The Apparent Requirement for Protein Synthesis during G2 Phase Is due to Checkpoint Activation

Protein synthesis inhibitors have long been known to prevent G2 phase cells from entering mitosis. Lockhead et al. demonstrate that this G2 arrest is due to the activation of p38 MAPK, not insufficient protein synthesis, arguing that protein synthesis in G2 phase is not absolutely required for mitotic entry

Design, Synthesis and Characterization of N-oxide-containing Heterocycles with In vivo Sterilizing Antitubercular Activity

Tuberculosis, caused by the Mycobacterium tuberculosis (Mtb), is the infectious disease responsible for the highest number of deaths worldwide. Herein, 22 new N-oxide- containing compounds were synthesized followed by in vitro and in vivo evaluation of their antitubercular potential against Mtb. Compound 8 was found to be the most promising compound, with MIC90 values of 1.10 and 6.62 μM against active and non- replicating Mtb, respectively. Additionally, we carried out in vivo experiments to confirm the safety and efficacy of compound 8; the compound was found to be orally bioavailable and highly effective leading to the reduction of the number of Mtb to undetected levels in a mouse model of infection. Microarray-based initial studies on the mechanism of action suggest that compound 8 blocks the process of translation. Altogether, these results indicated benzofuroxan derivative 8 to be a promising lead compound for the development of a novel chemical class of antitubercular drugs

Astronomical Distance Determination in the Space Age: Secondary Distance Indicators

The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)

An atlas of human kinase regulation

The coordinated regulation of protein kinases is a rapid mechanism that integrates diverse cues and swiftly determines appropriate cellular responses. However, our understanding of cellular decision-making has been limited by the small number of simultaneously monitored phospho-regulatory events. Here, we have estimated changes in activity in 215 human kinases in 399 conditions derived from a large compilation of phosphopeptide quantifications. This atlas identifies commonly regulated kinases as those that are central in the signaling network and defines the logic relationships between kinase pairs. Co-regulation along the conditions predicts kinase–complex and kinase–substrate associations. Additionally, the kinase regulation profile acts as a molecular fingerprint to identify related and opposing signaling states. Using this atlas, we identified essential mediators of stem cell differentiation, modulators of Salmonella infection, and new targets of AKT1. This provides a global view of human phosphorylation-based signaling and the necessary context to better understand kinase-driven decision-making.ISSN:1744-429

Phosphate solubilization by endophytic bacteria isolated from banana trees

<div><p>ABSTRACT Forty isolates of endophytic bacteria isolated from banana tree roots were assessed as to their capacity to solubilize phosphate in a solid culture medium supplemented with different inorganic and one organic source of phosphorus. The amount of phosphorus (P) in each liquid medium was quantified, and an indirect assessment of acid phosphatase activity was performed. All assays had a fully randomized design, with three repetitions. Approximately 67.5% of the 40 isolates assessed in solid medium solubilized phosphorus from tricalcium phosphate and 7.5% of the isolates solubilized phosphorus from soy lecithin; no isolates exhibited P solubilization capacity in medium supplemented with iron phosphate. Acid phosphatase activity was detected in 65% of the isolates; Aneurinibacillus sp. and Lysinibacillus sp. isolates presented with the best solubilization indexes. All of the assessed isolates exhibited a capacity to reduce the potential of hydrogen in liquid medium supplemented with tricalcium phosphate. Isolate EB. 78 (Bacillus sp.) exhibited P solubilization capacity in solid media when Ca3(PO4)2 and soy lecithin were used as P sources; this isolate significantly reduced the pH of the liquid medium and exhibited acid phosphatase activity. The results of the present study highlight isolates that exhibit variations in their capacity to solubilize P. These isolates should be used in future tests to assess their field performance.</p></div

Extended-spectrum beta-lactamases among Enterobacteriaceae isolated in a public hospital in Brazil Beta-lactamases de espectro estendido em Enterobacteriaceae isoladas de Hospital Público no Brasil

Extended-spectrum &#946;-lactamases (ESBL) in enterobacteria are recognized worldwide as a great hospital problem. In this study, 127 ESBL-producing Enterobacteriaceae isolated in one year from inpatients and outpatients at a public teaching hospital at São Paulo, Brazil, were submitted to analysis by PCR with specific primers for blaSHV, blaTEM and blaCTX-M genes. From the 127 isolates, 96 (75.6%) Klebsiella pneumoniae, 12 (9.3%) Escherichia coli, 8 (6.2%) Morganella morganii, 3 (2.3%) Proteus mirabilis, 2 (1.6%) Klebsiella oxytoca, 2 (1.6%) Providencia rettgeri, 2 (1.6%) Providencia stuartti, 1 (0.8%) Enterobacter aerogenes and 1 (0.8%) Enterobacter cloacae were identified as ESBL producers. BlaSHV, blaTEM and blaCTX-M were detected in 63%, 17.3% and 33.9% strains, respectively. Pulsed field gel eletrophoresis genotyping of K. pneumoniae revealed four main molecular patterns and 29 unrelated profiles. PCR results showed a high variety of ESBL groups among strains, in nine different species. The results suggest the spread of resistance genes among genetically different strains of ESBL-producing K. pneumoniae in some hospital wards, and also that some strongly related strains were identified in different hospital wards, suggesting clonal spread in the institutional environment.<br>Beta-lactamases de espectro estendido (ESBL) em enterobactérias são reconhecidas mundialmente como um grande problema hospitalar. Neste estudo, 127 Enterobacteriaceae produtoras de ESBL isoladas por um ano, de pacientes internados e ambulatoriais de um hospital público de ensino em São Paulo, Brasil, foram submetidas à análise pela PCR com iniciadores específicos para os genes blaSHV, blaTEM e blaCTX-M. Dos 127 isolados, 96 (75,6%) K. pneumoniae, 12 (9,3%) E. coli, 8 (6,2%) M. morganii, 3 (2,3%) Proteus mirabilis, 2 (1,6%) Klebsiella oxytoca, 2 (1,6%) Providencia rettgeri, 2 (1,6%) Providencia stuartti, 1 (0,8%) Enterobacter aerogenes e 1 (0,8%) Enterobacter cloacae foram identificados como produtores de ESBL. BlaSHV, blaTEM e blaCTX-M foram detectados em 63%, 17,3% e 33,9% das cepas, respectivamente. A genotipagem de K. pneumoniae por eletroforese em campo pulsado revelou quatro padrões moleculares principais e 29 perfis não relacionados. Os resultados da PCR demonstraram alta variedade de grupos de ESBL entre as cepas, em nove espécies diferentes. Os resultados sugerem a disseminação de genes de resistência entre cepas geneticamente diferentes de K. pneumoniae produtoras de ESBL em algumas unidades do hospital, e também que algumas cepas fortemente relacionadas foram identificadas em unidades hospitalares diferentes, sugerindo disseminação clonal no ambiente da instituição