308 research outputs found
Glauber theory of initial- and final-state interactions in (p,2p) scattering
We develop the Glauber theory description of initial- and final-state
interactions (IFSI) in quasielastic A(p,2p) scattering. We study the
IFSI-distortion effects both for the inclusive and exclusive conditions. In
inclusive reaction the important new effect is an interaction between the two
sets of the trajectories which enter the calculation of IFSI-distorted one-body
density matrix for inclusive (p,2p) scattering and are connected with
incoherent elastic rescatterings of the initial and final protons on spectator
nucleons. We demonstrate that IFSI-distortions of the missing momentum
distribution are large over the whole range of missing momentum both for
inclusive and exclusive reactions and affect in a crucial way the
interpretation of the BNL data on (p,2p) scattering. Our numerical results show
that in the region of missing momentum p_{m}\lsim 100-150 MeV/c the
incoherent IFSI increase nuclear transparency by 5-10\%. The incoherent IFSI
become dominant at p_{m}\gsim 200 MeV/c.Comment: Accepted in Z. Phys.A, Latex, 26 pages, uuencoded 9 figure
Exclusive Production of Higgs Bosons in Hadron Colliders
We study the exclusive, double--diffractive production of the Standard Model
Higgs particle in hadronic collisions at LHC and FNAL (upgraded) energies. Such
a mechanism would provide an exceptionally clean signal for experimental
detection in which the usual penalty for triggering on the rare decays of the
Higgs could be avoided. In addition, because of the color singlet nature of the
hard interaction, factorization is expected to be preserved, allowing the
cross--section to be related to similar hard--diffractive events at HERA.
Starting from a Fock state expansion in perturbative QCD, we obtain an estimate
for the cross section in terms of the gluon structure functions squared of the
colliding hadrons. Unfortunately, our estimates yield a production rate well
below what is likely to be experimentally feasible.Comment: 17 pages, RevTeX file, four uufiled PostScript figures. UMPP #94-177.
(Revised version. Some mistakenly missing Feynman diagrams are now added.
Results do not change qualitatively. Paper reorganized.
Derlin-1 is overexpressed in human breast carcinoma and protects cancer cells from endoplasmic reticulum stress-induced apoptosis
A Yersinia Effector with Enhanced Inhibitory Activity on the NF-κB Pathway Activates the NLRP3/ASC/Caspase-1 Inflammasome in Macrophages
A type III secretion system (T3SS) in pathogenic Yersinia
species functions to translocate Yop effectors, which modulate cytokine
production and regulate cell death in macrophages. Distinct pathways of
T3SS-dependent cell death and caspase-1 activation occur in
Yersinia-infected macrophages. One pathway of cell death
and caspase-1 activation in macrophages requires the effector YopJ. YopJ is an
acetyltransferase that inactivates MAPK kinases and IKKβ to cause
TLR4-dependent apoptosis in naïve macrophages. A YopJ isoform in Y.
pestis KIM (YopJKIM) has two amino acid substitutions,
F177L and K206E, not present in YopJ proteins of Y.
pseudotuberculosis and Y. pestis CO92. As compared
to other YopJ isoforms, YopJKIM causes increased apoptosis, caspase-1
activation, and secretion of IL-1β in Yersinia-infected
macrophages. The molecular basis for increased apoptosis and activation of
caspase-1 by YopJKIM in Yersinia-infected
macrophages was studied. Site directed mutagenesis showed that the F177L and
K206E substitutions in YopJKIM were important for enhanced apoptosis,
caspase-1 activation, and IL-1β secretion. As compared to
YopJCO92, YopJKIM displayed an enhanced capacity to
inhibit phosphorylation of IκB-α in macrophages and to bind IKKβ in
vitro. YopJKIM also showed a moderately increased ability to inhibit
phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1β secretion
occurred in IKKβ-deficient macrophages infected with Y.
pestis expressing YopJCO92, confirming that the
NF-κB pathway can negatively regulate inflammasome activation.
K+ efflux, NLRP3 and ASC were important for secretion of
IL-1β in response to Y. pestis KIM infection as shown using
macrophages lacking inflammasome components or by the addition of exogenous KCl.
