Non-linear dynamics in muscle fatigue and strength model during maximal self-perceived elbow extensors training

Our aim was to determine the dynamics in muscle strength increase and fatigue development during repetitive maximal contraction in specific maximal self-perceived elbow extensors training program. We will derive our functional model for m. triceps brachii in spirit of traditional Hill’s two-component muscular model and after fitting our data, develop a prediction tool for this specific training system. Thirty-six healthy young men (21±1.0 y, BMI 25.4±7.2 kg/m²), who did not take part in any formal resistance exercise regime, volunteered for this study. The training protocol was performed on the isoacceleration dynamometer, lasted for 12 weeks, with a frequency of five sessions per week. Each training session included five sets of 10 maximal contractions (elbow extensions) with a 1 min resting period between each set. The non-linear dynamic system model was used for fitting our data in conjunction with the Levenberg–Marquardt regression algorithm. As a proper dynamical system, our functional model of m. triceps brachii can be used for prediction and control. The model can be used for the predictions of muscular fatigue in a single series, the cumulative daily muscular fatigue and the muscular growth throughout the training process. In conclusion, the application of non-linear dynamics in this particular training model allows us to mathematically explain some functional changes in the skeletal muscle as a result of its adaptation to programmed physical activity—training.     

Adaptations of microbial communities and dissolved organics to seasonal pressures in a mesotrophic coastal Mediterranean lake

In lake ecosystems, changes in eukaryotic and prokaryotic microbes and the concentration and availability of dissolved organic matter (DOM) produced within or supplied to the system by allochthonous sources are components that characterize complex processes in the microbial loop. We address seasonal changes of microbial communities and DOM in the largest Croatian lake, Vrana. This shallow lake is connected to the Adriatic Sea and is impacted by agricultural activity. Microbial community and DOM structure were driven by several environmental stressors, including drought, seawater intrusion and heavy precipitation events. Bacterial composition of different lifestyles (free-living and particle-associated) differed and only a part of the particle-associated bacteria correlated with microbial eukaryotes. Oscillations of cyanobacterial relative abundance along with chlorophyll a revealed a high primary production season characterized by increased levels of autochthonous DOM that promoted bacterial processes of organic matter degradation. From our results, we infer that in coastal freshwater lakes dependent on precipitation-evaporation balance, prolonged dry season coupled with heavy irrigation impact microbial communities at different trophic levels even if salinity increases only slightly and allochthonous DOM inputs decrease. These pressures, if applied more frequently or at higher concentrations, could have the potential to overturn the trophic state of the lake.     

Molecular phylogeny of the Paleogene fungus gnat tribe Exechiini (Diptera: Mycetophilidae) revisited: Monophyly of genera established and rapid radiation confirmed

The phylogeny of the fungus gnat tribe Exechiini (Diptera: Mycetophilidae) is reconstructed based on the combined analysis of five nuclear (18S, two parts of 28S, CAD, EF1α) and two mitochondrial (12S, COI) gene markers. According to known fossil record, and recent higher‐level phylogenies, the tribe constitutes the most apomorphic, distinctly monophyletic clade of the family Mycetophilidae. The tribe originated in the Paleogene and apparently quickly diversified in the Neogene with an unusual rapid radiation of complex male terminalia. Earlier attempts to reconstruct the phylogeny of the tribe, based on both morphology and molecular methods, have not yielded reliable hypotheses, neither in terms of resolution nor in terms of support for major clades. Increased taxon sampling and wider gene sampling have been suggested to achieve better phylogenetic resolution. Aiming at this, we present new phylogenies, for the first time with all known genera and subgenera of Exechiini represented. While many terminal intergeneric relationships are well supported, both in maximum likelihood and in Bayesian analyses, most of the major, deeper clades remain poorly supported. We suggest that a rapid radiation event close to the root may be causing the low resolution at this level in the phylogeny. This contrasts parallel phylogenies of the older subfamilies and tribes of the family Mycetophilidae, where traditional clades have usually been recovered with high support. Further in‐depth studies into the evolutionary history of the tribe are needed to enlighten and coalesce the specific phenomena driving their unique morphological, genetic and phylogeographic histories.     

VIPER: an advanced software package to support high-throughput LC-MS peptide identification

SUMMARY: The accurate mass and time (AMT) tag approach is used for analysis of large scale experiments by combining information generated over multiple datasets and instrument types. The VIPER software package is one of the key components of the data processing pipeline and implements automated algorithms to discover LC-MS features, align and match these LC-MS features to a database of peptides previously identified in LC-MS/MS analyses, and identify and quantify pairs of isotopically labeled peptides. AVAILABILITY: VIPER may be downloaded free of charge at http://ncrr.pnl.gov/software/     

