Degradability of cross-linked polyurethanes based on synthetic polyhydroxybutyrate and modified with polylactide

In many areas of application of conventional non-degradable cross-linked polyurethanes (PUR), there is a need for their degradation under the influence of specific environmental factors. It is practiced by incorporation of sensitive to degradation compounds (usually of natural origin) into the polyurethane structure, or by mixing them with polyurethanes. Cross-linked polyurethanes (with 10 and 30%wt amount of synthetic poly([R,S]-3-hydroxybutyrate) (R,S-PHB) in soft segments) and their physical blends with poly([d,l]-lactide) (PDLLA) were investigated and then degraded under hydrolytic (phosphate buffer solution) and oxidative (CoCl2/H2O2) conditions. The rate of degradation was monitored by changes of samples mass, morphology of surface and their thermal properties. Despite the small weight losses of samples, the changes of thermal properties of polymers and topography of their surface indicated that they were susceptible to gradual degradation under oxidative and hydrolytic conditions. Blends of PDLLA and polyurethane with 30 wt% of R,S-PHB in soft segments and PUR/PDLLA blends absorbed more water and degraded faster than polyurethane with low amount of R,S-PHB

A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi Metallo-beta-lactamase (NDM) producing Enterobacterales infection

Background: In response to infection with New Delhi Metallo-beta-lactamase (NDM) producing Enterobacterales, combination antimicrobial therapy with ceftazidime/avibactam (CAZ/AVI) plus aztreonam (ATM) has been explored. This study evaluated a practical laboratory method of testing for clinically significant synergy between CAZ/AVI+ATM in NDM producing Enterobacterales. Methods: Minimum inhibitory concentration (MIC) of clinical NDM producing isolates were determined for ATM alone and CAZ/AVI+ATM using broth dilution. Restoration of ATM breakpoint following the addition of CAZ/AVI was explored. A CAZ/AVI E-test/ATM disc method was compared to broth dilution. Results: Of 43 isolates, 33/43 (77%) isolates were ATM resistant (median [range] MIC=56 [16 – 512] mg/L). Addition of CAZ/AVI restored the ATM breakpoint (MIC <4mg/L) in 29/33 (89%) of resistant isolates. Overall, the E-test/disc method correlated with findings from broth dilution in 35/43 (81%) of cases. E-test/disc sensitivity was 77% and specificity 85%. Positive predictive value was 92% and negative predictive value 61%. Conclusion: CAZ/AVI+ATM demonstrated significant synergy in most ATM resistant NDM producing Enterobacterales. The E-test/disc method is a quick, reproducible, and reliable method of testing for clinically relevant synergy in the microbiology laboratory

INP1 involvement in pollen aperture formation is evolutionarily conserved and may require species-specific partners

Pollen wall exine is usually deposited non-uniformly on the pollen surface, with areas of low exine deposition corresponding to pollen apertures. Little is known about how apertures form, with the novel Arabidopsis INP1 (INAPERTURATE POLLEN1) protein currently being the only identified aperture factor. In developing pollen, INP1 localizes to three plasma membrane domains and underlies formation of three apertures. Although INP1 homologs are found across angiosperms, they lack strong sequence conservation. Thus, it has been unclear whether they also act as aperture factors and whether their sequence divergence contributes to interspecies differences in aperture patterns. To explore the functional conservation of INP1 homologs, we used mutant analysis in maize and tested whether homologs from several other species could function in Arabidopsis. Our data suggest that the INP1 involvement in aperture formation is evolutionarily conserved, despite the significant divergence of INP1 sequences and aperture patterns, but that additional species-specific factors are likely to be required to guide INP1 and to provide information for aperture patterning. To determine the regions in INP1 necessary for its localization and function, we used fragment fusions, domain swaps, and interspecific protein chimeras. We demonstrate that the central portion of the protein is particularly important for mediating the species-specific functionality.Funding was provided to AAD by the US National Science Foundation (MCB-1517511) and to VNSS by the Spanish Ministry of Economy and Competitiveness (CGL2015-70290-P). PL was supported by the China Scholarship Council. SB-MS was supported by the University of Granada, Spain (grant Cei BioTic). We thank the Arabidopsis Biological Resource Center (OSU) and the Maize Genetics Cooperation Stock Center (USDA/ ARS) for seed stocks, Priscila Rodriguez Garcia (OSU) for help with characterizing Arabidopsis–tomato INP1 chimeras, and Jay Hollick (OSU) for advice on all things maize

p21-activated kinase signaling in breast cancer

The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials

A Small-Molecule Inhibitor of T. gondii Motility Induces the Posttranslational Modification of Myosin Light Chain-1 and Inhibits Myosin Motor Activity