These data show that caspase-1 is activated in naïve macrophages in
response to infection with a pathogen that inhibits IKKβ and MAPK kinases
and induces TLR4-dependent apoptosis. This pro-inflammatory form of apoptosis
may represent an early innate immune response to highly virulent pathogens such
as Y. pestis KIM that have evolved an enhanced ability to
inhibit host signaling pathways
PPS, a Large Multidomain Protein, Functions with Sex-Lethal to Regulate Alternative Splicing in Drosophila
Alternative splicing controls the expression of many genes, including the Drosophila sex determination gene Sex-lethal (Sxl). Sxl expression is controlled via a negative regulatory mechanism where inclusion of the translation-terminating male exon is blocked in females. Previous studies have shown that the mechanism leading to exon skipping is autoregulatory and requires the SXL protein to antagonize exon inclusion by interacting with core spliceosomal proteins, including the U1 snRNP protein Sans-fille (SNF). In studies begun by screening for proteins that interact with SNF, we identified PPS, a previously uncharacterized protein, as a novel component of the machinery required for Sxl male exon skipping. PPS encodes a large protein with four signature motifs, PHD, BRK, TFS2M, and SPOC, typically found in proteins involved in transcription. We demonstrate that PPS has a direct role in Sxl male exon skipping by showing first that loss of function mutations have phenotypes indicative of Sxl misregulation and second that the PPS protein forms a complex with SXL and the unspliced Sxl RNA. In addition, we mapped the recruitment of PPS, SXL, and SNF along the Sxl gene using chromatin immunoprecipitation (ChIP), which revealed that, like many other splicing factors, these proteins bind their RNA targets while in close proximity to the DNA. Interestingly, while SNF and SXL are specifically recruited to their predicted binding sites, PPS has a distinct pattern of accumulation along the Sxl gene, associating with a region that includes, but is not limited to, the SxlPm promoter. Together, these data indicate that PPS is different from other splicing factors involved in male-exon skipping and suggest, for the first time, a functional link between transcription and SXL–mediated alternative splicing. Loss of zygotic PPS function, however, is lethal to both sexes, indicating that its role may be of broad significance
Role of potassium and calcium channels in sevoflurane-mediated vasodilation in the foeto-placental circulation
<p>Abstract</p> <p>Background</p> <p>Sevoflurane has been demonstrated to vasodilate the foeto-placental vasculature. We aimed to determine the contribution of modulation of potassium and calcium channel function to the vasodilatory effect of sevoflurane in isolated human chorionic plate arterial rings.</p> <p>Methods</p> <p>Quadruplicate <it>ex vivo </it>human chorionic plate arterial rings were used in all studies. <b><it>Series 1 and 2 </it></b>examined the role of the K<sup>+ </sup>channel in sevoflurane-mediated vasodilation. Separate experiments examined whether tetraethylammonium, which blocks large conductance calcium activated K<sup>+ </sup>(K<sub>Ca++</sub>) channels (<b><it>Series 1A+B</it></b>) or glibenclamide, which blocks the ATP sensitive K<sup>+ </sup>(K<sub>ATP</sub>) channel (<b><it>Series 2</it></b>), modulated sevoflurane-mediated vasodilation. <b><it>Series 3 – 5 </it></b>examined the role of the Ca<sup>++ </sup>channel in sevoflurane induced vasodilation. Separate experiments examined whether verapamil, which blocks the sarcolemmal voltage-operated Ca<sup>++ </sup>channel (<b><it>Series 3</it></b>), SK&F 96365 an inhibitor of sarcolemmal voltage-independent Ca<sup>++ </sup>channels (<b><it>Series 4A+B</it></b>), or ryanodine an inhibitor of the sarcoplasmic reticulum Ca<sup>++ </sup>channel (<b><it>Series 5A+B</it></b>), modulated sevoflurane-mediated vasodilation.</p> <p>Results</p> <p>Sevoflurane produced dose dependent vasodilatation of chorionic plate arterial rings in all studies. Prior blockade of the K<sub>Ca++ </sub>and K<sub>ATP </sub>channels augmented the vasodilator effects of sevoflurane. Furthermore, exposure of rings to sevoflurane in advance of TEA occluded the effects of TEA. Taken together, these findings suggest that sevoflurane blocks K<sup>+ </sup>channels. Blockade of the voltage-operated Ca<sup>++</sup>channels inhibited the vasodilator effects of sevoflurane. In contrast, blockade of the voltage-independent and sarcoplasmic reticulum Ca<sup>++</sup>channels did not alter sevoflurane vasodilation.</p> <p>Conclusion</p> <p>Sevoflurane appears to block chorionic arterial K<sub>Ca++ </sub>and K<sub>ATP </sub>channels. Sevoflurane also blocks voltage-operated calcium channels, and exerts a net vasodilatory effect in the <it>in vitro </it>foeto-placental circulation.</p
