Quorum Sensing in <Emphasis Type="Italic">Aeromonas</Emphasis> Species Isolated from Patients in Malaysia

Bacterial quorum sensing signal molecules called N-acylhomoserine lactone (AHL) controls the expression of virulence determinants in many Gram-negative bacteria. We determined AHL production in 22 Aeromonas strains isolated from various infected sites from patients (bile, blood, peritoneal fluid, pus, stool and urine). All isolates produced the two principal AHLs, N-butanoylhomoserine lactone (C4-HSL) and N-hexanoyl homoserine lactone (C6-HSL). Ten isolates also produced additional AHLs. This report is the first documentation of Aeromonas sobria producing C6-HSL and two additional AHLs with N-acyl side chain longer than C₆. Our data provides a better understanding of the mechanism(s) of this environmental bacterium emerging as a human pathogen.     

N-Arylalkyl-2-azaadamantanes as cage-expanded polycarbocyclic sigma (σ) receptor ligands

A series of racemic N-arylalkyl-2-azaadamantan-1-ols (9-15) and the corresponding deoxygenated, achiral N-arylalkyl-2-azaadamantanes (23-29) were synthesized and screened in competition binding assays against a panel of CNS targets. Adamantyl hemiaminals 9-15 displayed generally low affinity for both σ(1) (K(i) values= 294-1950 nM) and σ(2) receptors (K(i) values=201-1020 nM), and negligible affinity for 42 other CNS proteins. Deoxygenation of 9-15 to give the corresponding achiral azaadamantanes 23-29 greatly improved affinity for σ(1) (K(i) values=8.3-239 nM) and σ(2) receptors (K(i) values=34-312 nM).     

Effects of linker elongation in a series of N-(2-benzofuranylmethyl)-N'-(methoxyphenylalkyl)piperazine σ₁ receptor ligands

In our continued exploration of disubstituted piperazine derivatives as sigma (σ) receptor ligands with central nervous system (CNS) activity, a series of N-(2-benzofuranylmethyl)-N'-(methoxyphenylalkyl)piperazines (16-21 and 26-31) were synthesized, anticipating that these ligands would better suit the structural requirements of the current σ(1) pharmacophore. Affinities of these ligands for σ(1) and σ(2) receptors were investigated by means of radioligand binding assays, with the identification of N-(2-benzofuranylmethyl)-N'-[3-(4-methoxyphenyl)propyl]piperazine (29, K(i)=3.1 nM, σ(2)/σ(1)=45) as a selective σ(1) ligand. The σ(1) affinities and subtype selectivities of piperazines 16-21 and 26-31 were generally comparable to the corresponding benzylic analogs. Additionally, the affinities of 16-21 and 26-31 for the 5-HT(2B) receptor were much lower than the relatively nonselective methoxybenzylic analogs 2-4, indicating that elongation of the alkyl tether generally improved selectivity for σ(1) receptors.     

Kidney injury molecule‐1: More than just an injury marker of tubular epithelial cells?

Regardless of the original causes and etiology, the progression to renal function declines follows a final common pathway associated with tubulointerstitial injury, in which the proximal tubular epithelial cells (PTEC) are instrumental. Kidney injury molecule‐1 (KIM‐1) is an emerging biomarker, and its expression and release are induced in PTEC upon injury. KIM‐1 plays the role as a double‐edged sword and implicates in the process of kidney injury and healing. Expression of KIM‐1 is also associated with tubulointerstitial inflammation and fibrosis. More importantly, KIM‐1 expressing PTEC play the role as the residential phagocytes, contribute to the removal of apoptotic cells and facilitate the regeneration of injured tubules. The precise mechanism of KIM‐1 and its sheded ectodomain on restoration of tubular integrity after injury is not fully understood. Other than PTEC, macrophages (Mø) also implicate in tubular repair. Understanding the crosstalk between Mø and the injured PTEC is essential for designing appropriate methods for controlling the sophisticated machinery in tubular regeneration and healing. This article will review the current findings of KIM‐1, beginning with its basic structure, utility as a biomarker, and possible functions, with focus on the role of KIM‐1 in regeneration and healing of injured PTEC. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.     

