617 research outputs found
An ancient anterior patterning system promotes Caudal repression and head formation in Ecdysozoa.
SummaryPosterior expression of Caudal is required for early embryonic development in nematodes, arthropods, and vertebrates [1–9]. In Drosophila, ectopic Caudal in anterior cells can induce head defects, and in Caenorhabditis the absence of Caudal in anterior embryonic cells is required for proper development [6, 10]. Anterior Caudal repression in these species is achieved through unrelated translational repressors, the homeodomain protein Bicoid [11] and the KH domain factor Mex-3 [6, 12], respectively. Here we report that the Mex-3 ortholog in the flour beetle Tribolium plays a crucial role in head formation and that Caudal in this species is repressed by the combined activities of Mex-3 and Zen-2, a protein sharing common ancestry with the dipteran morphogen Bicoid. We propose that Mex-3 represents an ancient “anterior” promoting factor common to all Ecdysozoa (and maybe all Bilateria), whose role has been usurped in higher dipterans by Bicoid
Life-threatening intoxication with methylene bis(thiocyanate): clinical picture and pitfalls. A case report
BACKGROUND: Methylene bis(thiocyanate) (MBT) is a microbiocidal agent mainly used in industrial water cooling systems and paper mills as an inhibitor of algae, fungi, and bacteria. CASE PRESENTATION: We describe the first case of severe intoxication following inhalation of powder in an industrial worker. Profound cyanosis and respiratory failure caused by severe methemoglobinemia developed within several minutes. Despite immediate admission to the intensive care unit, where mechanical ventilation and hemodialysis for toxin elimination were initiated, multi-organ failure involving liver, kidneys, and lungs developed. While liver failure was leading, the patient was successfully treated with the MARS (molecular adsorbent recirculating system) procedure. CONCLUSION: Intoxication with MBT is a potentially life-threatening intoxication causing severe methemoglobinemia and multi-organ failure. Extracorporeal liver albumin dialysis (MARS) appears to be an effective treatment to allow recovery of hepatic function
The Role of Regulated mRNA Stability in Establishing Bicoid Morphogen Gradient in Drosophila Embryonic Development
The Bicoid morphogen is amongst the earliest triggers of differential spatial pattern of gene expression and subsequent cell fate determination in the embryonic development of Drosophila. This maternally deposited morphogen is thought to diffuse in the embryo, establishing a concentration gradient which is sensed by downstream genes. In most model based analyses of this process, the translation of the bicoid mRNA is thought to take place at a fixed rate from the anterior pole of the embryo and a supply of the resulting protein at a constant rate is assumed. Is this process of morphogen generation a passive one as assumed in the modelling literature so far, or would available data support an alternate hypothesis that the stability of the mRNA is regulated by active processes? We introduce a model in which the stability of the maternal mRNA is regulated by being held constant for a length of time, followed by rapid degradation. With this more realistic model of the source, we have analysed three computational models of spatial morphogen propagation along the anterior-posterior axis: (a) passive diffusion modelled as a deterministic differential equation, (b) diffusion enhanced by a cytoplasmic flow term; and (c) diffusion modelled by stochastic simulation of the corresponding chemical reactions. Parameter estimation on these models by matching to publicly available data on spatio-temporal Bicoid profiles suggests strong support for regulated stability over either a constant supply rate or one where the maternal mRNA is permitted to degrade in a passive manner
Metastasis associated in colorectal cancer 1 (MACC1) mRNA expression is enhanced in sporadic vestibular schwannoma and correlates to deafness
Vestibular schwannoma (VS) are benign cranial nerve sheath tumors of the vestibulocochlear nerve. Their incidence is mostly sporadic, but they can also be associated with NF2-related schwannomatosis (NF2), a hereditary tumor syndrome. Metastasis associated in colon cancer 1 (MACC1) is known to contribute to angiogenesis, cell growth, invasiveness, cell motility and metastasis of solid malignant cancers. In addition, MACC1 may be associated with nonsyndromic hearing impairment. Therefore, we evaluated whether MACC1 may be involved in the pathogenesis of VS. Sporadic VS, recurrent sporadic VS, NF2-associated VS, recurrent NF2-associated VS and healthy vestibular nerves were analyzed for MACC1 mRNA and protein expression by quantitative polymerase chain reaction and immunohistochemistry. MACC1 expression levels were correlated with the patients’ clinical course and symptoms. MACC1 mRNA expression was significantly higher in sporadic VS compared to NF2-associated VS (p < 0.001). The latter expressed similar MACC1 concentrations as healthy vestibular nerves. Recurrent tumors resembled the MACC1 expression of the primary tumors. MACC1 mRNA expression was significantly correlated with deafness in sporadic VS patients (p = 0.034). Therefore, MACC1 might be a new molecular marker involved in VS pathogenesis
Limits on the effective quark radius from inclusive scattering at HERA
The high-precision HERA data allows searches up to TeV scales for Beyond the
Standard Model contributions to electron-quark scattering. Combined
measurements of the inclusive deep inelastic cross sections in neutral and
charged current scattering corresponding to a luminosity of around 1
fb have been used in this analysis. A new approach to the beyond the
Standard Model analysis of the inclusive data is presented; simultaneous
fits of parton distribution functions together with contributions of "new
physics" processes were performed. Results are presented considering a finite
radius of quarks within the quark form-factor model. The resulting 95% C.L.