RNA localization in neurite morphogenesis and synaptic regulation: current evidence and novel approaches
It is now generally accepted that RNA localization in the central nervous system conveys important roles both during development and in the adult brain. Of special interest is protein synthesis located at the synapse, as this potentially confers selective synaptic modification and has been implicated in the establishment of memories. However, the underlying molecular events are largely unknown. In this review, we will first discuss novel findings that highlight the role of RNA localization in neurons. We will focus on the role of RNA localization in neurotrophin signaling, axon outgrowth, dendrite and dendritic spine morphogenesis as well as in synaptic plasticity. Second, we will briefly present recent work on the role of microRNAs in translational control in dendrites and its implications for learning and memory. Finally, we discuss recent approaches to visualize RNAs in living cells and their employment for studying RNA trafficking in neurons
Prediction of sinus rhythm maintenance following DC-cardioversion of persistent atrial fibrillation – the role of atrial cycle length
BACKGROUND: Atrial electrical remodeling has been shown to influence the outcome the outcome following cardioversion of atrial fibrillation (AF) in experimental studies. The aim of the present study was to find out whether a non-invasively measured atrial fibrillatory cycle length, alone or in combination with other non-invasive parameters, could predict sinus rhythm maintenance after cardioversion of AF. METHODS: Dominant atrial cycle length (DACL), a previously validated non-invasive index of atrial refractoriness, was measured from lead V1 and a unipolar oesophageal lead prior to cardioversion in 37 patients with persistent AF undergoing their first cardioversion. RESULTS: 32 patients were successfully cardioverted to sinus rhythm. The mean DACL in the 22 patients who suffered recurrence of AF within 6 weeks was 152 ± 15 ms (V1) and 147 ± 14 ms (oesophagus) compared to 155 ± 17 ms (V1) and 151 ± 18 ms (oesophagus) in those maintaining sinus rhythm (NS). Left atrial diameter was 48 ± 4 mm and 44 ± 7 mm respectively (NS). The optimal parameter predicting maintenance of sinus rhythm after 6 weeks appeared to be the ratio of the lowest dominant atrial cycle length (oesophageal lead or V1) to left atrial diameter. This ratio was significantly higher in patients remaining in sinus rhythm (3.4 ± 0.6 vs. 3.1 ± 0.4 ms/mm respectively, p = 0.04). CONCLUSION: In this study neither an index of atrial refractory period nor left atrial diameter alone were predictors of AF recurrence within the 6 weeks of follow-up. The ratio of the two (combining electrophysiological and anatomical measurements) only slightly improve the identification of patients at high risk of recurrence of persistent AF. Consequently, other ways to asses electrical remodeling and / or other variables besides electrical remodeling are involved in determining the outcome following cardioversion
High Resolution Methylome Map of Rat Indicates Role of Intragenic DNA Methylation in Identification of Coding Region
DNA methylation is crucial for gene regulation and maintenance of genomic stability. Rat has been a key model system in understanding mammalian systemic physiology, however detailed rat methylome remains uncharacterized till date. Here, we present the first high resolution methylome of rat liver generated using Methylated DNA immunoprecipitation and high throughput sequencing (MeDIP-Seq) approach. We observed that within the DNA/RNA repeat elements, simple repeats harbor the highest degree of methylation. Promoter hypomethylation and exon hypermethylation were common features in both RefSeq genes and expressed genes (as evaluated by proteomic approach). We also found that although CpG islands were generally hypomethylated, about 6% of them were methylated and a large proportion (37%) of methylated islands fell within the exons. Notably, we obeserved significant differences in methylation of terminal exons (UTRs); methylation being more pronounced in coding/partially coding exons compared to the non-coding exons. Further, events like alternate exon splicing (cassette exon) and intron retentions were marked by DNA methylation and these regions are retained in the final transcript. Thus, we suggest that DNA methylation could play a crucial role in marking coding regions thereby regulating alternative splicing. Apart from generating the first high resolution methylome map of rat liver tissue, the present study provides several critical insights into methylome organization and extends our understanding of interplay between epigenome, gene expression and genome stability
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