363 research outputs found
Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of Aspergillus fumigatus to Different Stressors and Carbon Sources
This is the final version. Available on open access from the American Society for Microbiology via the DOI in this recordData availability. The proteomic data set can be accessed in Table S1 at https://figshare.com/
articles/Membrane_receptors_contribute_to_activation_and_efficient_signaling_of_Mitogen-Activated
_Protein_Kinase_cascades_during_adaptation_of_Aspergillus_fumigatus_to_different_stressors_and
_carbon_sources/12402125The high-osmolarity glycerol (HOG) response pathway is a multifunctional signal transduction pathway that specifically transmits ambient osmotic signals. Saccharomyces cerevisiae Hog1p has two upstream signaling branches, the sensor histidine kinase Sln1p and the receptor Sho1p. The Sho1p branch includes two
other proteins, the Msb2p mucin and Opy2p. Aspergillus fumigatus is the leading
cause of pulmonary fungal diseases. Here, we investigated the roles played by A. fumigatus SlnASln1p, ShoASho1p, MsbAMsb2p, and OpyAOpy2p putative homologues during the activation of the mitogen-activated protein kinase (MAPK) HOG pathway.
The shoA, msbA, and opyA singly and doubly null mutants are important for the cell
wall integrity (CWI) pathway, oxidative stress, and virulence as assessed by a Galleria
mellonella model. Genetic interactions of ShoA, MsbA, and OpyA are also important
for proper activation of the SakAHog1p and MpkASlt2 cascade and the response to osmotic and cell wall stresses. Comparative label-free quantitative proteomics analysis
of the singly null mutants with the wild-type strain upon caspofungin exposure indicates that the absence of ShoA, MsbA, and OpyA affects the osmotic stress response, carbohydrate metabolism, and protein degradation. The putative receptor
mutants showed altered trehalose and glycogen accumulation, suggesting a role for
ShoA, MsbA, and OpyA in sugar storage. Protein kinase A activity was also decreased in these mutants. We also observed genetic interactions between SlnA,
ShoA, MsbA, and OpyA, suggesting that both branches are important for activation
of the HOG/CWI pathways. Our results help in the understanding of the activation
and modulation of the HOG and CWI pathways in this important fungal pathogen.São Paulo Research Foundation (FAPESP)Conselho Nacional de Desenvolvimento CientÃfico e Tecnológico (CNPq)Irish Research CouncilScience Foundation Irelan
The High Osmolarity Glycerol Mitogen-Activated Protein Kinase regulates glucose catabolite repression in filamentous fungi
This is the final version. Available from the publisher via the DOI in this record.The utilization of different carbon sources in filamentous fungi underlies a complex regulatory network governed by signaling events of different protein kinase pathways, including
the high osmolarity glycerol (HOG) and protein kinase A (PKA) pathways. This work unraveled cross-talk events between these pathways in governing the utilization of preferred (glucose) and non-preferred (xylan, xylose) carbon sources in the reference fungus Aspergillus
nidulans. An initial screening of a library of 103 non-essential protein kinase (NPK) deletion
strains identified several mitogen-activated protein kinases (MAPKs) to be important for carbon catabolite repression (CCR). We selected the MAPKs Ste7, MpkB, and PbsA for further
characterization and show that they are pivotal for HOG pathway activation, PKA activity,
CCR via regulation of CreA cellular localization and protein accumulation, as well as for
hydrolytic enzyme secretion. Protein-protein interaction studies show that Ste7, MpkB, and
PbsA are part of the same protein complex that regulates CreA cellular localization in the
presence of xylan and that this complex dissociates upon the addition of glucose, thus allowing CCR to proceed. Glycogen synthase kinase (GSK) A was also identified as part of this
protein complex and shown to potentially phosphorylate two serine residues of the HOG
MAPKK PbsA. This work shows that carbon source utilization is subject to cross-talk regulation by protein kinases of different signaling pathways. Furthermore, this study provides a
model where the correct integration of PKA, HOG, and GSK signaling events are required
for the utilization of different carbon sources.Fundac¸ão de Amparo à Pesquisa do Estado de São Paulo (FAPESP
The Quantized Hall Insulator: A New Insulator in Two-Dimensions
Quite generally, an insulator is theoretically defined by a vanishing
conductivity tensor at the absolute zero of temperature. In classical
insulators, such as band insulators, vanishing conductivities lead to diverging
resistivities. In other insulators, in particular when a high magnetic field
(B) is added, it is possible that while the magneto-resistance diverges, the
Hall resistance remains finite, which is known as a Hall insulator. In this
letter we demonstrate experimentally the existence of another, more exotic,
insulator. This insulator, which terminates the quantum Hall effect series in a
two-dimensional electron system, is characterized by a Hall resistance which is
approximately quantized in the quantum unit of resistance h/e^2. This insulator
is termed a quantized Hall insulator. In addition we show that for the same
