bounds on various possible
colored resonant states. The current bounds range from 0.9 to 2.7 TeV. The
formulation is readily applicable for future searches including other decay
modes.Comment: 29 pages, 9 figures. References updated and additional K-factors
include
Fibrinogen-related proteins in ixodid ticks
<p>Abstract</p> <p>Background</p> <p>Fibrinogen-related proteins with lectin activity are believed to be part of the tick innate immune system. Several fibrinogen-related proteins have been described and characterised mainly on the basis of their cDNA sequences while direct biochemical evidence is missing. One of them, the haemolymph lectin Dorin M from the tick <it>Ornithodoros moubata </it>was isolated and characterised in more depth.</p> <p>Results</p> <p>Several fibrinogen-related proteins were detected in the haemolymph of ixodid ticks <it>Dermacentor marginatus</it>, <it>Rhipicephalus appendiculatus</it>, <it>R. pulchellus</it>, and <it>R. sanguineus</it>. These proteins were recognised by sera directed against the tick lectin Dorin M and the haemagglutination activity of the ticks <it>R. appendiculatus </it>and <it>D. marginatus</it>. Cross-reactivity of the identified proteins with antibodies against the fibrinogen domain of the human ficolin was also shown. The carbohydrate-binding ability of tick haemolymph was confirmed by haemagglutination activity assays, and this activity was shown to be inhibited by neuraminic acid and sialylated glycoproteins as well as by N-acetylated hexosamines. The fibrinogen-related proteins were shown to be glycosylated and they were localised in salivary glands, midguts, and haemocytes of <it>D. marginatus</it>. Hemelipoglycoprotein was also recognised by sera directed against the fibrinogen-related proteins in all three <it>Rhipicephalus </it>species as well as in <it>D. marginatus</it>. However, this protein does not contain the fibrinogen domain and thus, the binding possibly results from the structure similarity between hemelipoglycoprotein and the fibrinogen domain.</p> <p>Conclusions</p> <p>The presence of fibrinogen-related proteins was shown in the haemolymph of four tick species in high abundance. Reactivity of antibodies directed against ficolin or fibrinogen-related proteins with proteins which do not contain the fibrinogen domain points out the importance of sequence analysis of the identified proteins in further studies. Previously observed expression of fibrinogen-related proteins in haemocytes together with the results of this study suggest involvement of fibrinogen-related proteins in tick immunity processes. Thus, they have potential as targets for anti-tick vaccines and as antimicrobial proteins in pharmacology. Research on fibrinogen-related proteins could reveal further details of tick innate immunity processes.</p
Biofilms of non-Candida albicans Candida species : quantification, structure and matrix composition
Most cases of candidiasis have been attributed to C. albicans, but recently, non-
Candida albicans Candida (NCAC) species have been identified as common
pathogens. The ability of Candida species to form biofilms has important clinical
repercussions due to their increased resistance to antifungal therapy and the ability
of yeast cells within the biofilms to withstand host immune defenses. Given this
clinical importance of the biofilm growth form, the aim of this study was
to characterize biofilms produced by three NCAC species, namely C. parapsilosis,
C. tropicalis and C. glabrata. The biofilm forming ability of clinical isolates of
C. parapsilosis, C. tropicalis and C. glabrata recovered from different sources, was
evaluated by crystal violet staining. The structure and morphological characteristics
of the biofilms were also assessed by scanning electron microscopy and the
biofilm matrix composition analyzed for protein and carbohydrate content. All
NCAC species were able to form biofilms although these were less extensive for
C. glabrata compared with C. parapsilosis and C. tropicalis. It was evident that C.
parapsilosis biofilm production was highly strain dependent, a feature not evident
with C. glabrata and C. tropicalis. Scanning electron microscopy revealed structural
differences for biofilms with respect to cell morphology and spatial arrangement.
Candida parapsilosis biofilm matrices had large amounts of carbohydrate with less
protein. Conversely, matrices extracted from C. tropicalis biofilms had low
amounts of carbohydrate and protein. Interestingly, C. glabrata biofilm matrix
was high in both protein and carbohydrate content. The present work demonstrates
that biofilm forming ability, structure and matrix composition are highly
species dependent with additional strain variability occurring with C. parapsilosis.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/28341/2006, PDTC/BIO/61112/200
Use of horseradish peroxidase for gene-directed enzyme prodrug therapy with paracetamol
Gene therapy is a potential method of treating cancer with a greater degree of targeting than conventional therapies. In addition, therapy can be directed towards cells within the tumour population that are traditionally resistant to current treatment schedules. Horseradish peroxidase (HRP) can oxidise paracetamol to N-acetyl-p-benzoquinoneimine via a one-electron pathway. Incubation of human cells expressing HRP with 0.5–10 mm paracetamol reduced clonogenic survival, but had little effect on control cells. A small increase in apoptosis was seen and a decrease in the number of cells undergoing mitosis, consistent with reports in hepatocytes using higher paracetamol concentrations. The cytotoxicity was also seen under conditions of severe hypoxia (catalyst induced anoxia), indicating that the HRP/paracetamol combination may be suitable for hypoxia-targeted gene therapy
A intervenção de enfermagem : relaxamento e seus efeitos no sistema imunológico de puérperas
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