THE FINE STRUCTURE OF DIPLOCOCCUS PNEUMONIAE

The fine structure of an unencapsulated strain of Diplococcus pneumoniae is described. A striking feature of these bacteria is an intracytoplasmic membrane system which appears to be an extension of septa of dividing bacteria. The possible function of these structures and their relationship to the plasma membrane and other types of intracytoplasmic membranes found in pneumococcus is discussed.     

Size extensivity of elastic properties of alkane fragments

Using MP2, CCSD, and B3LYP methods of computational chemistry, we show length dependence in the intrinsic elastic properties of short alkane fragments. For isolated alkane fragments of finite length in the gas phase and zero temperature, the intrinsic elasticity constants are found to vary with the number of carbon atoms and its parity. From extrapolation of the elasticity constants calculations to infinite chain length, and by comparing with in-situ elasticity constant of single poly(ethylene) molecule obtained with atomic force microscopy, we estimate the softening effect of environment on the extension response of the polymer.     

Microenvironment‐induced PIM kinases promote CXCR4‐triggered mTOR pathway required for chronic lymphocytic leukaemia cell migration

Lymph node microenvironment provides chronic lymphocytic leukaemia (CLL) cells with signals promoting their survival and granting resistance to chemotherapeutics. CLL cells overexpress PIM kinases, which regulate apoptosis, cell cycle and migration. We demonstrate that BCR crosslinking, CD40 stimulation, and coculture with stromal cells increases PIMs expression in CLL cells, indicating microenvironment‐dependent PIMs regulation. PIM1 and PIM2 expression at diagnosis was higher in patients with advanced disease (Binet C vs. Binet A/B) and in those, who progressed after first‐line treatment. In primary CLL cells, inhibition of PIM kinases with a pan‐PIM inhibitor, SEL24‐B489, decreased PIM‐specific substrate phosphorylation and induced dose‐dependent apoptosis in leukaemic, but not in normal B cells. Cytotoxicity of SEL24‐B489 was similar in TP53‐mutant and TP53 wild‐type cells. Finally, inhibition of PIM kinases decreased CXCR4‐mediated cell chemotaxis in two related mechanisms‐by decreasing CXCR4 phosphorylation and surface expression, and by limiting CXCR4‐triggered mTOR pathway activity. Importantly, PIM and mTOR inhibitors similarly impaired migration, indicating that CXCL12‐triggered mTOR is required for CLL cell chemotaxis. Given the microenvironment‐modulated PIM expression, their pro‐survival function and a role of PIMs in CXCR4‐induced migration, inhibition of these kinases might override microenvironmental protection and be an attractive therapeutic strategy in this disease.     

Immunogenicity of parenterally delivered plant-derived small and medium surface antigens of hepatitis B virus

Key message

Intramuscularly delivered plant-derived M-HBsAg was compared to S-HBsAg, and as a result elicited specific anti-preS2 antibodies and significantly higher titre of anti-HBs antibodies, together with IgG isotype profile indicating some Th1 polarisation, apart from the main Th2 response.

Abstract

HBV prevalence is still threatening, regardless of prevention programmes using vaccines containing S-HBsAg, supplemented by third-generation vaccines, comprising also M- and L-HBsAg. Plant expression systems offer a cost-effective production option of the antigens. Plant-derived S- and M-HBsAg, intramuscularly delivered to mice, elicited anti-HBs antibodies several times higher than high responsiveness threshold titre. M-HBsAg induced stronger response of anti-HBs and also specific anti-preS2 antibodies. IgG isotype profiles indicated mainly Th2 response, yet Th1 polarisation was also pointed out, in some larger extent for M-HBsAg. These results correspond to research on CHO-derived M-HBsAg vs. commercial vaccines based on S-HBsAg and support potency of plant-derived antigens as alternative injection vaccines.

     

Surface properties of Enterococcus faecalis cells isolated from chicken hearts determine their low ability to form biofilms

Enterococcus faecalis is one of the most significant bacterial pathogens associated with the first-week mortality of chickens. Here, the surface properties of bacterial cells and the selected virulence factors of E. faecalis strains isolated from the hearts of clinically healthy broiler chickens were studied. Investigations were carried out on live and autoclaved cells. E. faecalis (ATCC 29212) was used as a reference strain. The bacterial cells revealed different haemolytic activities. Their surface free energy was dominated by the hydrophobic component. The cell walls of the bird isolates showed slightly weaker acidic characteristics than those of E. faecalis (ATCC 29212). Moreover, the bacterial cells from the chicken hearts showed higher electrophoretic mobility and surface electrical charge than the reference strain, and consequently demonstrated a low ability to form biofilms.     

