Pulsed magnetohydrodynamic blood flow in a rigid vessel under physiological pressure gradient

Blood flow in a steady magnetic field has been of great interest over recent years. Many researchers have examined the effects of magnetic fields on velocity profiles and arterial pressure, and major studies have focused on steady or sinusoidal flows. In this paper, we present a solution for pulsed magnetohydrodynamic blood flow with a somewhat realistic physiological pressure wave obtained using a Windkessel lumped model. A pressure gradient is derived along a rigid vessel placed at the output of a compliant module which receives the ventricle outflow. Then, velocity profile and flow rate expressions are derived in the rigid vessel in the presence of a steady transverse magnetic field. As expected, results showed flow retardation and flattening. The adaptability of our solution approach allowed a comparison with previously addressed flow cases and calculations presented a good coherence with those well established solutions.     

Type-1 (CB1) Cannabinoid Receptor Promotes Neuronal Differentiation and Maturation of Neural Stem Cells

Neural stem cells (NSCs) are self-renewing cells that can differentiate into multiple neural lineages and repopulate regions of the brain after injury. We have investigated the role of endocannabinoids (eCBs), endogenous cues that modulate neuronal functions including neurogenesis, and their receptors CB₁ and CB₂ in mouse NSCs. Real-time PCR and Western blot analyses indicated that CB₁ is present at higher levels than CB₂ in NSCs. The eCB anandamide (AEA) or the CB₁-specific agonist ACEA enhanced NSC differentiation into neurons, but not astrocytes and oligodendrocytes, whereas the CB₂-specific agonist JWH133 was ineffective. Conversely, the effect of AEA was inhibited by CB₁, but not CB₂, antagonist, corroborating the specificity of the response. CB₁ activation also enhanced maturation of neurons, as indicated by morphometric analysis of neurites. CB₁ stimulation caused long-term inhibition of the ERK1/2 pathway. Consistently, pharmacological inhibition of the ERK1/2 pathway recapitulated the effects exerted by CB₁ activation on neuronal differentiation and maturation. Lastly, gene array profiling showed that CB₁ activation augmented the expression of genes involved in neuronal differentiation while decreasing that of stemness genes. These results highlight the role of CB₁ in the regulation of NSC fate and suggest that its activation may represent a pro-neuronal differentiation signal.     

The N terminus of the anti-apoptotic BCL-2 homologue MCL-1 regulates its localization and function

The BCL-2 homologue MCL-1 plays an important role in the regulation of cell fate by blocking apoptosis as well as regulating cell cycle. MCL-1 has an unusual N-terminal extension, which contains a PEST domain and several phosphorylation sites that have been suggested to regulate its turnover. Here we report that the first 79 amino acids of MCL-1 regulate its subcellular localization. Deletion of this domain impairs both its mitochondrial localization and its anti-apoptotic activity. Conversely, expression of the N terminus of MCL-1 promotes both the association of MCL-1 with mitochondria and cell survival in a fashion that is dependent on the presence of endogenous MCL-1. In addition, the N terminus of MCL-1 has an antagonistic effect on proliferation. Although MCL-1 decreases proliferation through binding to proliferating cell nuclear antigen and cyclin-dependent kinase 1 in the nucleus, the N terminus of MCL-1 accelerates cell division. On the other hand, deletion of this region further increases the anti-proliferative activity of MCL-1. These results suggest that the N terminus of MCL-1 plays a major regulatory role, regulating coordinately the mitochondrial (anti-apoptotic) and nuclear (anti-proliferative) functions of MCL-1.     

Association and redox properties of the putidaredoxin reductase-nicotinamide adenine dinucleotide complex