sample, the insulating state preceding the QHE series, at low-B, is of the HI
kind.Comment: 4 page
Composite Fermion Metals from Dyon Black Holes and S-Duality
We propose that string theory in the background of dyon black holes in
four-dimensional anti-de Sitter spacetime is holographic dual to conformally
invariant composite Dirac fermion metal. By utilizing S-duality map, we show
that thermodynamic and transport properties of the black hole match with those
of composite fermion metal, exhibiting Fermi liquid-like. Built upon
Dirac-Schwinger-Zwanziger quantization condition, we argue that turning on
magnetic charges to electric black hole along the orbit of Gamma(2) subgroup of
SL(2,Z) is equivalent to attaching even unit of statistical flux quanta to
constituent fermions. Being at metallic point, the statistical magnetic flux is
interlocked to the background magnetic field. We find supporting evidences for
proposed holographic duality from study of internal energy of black hole and
probe bulk fermion motion in black hole background. They show good agreement
with ground-state energy of composite fermion metal in Thomas-Fermi
approximation and cyclotron motion of a constituent or composite fermion
excitation near Fermi-point.Comment: 30 pages, v2. 1 figure added, minor typos corrected; v3. revised
version to be published in JHE
Nonlinear Sigma Model for Disordered Media: Replica Trick for Non-Perturbative Results and Interactions
In these lectures, given at the NATO ASI at Windsor (2001), applications of
the replicas nonlinear sigma model to disordered systems are reviewed. A
particular attention is given to two sets of issues. First, obtaining
non-perturbative results in the replica limit is discussed, using as examples
(i) an oscillatory behaviour of the two-level correlation function and (ii)
long-tail asymptotes of different mesoscopic distributions. Second, a new
variant of the sigma model for interacting electrons in disordered normal and
superconducting systems is presented, with demonstrating how to reduce it,
under certain controlled approximations, to known ``phase-only'' actions,
including that of the ``dirty bosons'' model.Comment: 25 pages, Proceedings of the NATO ASI "Field Theory of Strongly
Correlated Fermions and Bosons in Low - Dimensional Disordered Systems",
Windsor, August, 2001; to be published by Kluwe
The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence
This is the final version (corrected proof). The final published version is available from Public Library of Science via the DOI in this recordData Availability: Short reads were submitted to the NCBI’s Sequence Read Archive under accession number SRP154617 (https://www.ncbi.nlm.nih.gov/sra/?term=SRP154617). The ChIPseq data are available from NCBI SRA (sequence read archive) database under accession number PRJNA574873 (https://www.ncbi.nlm.nih.gov/Traces/study/?acc=PRJNA574873&o=acc_s%3Aa).Aspergillus fumigatus is an opportunistic fungal pathogen that secretes an array of immune-modulatory molecules, including secondary metabolites (SMs), which contribute to enhancing fungal fitness and growth within the mammalian host. Gliotoxin (GT) is a SM that interferes with the function and recruitment of innate immune cells, which are essential for eliminating A. fumigatus during invasive infections. We identified a C6 Zn cluster-type transcription factor (TF), subsequently named RglT, important for A. fumigatus oxidative stress resistance, GT biosynthesis and self-protection. RglT regulates the expression of several gli genes of the GT biosynthetic gene cluster, including the oxidoreductase-encoding gene gliT, by directly binding to their respective promoter regions. Subsequently, RglT was shown to be important for virulence in a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA). Homologues of RglT and GliT are present in eurotiomycete and sordariomycete fungi, including the non-GT-producing fungus A. nidulans, where a conservation of function was described. Phylogenetically informed model testing led to an evolutionary scenario in which the GliT-based resistance mechanism is ancestral and RglT-mediated regulation of GliT occurred subsequently. In conclusion, this work describes the function of a previously uncharacterised TF in oxidative stress resistance, GT biosynthesis and self-protection in both GT-producing and non-producing Aspergillus species.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESPConselho Nacional de Desenvolvimento CientÃfico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de NÃvel Superior – Brasil (CAPES)Wellcome TrustUniversity of MacauNational Science Foundation (NSF)Vanderbilt UniversityHoward Hughes Medical Institut
Dynamics and transport near quantum-critical points
The physics of non-zero temperature dynamics and transport near
quantum-critical points is discussed by a detailed study of the O(N)-symmetric,
relativistic, quantum field theory of a N-component scalar field in spatial
dimensions. A great deal of insight is gained from a simple, exact solution of
the long-time dynamics for the N=1 d=1 case: this model describes the critical
point of the Ising chain in a transverse field, and the dynamics in all the
distinct, limiting, physical regions of its finite temperature phase diagram is
