Tec family kinases: regulation of FcεRI-mediated mast-cell activation

Mast cells express the high-affinity receptor for IgE (FcεRI) and are key players in type I hypersensitivity reactions. They are critically involved in the development of allergic rhinitis, allergic asthma and systemic anaphylaxis, however, they also regulate normal physiological processes that link innate and adaptive immune responses. Thus, their activation has to be tightly controlled. One group of signaling molecules that are activated upon FcεRI stimulation is formed by Tec family kinases, and three members of this kinase family (Btk, Itk and Tec) are expressed in mast cells. Many studies have revealed important functions of Tec kinases in signaling pathways downstream of the antigen receptors in lymphocytes. This review summarizes the current knowledge about the function of Tec family kinases in FcεRI-mediated signaling pathways in mast cell.     

Systematic exploration of synergistic drug pairs

Drug synergy allows a therapeutic effect to be achieved with lower doses of component drugs. Drug synergy can result when drugs target the products of genes that act in parallel pathways (‘specific synergy’). Such cases of drug synergy should tend to correspond to synergistic genetic interaction between the corresponding target genes. Alternatively, ‘promiscuous synergy’ can arise when one drug non‐specifically increases the effects of many other drugs, for example, by increased bioavailability. To assess the relative abundance of these drug synergy types, we examined 200 pairs of antifungal drugs in S. cerevisiae. We found 38 antifungal synergies, 37 of which were novel. While 14 cases of drug synergy corresponded to genetic interaction, 92% of the synergies we discovered involved only six frequently synergistic drugs. Although promiscuity of four drugs can be explained under the bioavailability model, the promiscuity of Tacrolimus and Pentamidine was completely unexpected. While many drug synergies correspond to genetic interactions, the majority of drug synergies appear to result from non‐specific promiscuous synergy.     

Unadapted and adapted to starvation Acholeplasma laidlawii cells induce different responses of Oryza sativa, as determined by proteome analysis

For the first time, we studied the phytopathogenicity toward Oryza sativa L. of unadapted and adapted to unfavorable environment (starvation) cells of Acholeplasma laidlawii PG8--ubiquitous mycoplasma found in the soil, waste waters, tissues of the highest eukaryotes and being the basic contaminant of cell cultures and a causative agent of phytomycoplasmoses. The features of morphology, ultrastructural organization and proteomes of unadapted and adapted cells of the mycoplasma and infected plants were presented. Using 2D-DIGE and MS, 43 proteins of O. sativa L. that were differentially expressed in the leaves of plants cultivated in media with A. laidlawii PG8 were identified. The qualitative and quantitative responses of the plant proteome toward adapted and unadapted mycoplasma cells differed. That may be explained by differences in the virulence of the corresponding bacterial cells. Using 2D-DIGE and MS, 82 proteins that were differentially expressed in adapted and unadapted mycoplasma cells were detected. In adapted cells of the mycoplasma, in comparison with unadapted ones, a significant increase in the expression of PNPase--a global regulator of virulence in phytopathogenic bacteria occurred; there was also decreased expression of 40 proteins including 14 involved in bacterial virulence and the expression of 31 proteins including 5 involved in virulence was not detected. We propose that differences in the phytopathogenicity of adapted and unadapted A. laidlawii PG8 cells may be related to features of their proteomes and membrane vesicles.     

Genome of a low-salinity ammonia-oxidizing archaeon determined by single-cell and metagenomic analysis

Ammonia-oxidizing archaea (AOA) are thought to be among the most abundant microorganisms on Earth and may significantly impact the global nitrogen and carbon cycles. We sequenced the genome of AOA in an enrichment culture from low-salinity sediments in San Francisco Bay using single-cell and metagenomic genome sequence data. Five single cells were isolated inside an integrated microfluidic device using laser tweezers, the cells' genomic DNA was amplified by multiple displacement amplification (MDA) in 50 nL volumes and then sequenced by high-throughput DNA pyrosequencing. This microscopy-based approach to single-cell genomics minimizes contamination and allows correlation of high-resolution cell images with genomic sequences. Statistical properties of coverage across the five single cells, in combination with the contrasting properties of the metagenomic dataset allowed the assembly of a high-quality draft genome. The genome of this AOA, which we designate Candidatus Nitrosoarchaeum limnia SFB1, is ～1.77 Mb with >2100 genes and a G+C content of 32%. Across the entire genome, the average nucleotide identity to Nitrosopumilus maritimus, the only AOA in pure culture, is ～70%, suggesting this AOA represents a new genus of Crenarchaeota. Phylogenetically, the 16S rRNA and ammonia monooxygenase subunit A (amoA) genes of this AOA are most closely related to sequences reported from a wide variety of freshwater ecosystems. Like N. maritimus, the low-salinity AOA genome appears to have an ammonia oxidation pathway distinct from ammonia oxidizing bacteria (AOB). In contrast to other described AOA, these low-salinity AOA appear to be motile, based on the presence of numerous motility- and chemotaxis-associated genes in the genome. This genome data will be used to inform targeted physiological and metabolic studies of this novel group of AOA, which may ultimately advance our understanding of AOA metabolism and their impacts on the global carbon and nitrogen cycles.     

Effects of inbreeding on behavioural plasticity of parent–offspring interactions in a burying beetle

Inbreeding depression is defined as a fitness decline in progeny resulting from mating between related individuals, the severity of which may vary across environmental conditions. Such inbreeding‐by‐environment interactions might reflect that inbred individuals have a lower capacity for adjusting their phenotype to match different environmental conditions better, as shown in prior studies on developmental plasticity. Behavioural plasticity is more flexible than developmental plasticity because it is reversible and relatively quick, but little is known about its sensitivity to inbreeding. Here, we investigate effects of inbreeding on behavioural plasticity in the context of parent–offspring interactions in the burying beetle Nicrophorus vespilloides. Larvae increase begging with the level of hunger, and parents increase their level of care when brood sizes increase. Here, we find that inbreeding increased behavioural plasticity in larvae: inbred larvae reduced their time spent associating with a parent in response to the length of food deprivation more than outbred larvae. However, inbreeding had no effect on the behavioural plasticity of offspring begging or any parental behaviour. Overall, our results show that inbreeding can increase behavioural plasticity. We suggest that inbreeding‐by‐environment interactions might arise when inbreeding is associated with too little or too much plasticity in response to changing environmental conditions.     

Ammonium‐Charged Sterically Hindered Phenols with Antioxidant and Selective Anti‐Gram‐Positive Bacterial Activity

The increase in the resistance of pathogens, in particular Staphylococcus aureus, to the action of antibiotics necessitates the search for new readily available and non‐toxic drugs. In solving this problem, phenolic acylhydrazones have high potential. In this communication, the synthesis of quaternary ammonium compounds containing a differently substituted phenolic moiety has been performed. An initial study of antimicrobial activity showed that these compounds are highly selective against S. aureus and B. cereus. The highest activity (MIC 2.0 μm ) was shown by hydrazones containing a catechol fragment. These compounds are more than 3‐fold more active against S. aureus and 3–10‐fold more active against B. cereus than norfloxacin. Low hemolytic and high antioxidant activities of all new compounds were also established.