415 research outputs found
Proteomic analyses reveal misregulation of LIN28 expression and delayed timing of glial differentiation in human iPS cells with MECP2 loss-of-function.
Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function in males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring mutations in MECP2, along with control lines from their unaffected fathers, give us an opportunity to identify some of the earliest cellular and molecular changes associated with MECP2 loss-of-function (LOF). We differentiated iPSC-derived neural progenitor cells (NPCs) using retinoic acid (RA) and found that astrocyte differentiation is perturbed in iPSC lines derived from two different patients. Using highly stringent quantitative proteomic analyses, we found that LIN28, a gene important for cell fate regulation and developmental timing, is upregulated in mutant NPCs compared to WT controls. Overexpression of LIN28 protein in control NPCs suppressed astrocyte differentiation and reduced neuronal synapse density, whereas downregulation of LIN28 expression in mutant NPCs partially rescued this synaptic deficiency. These results indicate that the pathophysiology of RTT may be caused in part by misregulation of developmental timing in neural progenitors, and the subsequent consequences of this disruption on neuronal and glial differentiation
Expression of a Serine Protease Gene prC Is Up-Regulated by Oxidative Stress in the Fungus Clonostachys rosea: Implications for Fungal Survival
BACKGROUND: Soil fungi face a variety of environmental stresses such as UV light, high temperature, and heavy metals. Adaptation of gene expression through transcriptional regulation is a key mechanism in fungal response to environmental stress. In Saccharomyces cerevisiae, the transcription factors Msn2/4 induce stress-mediated gene expression by binding to the stress response element. Previous studies have demonstrated that the expression of extracellular proteases is up-regulated in response to heat shock in fungi. However, the physiological significance of regulation of these extracellular proteases by heat shock remains unclear. The nematophagous fungus Clonostachys rosea can secret an extracellular serine protease PrC during the infection of nematodes. Since the promoter of prC has three copies of the stress response element, we investigated the effect of environmental stress on the expression of prC. METHODOLOGY/PRINCIPAL FINDINGS: Our results demonstrated that the expression of prC was up-regulated by oxidants (H(2)O(2) or menadione) and heat shock, most likely through the stress response element. After oxidant treatment or heat shock, the germination of conidia in the wild type strain was significantly higher than that in the prC mutant strain in the presence of nematode cuticle. Interestingly, the addition of nematode cuticle significantly attenuated the production of reactive oxygen species (ROS) induced by oxidants and heat shock in the wild type strain, but not in prC mutant strain. Moreover, low molecule weight (<3 kD) degradation products of nematode cuticle suppressed the inhibitory effect of conidial germination induced by oxidants and heat shock. CONCLUSIONS/SIGNIFICANCE: These results indicate that PrC plays a protective role in oxidative stress in C. rosea. PrC degrades the nematode cuticle to produce degradation products, which in turn offer a protective effect against oxidative stress by scavenging ROS. Our study reveals a novel strategy for fungi to adapt to environmental stress
General analysis of signals with two leptons and missing energy at the Large Hadron Collider
A signal of two leptons and missing energy is challenging to analyze at the
Large Hadron Collider (LHC) since it offers only few kinematical handles. This
signature generally arises from pair production of heavy charged particles
which each decay into a lepton and a weakly interacting stable particle. Here
this class of processes is analyzed with minimal model assumptions by
considering all possible combinations of spin 0, 1/2 or 1, and of weak
iso-singlets, -doublets or -triplets for the new particles. Adding to existing
work on mass and spin measurements, two new variables for spin determination
and an asymmetry for the determination of the couplings of the new particles
are introduced. It is shown that these observables allow one to independently
determine the spin and the couplings of the new particles, except for a few
cases that turn out to be indistinguishable at the LHC. These findings are
corroborated by results of an alternative analysis strategy based on an
automated likelihood test.Comment: 18 pages, 3 figures, LaTe
Supersymmetric mass spectra and the seesaw type-I scale
We calculate supersymmetric mass spectra with cMSSM boundary conditions and a
type-I seesaw mechanism added to explain current neutrino data. Using
published, estimated errors on SUSY mass observables for a combined LHC+ILC
analysis, we perform a theoretical analysis to identify parameter
regions where pure cMSSM and cMSSM plus seesaw type-I might be distinguishable
with LHC+ILC data. The most important observables are determined to be the
(left) smuon and selectron masses and the splitting between them, respectively.
Splitting in the (left) smuon and selectrons is tiny in most of cMSSM parameter
space, but can be quite sizeable for large values of the seesaw scale,
. Thus, for very roughly GeV hints for type-I
seesaw might appear in SUSY mass measurements. Since our numerical results
depend sensitively on forecasted error bars, we discuss in some detail the
accuracies, which need to be achieved, before a realistic analysis searching
for signs of type-I seesaw in SUSY spectra can be carried out.Comment: 17 pages, 7 figure
Astrobiological Complexity with Probabilistic Cellular Automata
Search for extraterrestrial life and intelligence constitutes one of the
major endeavors in science, but has yet been quantitatively modeled only rarely
and in a cursory and superficial fashion. We argue that probabilistic cellular
automata (PCA) represent the best quantitative framework for modeling
astrobiological history of the Milky Way and its Galactic Habitable Zone. The
relevant astrobiological parameters are to be modeled as the elements of the
input probability matrix for the PCA kernel. With the underlying simplicity of
the cellular automata constructs, this approach enables a quick analysis of
large and ambiguous input parameters' space. We perform a simple clustering
analysis of typical astrobiological histories and discuss the relevant boundary
conditions of practical importance for planning and guiding actual empirical
astrobiological and SETI projects. In addition to showing how the present
framework is adaptable to more complex situations and updated observational
databases from current and near-future space missions, we demonstrate how
numerical results could offer a cautious rationale for continuation of
practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo
Discrimination of roast and ground coffee aroma
Background: Four analytical approaches were used to evaluate the aroma profile at key stages in roast and ground
coffee brew preparation (concentration within the roast and ground coffee and respective coffee brew;
concentration in the headspace of the roast and ground coffee and respective brew). Each method was evaluated
by the analysis of 15 diverse key aroma compounds that were predefined by odour port analysis.
Results: Different methods offered complimentary results for the discrimination of products; the concentration in
the coffee brew was found to be the least discriminatory and concentration in the headspace above the roast and
ground coffee was shown to be most discriminatory.
Conclusions: All approaches should be taken into consideration when classifying roast and ground coffee
especially for alignment to sensory perception and consumer insight data as all offer markedly different
discrimination abilities due to the variation in volatility, hydrophobicity, air-water partition coefficient and other physicochemical parameters of the key aroma compounds present
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