THE RED SEA — GULF OF ADEN: BIOSTRATIGRAPHY, LITHOSTRATIGRAPHY AND PALAEOENVIRONMENTS

Sediments of Palaeozoic, Mesozoic and early Palaeogene ages experienced a similar geological history in Ethiopia, Yemen and Somalia. During the late Eocene, however, uplift and differential erosion took place, prior to rift development in the middle Oligocene, when the proto-Gulf of Aden became established. To a certain extent, a similar sequence of events had also taken place in those regions of Egypt, Sudan, Ethiopia, Yemen and Saudi Arabia which border the Red Sea, but post-Eocene subsidence is now believed to have commenced during the late Oligocene in the southern Red Sea and progressed later, during the early Miocene, in the northern Red Sea and Gulf of Suez. Timing of this progressive development of the Gulf of Aden rift complex through the Red Sea and Gulf of Suez is well constrained by biostratigraphy, and provides a new approach to the understanding of lithological variations within the region.
These lithological variations have, until now, only been considered on a country-specific basis, thus hindering establishment of a regional history of sedimentation. The well-understood and well-documented lithostratigraphic nomenclature of the Miocene succession of the Gulf of Suez has been used as a reference, or type, with which the lateral facies variations within the Red Sea have been compared. By this method only has it been possible to produce palaeoenvironmental maps for the entire study region, and for each formation and member. Lateral equivalents of the Gulf of Suez Nukhul, Rudeis, Kareem, Belayim, South Gharib. Zeit, Wardan and Shagara Formations have been identified within the Red Sea syn-rift and post-rift episodes.     

T lymphocyte responses to anti-neutrophil cytoplasmic autoantibody (ANCA) antigens are present in patients with ANCA-associated systemic vasculitis and persist during disease remission

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel has been identified in the cardiac muscle of a number of mammalian species, including humans. The goal of this study was to begin quantifying the structural requirements necessary for arylaminobenzoate block of the CFTR channel. The cardiac cAMP-dependent Cl- current (ICl) was measured using the whole-cell arrangement of the patch-clamp technique in guinea pig ventricular myocytes during stimulation of protein kinase A with forskolin. At drug concentrations below the IC50 value for channel block, reduction of ICl by the arylaminobenzoates occurred in a strongly voltage-dependent manner with preferential inhibition of the inward currents. At higher drug concentrations, block of both the inward and outward ICl was observed. Increasing the length of the carbon chain between the benzoate and phenyl rings of the arylaminobenzoates resulted in a marked increase in drug block of the channel, with IC50 values of 47, 17, and 4 microM for 2-benzylamino-5-nitro-benzoic acid, 5-nitro-2-(2-phenylethylamino)-benzoic acid, and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), respectively. Increasing the carbon chain length further with the compound 5-nitro-2-(4-phenylbutylamino)-benzoic acid, caused no additional increase in the potency of drug block (IC50 = 4 microM). Inhibition of ICl by the arylaminobenzoates was modulated by the pH of the external solution; increasing the pH from 7.4 to 10.0 greatly weakened NPPB block, whereas decreasing the pH to 6.4 enhanced block. In addition, block of ICl was observed during intracellular dialysis of NPPB, and this action was not affected by raising the external pH.     

Finite element modeling of three-dimensional pulsatile flow in the abdominal aorta: relevance to atherosclerosis

