Geographical Pattern and Environmental Correlates of Regional-Scale General Flowering in Peninsular Malaysia

In South-East Asian dipterocarp forests, many trees synchronize their reproduction at the community level, but irregularly, in a phenomenon known as general flowering (GF). Several proximate cues have been proposed as triggers for the synchronization of Southeast Asian GF, but the debate continues, as many studies have not considered geographical variation in climate and flora. We hypothesized that the spatial pattern of GF forests is explained by previously proposed climatic cues if there are common cues for GF among regions. During the study, GF episodes occurred every year, but the spatial occurrence varied considerably from just a few forests to the whole of Peninsular Malaysia. In 2001, 2002 and 2005, minor and major GF occurred widely throughout Peninsular Malaysia (GF2001, GF2002, and GF2005), and the geographical patterns of GF varied between the episodes. In the three regional-scale GF episodes, most major events occurred in regions where prolonged drought (PD) had been recorded prior, and significant associations between GF scores and PD were found in GF2001 and GF2002. However, the frequency of PD was higher than that of GF throughout the peninsula. In contrast, low temperature (LT) was observed during the study period only before GF2002 and GF2005, but there was no clear spatial relationship between GF and LT in the regional-scale episodes. There was also no evidence that last GF condition influenced the magnitude of GF. Thus, our results suggest that PD would be essential to trigger regional-scale GF in the peninsula, but also that PD does not fully explain the spatial and temporal patterns of GF. The coarse relationships between GF and the proposed climatic cues may be due to the geographical variation in proximate cues for GF, and the climatic and floristic geographical variations should be considered to understand the proximate factors of GF.     

Catch composition,reproductive biology and diet of the bramble shark Echinorhinus brucus (Squaliformes: Echinorhinidae) from the south‐eastern Arabian Sea

Fishery and biological data are presented for the poorly known bramble shark Echinorhinus brucus (Squaliformes: Echinorhinidae), from the deep waters of the south‐eastern Arabian Sea. A total of 5318 individuals from by‐catch landings of deep‐water bottom set longlines, gillnets and shrimp trawl fisheries operating at depths of 200–1200 m were recorded between January 2008 and December 2011 at the Kochi Fisheries Harbour (Kerala). A total of 431 individuals, from 46 to 318 cm total length (L_T) and 0·8 to 132 kg total mass (M_T), were examined to determine biological data for this species. The L_T at which 50% were mature (L_T50) for females and males was estimated at 189 and 187 cm L_T. Litter size ranged from 10 to 36 and size at birth was between 42 and 46 cm L_T. Dietary analysis of stomach contents revealed E. brucus feeds on a variety of prey including crustaceans (69% index of relative importance, I_RI), teleosts (25·8% I_RI), cephalopods (1·7% I_RI) and elasmobranchs (0·7% I_RI). This study provides the first detailed biological data for this species and also highlights the extent of the by‐catch fishery for this species in Indian waters.     

Exploration of pyridine containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors

The diacylglycerol acyltransferase enzyme, DGAT1, presents itself as a potential target for obesity as this enzyme is dedicated to the final committed step in triglyceride biosynthesis. Biphenyl ureas, exemplified by compound 4, have been reported to be potent hDGAT1 inhibitors. We have synthesized and evaluated 2-pyridyl and 3-pyridyl containing biaryl ureas as hDGAT1 inhibitors. Our aim was to incorporate a heteroaryl scaffold within these molecules thereby improving the cLogP profile and making these compounds more drug-like. Compounds within this series exhibited potent hDGAT1 inhibition when evaluated using an in vitro enzymatic assay. Selected compounds were also subjected to an oral fat tolerance test in mice where the percent triglyceride reduction versus a vehicle control was evaluated. Of the studied heteroaryl analogs compound 44 exhibited an in vitro IC(50) of 17nM and a plasma triglyceride reduction of 79% along with a 12-fold improvement in solubility over the biphenyl urea compound 4.     

