LOV‐domain photoreceptor,encoded in a genomic island,attenuates the virulence of Pseudomonas syringae in light‐exposed Arabidopsis leaves

In Arabidopsis thaliana, light signals modulate the defences against bacteria. Here we show that light perceived by the LOV domain‐regulated two‐component system (Pst–Lov) of Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) modulates virulence against A. thaliana. Bioinformatic analysis and the existence of an episomal circular intermediate indicate that the locus encoding Pst–Lov is present in an active genomic island acquired by horizontal transfer. Strains mutated at Pst–Lov showed enhanced growth on minimal medium and in leaves of A. thaliana exposed to light, but not in leaves incubated in darkness or buried in the soil. Pst–Lov repressed the expression of principal and alternative sigma factor genes and their downstream targets linked to bacterial growth, virulence and quorum sensing, in a strictly light‐dependent manner. We propose that the function of Pst–Lov is to distinguish between soil (dark) and leaf (light) environments, attenuating the damage caused to host tissues while releasing growth out of the host. Therefore, in addition to its direct actions via photosynthesis and plant sensory receptors, light may affect plants indirectly via the sensory receptors of bacterial pathogens.     

Structure–activity relationships of 6-(aminomethylphenoxy)-benzoxaborole derivatives as anti-inflammatory agent

A series of novel 6-(aminomethylphenoxy)benzoxaborole analogs was synthesized for the investigation of the structure–activity relationship of the inhibition of TNF-alpha, IL-1beta, and IL-6, from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compounds 9d and 9e showed potent activity against all three cytokines with IC₅₀ values between 33 and 83 nM. Chloro substituted analog 9e (AN3485) is considered to be a promising lead for novel anti-inflammatory agent with a favorable pharmacokinetic profile.     

‘What Do I Know? Should I Participate?’ Considerations on Participation in HIV Related Research among HIV Infected Adults in Bangalore,South India

Background

India has the highest number of HIV infected persons in the world after South Africa. Much HIV related behavioral, clinical and laboratory based research is ongoing in India. Yet little is known on Indian HIV patients'' knowledge of research, their processes of decision making and motives for participation. We aimed to explore these areas among HIV infected individuals to understand their reasons for participating in research.

Methodology/Principal Findings

This is a cross sectional survey among 173 HIV infected adults at a tertiary level hospital in Bangalore, India, done between October 2010 and January 2011. A pre-tested questionnaire was administered to the participants by trained research assistants to assess their knowledge regarding research, willingness to participate, decision making and determinants of participation. Participants were presented with five hypothetical HIV research studies. Each study had a different level of intervention and time commitment. Of respondents, 103(60%), said that research meant ‘to discover something new’ and 138(80%) were willing to participate in research. A third of the respondents were unaware of their right to refuse participation. Willingness to participate in research varied with level of intervention. It was the lowest for the hypothetical study involving sensitive questions followed by the hypothetical drug trial; and was the highest for the hypothetical cross sectional questionnaire based study (p<0.0015). Individual health benefits and altruism were the primary motives for participation in research and indicate the presence of therapeutic misconception. Women were less likely to make autonomous decisions for participation in interventional studies.

Conclusions/Significance

Despite a majority willing to participate, over a third of respondents did not have any knowledge of research or the voluntary nature of participation. This has ethical implications. Researchers need to focus on enabling potential research participants understand the concepts of research, promote autonomous decisions, especially by women and restrict therapeutic misconception.     

Coronin 1B supports RhoA signaling at cell-cell junctions through Myosin II

Non-muscle myosin II (NMII) motor proteins are responsible for generating contractile forces inside eukaryotic cells. There is also a growing interest in the capacity for these motor proteins to influence cell signaling through scaffolding, especially in the context of RhoA GTPase signaling. We previously showed that NMIIA accumulation and stability within specific regions of the cell cortex, such as the zonula adherens (ZA), allows the formation of a stable RhoA signaling zone. Now we demonstrate a key role for Coronin 1B in maintaining this junctional pool of NMIIA, as depletion of Coronin 1B significantly compromised myosin accumulation and stability at junctions. The loss of junctional NMIIA, upon Coronin 1B knockdown, perturbed RhoA signaling due to enhanced junctional recruitment of the RhoA antagonist, p190B Rho GAP. This effect was blocked by the expression of phosphomimetic MRLC-DD, thus reinforcing the central role of NMII in regulating RhoA signaling.     

Galectin-9: From cell biology to complex disease dynamics

Galectins is a family of non-classically secreted, β-galactoside-binding proteins that has recently received considerable attention in the spatio-temporal regulation of surface ‘signal lattice’ organization, membrane dynamics, cell-adhesion and disease therapeutics. Galectin-9 is a unique member of this family, with two non-homologous carbohydrate recognition domains joined by a linker peptide sequence of variable lengths, generating isoforms with distinct properties and functions in both physiological and pathological settings, such as during development, immune reaction, neoplastic transformations and metastasis. In this review, we summarize the latest knowledge on the structure, receptors, cellular targets, trafficking pathways and functional properties of galectin-9 and discuss how galectin-9-mediated signalling cascades can be exploited in cancers and immunotherapies.