Research report: The study of ethnic alignment: A new technique and an application in Malaysia

In some circumstances, like driving a motor vehicle, group membership is irrelevant. In others, individual interest motivates group alignment. Sometimes choices have to be made between individual responses and group alignment, or between alignment on the basis of class, or ethnicity, or religion. The authors describe a technique used to assess the strength of ethnic loyalty relative to self‐interest and personal obligation among an urban sample in Malaysia. Predictions of how a representative Malay would react in situations of value conflict made possible the measurement of pluralistic ignorance. The technique could be used elsewhere. It could be used to generate predictions about trends in the strengthening, maintenance or weakening of ethnic boundaries.     

Sucutiniranes A and B, new cassane-type diterpenes from Bowdichia nitida

Two new cassane-type diterpenes, sucutiniranes A (1) and B (2), have been isolated from the seeds of Bowdichia nitida together with 6alpha-acetoxyvouacapane (3) and 6alpha,7beta-diacetoxyvouacapane (4), and the structures of 1 and 2 were elucidated by using 2D NMR data and chemical correlations. Sucutinirane A (1) and 3 showed a moderate cytotoxicity against human colon carcinoma COLO201 cells, and 6alpha,7beta-diacetoxyvouacapane (4) showed in vitro antiplasmodial activity against parasite Plasmodium falciparum 3D7.     

Avian epidermis contains ATPase- and Ia-positive Langerhans-like cells

Summary The occurrence of cells resembling mammalian Langerhans cells in the avian epidermis was studied by ATPase histochemistry, Ia immunoreactivity and electron microscopy. The existence of MHC class II antigen-(Ia) expressing, ATPase-positive dendritic cells, which are ultrastructurally similar to mammalian Langerhans cells except for the absence of Birbeck granules, was demonstrated. These cells may be a basic component of the immune system of birds.     

The Plasmodium Class XIV Myosin,MyoB, Has a Distinct Subcellular Location in Invasive and Motile Stages of the Malaria Parasite and an Unusual Light Chain

Myosin B (MyoB) is one of the two short class XIV myosins encoded in the Plasmodium genome. Class XIV myosins are characterized by a catalytic “head,” a modified “neck,” and the absence of a “tail” region. Myosin A (MyoA), the other class XIV myosin in Plasmodium, has been established as a component of the glideosome complex important in motility and cell invasion, but MyoB is not well characterized. We analyzed the properties of MyoB using three parasite species as follows: Plasmodium falciparum, Plasmodium berghei, and Plasmodium knowlesi. MyoB is expressed in all invasive stages (merozoites, ookinetes, and sporozoites) of the life cycle, and the protein is found in a discrete apical location in these polarized cells. In P. falciparum, MyoB is synthesized very late in schizogony/merogony, and its location in merozoites is distinct from, and anterior to, that of a range of known proteins present in the rhoptries, rhoptry neck or micronemes. Unlike MyoA, MyoB is not associated with glideosome complex proteins, including the MyoA light chain, myosin A tail domain-interacting protein (MTIP). A unique MyoB light chain (MLC-B) was identified that contains a calmodulin-like domain at the C terminus and an extended N-terminal region. MLC-B localizes to the same extreme apical pole in the cell as MyoB, and the two proteins form a complex. We propose that MLC-B is a MyoB-specific light chain, and for the short class XIV myosins that lack a tail region, the atypical myosin light chains may fulfill that role.     

Rac1-PAK1 regulation of Rab11 cycling promotes junction destabilization

Rac1 GTPase is hyperactivated in tumors and contributes to malignancy. Rac1 disruption of junctions requires its effector PAK1, but the precise mechanisms are unknown. Here, we show that E-cadherin is internalized via micropinocytosis in a PAK1–dependent manner without catenin dissociation and degradation. In addition to internalization, PAK1 regulates E-cadherin transport by fine-tuning Rab small GTPase function. PAK1 phosphorylates a core Rab regulator, RabGDIβ, but not RabGDIα. Phosphorylated RabGDIβ preferentially associates with Rab5 and Rab11, which is predicted to promote Rab retrieval from membranes. Consistent with this hypothesis, Rab11 is activated by Rac1, and inhibition of Rab11 function partially rescues E-cadherin destabilization. Thus, Rac1 activation reduces surface cadherin levels as a net result of higher bulk flow of membrane uptake that counteracts Rab11-dependent E-cadherin delivery to junctions (recycling and/or exocytosis). This unique small GTPase crosstalk has an impact on Rac1 and PAK1 regulation of membrane remodeling during epithelial dedifferentiation, adhesion, and motility.     