Putidaredoxin reductase (PdR) is the flavin protein that carries out the first electron transfer involved in the cytochrome P450cam catalytic cycle. In PdR, the flavin adenine dinucleotide (FAD/FADH2) redox center acts as a transformer by accepting two electrons from soluble nicotinamide adenine dinucleotide (NAD+/NADH) and donating them in two separate, one-electron-transfer steps to the iron-sulfur protein putidaredoxin (Pdx). PdR, like the two more intensively studied monoflavin reductases, adrenodoxin reductase (AdR) and ferredoxin-NADP+ reductase (FNR), has no other active redox moieties (e.g., sulfhydryl groups) and can exist in three different oxidation states: (i) oxidized quinone, (ii) one-electron reduced semiquinone (stable neutral species (blue) or unstable radical anion (red)), and (iii) two-electron fully reduced hydroquinone. Here, we present reduction potential measurements for PdR in support of a thermodynamic model for the modulation of equilibria among the redox components in this initial electron-transfer step of the P450 cycle. A spectroelectrochemical technique was used to measure the midpoint oxidation-reduction potential of PdR that had been carefully purified of all residual NAD+, E0' = -369 +/- 10 mV at pH 7.6, which is more negative than previously reported and more negative than the pyridine nucleotide NADH/NAD+ (-330 mV). After addition of NAD+, the formation of the oxidized reductase-oxidized pyridine nucleotide complex was followed by the two-electron-transfer redox reaction, PdRox:NAD+ + 2e- --> PdRrd:NAD+, when the electrode potential was lowered. The midpoint potential was a hyperbolic function of increasing NAD+ concentration, such that at concentrations of pyridine nucleotide typically found in an intracellular environment, the midpoint potential would be E0' = -230 +/- 10 mV, thereby providing the thermodynamically favorable redox equilibria that enables electron transfer from NADH. This thermodynamic control of electron transfer is a shared mechanistic feature with the adrenodoxin P450 and photosynthetic electron-transfer systems but is different from the kinetic control mechanisms in the microsomal P450 systems where multiple reaction pathways draw on reducing power held by NADPH-cytochrome P450 reductase. The redox measurements were combined with protein fluorescence quenching of NAD+ binding to oxidized PdR to establish that the PdRox:NAD+ complex (KD = 230 microM) is about 5 orders of magnitude weaker than PdRrd:NAD+ binding. These results are integrated with known structural and kinetic information for PdR, as well as for AdR and FNR, in support of a compulsory ordered pathway to describe the electron-transfer processes catalyzed by all three reductases.     

Comparison of pyloric ligation and pyloric cuff techniques for collecting gastric secretion in the rat.

A comparison was made between two methods for collecting gastric secretion in the rat. The two included a pyloric ligation technique and a snare-type pyloric cuff which was surgically implanted 2 weeks before the collection was initiated. It was hypothesized that the surgical trauma associated with pyloric ligation would inhibit gastric secretion and thus yield smaller gastric samples with this procedure as compared to the cuff technique. No differences in volume of gastric secretion or total acid output were observed between the two methods.     

Isolation and synthesis of trans- and cis-(−)-clovamides and their deoxy analogues from the bark of Dalbergia melanoxylon

N-(3′,4′-Dihydroxy-trans-cinnamoyl)-3-(3,4-dihydroxyphenyl)-L-alanine [(?)-clovamide], the major phenolic metabolite (0.1%) in the bark of Dalbergia melanoxylon, is associated with minor proportions of its cis-isomer, and similar pairs of geometrical isomers of their deoxy analogues N-(4′-hydroxycinnamoyl)-3-(3,4-dihydroxyphenyl)-L-alanine and N-(4′-hydroxycinnamoyl)-3-(4-hydroxyphenyl)-L-alanine. (?)-Trans-clovamide is synthesized by direct condensation of the acid chloride of caffeic acid with L-DOPA. Diagnostic CD spectra of these compounds and ¹³C spectra of (?)-trans- and (?)-cis-clovamides are recorded.     

Interaction of vitamin K dependent proteins with membranes

The membrane-binding characteristics of six vitamin K dependent plasma proteins, which have homologous amino acid sequences, were compared. All of these proteins display calcium-dependent membrane binding and the identified equilibria for protein-membrane binding are qualitatively the same for all proteins. Quantitative characteristics of these protein-membrane interactions allow organization into distinct subgroups. Protein C and factor VII form a subgroup which has extemely low affinity for bilayer membranes; prothrombin, factor X, and protein S form the tightest complexes with membranes and factor IX displays intermediate affinity. In the presence of manganese (which substitutes for calcium in a cation-dependent protein transition), calcium titration of protein-membrane binding shows the same calcium dependence for all proteins except prothrombin which requires lower calcium. These protein-membrane binding characteristics agree very well with the relatedness of these proteins based on their partial amino-terminal sequences.     

