Site-specific modification of Shigella flexneri virF mRNA by tRNA-guanine transglycosylase in vitro

Shigella flexneri is an enteropathogen responsible for severe dysentery in humans. VirF is a key transcriptional regulator that activates the expression of the downstream virulence factors required for cellular invasion and cell-to-cell spread of this pathogen. There are several environmental factors that induce the translation of VirF including temperature, pH, osmolarity and post-transcriptional RNA modification. Durand and colleagues (vacC, a virulence-associated chromosomal locus of Shigella flexneri, is homologous to tgt, a gene encoding tRNA-guanine transglycosylase of Escherichia coli K-12. J. Bacteriol., 176, 4627–4634) have demonstrated a correlation between VirF and tRNA-guanine transglycosylase (TGT), which catalyzes the exchange of the hypermodified base queuine for the guanine in the wobble position of certain tRNAs. They characterized tgt- mutant S. flexneri strains in which the translation of VirF is markedly reduced and the bacteria are unable to invade host cells. Although the function of TGT is to modify tRNA, we report that the virF mRNA is recognized by the Escherichia coli TGT (99% identity to the S. flexneri TGT) in vitro. Further, we show that this recognition results in the site-specific modification of a single base in the virF mRNA. In the context of previous reports that small molecule binding motifs (‘riboswitches’) in mRNAs modulate mRNA conformation and translation, our observations suggest that TGT may modulate the translation of VirF by base modification of the VirF encoding mRNA

3-Bromo­meth­yl-2-chloro­meth­yl-1-phenyl­sulfon­yl-1H-indole

In the title compound, C16H13BrClNO2S, the indole mean plane forms a dihedral angle of 73.59 (19)° with the phenyl ring. The mol­ecular structure is stabilized by weak intra­molecular C—H⋯O inter­actions. The Br atom is disordered over two positions with site occupancy factors of 0.7 and 0.3

Combining biochar with low rate of chemical fertiliser boosts maize biomass yield, regardless of tillage system, under humid conditions

Biochar application to soils increases biomass and crop yields, especially with rates higher than 100 t ha−1. Yet, there is limited knowledge on the combined effect of biochar and chemical fertiliser under different tillage systems. The objective of this study is to investigate the effect of maize-cob biochar (BC) (rates of 5 and 10 t ha−1) combined with chemical fertiliser micro-dosing (MD) at a rate of 25% of the recommended quantity on total shoot dry matter (DM) and plant height of maize cultivated under flat (F) and tied-ridge (R) practices during a humid season in Tanzania. The results indicate that combining 5 t ha−1 BC with 25% MD increases DM at harvest by 83% (4.16 t ha−1) compared to the control (2.27 t ha−1) and was in the same range as the DM obtained from the treatment with the recommended fertiliser rate (100% FD). The treatments with single applications of 25% MD, 5 t ha−1 BC, and 10 t ha−1 BC only tended to exceed the control of DM yield. Therefore, we recommend that small-scale farmers aiming at DM for livestock or grain yield with limited access to chemical fertilisers to combine biochar with 25% MD, rather than applying biochar or low chemical fertiliser rates alone

Structure–Activity Relationship of Halophenols as a New Class of Protein Tyrosine Kinase Inhibitors

A series of new benzophenone and diphenylmethane halophenol derivatives were prepared. Their structures were established based on 1H NMR, 13C NMR and HRMS data. All prepared compounds were screened for their in vitro protein tyrosine kinase (PTK) inhibitory activities. The effects of modification of the linker, functional groups and substituted positions at the phenyl ring on PTK inhibitory activity were investigated. Twelve halophenols showed significant PTK inhibitory activity. Among them, compounds 6c, 6d, 7d, 9d, 10d, 11d and 13d exhibited stronger activities than that of genistein, the positive reference compound. The results gave a relatively full and definite description of the structure–activity relationship and provided a foundation for further design and structure optimization of the halophenols

Emerging roles for hyaluronidase in cancer metastasis and therapy

Hyaluronidases are a family of five human enzymes that have been differentially implicated in the progression of many solid tumor types, both clinically and in functional studies. Advances in the past five years have clarified many apparent contradictions, (1) by demonstrating that specific hyaluronidases have alternative substrates to hyaluronan (HA) or do not exhibit any enzymatic activity, (2) that high molecular weight HA polymers elicit signaling effects that are opposite those of the hyaluronidase-digested HA oligomers, and (3) that it is actually the combined overexpression of HA synthesizing enzymes with hyaluronidases that confers tumorigenic potential. This review examines the literature supporting these conclusions and discusses novel mechanisms by which hyaluronidases impact invasive tumor cell processes. In addition, a detailed structural and functional comparison of the hyaluronidases is presented with insights into substrate selectivity and potential for therapeutic targeting. Finally, technological advances in targeting hyaluronidase for tumor imaging and cancer therapy are summarized

Bi-directional cell-pericellular matrix interactions direct stem cell fate

Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells’ 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells’ reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC’s interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate

KAFKAS UNIVERSITESI VETERINER FAKULTESI DERGISI

Leishmaniases are present in two clinical forms, as visceral and cutaneous, in Turkey showing a tendency of spreading throughout the country. The aim of the present study was to produce a new model for determining the spatial risk levels using the data in a selected study site in the western part of Turkey. The results of entomological studies in this leishmaniasis focus indicated the presence of suspected vector species Phlebotomus (Larroussius) tobbi and P (Larroussius) neglectus for the visceral, P (Paraphlebotomus) similis for cutaneous forms of the disease. The new risk model was developed based on univariate and multivariate binary logistic regression analyses of geographical variables as altitude, aspect, Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index (EVI) and Land Surface Temperature (LST) values related to the distribution of these three species. The results of the new model were used to produce the risk maps and the potential distribution areas of the incriminated vector species with the use of geographical technologies which allowed the identification of the leishmaniasis risk levels that may provide useful information to guide the control program interventions

Manejo integrado de la enfermedad del decaimiento progresivo del limón sutil (Citrus aurantifolia Swing/Citrus jambhiri Lush) en el valle de San Lorenzo - Piura

En la costa norte del país, los departamentos de Piura, Lambayeque y Tumbes; tienen condiciones de clima y suelo excepcionales para el cultivo de Limón Sutil (Citrus trantifolia Swing), cuya cosecha es continua durante todo el ario, genera una actividad sólida en lo económico y social. En el departamento de Piura se cultivan 14,600 ha, (regas y Narrea, 2013), con rendimientos de 9 a 14 T/ha producción que está destinada principalmente al mercado nacional para el consumo fresco, sin embargo, los bajos precios de la fruta en los meses de verano sumados a la baja calidad de la mayor parte de los frutos que producen los árboles, atentan contra la estabilidad económica de tienes están involucrados en el cultivo. Para atenuar esto, en la actualidad la empresa privada, se está dedicando a la producción y exportación a Chile y Estados Unidos de nón sutil, aceite esencial y cáscara deshidratada (Vegas y Narrea, 2013).Tesi