Fouling of nanostructured insect cuticle: adhesion of natural and artificial contaminants

The adhesional properties of contaminating particles of scales of various lengths were investigated for a wide range of micro- and nanostructured insect wing cuticles. The contaminating particles consisted of artificial hydrophilic (silica) and spherical hydrophobic (C(18)) particles, and natural pollen grains. Insect wing cuticle architectures with an open micro-/nanostructure framework demonstrated topographies for minimising solid-solid and solid-liquid contact areas. Such structuring of the wing membranes allows for a variety of removal mechanisms to contend with particle contact, such as wind and self-cleaning droplet interactions. Cuticles exhibiting high contact angles showed considerably lower particle adhesional forces than more hydrophilic insect surfaces. Values as low as 3 nN were recorded in air for silica of ~28 nm in diameter and <25 nN for silica particles 30 μm in diameter. A similar adhesional trend was also observed for contact with pollen particles.     

Synthesis and anticonvulsant activity of new N-Mannich bases derived from 5-cyclopropyl-5-phenyl- and 5-cyclopropyl-5-(4-chlorophenyl)-imidazolidine-2,4-diones

Synthesis, physicochemical and anticonvulsant properties of new N-Mannich bases derived from 5-cyclopropyl-5-phenyl- and 5-cyclopropyl-5-(4-chlorophenyl)-imidazolidine-2,4-diones have been described. Initial anticonvulsant screening was performed using intraperitoneal (ip.) maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The neurotoxicity was determined applying the rotarod test. The in vivo results in mice showed that all compounds were effective especially in the MES screen. The quantitative evaluation after oral administration in rats showed that the most active was 5-cyclopropyl-5-phenyl-imidazolidine-2,4-dione (1) with ED(50) values of 5.76 mg/kg (MES) and 57.31 mg/kg (scPTZ). This molecule was more potent than phenytoin and ethosuximide which were used as reference antiepileptic drugs. Additionally compound 1 with ED(50) of 26.06 mg/kg in psychomotor seizure test (6-Hz) in mice showed comparable activity to new generation anticonvulsant - levetiracetam.     

PP2A phosphatase acts upon SAS-5 to ensure centriole formation in C. elegans embryos

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Highlights? PP2A phosphatase is essential for centriole formation in C. elegans ? PP2A subunits genetically and physically interact with the SAS-5/SAS-6 complex ? PP2A-mediated dephosphorylation of SAS-5 is required for SAS-5/SAS-6 centriolar targeting ? Human PP2A is required for HsSAS-6 centriolar targeting and centriole formation     

Ischemia induced peroxynitrite dependent modifications of cardiomyocyte MLC1 increases its degradation by MMP‐2 leading to contractile dysfunction

Damage to cardiac contractile proteins during ischemia followed by reperfusion is mediated by reactive oxygen species such as peroxynitrite (ONOO⁻), resulting in impairment of cardiac systolic function. However, the pathophysiology of systolic dysfunction during ischemia only, before reperfusion, remains unclear. We suggest that increased ONOO⁻ generation during ischemia leads to nitration/nitrosylation of myosin light chain 1 (MLC1) and its increased degradation by matrix metalloproteinase-2 (MMP-2), which leads to impairment of cardiomyocyte contractility. We also postulate that inhibition of ONOO⁻ action by use of a ONOO⁻ scavenger results in improved recovery from ischemic injury. Isolated rat cardiomyocytes were subjected to 15 and 60 min. of simulated ischemia. Intact MLC1 levels, measured by 2D gel electrophoresis and immunoblot, were shown to decrease with increasing duration of ischemia, which correlated with increasing levels of nitrotyrosine and nitrite/nitrate. In vitro degradation of human recombinant MLC1 by MMP-2 increased after ONOO⁻ exposure of MLC1 in a concentration-dependent manner. Mass spectrometry analysis of ischemic rat cardiomyocyte MLC1 showed nitration of tyrosines 78 and 190, as well as of corresponding tyrosines 73 and 185 within recombinant human cardiac MLC1 treated with ONOO⁻. Recombinant human cardiac MLC1 was additionally nitrosylated at cysteine 67 and 76 corresponding to cysteine 81 of rat MLC1. Here we show that increased ONOO⁻ production during ischemia induces MLC1 nitration/nitrosylation leading to its increased degradation by MMP-2. Inhibition of MLC1 nitration/nitrosylation during ischemia by the ONOO⁻ scavenger FeTPPS (5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron[III]), or inhition of MMP-2 activity with phenanthroline, provides an effective protection of cardiomyocyte contractility.     