Restoration of hydro-ecological conditions in Carpathian forested mountain fens

The research was designed to assess benefits of passive restoration, consisting of blocking from drainage ditches and in effect raise the groundwater level, its influence on properties of soil, water, species of plants and mesofauna in the fen Caltho-Alnetum community. The research was carried out in Outer Flysh Carpathians, the area of the Babiogórski National Park (Poland) in 2011–2014. It was established that the degraded communities showed positive reaction to an attempt to restore the original groundwater level. The increase in the groundwater level changed chemical properties of soil and water of the community such as: pH, sorption properties and the ionic composition of groundwater. Changes in habitat conditions resulted in different species composition of soil mesofauna and plants growing in the restorative community.     

Nucleoside imidodiphosphates synthesis and biological activities.

The synthesis of imidodiphosphate analogues of natural nucleoside 5'-diphosphates including adenosine 5'-imidodiphosphate (4a), guanosine 5'-imidodiphosphate (4b), 2'-deoxyadenosine 5'-imidodiphosphate (4c), and 2'-deoxy-guanosine 5'-imidodiphosphate (4d) has been accomplished for the first time. These compounds are the products of the reaction between nucleosides and trichloro [(dichlorophosphoryl)imido] phosphorane in trimethyl phosphate. Some of the major by-products of the reaction including 5'-deoxy-5'-chloro nucleosides are discussed. Compounds 4b, 4c, and 4d are potent inhibitors of ecto-5'-nucleotidase whereas compound 4a also active but less potent inhibitor. Compound 4b is the most potent inhibitor of phosphoribosyl pyrophosphate (PPRP) synthetase which follows by 4c, 4d and 4a. All of these compounds were more potent inhibitor of PPRP-synthetase than ADP or GDP. Ribavirin imidodiphosphate (4e) was also synthesized and tested for its inhibitory effect on ecto-5'-nucleotidase, PPRP-synthetase as well as IMP dehydrogenase. Compound 4e is the most potent inhibitor of IMP dehyrogenase but was a weak inhibitor of the other two enzymes. compound 4a, 4b, 4c and 4d are weak inhibitors of IMP dehydrogenase.     

Impedance Changes and Fibrous Tissue Growth after Cochlear Implantation Are Correlated and Can Be Reduced Using a Dexamethasone Eluting Electrode

Background

The efficiency of cochlear implants (CIs) is affected by postoperative connective tissue growth around the electrode array. This tissue formation is thought to be the cause behind post-operative increases in impedance. Dexamethasone (DEX) eluting CIs may reduce fibrous tissue growth around the electrode array subsequently moderating elevations in impedance of the electrode contacts.

Methods

For this study, DEX was incorporated into the silicone of the CI electrode arrays at 1% and 10% (w/w) concentration. Electrodes prepared by the same process but without dexamethasone served as controls. All electrodes were implanted into guinea pig cochleae though the round window membrane approach. Potential additive or synergistic effects of electrical stimulation (60 minutes) were investigated by measuring impedances before and after stimulation (days 0, 7, 28, 56 and 91). Acoustically evoked auditory brainstem responses were recorded before and after CI insertion as well as on experimental days 7, 28, 56, and 91. Additionally, histology performed on epoxy embedded samples enabled measurement of the area of scala tympani occupied with fibrous tissue.

Results

In all experimental groups, the highest levels of fibrous tissue were detected in the basal region of the cochlea in vicinity to the round window niche. Both DEX concentrations, 10% and 1% (w/w), significantly reduced fibrosis around the electrode array of the CI. Following 3 months of implantation impedance levels in both DEX-eluting groups were significantly lower compared to the control group, the 10% group producing a greater effect. The same effects were observed before and after electrical stimulation.

Conclusion

To our knowledge, this is the first study to demonstrate a correlation between the extent of new tissue growth around the electrode and impedance changes after cochlear implantation. We conclude that DEX-eluting CIs are a means to reduce this tissue reaction and improve the functional benefits of the implant by attenuating electrode impedance.     

Retrospective analysis of idiopathic scoliosis medical records coming from one out-patient clinic for compatibility with Scoliosis Research Society criteria for brace treatment studies

Background

First author attempted to analyse medical records of patients with idiopathic scoliosis for compliance with the Scoliosis Research Society brace studies criteria. A retrospective analysis of medical records of 2705 girls treated from 1989 to 2002 was carried out.

Methods

Age, Cobb, Risser and menarchal status were analyzed for compliance with the Scoliosis Research Society brace studies criteria: a) age ≥10 years, b) Risser 0–2, c) 25–40° Cobb angle, d) no earlier treatment, e) patients before first menses or not more than one year from first menses.

Results

It has been found that 183 girls out of 2705 were ≥10 years old and in the range 25–40° Cobb angle. One hundred two out of 2705 patients revealed eligible for brace effectiveness study according to SRS 2005 criteria. 120 out of 2705 patients revealed eligible for brace brace effectiveness study according to SRS-SOSORT 2014 criteria.

Conclusion

The excluded patients revealed too old or with too significant Cobb angles. This indicates the changing criteria for scoliosis brace treatment over the time. Direct comparison of current results of brace treatment with historical series of cases turns out to be very difficult.