The infrarenal abdominal aorta is particularly prone to atherosclerotic plaque formation while the thoracic aorta is relatively resistant. Localized differences in hemodynamic conditions, including differences in velocity profiles, wall shear stress, and recirculation zones have been implicated in the differential localization of disease in the infrarenal aorta. A comprehensive computational framework was developed, utilizing a stabilized, time accurate, finite element method, to solve the equations governing blood flow in a model of a normal human abdominal aorta under simulated rest, pulsatile, flow conditions. Flow patterns and wall shear stress were computed. A recirculation zone was observed to form along the posterior wall of the infrarenal aorta. Low time-averaged wall shear stress and high shear stress temporal oscillations, as measured by an oscillatory shear index, were present in this location, along the posterior wall opposite the superior mesenteric artery and along the anterior wall between the superior and inferior mesenteric arteries. These regions were noted to coincide with a high probability-of-occurrence of sudanophilic lesions as reported by Cornhill et al. (Monogr. Atheroscler. 15:13-19, 1990). This numerical investigation provides detailed quantitative data on hemodynamic conditions in the abdominal aorta heretofore lacking in the study of the localization of atherosclerotic disease.     

CCR5/delta(ccr5) heterozygosity: a selective pressure for the syncytium-inducing human immunodeficiency virus type 1 phenotype. NIAID AIDS Clinical Trials Group Protocol 241 Virology Team

Mechanisms underlying the delay in dominance of syncytium-inducing (SI) phenotype HIV-1 (human immunodeficiency virus type 1) in vivo are unknown. Both random mutational events and selective pressures operative only late in the disease process have been suggested to underlie the shift from CCR5 to alternative coreceptor usage. Among the moderately advanced patients who entered AIDS Clinical Trials Group protocol 241, SI viral phenotype was more common among CCRS/delta(ccr5) heterozygotes (7/7, 100%) than among CCR5/CCR5 homozygotes (29/88, 33%; P < .001, Fisher's exact test). Other characteristics did not differ at study entry by CCR5 genotype, including median CD4 cell counts, plasma RNA levels, and infectious HIV-1 titers in circulating cells. These data indicate that CCR5/delta(ccr5) heterozygosity, which decreases cell-surface levels of CCR5 available to serve as an HIV-1 entry coreceptor, is a selective pressure for evolution of T cell line-tropic viruses that use an alternative coreceptor.     

The estrogen dilemma

There are known 3 likely mechanisms of virus conveyance into the central nervous system (CNS). These include hematogenic penetration, spread along the peripheral nerves, and the olfactory pathway which begins from the infected olfactory neuroepithelial cells. The possibility of viral spread into CNS via the olfactory pathway was shown for the representatives of togaviruses, herpesviruses, coronaviruses, rhabdoviruses, and for some others. This study suggests that the olfactory pathway of viral conveyance into CNS may be blocked by specific mucosal antibodies in the nasal mucosa. The recombinant TK- variant of WR vaccinia strain with inserted genes coding structural and nonstructural proteins of TBE virus is accumulated in the branches of the respiratory tract only while the parenteral vaccinia strain is detected in the brain regions, spleen, respiratory tract, and in blood. The protective activity of recombinant strain and inactivated TBE vaccine after mice immunization by escarification or intranasally, or subcutaneously was comparatively studied. The findings indicate that intranasal immunization by recombinant strain is the most protective against intraperitoneal challenge by TBE virus. The mucosal and humoral immune response that was induced by intranasal immunization seems to provide the highest levels of protection, which was experimentally observed.     

Calmodulin dependence of NFkappaB activation

TF-1/TPO cells are derived from an erythroleukemia cell line, TF-1, and are absolutely dependent on either TPO or granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin-3 (IL3) for their continuous growth and survival. To gain insight into the molecular basis of hemopoietic activities shared by TPO and GM-CSF/IL3 in TF-1/TPO cells, we studied the cross-talk between signal transduction pathways elicited by these cytokines. Stimulation of TF-1/TPO cells with TPO resulted in tyrosine phosphorylation of the TPO receptor (c-Mpl) as well as the common beta subunit (beta c) of GM-CSF/IL3 receptor complex. GM-CSF, however, induced tyrosine phosphorylation of beta c but not c-Mpl. TPO-induced tyrosine phosphorylation of beta c was time- and dose-dependent. We next examined whether or not TPO-induced tyrosine phosphorylation of beta c led to recruitment of SH2-containing molecules such as Stat5 and Shc. While GM-CSF caused association of Stat5 and Shc with beta c, TPO caused association of Stat5, but not Shc, with beta c, suggesting that TPO and GM-CSF may not induce phosphorylation of the same sets of tyrosine residues in beta c. These results suggest that activation of c-Mpl affects the signaling pathway of GM-CSF/IL3 but not vice versa.     