Topological constraints: using RNA secondary structure to model 3D conformation, folding pathways, and dynamic adaptation

Accompanying recent advances in determining RNA secondary structure is the growing appreciation for the importance of relatively simple topological constraints, encoded at the secondary structure level, in defining the overall architecture, folding pathways, and dynamic adaptability of RNA. A new view is emerging in which tertiary interactions do not define RNA 3D structure, but rather, help select specific conformers from an already narrow, topologically pre-defined conformational distribution. Studies are providing fundamental insights into the nature of these topological constraints, how they are encoded by the RNA secondary structure, and how they interplay with other interactions, breathing new meaning to RNA secondary structure. New approaches have been developed that take advantage of topological constraints in determining RNA backbone conformation based on secondary structure, and a limited set of other, easily accessible constraints. Topological constraints are also providing a much-needed framework for rationalizing and describing RNA dynamics and structural adaptation. Finally, studies suggest that topological constraints may play important roles in steering RNA folding pathways. Here, we review recent advances in our understanding of topological constraints encoded by the RNA secondary structure.     

A steroid isolated from the water mold Achlya heterosexualis induces neurogenesis in vitro and in vivo

Using 22R-hydroxycholesterol as a sub-structure to screen natural compound databases, we identified a naturally occurring steroid (sc-7) with a 16-acetoxy-22R-hydroxycholesterol moiety, in which the hydroxyl groups in positions 3 and 22 are esterified by an acetoxy group and in which the carbon in position 26 carries a functional diacetylamino. sc-7 is an analog of the sex steroids dehydro-oogoniol and antheridiol, can be isolated from the water mold Achlya heterosexualis, and promoted neurogenesis in vitro and in vivo. Mouse embryonic teratocarcinoma P19 cells exposed to sc-7 for 2days followed by a 5-day wash-out differentiated into cholinergic neurons that expressed specific neuronal markers and displayed axonal formation. Axons continued growing up to 28days after treatment. In vivo, infusion of sc-7 for 2weeks into the left ventricle of the rat brain followed by a 3-week wash-out induced bromodeoxyuridine uptake by cells of the ependymal layer and subventricular zone that co-localized with doublecortin and glial fibrillary acidic protein immunostaining, demonstrating induction of proliferation and differentiation of neuronal progenitors. Migrating neuroblasts were also observed in the corpus callosum. Thus, under these experimental conditions, adult ependymal cells resumed proliferation and differentiation. Taken together, these results suggest that sc-7 is an interesting molecule for stimulating in situ neurogenesis from resident neuronal progenitors as part of neuron replacement therapy. sc-7 did not bind to nuclear steroid receptors and was not metabolized as a steroid, supporting our hypothesis that the neurogenic effect of sc-7 is not likely due to a steroid-like effect.     

Treatment with captopril abrogates the altered expression of alpha1 macroglobulin and alpha1 antiproteinase in sera of spontaneously hypertensive rats

Background

Proteins that are associated with hypertension may be identified by comparing the 2-dimensional gel electrophoresis (2-DE) profiles of the sera of spontaneously hypertensive rats (SHR) with those generated from normotensive Spraque-Dawley rats (SDR).

Results

Five proteins of high abundance were found to be significantly altered when the 2-DE serum profiles of the SHR were compared to those that were similarly generated from the SDR. Analysis by mass spectrometry and database search identified the proteins as retinol binding protein 4, complement C3, albumin (19.9 kDa fragment), alpha1 macroglobulin and alpha1 antiproteinase, which are all known to be associated with hypertension. The altered expression of the two latter proteins was found to be abrogated when similar analysis was performed on sera of the SHR that were treated with captopril.

Conclusion

Our data suggests that serum alpha1 macroglobulin and alpha1 antiproteinase are potentially useful complementary biomolecular indicators for monitoring of hypertension.     

