Comparison of linkage disequilibrium and haplotype diversity on macro- and microchromosomes in chicken

Background

Toll like receptors (TLR) play the central role in the recognition of pathogen associated molecular patterns (PAMPs). Mutations in the TLR1, TLR2 and TLR4 genes may change the ability to recognize PAMPs and cause altered responsiveness to the bacterial pathogens.

Results

The study presents association between TLR gene mutations and increased susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP) infection. Novel mutations in TLR genes (TLR1- Ser150Gly and Val220Met; TLR2 – Phe670Leu) were statistically correlated with the hindrance in recognition of MAP legends. This correlation was confirmed subsequently by measuring the expression levels of cytokines (IL-4, IL-8, IL-10, IL-12 and IFN-γ) in the mutant and wild type moDCs (mocyte derived dendritic cells) after challenge with MAP cell lysate or LPS. Further in silico analysis of the TLR1 and TLR4 ectodomains (ECD) revealed the polymorphic nature of the central ECD and irregularities in the central LRR (leucine rich repeat) motifs.

Conclusion

The most critical positions that may alter the pathogen recognition ability of TLR were: the 9^th amino acid position in LRR motif (TLR1–LRR10) and 4^th residue downstream to LRR domain (exta-LRR region of TLR4). The study describes novel mutations in the TLRs and presents their association with the MAP infection.     

Do synovial biopsies help to support evidence for involvement of innate immunity in the immunopathology of Beh?et's disease?

Behçet's disease is a complex vasculitis of unknown etiology. Abundant neutrophils suggest the involvement of innate immunity. Cytokines are skewed to the T-helper-1 pattern. Few sterile organs are easily accessible for analysis in Behçet's disease. Cañete and coworkers identify inflamed joints as a feasible model and suggest the involvement of innate immunity in Behçet's disease.     

<Emphasis Type="Italic">Demodex gatoi</Emphasis> -associated contagious pruritic dermatosis in cats - a report from six households in Finland

Background  

Demodex gatoi is unique among demodectic mites. It possesses a distinct stubby appearance, and, instead of residing in the hair follicles, it dwells in the keratin layer of the epidermis, causing a pruritic and contagious skin disease in cats. Little is known of the occurrence of D. gatoi in Europe or control of D. gatoi infestation.     

Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury

Human ESC-derived mesenchymal stem cell (MSC)-conditioned medium (CM) was previously shown to mediate cardioprotection during myocardial ischemia/reperfusion injury through large complexes of 50–100 nm. Here we show that these MSCs secreted 50- to 100-nm particles. These particles could be visualized by electron microscopy and were shown to be phospholipid vesicles consisting of cholesterol, sphingomyelin, and phosphatidylcholine. They contained coimmunoprecipitating exosome-associated proteins, e.g., CD81, CD9, and Alix. These particles were purified as a homogeneous population of particles with a hydrodynamic radius of 55–65 nm by size-exclusion fractionation on a HPLC. Together these observations indicated that these particles are exosomes. These purified exosomes reduced infarct size in a mouse model of myocardial ischemia/reperfusion injury. Therefore, MSC mediated its cardioprotective paracrine effect by secreting exosomes. This novel role of exosomes highlights a new perspective into intercellular mediation of tissue injury and repair, and engenders novel approaches to the development of biologics for tissue repair.     

Morphology and anatomy of root nodules of Retama monosperma (L.)Boiss.

Background and aims

In spite of the importance of Retama species for dune stabilization and re-vegetation and the contribution to the bio-fertilization of semi-arid and arid ecosystems, the symbiotic interaction of Retama species with rhizobia remains largely unstudied. In this paper, we aim to provide the first detailed study on nodule morphology and anatomy of Retama monosperma.

Methods

We collected nodules from coastal areas nearby Oran (Algeria) and studied in detail their anatomy and ultrastructure by light and electron microscopy.

Results

First, we confirmed the likely identity of the microsymbiont as B. retamae and found that nodules of R. monosperma belong to the genistoid type of indeterminate nodules. Infection threads, typical for most nodules of legumes, are absent in nodules of R. monosperma and bacterial spread is associated with plant cell division. The nitrogen fixation zone is homogenous with only invaded cells and a network of non-invaded cells found in many nodules, is absent. Moreover, endoreduplication does not take place in bacteroids in nodules of R. monosperma.

Conclusions

The features observed in this study are compared to the morphology and anatomy of nodules of other legumes and the possible consequences for nodule functioning and the mode of infection during the establishment of the interaction are discussed.     

Crystal structure determination and dynamic studies of Mycobacterium tuberculosis Cytidine deaminase in complex with products

Cytidine deaminase (CDA) is a key enzyme in the pyrimidine salvage pathway. It is involved in the hydrolytic deamination of cytidine or 2′-deoxycytidine to uridine or 2′-deoxyuridine, respectively. Here we report the crystal structures of Mycobacterium tuberculosis CDA (MtCDA) in complex with uridine (2.4 Å resolution) and deoxyuridine (1.9 Å resolution). Molecular dynamics (MD) simulation was performed to analyze the physically relevant motions involved in the protein–ligand recognition process, showing that structural flexibility of some protein regions are important to product binding. In addition, MD simulations allowed the analysis of the stability of tetrameric MtCDA structure. These findings open-up the possibility to use MtCDA as a target in future studies aiming to the rational design of new inhibitor of MtCDA-catalyzed chemical reaction with potential anti-proliferative activity on cell growth of M. tuberculosis, the major causative agent of tuberculosis.