Toxoplasma gondii is an obligate intracellular parasite that enters cells by a process of active penetration. Host cell penetration and parasite motility are driven by a myosin motor complex consisting of four known proteins: TgMyoA, an unconventional Class XIV myosin; TgMLC1, a myosin light chain; and two membrane-associated proteins, TgGAP45 and TgGAP50. Little is known about how the activity of the myosin motor complex is regulated. Here, we show that treatment of parasites with a recently identified small-molecule inhibitor of invasion and motility results in a rapid and irreversible change in the electrophoretic mobility of TgMLC1. While the precise nature of the TgMLC1 modification has not yet been established, it was mapped to the peptide Val46-Arg59. To determine if the TgMLC1 modification is responsible for the motility defect observed in parasites after compound treatment, the activity of myosin motor complexes from control and compound-treated parasites was compared in an in vitro motility assay. TgMyoA motor complexes containing the modified TgMLC1 showed significantly decreased motor activity compared to control complexes. This change in motor activity likely accounts for the motility defects seen in the parasites after compound treatment and provides the first evidence, in any species, that the mechanical activity of Class XIV myosins can be modulated by posttranslational modifications to their associated light chains

Influence of polyurethanes based on synthetic poly([R,S]-3-hydroxybutyrate) on micoorganisms growth

W pracy przedstawiono wyniki badań oddziaływania nowych alifatycznych poliuretanów (PUR), otrzymanych z udziałem ataktycznego poli([R,S]-3- hydroksymaślanu (a-PHB), na wzrost Staphylococcus aureus, Escherichia coli i Candida albicans wokół próbek polimerów. Strefa zahamowania wzrostu mikroorganizmów oznaczona została także dla handlowego, biomedycznego poliuretanu - ChronoThane T oraz dla czystego rozpuszczalnika, użytego do syntezy poliuretanów (N,N-dimetyloformamidu). Najbardziej wrażliwym na działanie materiału poliuretanowego w warunkach prowadzenia doświadczenia był szczep Staphylococcus aureus, najmniej zaś - Candida albicans. Wykluczono wpływ czystego rozpuszczalnika na wzrost mikroorganizmów. Natomiast ChronoThane T tylko w niewielkim stopniu ograniczył ich wzrost. Stwierdzono więc, że obecność poli([R,S]- 3-hydroksymaślanu w strukturze poliuretanów wpłynęła na ich właściwości biostatyczne.In the present study the influence of novel aliphatic polyurethanes (PUR), based on atactic poly([R,S]-3- hydroxybutyrate) (a-PHB), on growth of Staphylococcus aureus, Escherichia coli and Candida albicans in the area around polymer samples has been estimated. For comparison measurement of zone of inhibition was also performed for ChronoThane T – the medical grade aliphatic polyurethane and for pure solvent - N,N-dimethylformamide used in the synthesis of polyurethanes. Staphylococcus aureus was the most sensitive microorganism to polymer material in conditions of investigation whereas Candida albicans – the most resistant. The influence of pure solvent on microorganisms growth was excluded and ChronoThane T only in small degree restricted bacterial vitality so it was concluded that presence of poly([R,S]-hydroxybutyrate) in polymer structure was responsible for biostatic properties of obtained polyurethanes

Preliminary investigations of biocompatibility of polyurethanes based on synthetic polyhydroxybutyrate

Zastosowanie w syntezie poliuretanów niemal zupełnie amorficznego ataktycznego poli([R,S]-3- hydroksmaślanu), bliskiego stanu, w jakim polihydroksymaślan naturalnie występuje w komórce, prowadzić może do otrzymania biokompatybilnego i biodegradowalnego materiału dla zastosowań medycznych. Celem pracy było oznaczenie sorpcji oleju, ekstrakcja wodą i heksanem poliuretanów otrzymanych z udziałem poli([R,S]-3-hydroksmaślanu) oraz ich wpływu na parametry krwi. Wysoka sorpcja oleju roślinnego przez próbki poliuretanów otrzymane z udziałem PTMG i poli([R,S]-3-hydroksmaślanu) oraz przebieg widm FTIR po ekstrakcji heksanem wskazują na potencjalną podatność tych polimerów na działanie tłuszczy w organizmie żywym. Nieznaczny tylko wpływ na parametry krwi, oznaczony przez porównanie wartości parametrów hematologicznych pełnej krwi po kontakcie z próbkami polimerów z próbką kontrolną, wskazuje na celowość dalszych badań w kierunku oznaczenia potencjalnej hemokompatybilności otrzymanych poliuretanów.Using in polyurethanes synthesis almost completely amorphous, atactic poly([R,S]-3-hydroxybutyrate) which is close to its original state in the cell, ought to let to obtain biocompatible and biodegradable material useful for medical application. The aim of work was to measure of oil sorption by obtained polyurethanes, based on poly([R,S]-3-hydroxy- butyrate), and their water and hexane extraction and the estimation of their influence on blood parameters. The high oil sorption by polyurethane samples synthesized with polyoxytetramethylene diol and poly([R,S]- 3-hydroxybutyrate) in soft segments and FTIR spectra of dry residue after hexane extraction indicate on potential susceptibility of those polyurethanes to lipids in living organism. Insignificant influence on blood parameters, estimated by comparison of values of hematologic parameters of whole blood contacted to polymers’ samples and control probe indicate on purposefulness of further tests to verify the hemocompatibility of obtained polyurethanes