Synthetic peptides from region 65–84 of bovine myelin basic protein: Radioimmunoassays and equilibrium competitive inhibition studies with antibodies prepared against myelin basic protein

Synthetic peptides with various and overlapping sequences represented by the residue region 65–84 of bovine myelin basic protein (MBP-bov) were tested in sodium sulfate radioimmunoassays for their reactivity with 15 rabbit antisera against MBPs from six different animal species and nine pools of syngeneic Lewis rat anti-MBP antisera. Three of the peptides were labeled with¹²⁵I and studied by direct binding reactions: (1) the prototype peptide S82 sequence TTHYG-SLPQKAQGHRPQDEG, corresponding to residues 65–84 of bovine MBP except for the C-terminal glycine, which is encephalitogenic in rabbits: (2) S81, which lacks the first three residues of S82 and is nonencephalitogenic in rabbits; and (3) S79, which represents the C-terminal half of S82 and which, because of its C-terminal glycine instead of asparagine, is nonencephalitogenic in Lewis rats. Fourteen of the rabbit anti-MBP antisera were reactive with [¹²⁵I]S82 (two borderline) including 2 of 3 antisera against human MBP, one against monkey MBP, and one against chicken MBP. The cross-reactions with [¹²⁵I]S81 were somewhat fewer and less intense. There were no cross-reactions with [¹²⁵I]S79. None of nine different pools of syngeneic rat MBP antisera cross-reacted with any of the three labeled peptides. With the use of a rabbit anti-MBP-rat antiserum that crossreacted strongly with [¹²⁵I]S82, 15 additional peptides with overlapping sequences within the residue region 65–84, as well as five MBP preparations from four different species, were tested by equilibrium and nonequilibrium competitive inhibition RIAs. Unlabeled S82 and MBP-bov were completely competitive with [¹²⁵I]S82 in the equilibrium assays; S81 and three other peptides had low degrees of cross-reactivity; but none of the remaining eight unlabeled peptides or unlabeled MBP preparations of guinea pig, rat, or mouse origin gave any evidence of competitive activity. Nonequilibrium competitive inhibition RIAs, however, did reveal cross-reactivities among several of the peptides as well as guinea pig and rat MBP. It was concluded that the N-terminal half of S82, particularly residues 68–74 (YGSLPQK), must contain an immunodeterminant of amino acid residues which identifies with the corresponding and exposed sequence in intact MBP-bov.This research was supported at Duke University by research grants 833-E-5 from the National Multiple Sclerosis Society and NS-10237 from the National Institutes of Health of the U.S. Public Health Service; at St. Luke's Hospital Center and Columbia University by grant RG1197-A-5 from the National Multiple Sclerosis Society; and at Northwestern University by grant NS-06262 from the National Institutes of Health of the U.S. Public Health Service.     

Probing Na(+)-induced changes in the HIV-1 TAR conformational dynamics using NMR residual dipolar couplings: new insights into the role of counterions and electrostatic interactions in adaptive recognition

Many regulatory RNAs undergo large changes in structure upon recognition of proteins and ligands, but the mechanism by which this occurs remains poorly understood. Using NMR residual dipolar coupling (RDCs), we characterized Na+-induced changes in the structure and dynamics of the bulge-containing HIV-1 transactivation response element (TAR) RNA that mirrors changes induced by small molecules bearing a different number of cationic groups. Increasing the Na+ concentration from 25 to 320 mM led to a continuous reduction in the average inter-helical bend angle (from 46 degrees to 22 degrees ), inter-helical twist angle (from 66 degrees to -18 degrees ), and inter-helix flexibility (as measured by an increase in the internal generalized degree of order from 0.56 to 0.74). Similar conformational changes were observed with Mg2+, indicating that nonspecific electrostatic interactions drive the conformational transition, although results also suggest that Na+ and Mg2+ may associate with TAR in distinct modes. The transition can be rationalized on the basis of a population-weighted average of two ensembles comprising an electrostatically relaxed bent and flexible TAR conformation that is weakly associated with counterions and a globally rigid coaxial conformation that has stronger electrostatic potential and association with counterions. The TAR inter-helical orientations that are stabilized by small molecules fall around the metal-induced conformational pathway, indicating that counterions may help predispose the TAR conformation for target recognition. Our results underscore the intricate sensitivity of RNA conformational dynamics to environmental conditions and demonstrate the ability to detect subtle conformational changes using NMR RDCs.