New England's small cities: a mostly untapped resource

With a different policy mind-set, small cities could boost the region’s overall competitiveness and provide appealing alternatives for suburbanites tired of living behind the wheel of a car.Cities and towns - New England ; Economic policy - New England

Controlled synthesis of CoFe2O4 nano-octahedra

International audienceNano-octahedral grains of cobalt ferrite (CoFe2O4) with size around 20 nm were synthesized by a hydrothermal route. X-rays and electron diffraction, along with scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy and thermogravimetric analysis were used to characterize the powders. Images and simulations of high-resolution electron microscopy allowed the identification of the shape of the grains. Process parameters such as temperature and time of reaction, reagents concentration, and pH of the reacting medium were optimized. The surfactant cetyltrimethylammonium bromide (CTAB) hindered the formation of goethite, which favored the production of a pure CoFe2O4 powder. The oxidation state of cobalt atoms on the ferrite structure was also influenced by CTAB. The control of the shape of the grains was associated mainly to the nature of the precipitating agent

Structure-based virtual screening to get new scaffold inhibitors of the Ser/Thr protein kinase PknB from mycobacterium tuberculosis

In search of new inhibitors of the Ser/Thr protein kinase PknB from Mycobacterium tuberculosis we carried out a structure-based virtual screening study to identify ATP-competitive inhibitors of this enzyme. These studies point out that N-phenylmethylindole-2-carboxamide is a promising scaffold for the development of new PknB inhibitors. We synthesized a small set of analogue compounds to assess the pharmacophore structural requirements and to optimize the inhibitory activity against PknB. This strategy led to the identification of compound 3, endowed with an IC50 of 20 μM, which provides a novel scaffold for further improvement of PknB inhibitors

Immune responses in healthy adults elicited by a bivalent norovirus vaccine candidate composed of GI.4 and GII.4 VLPs without adjuvant

The development of an efficacious vaccine against norovirus is of paramount importance given its potential to reduce the global burden of norovirus-associated morbidity and mortality. Here, we report a detailed immunological analysis of a phase I, double-blind, placebo-controlled clinical trial performed on 60 healthy adults, ages 18 to 40. Total serum immunoglobulin and serum IgA against vaccine strains and cross-reactive serum IgG against non-vaccine strains were measured by enzyme immunoassays, whereas cell-mediated immune responses were quantified using intracellular cytokine staining by flow cytometry. A significant increase in humoral and cellular responses, e.g., IgA and CD4+ polypositive T cells, was triggered by the GI.4 Chiba 407 (1987) and GII.4 Aomori 2 (2006) VLP-based norovirus vaccine candidate rNV-2v, which is formulated without adjuvant. No booster effect was observed after the second administration in the pre-exposed adult study population. Furthermore, a cross-reactive immune response was elicited, as shown by IgG titers against GI.3 (2002), GII.2 OC08154 (2008), GII.4 (1999), GII.4 Sydney (2012), GII.4 Washington (2018), GII.6 Maryland (2018), and GII.17 Kawasaki 308 (2015). Due to viral infection via mucosal gut tissue and the high variety of potentially relevant norovirus strains, a focus should be on IgA and cross-protective humoral and cell-mediated responses in the development of a broadly protective, multi-valent norovirus vaccine.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT05508178. EudraCT number: 2019-003226-25

On the simulation of enzymatic digest patterns: the fragmentation of oligomeric and polymeric galacturonides by endo-polygalacturonase II

A simulation methodology for predicting the time-course of enzymatic digestions is described. The model is based solely on the enzyme's subsite architecture and concomitant binding energies. This allows subsite binding energies to be used to predict the evolution of the relative amounts of different products during the digestion of arbitrary mixtures of oligomeric or polymeric substrates. The methodology has been specifically demonstrated by studying the fragmentation of a population of oligogalacturonides of varying degrees of polymerization, when digested by endo-polygalacturonase II (endo-PG II) from Aspergillus niger.Comment: Preprint - has been accepted to Biochimica et Biophysica Act

PlcRa, a new quorum-sensing regulator from Bacillus cereus, plays a role in oxidative stress responses and cysteine metabolism in stationary phase

We characterized a new quorum-sensing regulator, PlcRa, which is present in various members of the B. cereus group and identified a signaling heptapeptide for PlcRa activity: PapRa7. We demonstrated that PlcRa is a 3D structural paralog of PlcR using sequence analysis and homology modeling. A comparison of the transcriptomes at the onset of stationary phase of a ¿plcRa mutant and the wild-type B. cereus ATCC 14579 strain showed that 68 genes were upregulated and 49 genes were downregulated in the ¿plcRa mutant strain (>3-fold change). Genes involved in the cysteine metabolism (putative CymR regulon) were downregulated in the ¿plcRa mutant strain. We focused on the gene with the largest difference in expression level between the two conditions, which encoded -AbrB2- a new regulator of the AbrB family. We demonstrated that purified PlcRa bound specifically to the abrB2 promoter in the presence of synthetic PapRa7, in an electrophoretic mobility shift assay. We further showed that the AbrB2 regulator controlled the expression of the yrrT operon involved in methionine to cysteine conversion. We found that the ¿plcRa mutant strain was more sensitive to hydrogen peroxide- and disulfide-induced stresses than the wild type. When cystine was added to the culture of the ¿plcRa mutant, challenged with hydrogen peroxide, growth inhibition was abolished. In conclusion, we identified a new RNPP transcriptional regulator in B. cereus that activated the oxidative stress response and cysteine metabolism in transition state cells