Opposing actions of CSW and RasGAP modulate the strength of Torso RTK signaling in the Drosophila terminal pathway

The NMDA receptor antagonistic effects of budipine were assessed using concentration- and patch-clamp techniques on cultured striatal, hippocampal, cortical and superior colliculus neurones. Inward current responses of striatal neurones to NMDA (200 microM) at -70 mV were antagonized by budipine in a concentration-dependent manner (50% inhibitory concentration (IC50) 59.4 +/- 10.7 microM, n = 17) with 24 times lower potency than memantine but similar potency to amantadine. In striatal neurones, budipine blocked outward currents at +70 mV with an IC50 of 827 microM, suggesting that the binding site is less deep in the channel (delta = 0.45) than for memantine. However, more detailed analysis of the fractional block by budipine 300 microM in hippocampal neurones gave a delta-value of 0.90, but revealed that 28% block is mediated at a voltage-independent site. This voltage-insensitive site was accessible in the absence of agonist. Budipine exhibited concentration-dependent open channel blocking kinetics (kappa(on) = 0.71 x 10(4) M(-1) s(-1)) whereas the fast offset rate was concentration-independent (kappa(off) = 0.63 s(-1)). Calculation of the ratio kappa(off)/kappa(on) revealed an apparent Kd value of 88.7 microM. Budipine, memantine and amantadine had similar effects against NMDA-induced currents in cultured hippocampal, cortical and superior colliculus neurones, although amantadine was somewhat more potent in cultured striatal neurones. The relevance of NMDA receptor antagonism to the anti-Parkinsonian effects of budipine remains to be established.     

Segregation distortion in myotonic dystrophy

Myotonic dystrophy (DM) is an autosomal dominant disease which, in the typical pedigree, shows a three generation anticipation cascade. This results in infertility and congenital myotonic dystrophy (CDM) with the disappearance of DM in that pedigree. The concept of segregation distortion, where there is preferential transmission of the larger allele at the DM locus, has been put forward to explain partially the maintenance of DM in the population. In a survey of DM in Northern Ireland, 59 pedigrees were ascertained. Sibships where the status of all the members had been identified were examined to determine the transmission of the DM expansion from affected parents to their offspring. Where the transmitting parent was male, 58.3% of the offspring were affected, and in the case of a female transmitting parent, 68.7% were affected. Studies on meiotic drive in DM have shown increased transmission of the larger allele at the DM locus in non-DM heterozygotes for CTGn. This study provides further evidence that the DM expansion tends to be transmitted preferentially.     

Cocaine-conditioned place preference in young precocial domestic fowl.

Experiment 1 established conditioned place preference (CPP) control procedures for young precocial domestic fowl (test day age?=?13–25 days). Chicks displayed a preference (greater choice time) for white stimulus cards on first exposure to white versus red cards and equivalent preference for these stimulus cards after 6 exposures. Chicks in Experiment 2 displayed a cocaine CPP at each dose (0.5, 1.0, and 2.0 mg/kg intraperitoneally) after 6 cocaine-red card and 6 saline-white card pairings. This CPP decreased and was no longer significant over 2 additional nonreinforced test days. Experiment 3 results replicated the cocaine CPP (2.0 mg/kg) and demonstrated that the CPP did not develop when cocaine was administered several hours after card exposure. To our knowledge, these results are the first to demonstrate drug CPP in a nonmammalian model and support the notion that drug reinforcement processes are highly conserved. This precocial avian model may prove a useful addition to existing altricial models for the study of determinants of human drug use and abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)