Extremely low frequency magnetic field induces hyperalgesia in mice modulated by nitric oxide synthesis

We investigated an effect of extremely low frequency magnetic field (ELF-MF, 60 Hz) on hyperalgesia using hot plate test. The level of nitric oxide (NO) and the expression of nitric oxide synthase (NOS) were measured to determine if ELF-MF is engaged in NO mediated pain mechanism. Additionally, the involvement of Ca2+-dependent NO pathway in ELF-MF induced hyperalgesia was evaluated by blocking Ca2+ sources with NMDA receptor antagonist and Ca2+ channel blocker. The exposure of mice to ELF-MF lowered pain threshold and elevated NO synthesis in brain and spinal cord. An NOS inhibitor blocked these effects of ELF-MF with attenuating the reduction of pain threshold and the rise of NO level in brain and spine by the exposure of ELF-MF. The hyperalgesic effects of ELF-MF were also blocked by a Ca2+ channel blocker, nimodipine, but not by a NMDA receptor antagonist, MK-801. The expression of Ca2+ -dependent nNOS and eNOS and Ca2+ -independent iNOS were not changed by ELF-MF. These results indicated that the exposure of ELF-MF might cause Ca2+ -dependent NOS activation, which then induces hyperalgesia with the increase in NO synthesis. In conclusion, ELF-MF may produce hyperalgesia by modulating NO synthesis via Ca2+ -dependent NOS.     

Overexpression of Cold Shock Protein A of <Emphasis Type="Italic">Psychromonas arctica</Emphasis> KOPRI 22215 Confers Cold-Resistance

A polar bacterium was isolated from Arctic sea sediments and identified as Psychromonas artica, based on 16S rDNA sequence. Psychromonas artica KOPRI 22215 has an optimal growth temperature of 10 °C and a maximum growth temperature of 25 °C, suggesting this bacterium is a psychrophile. Cold shock proteins (Csps) are induced upon temperature downshift by more than 10 °C. Functional studies have researched mostly Csps of a mesophilic bacterium Escherichia coli, but not on those of psychrophilic bacteria. In an effort to understand the molecular mechanisms of psychrophilic bacteria that allow it withstand freezing environments, we cloned a gene encoding a cold shock protein from P. artica KOPRI 22215 (CspA_Pa) using the conserved sequences in csp genes. The 204 bp-long ORF encoded a protein of 68 amino acids, sharing 56% homology to previously reported E. coli CspA protein. When CspA_Pa was overexpressed in E. coli, it caused cell growth-retardation and morphological elongation. Interestingly, overexpression of CspA_Pa drastically increased the host’s cold-resistance by more than ten times, suggesting the protein aids survival in polar environments.     

Meta-Analysis of Combined Therapy with Angiotensin Receptor Antagonists versus ACE Inhibitors Alone in Patients with Heart Failure

Background

There is insufficient evidence whether the benefit of adding angiotensin II receptor blockers (ARBs) to angiotensin-converting enzyme (ACE) inhibitors outweighs the increased risk of adverse effects in patients with heart failure.

Methodology/Principal Findings

Two independent reviewers searched and abstracted randomized controlled trials of ARBs and ACE inhibitors compared to ACE inhibitor therapy alone in patients with heart failure reporting mortality and hospitalizations having a follow-up of at least 6 months identified by a systematic literature search. Eight trials including a total of 18,061 patients fulfilled our inclusion criteria. There was no difference between patients treated with combination therapy and ACE inhibitor therapy alone for overall mortality, hospitalization for any reason, fatal or nonfatal MI. Combination therapy was, however, associated with fewer hospital admissions for heart failure (RR 0.81, 95%CI 0.72–0.91), although there was significant heterogeneity across trials (p-value for heterogeneity = 0.04; I² = 57% [95%CI 0–83%]). Patients treated with combination therapy had a higher risk of worsening renal function and symptomatic hypotension, and their trial medications were more often permanently discontinued. Lack of individual patient data precluded the analysis of time-to-event data and identification of subgroups which potentially benefit more from combination therapy such as younger patients with preserved renal function and thus at lower risk to experience worsening renal function or hyperkalemia.

Conclusions/Significance

Combination therapy with ARBs and ACE inhibitors reduces admissions for heart failure in patients with congestive heart failure when compared to ACE inhibitor therapy alone, but does not reduce overall mortality or all-cause hospitalization and is associated with more adverse events. Thus, based on current evidence, combination therapy with ARBs and ACE inhibitors may be reserved for patients who remain symptomatic on therapy with ACE inhibitors under strict monitoring for any signs of worsening renal function and/or symptomatic hypotension.     