upper limit on the effective quark radius is cm.Comment: 10 pages, 4 figures, accepted by Phys. Lett.
Measurement of the cross-section ratio sigma_{psi(2S)}/sigma_{J/psi(1S)} in deep inelastic exclusive ep scattering at HERA
The exclusive deep inelastic electroproduction of and
at an centre-of-mass energy of 317 GeV has been studied with the ZEUS
detector at HERA in the kinematic range GeV,
GeV and GeV, where is the photon virtuality, is the
photon-proton centre-of-mass energy and is the squared four-momentum
transfer at the proton vertex. The data for GeV were taken in
the HERA I running period and correspond to an integrated luminosity of 114
pb. The data for GeV are from both HERA I and HERA II
periods and correspond to an integrated luminosity of 468 pb. The decay
modes analysed were and for the
and for the . The cross-section ratio
has been measured as a function of
and . The results are compared to predictions of QCD-inspired
models of exclusive vector-meson production.Comment: 24 pages, 8 figure
Chronic hyperglycemia induces trans-differentiation of human pancreatic stellate cells and enhances the malignant molecular communication with human pancreatic cancer cells
BACKGROUND:
Diabetes mellitus is linked to pancreatic cancer. We hypothesized a role for pancreatic stellate cells (PSC) in the hyperglycemia induced deterioration of pancreatic cancer and therefore studied two human cell lines (RLT-PSC, T3M4) in hyperglycemic environment.
METHODOLOGY/PRINCIPAL FINDINGS:
The effect of chronic hyperglycemia (CHG) on PSCs was studied using mRNA expression array with real-time PCR validation and bioinformatic pathway analysis, and confirmatory protein studies. The stress fiber formation (IC: αSMA) indicated that PSCs tend to transdifferentiate to a myofibroblast-like state after exposure to CHG. The phosphorylation of p38 and ERK1/2 was increased with a consecutive upregulation of CDC25, SP1, cFOS and p21, and with downregulation of PPARγ after PSCs were exposed to chronic hyperglycemia. CXCL12 levels increased significantly in PSC supernatant after CHG exposure independently from TGF-β1 treatment (3.09-fold with a 2.73-fold without TGF-β1, p<0.05). The upregualtion of the SP1 transcription factor in PSCs after CHG exposure may be implicated in the increased CXCL12 and IGFBP2 production. In cancer cells, hyperglycemia induced an increased expression of CXCR4, a CXCL12 receptor that was also induced by PSC's conditioned medium. The receptor-ligand interaction increased the phosphorylation of ERK1/2 and p38 resulting in activation of MAP kinase pathway, one of the most powerful stimuli for cell proliferation. Certainly, conditioned medium of PSC increased pancreatic cancer cell proliferation and this effect could be partially inhibited by a CXCR4 inhibitor. As the PSC conditioned medium (normal glucose concentration) increased the ERK1/2 and p38 phosphorylation, we concluded that PSCs produce other factor(s) that influence(s) pancreatic cancer behaviour.
CONCLUSIONS:
Hyperglycemia induces increased CXCL12 production by the PSCs, and its receptor, CXCR4 on cancer cells. The ligand-receptor interaction activates MAP kinase signaling that causes increased cancer cell proliferation and migration
Measurement of (anti)deuteron and (anti)proton production in DIS at HERA
The first observation of (anti)deuterons in deep inelastic scattering at HERA
has been made with the ZEUS detector at a centre-of-mass energy of 300--318 GeV
using an integrated luminosity of 120 pb-1. The measurement was performed in
the central rapidity region for transverse momentum per unit of mass in the
range 0.3<p_T/M<0.7. The particle rates have been extracted and interpreted in
terms of the coalescence model. The (anti)deuteron production yield is smaller
than the (anti)proton yield by approximately three orders of magnitude,
consistent with the world measurements.Comment: 26 pages, 9 figures, 5 tables, submitted to Nucl. Phys.
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