Synthesis and structure–activity relationships of cassiarin A as potential antimalarials with vasorelaxant activity

Cassiarin A 1, a tricyclic alkaloid, isolated from the leaves of Cassia siamea (Leguminosae), shows powerful antimalarial activity against Plasmodium falciparum in vitro as well as P. berghei in vivo, which may be valuable leads for novel antimalarials. Interactions of parasitized red blood cells (pRBCs) with endothelium in aorta are especially important in the processes contribute to the pathogenesis of severe malaria. Nitric oxide (NO) reduces endothelial expression of receptors/adhesion molecules used by pRBC to adhere to vascular endothelium, and reduces cytoadherence of pRBC to vascular endothelium. Cassiarin A 1 showed vasorelaxation activity against rat aortic ring, which may be related with NO production. A series of a hydroxyl and a nitrogen-substituted derivatives and a dehydroxy derivative of 1 have been synthesized as having potent antimalarials against P. falciparum with vasodilator activity, which may reduce cytoadherence of pRBC to vascular endothelium. Cassiarin A 1 exhibited a potent antimalarial activity and a high selectivity index in vitro, suggesting that the presence of a hydroxyl and a nitrogen atom without any substituents may be important to show antimalarial activity. Relative to cassiarin A, a methoxy derivative showed more potent vasorelaxant activity, although it did not show improvement for inhibition of P. falciparum in vitro. These cassiarin derivatives may be promising candidates as antimalarials with different mode of actions.     

Pervasive gene conversion in chromosomal inversion heterozygotes

Chromosomal inversions shape recombination landscapes, and species differing by inversions may exhibit reduced gene flow in these regions of the genome. Though single crossovers within inversions are not usually recovered from inversion heterozygotes, the recombination barrier imposed by inversions is nuanced by noncrossover gene conversion. Here, we provide a genomewide empirical analysis of gene conversion rates both within species and in species hybrids. We estimate that gene conversion occurs at a rate of 1 × 10^–5 to 2.5 × 10^–5 converted sites per bp per generation in experimental crosses within Drosophila pseudoobscura and between D. pseudoobscura and its naturally hybridizing sister species D. persimilis. This analysis is the first direct empirical assessment of gene conversion rates within inversions of a species hybrid. Our data show that gene conversion rates in interspecies hybrids are at least as high as within‐species estimates of gene conversion rates, and gene conversion occurs regularly within and around inverted regions of species hybrids, even near inversion breakpoints. We also found that several gene conversion events appeared to be mitotic rather than meiotic in origin. Finally, we observed that gene conversion rates are higher in regions of lower local sequence divergence, yet our observed gene conversion rates in more divergent inverted regions were at least as high as in less divergent collinear regions. Given our observed high rates of gene conversion despite the sequence differentiation between species, especially in inverted regions, gene conversion has the potential to reduce the efficacy of inversions as barriers to recombination over evolutionary time.     

Stress-Induced Visceral Hypersensitivity in Maternally Separated Rats Can Be Reversed by Peripherally Restricted Histamine-1-Receptor Antagonists

Background

The histamine-1 receptor (H1R) antagonist ketotifen increased the threshold of discomfort in hypersensitive IBS patients. The use of peripherally restricted and more selective H1R antagonists may further improve treatment possibilities. We examined the use of fexofenadine and ebastine to reverse post-stress visceral hypersensitivity in maternally separated rats.

Methods

The visceromotor response to colonic distension was assessed in adult maternally separated and nonhandled rats pre- and 24 hours post water avoidance. Subsequently rats were treated with vehicle alone or different dosages of fexofenadine (1.8 and 18 mg/kg) or ebastine (0.1 and 1.0 mg/kg) and re-evaluated. Colonic tissue was collected to assess relative RMCP-2 and occludin expression levels by Western blot and histamine-1 receptor by RT-qPCR. β-hexosaminidase release by RBL-2H3 cells was used to establish possible mast cell stabilizing properties of the antagonists.

Key results

Water avoidance only induced enhanced response to distension in maternally separated rats. This response was reversed by 1.8 and 18 mg/kg fexofenadine. Reversal was also obtained by 1.0 but not 0.1 mg/kg ebastine. RMCP-2 expression levels were comparable in these two ebastine treatment groups but occludin was significantly higher in 1.0 mg/kg treated rats. There were no differences in histamine-1 receptor expression between nonhandled and maternally separated rats. Fexofenadine but not ebastine showed mast cell stabilizing quality.

Conclusions

Our results indicate that the peripherally restricted 2^nd generation H1-receptor antagonists fexofenadine and ebastine are capable of reversing post stress visceral hypersensitivity in rat. These data justify future IBS patient trials with these well tolerated compounds.