Characterization of bone-marrow-derived rat mesenchymal stem cells depending on donor age

It is generally accepted that autologous transfers, as non-immunogenic, constitute the safest approach in cellular transplantations. However, this attitude is often associated with the need for isolation and extracorporeal propagation of cells derived from aged patients. Thus the knowledge about relationship between aging and the properties of MSCs (mesenchymal stem cells) is crucial in developing new clinical strategies. The aim of this study was to perform complex comparison of MSC derived from young and aged individuals, which included phenotype, proliferating rate, osteogenic and adipogenic potential and secretory activity. Evaluated populations were isolated from bone marrow of 3-month-old and 24-month-old rats. There was no significant difference in membrane antigen expression and PDT (population doubling time). Additionally, the adipogenic and osteogenic potential did not vary between studied populations. The reaction of MSCs to either mitogen [bFGF (basic fibroblas t growth factor)] or oxidative stress (H2O2) in vitro displayed a very similar pattern in both analysed populations. There was no difference in TGFβ1 (transforming growth factor β1) and VEGF (vascular endothelial growth factor) secretion measured by ELISA test and gene expression evaluated by real-time PCR. However, the expression of the gene for IL-1α (interleukin-1α) was 8-fold lower in oMSC (MSC isolated from old rats). These results indicate that aging individuals can be considered as candidates for autologous transplantation of bone-marrow-derived MSCs.     

Prevalence of the most frequent BRCA1 mutations in Polish population

The purpose of our study was to establish the frequency and distribution of the four most common BRCA1 mutations in Polish general population and in a series of breast cancer patients. Analysis of the population frequency of 5382insC (c.5266dupC), 300T >G (p.181T >G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5) mutations of the BRCA1 gene were performed on a group of respectively 16,849, 13,462, 12,485 and 3923 anonymous samples collected at birth in seven Polish provinces. The patient group consisted of 1845 consecutive female breast cancer cases. The most frequent BRCA1 mutation in the general population was 5382insC found in 29 out of 16,849 samples (0.17%). 300T >G and 3819del5 mutations were found in respectively 11 of 13,462 (0.08%) and four of 3923 (0.1%) samples. The population prevalence for combined Polish founder 5382insC and 300T >G mutations was 0.25% (1/400). The frequencies of 5382insC and 300T >G carriers among consecutive breast cancer cases were, respectively, 1.9% (35/1845) and 1.2% (18/1486). Comparing these data with the population frequency, we calculated the relative risk of breast cancer for 5382insC mutation at OR = 17 and for 300T >G mutation at OR = 26. Our results, based on large population studies, show high frequencies of founder 5382insC and 300T >G BRCA1 mutations in Polish general population. Carriage of one of these mutations is connected with a very high relative risk of breast cancer.     

Prognostic role of c-met expression in breast cancer patients

Background

Hepatocyte growth factor plays an important role in tumor growth, metastasis and angiogenesis. C-met is HGF''s high affinity receptor.

Aim

The aim of the study was to assess the correlations between c-met expression and clinic-pathological factors in breast cancer tissues. Furthermore, the purpose of the study was to evaluate the prognostic value of the hepatocyte growth factor receptor (HGFR, c-met) expressions in homogenous group of breast cancer patients.

Materials and methods

Tumor samples were collected from 302 patients with breast carcinoma treated with primary surgery. We have assessed the percentage of tumor cells with c-met expression, the intensity of reaction and the ratio of these two factors—immunoreactivity according to the Remmele score.

Results

We have observed no correlations between HGFR immunoreactivities and clinical parameters (tumor size, grade, axillary lymph node status, age). In 5-year observation we have found prognostic value of assessing c-met immunoreactivity in primary tumor.

Conclusion

Our study has revealed prognostic value of c-met. Unlike in other authors’ studies, our patients’ group is very homogenous which might contribute to obtained results.     

Uncovering genomic causes of co-morbidity in epilepsy: gene-driven phenotypic characterization of rare microdeletions

Background

Patients with epilepsy often suffer from other important conditions. The existence of such co-morbidities is frequently not recognized and their relationship with epilepsy usually remains unexplained.

Methodology/Principal Findings

We describe three patients with common, sporadic, non-syndromic epilepsies in whom large genomic microdeletions were found during a study of genetic susceptibility to epilepsy. We performed detailed gene-driven clinical investigations in each patient. Disruption of the function of genes in the deleted regions can explain co-morbidities in these patients.

Conclusions/Significance

Co-morbidities in patients with epilepsy can be part of a genomic abnormality even in the absence of (known) congenital malformations or intellectual disabilities. Gene-driven phenotype examination can also reveal clinically significant unsuspected condition.