obtained. The N=3, d=1 model describes insulating, gapped, spin chain
compounds: the exact, low temperature value of the spin diffusivity is
computed, and compared with NMR experiments. The N=3, d=2,3 models describe
Heisenberg antiferromagnets with collinear N\'{e}el correlations, and
experimental realizations of quantum-critical behavior in these systems are
discussed. Finally, the N=2, d=2 model describes the superfluid-insulator
transition in lattice boson systems: the frequency and temperature dependence
of the the conductivity at the quantum-critical coupling is described and
implications for experiments in two-dimensional thin films and inversion layers
are noted.Comment: Lectures presented at the NATO Advanced Study Institute on "Dynamical
properties of unconventional magnetic systems", Geilo, Norway, April 2-12,
1997, edited by A. Skjeltorp and D. Sherrington, Kluwer Academic, to be
published. 46 page
Serum lipid responses to psyllium fiber: differences between pre- and post-menopausal, hypercholesterolemic women
<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease is the leading cause of death in women and men. Psyllium, a soluble fiber has been known to reduce serum lipids. In this pilot study, we evaluated whether menopausal status would affect the serum lipid responses to psyllium fiber in women.</p> <p>Methods</p> <p>Eleven post-menopausal and eight pre-menopausal women with serum total cholesterol >200 mg/dL were included in the study. Subjects consumed their habitual diet and 15 g psyllium/d for 6 weeks. Psyllium was incorporated into cookies. Each cookie contained ≈5 g of psyllium fiber. Subjects ate one cookie in each meal.</p> <p>Results</p> <p>With psyllium fiber, total cholesterol concentration was significantly lower (≈5.2%, P < 0.05) in post-menopausal women but not in pre-menopausal women (≈1.3%). Also, there was a significant decrease in HDL-cholesterol in post-menopausal women (≈10.2%, P < 0.05). There were no significant changes observed in concentrations of LDL-cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B in both pre- and post-menopausal women with psyllium.</p> <p>Conclusion</p> <p>In this pilot study, post- and pre-menopausal, hypercholesterolemic women responded differently to psyllium fiber supplementation. Post-menopausal women would benefit from addition of psyllium to their diets in reducing the risk for heart diseases. The results of this study should be used with caution because the study was based on a small sample size.</p
Effects of bromopride on the healing of left colon anastomoses of rats
Objetivo: Avaliar os efeitos da bromoprida sobre a formação de aderências e a cicatrização de anastomoses de cólon esquerdo de
ratos. Métodos: Foram incluÃdos 40 ratos, divididos em dois grupos contendo 20 animais, para administração de bromoprida (grupo
de estudo- E) ou solução fisiológica (grupo controle- C). Cada grupo foi dividido em subgrupos contendo 10 animais cada, para
eutanásia no terceiro (E3 e C3) ou no sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo
e anastomose término-terminal. No dia da relaparotomia, foi avaliada a quantidade total de aderências e removido um segmento
colônico contendo a anastomose para análise histopatológica, da força de ruptura e da concentração de hidroxiprolina. Resultados:
Não houve diferença entre os grupos em relação à evolução clÃnica. Dois animais do grupo de estudo apresentaram deiscência
de anastomose bloqueada. Os animais que receberam bromoprida apresentaram número de aderências intracavitárias e aderências
à anastomose semelhantes ao grupo controle. As anastomoses dos animais do grupo E3 apresentaram menor resistência de ruptura
do que as do grupo C3 (p=0,04). Este efeito não ocorreu no sétimo dia de pós-operatório (p=0,37). Não houve diferença significativa
entre os grupos em relação à histopatologia ou concentração de hidroxiprolina das anastomoses. Conclusão: O uso da bromoprida
está associado à diminuição da resistência tênsil de anastomoses do cólon esquerdo de ratos no terceiro dia de pós-operatório.Objective: To evaluate the effects of bromopride on the formation of adhesions and anastomotic healing in the left colon of rats.
Methods: We divided 40 rats into two groups of 20 animals, administration of bromopride (study group-E) or saline (control group-
C). Each group was divided into subgroups containing 10 animals each for euthanasia in the third (C3 and E3) or the seventh (E7 and
C7) postoperative days. The rats were submitted to section of the left colon and end-to-end anastomosis. On the day of reoperation,
we evaluated the total amount of adhesions and removed a colonic segment containing the anastomosis for histopathological
analysis, assessment of rupture strength and hydroxyproline concentration. Results: There was no difference between groups in
relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride
had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the
group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh
postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline
concentration in the anastomoses. Conclusion: The use of bromopride was associated with decreased tensile strength of left colon
anastomosis in rats in the third postoperative day
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