Conservation management of rare and predominantly selfing tropical trees: an example using Hopea bilitonensis (Dipterocarpaceae)

Hopea bilitonensis is an extremely rare and predominantly selfing dipterocarp in Peninsular Malaysia. A comprehensive research was initiated to assess the ecological genetics of H. bilitonensis to elucidate specific ecological and genetic requirements and subsequently to recommend conservation strategies. The objective for conservation of a rare plant such as H. bilitonensis differs from that of a common plant. For common plants, the conservation strategies are to prevent the species from becoming endangered. In contrast, for rare plants, the final race against extinction is being fought. Tropical forests are rich in plant species diversity and obtaining adequate knowledge to set conservation strategies for the majority of these species might be difficult. Thus, it is suggested that for the conservation of tree species, the species can be grouped according to their life history traits. The information generated for a species can then be adapted to species that have similar types of life history traits. We have recently generated the ecological genetics information for a rare and predominantly outcrossed dipterocarp (Shorea lumutensis). This study on H. bilitonensis will provide ecological genetics information for the conservation of rare and predominantly selfing dipterocarps.     

Model selection as a tool for phylogeographic inference: an example from the willow Salix melanopsis

Phylogeographic inference has typically relied on analyses of data from one or a few genes to provide estimates of demography and population histories. While much has been learned from these studies, all phylogeographic analysis is conditioned on the data, and thus, inferences derived from data that represent a small sample of the genome are unavoidably tenuous. Here, we demonstrate one approach for moving beyond classic phylogeographic research. We use sequence capture probes and Illumina sequencing to generate data from >400 loci in order to infer the phylogeographic history of Salix melanopsis, a riparian willow with a disjunct distribution in coastal and the inland Pacific Northwest. We evaluate a priori phylogeographic hypotheses using coalescent models for parameter estimation, and the results support earlier findings that identified post‐Pleistocene dispersal as the cause of the disjunction in S. melanopsis. We also conduct a series of model selection exercises using IMa2, Migrate‐n and ?a?i. The resulting ranking of models indicates that refugial dynamics were complex, with multiple regions in the inland regions serving as the source for postglacial colonization. Our results demonstrate that new sources of data and new approaches to data analysis can rejuvenate phylogeographic research by allowing for the identification of complex models that enable researchers to both identify and estimate the most relevant parameters for a given system.     

Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with pro-inflammatory,oxidative-glycation markers and sRAGE in diabetic retinopathy

Background

Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with diabetic retinopathy (DR). However, the mechanism on how it affects the disease development is still unclear.

Aim

This study aims to investigate the relationship between 2245G/A RAGE gene polymorphism and selected pro-inflammatory, oxidative-glycation markers in DR patients.

Methods

A total of 371 unrelated type 2 diabetic patients [200 with retinopathy, 171 without retinopathy (DNR)] and 235 healthy subjects were recruited. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method followed by DNA sequencing. The nuclear and cytosolic extracts from peripheral blood mononuclear cells were used for nuclear factor kappa B (NF-κB) p65 and superoxide dismutase activity measurement respectively. Plasma was used for glutathione peroxidase activity, advanced oxidation protein product (AOPP), monocyte chemoattractant protein (MCP)-1, pentosidine and soluble RAGE (sRAGE) measurements.

Results

DR patients with 2245GA genotype had significantly elevated levels of activated NF-κB p65, plasma MCP-1, AOPP and pentosidine but lower level of sRAGE when compared to DR patients with wild-type 2245GG.

Conclusion

The RAGE gene polymorphism 2245G/A is associated with pro-inflammatory, oxidative-glycation markers and circulating sRAGE in DR patients. Patients with 2245GA RAGE genotype could aggravate DR possibly via NF-κB mediated inflammatory pathway.     

Small-scale variability in a mosaic tropical rainforest influences habitat use of long-tailed macaques

Pristine habitats have generally been considered to be the most important ecological resource for wildlife conservation, but due to forest degradation caused by human activities, mosaics of secondary forests have become increasingly prominent. We studied three forest types in a mosaic tropical forest consisting of short secondary forest (SS), tall secondary forest (TS) and freshwater swamp forest (SF). These forests differed in stand structure and floristic composition, as well as phenological productivity of fruits, flowers and young leaves. We examined habitat use of long-tailed macaques (Macaca fascicularis) in relation to indices of phenological activity. The macaques used the SS for feeding/foraging more than the TS and the SF. This was because the SS had higher productivity of fruit, which is a preferred food resource for macaques. Stem densities of young leaves in the SS and the TS also influenced habitat use, as they provided more clumped resources. Use of SF was limited, but these forests provided more species-rich resources. Our results showed that M. fascicularis responded to small-scale variability in phenological activity between forest types found in a heterogeneous mosaic forest, with young secondary regrowth forests likely providing the most important food resources. Mosaic landscapes may be important as they can buffer the effects of temporal food resource variability in any given forest type. In our increasingly human-altered landscapes, a better understanding of the role of secondary forest mosaics is crucial to the conservation and management of wildlife habitats and the animals they support.