Bioremediation of Polyaromatic Hydrocarbon-Contaminated Sediments in Aerated Bioslurry Reactors

Treatment of dredged sediments contaminated by polyaromatic hydrocarbons (PAHs) is a significant problem in the New York/New Jersey (NY/NJ) Harbor. 0.5 m³-scale slurry-phase bioreactors were used to determine whether bioaugmentation with a PAH-degradative bacterial consortium, or with the salt marsh grass S. alterniflora, could enhance the biodegradation of PAHs added to dredged estuarine sediments from the NY/NJ Harbor. The results were compared to biodegradation effected by the indigenous sediment microbial community. Sediments were diluted 1:1 in tap water and spiked to a final concentration of 20 mg/kg dry weight sediment of phenanthrene, anthracene, acenaphthene, fluorene, fluoranthene, and pyrene. The sediment slurry was then continuously sparged with air over 3 months. In all bioreactors a rapid reduction of greater than 95% of the initial phenanthrene, acenaphthene, and fluorene occurred within 14 days. Pyrene and fluoranthene reductions of 70 to 90% were achieved by day 77 of treatment. Anthracene was more recalcitrant and reductions ranged from 30 to 85%. Separate experiments showed that the sediment microbial communities mineralized ¹⁴C-pyrene and ¹⁴C-phenanthrene. PAH degradation, and the number of phenanthrene-degrading bacteria, were not enhanced by microbial or plant bioaugmentation. These data demonstrate that bioaugmentation is not required to effect efficient remediation of PAH-contaminated dredged sediments in slurry-phase bioreactors.     

Detection of grain protein content QTLs across environments in tetraploid wheats

Grain protein content (GPC) is an important quality factor in both durum and bread wheats. GPC is considered to be a polygenic trait influenced by environmental factors and management practice. The objectives of this study were both to compare the quantitative trait loci (QTL) for GPC in a population of 65 recombinant inbred lines of tetraploid wheats evaluated in three locations for several years (eight data sets), and to investigate the genetic relationship among GPC and grain yield. QTLs were determined based on the Messapia × dicoccoides linkage map which covers 217 linked loci on the 14 chromosomes with 42 additional loci as yet unassigned to linkage groups. The map extends to 1352 cM; the average distance between adjacent markers was 6.3 cM. Seven QTLs for GPC, located on the chromosome arms 4BS, 5AL, 6AS (two loci), 6BS, 7AS and 7BS, were detected that were significant in at least one environment at P<0.001 or in at least two environments at P<0.01. One QTL was significant in all but one environment, two were significant in four or five environments, and four were significant in two out of eight environments. Six out of seven protein content QTLs had pleiotropic effects or were associated to QTLs for grain yield and explained the negative correlation among GPC and yield components. The present results support the concept that studies conducted in a single environment are likely to underestimate the number of QTLs that can influence a trait and that the phenotypic data for a quantitative trait should be collected over a range of locations to identify putative QTLs and determine their phenotypic effects.     

CYP3A4-V and prostate cancer in African Americans: causal or confounding association because of population stratification?

CYP3A4-V, an A to G promoter variant associated with prostate cancer in African Americans, exhibits large differences in allele frequency between populations. Given that the African American population is genetically heterogeneous because of its African ancestry and subsequent admixture with European Americans, case-control studies with African Americans are highly susceptible to spurious associations. To test for association with prostate cancer, we genotyped CYP3A4-V in 1376 (2 N) chromosomes from prostate cancer patients and age- and ethnicity-matched controls representing African Americans, Nigerians, and European Americans. To detect population stratification among the African American samples, 10 unlinked genetic markers were genotyped. To correct for the stratification, the uncorrected association statistic was divided by the average of association statistics across the 10 unlinked markers. Sharp differences in CYP3A4-V frequencies were observed between Nigerian and European American controls (0.87 and 0.10, respectively; P<0.0001). African Americans were intermediate (0.66). An association uncorrected for stratification was observed between CYP3A4-V and prostate cancer in African Americans (P=0.007). A nominal association was also observed among European Americans (P=0.02) but not Nigerians. In addition, the unlinked genetic marker test provided strong evidence of population stratification among African Americans. Because of the high level of stratification, the corrected P-value was not significant (P=0.25). Follow-up studies on a larger dataset will be needed to confirm whether the association is indeed spurious; however, these results reveal the potential for confounding of association studies by using African Americans and the need for study designs that take into account substructure caused by differences in ancestral proportions between cases and controls.