Predicting bone remodeling around tissue- and bone-level dental implants used in reduced bone width

The objective of this study was to predict time-dependent bone remodeling around tissue- and bone-level dental implants used in patients with reduced bone width. The remodeling of bone around titanium tissue-level, and titanium and titanium–zirconium alloy bone-level implants was studied under 100 N oblique load for one month by implementing the Stanford theory into three-dimensional finite element models. Maximum principal stress, minimum principal stress, and strain energy density in peri-implant bone and displacement in x- and y- axes of the implant were evaluated. Maximum and minimum principal stresses around tissue-level implant were higher than bone-level implants and both bone-level implants experienced comparable stresses. Total strain energy density in bone around titanium implants slightly decreased during the first two weeks of loading followed by a recovery, and the titanium–zirconium implant showed minor changes in the axial plane. Total strain energy density changes in the loading and contralateral sides were higher in tissue-level implant than other implants in the cortical bone at the horizontal plane. The displacement values of the implants were almost constant over time. Tissue-level implants were associated with higher stresses than bone-level implants. The time-dependent biomechanical outcome of titanium–zirconium alloy bone-level implant was comparable to the titanium implant.     

hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex

hSSB1 is a newly discovered single-stranded DNA (ssDNA)-binding protein that is essential for efficient DNA double-strand break signalling through ATM. However, the mechanism by which hSSB1 functions to allow efficient signalling is unknown. Here, we show that hSSB1 is recruited rapidly to sites of double-strand DNA breaks (DSBs) in all interphase cells (G1, S and G2) independently of, CtIP, MDC1 and the MRN complex (Rad50, Mre11, NBS1). However expansion of hSSB1 from the DSB site requires the function of MRN. Strikingly, silencing of hSSB1 prevents foci formation as well as recruitment of MRN to sites of DSBs and leads to a subsequent defect in resection of DSBs as evident by defective RPA and ssDNA generation. Our data suggests that hSSB1 functions upstream of MRN to promote its recruitment at DSBs and is required for efficient resection of DSBs. These findings, together with previous work establish essential roles of hSSB1 in controlling ATM activation and activity, and subsequent DSB resection and homologous recombination (HR).     

<Emphasis Type="Italic">Actimicrobium antarcticum</Emphasis> gen. nov., sp. nov., of the Family <Emphasis Type="Italic">Oxalobacteraceae</Emphasis>, Isolated from Antarctic Coastal Seawater

A Gram-negative, non-motile, catalase- and oxidase- positive, strictly aerobic, and short rod-shaped bacterium that was designated strain KOPRI 25157^T was isolated from coastal seawater sample in Antarctica. The temperature and pH ranges for growth on R2A agar were 10–20°C, and 5.0–10.0, respectively. Phylogenetic analyses of the 16S rRNA gene sequence of strain KOPRI 25157^T showed it to belong to the family Oxalobacteraceae of the class Betaproteobacteria, and it formed a distinct clade from other recognized members of the family. DNA G + C content was 65.9 mol%. Major ubiquinone was Q-8. Predominant cellular fatty acids were C_16:1 ω7c/15 iso 2OH (56.4%) and C_16:1 (30.5%). Major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, and unknown lipid. On the basis of these data, it is proposed that strain KOPRI 25157^T is the representative of a novel genus, for which the name Actimicrobium gen. nov. is proposed in the family Oxalobacteraceae. The type strain for Actimicrobium antarcticum sp. nov. is KOPRI 25157^T (=JCM 16673^T=KCTC 23040^T).     

Polar and Alpine Microbial Collection (PAMC): a culture collection dedicated to polar and alpine microorganisms

Microorganisms in polar areas may have important ecological roles in biogeochemical cycles and the food chain. They are adapted to polar environments by means of special physiological adaptation mechanisms that include cold-adapted enzymes and cryoprotectants such as exopolysaccharides. Culture collections for polar microorganisms can provide research resources for ecological and physiological studies. The Polar and Alpine Microbial Collection (PAMC) is a specialized culture collection for maintenance and distribution of polar and alpine microorganisms. A database system was developed to share important data fields with DarwinCore2 and Ocean Biogeographic Information System database schemas. Approximately 1,500 out of 5,500 strains maintained in PAMC have been identified and belonged primarily to the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. Many of the microbial strains can grow at low temperature and produce proteases, lipases, and/or exopolysaccharides. PAMC provides search tools based on keywords such as taxonomy, geographical origin, habitat, and physiological characteristics. Biological materials and information provided by PAMC will be important resources for ecological and physiological studies on polar and alpine microorganisms.