Developing the ethics of implementation research in health

Implementation research (IR) is growing in recognition as an important generator of practical knowledge that can be translated into health policy. With its aim to answer questions about how to improve access to interventions that have been shown to work but have not reached many of the people who could benefit from them, IR involves a range of particular ethical considerations that have not yet been comprehensively covered in international guidelines on health research ethics. The fundamental ethical principles governing clinical research apply equally in IR, but the application of these principles may differ depending on the IR question, context, and the nature of the proposed intervention. IR questions cover a broad range of topics that focus on improving health system functioning and improving equitable and just access to effective health care interventions. As such, IR designs are flexible and often innovative, and ethical principles cannot simply be extrapolated from their applications in clinical research. Meaningful engagement with all stakeholders including communities and research participants is a fundamental ethical requirement that cuts across all study phases of IR and links most ethical concerns. Careful modification of the informed consent process may be required in IR to permit study of a needed intervention. The risks associated with IR may be difficult to anticipate and may be very context-specific. The benefits of IR may not accrue to the same groups who participate in the research, therefore justifying the risks versus benefits of IR may be ethically challenging. The expectation that knowledge generated through IR should be rapidly translated into health policy and practice necessitates up-front commitments from decision-makers to sustainability and scalability of effective interventions. Greater awareness of the particular ethical implications of the features of IR is urgently needed to facilitate optimal ethical conduct of IR and uniform ethical review.     

A novel function for Cyclin A2: control of cell invasion via RhoA signaling

Cyclin A2 plays a key role in cell cycle regulation. It is essential in embryonic cells and in the hematopoietic lineage yet dispensable in fibroblasts. In this paper, we demonstrate that Cyclin A2-depleted cells display a cortical distribution of actin filaments and increased migration. These defects are rescued by restoration of wild-type Cyclin A2, which directly interacts with RhoA, or by a Cyclin A2 mutant unable to associate with Cdk. In vitro, Cyclin A2 potentiates the exchange activity of a RhoA-specific guanine nucleotide exchange factor. Consistent with this, Cyclin A2 depletion enhances migration of fibroblasts and invasiveness of transformed cells via down-regulation of RhoA activity. Moreover, Cyclin A2 expression is lower in metastases relative to primary colon adenocarcinoma in matched human tumors. All together, these data show that Cyclin A2 negatively controls cell motility by promoting RhoA activation, thus demonstrating a novel Cyclin A2 function in cytoskeletal rearrangements and cell migration.     

Synthesis and biological activity of new series of N-modified analogues of the N/OFQ(1–13)NH2 with aminophosphonate moiety

New series of N-modified analogues of the N/OFQ(1-13)NH(2) with aminophosphonate moiety have been synthesized and investigated for biological activity. These peptides were prepared by solid-phase peptide synthesis-Fmoc-strategy. The N/OFQ(1-13)NH(2) analogues were tested for agonistic activity in vitro on electrically stimulated rat vas deferens smooth-muscle preparations isolated from Wistar albino rats. Our study has shown that the selectivity of the peptides containing 1-[(methoxyphosphono)methylamino]cycloalkanecarboxylic acids to the N-side of Phe is not changed-they remain selective agonists of NOP receptors. The derivative with the largest ring (NOC-6) demonstrated efficacy similar to that of N/OFQ(1-13)NH(2), but in a 10-fold higher concentration. The agonistic activity of newly synthesized N-modified analogues of N/OFQ(1-13)NH(2) with aminophosphonate moiety was investigated for the first time.     

A Spanish founder mutation in the chloride channel gene, CLCNKB, as a cause of atypical Bartter syndrome in adult age

BACKGROUND: Mutations in the chloride channel gene, CLCNKB, usually cause classic Bartter syndrome (cBS) or a mixed Bartter-Gitelman phenotype in the first years of life. METHODS: We report an adult woman with atypical BS caused by a homozygous missense mutation, A204T, in the CLCNKB gene, which has previously been described as the apparently unique cause of cBS in Spain. RESULTS: The evaluation of this patient revealed an overlap of phenotypic features ranging from severe biochemical and systemic disturbances typical of cBS to scarce symptoms and diagnosis in the adult age typical of Gitelman syndrome. The tubular disease caused a dramatic effect on mental, growth and puberal development leading to low IQ, final short stature and abnormal ovarian function. Furthermore, low serum PTH concentrations with concomitant nephrocalcinosis and normocalcaemia were observed. Both ovarian function and serum PTH levels were normalized after treatment with cyclooxygenase inhibitors. CONCLUSIONS: The present report confirms a weak genotype-phenotype correlation in patients with CLCNKB mutations and supports the founder effect of the A204T mutation in Spain. In our country, the genetic diagnosis of adult patients with hereditary hypokalaemic tubulopathies should include a screening of A204T mutation in the CLCNKB gene.     

Distribution of hepatitis C virus genotypes in Croatia--a 10 year retrospective study of four geographic regions

The aim of this 10-year retrospective study was to investigate the distribution of HCV genotypes in patients with chronic hepatitis C monitored in the largest center for molecular diagnostics of HCV infection in Croatia. The study enrolled 1163 anti-HCV positive adults with detectable HCV RNA in the plasma. The patients were classified in four regions: Zagreb and surrounding continental area, Split, Slavonija and Rijeka. HCV genotyping was performed by using VERSANT HCV Genotyping Assay (LIPA) (Bayer Diagnostics, Puteaux Cedex, France). Statistical analysis was performed by using Statistica for Windows V.5.1. The majority of HCV infections in the study population were caused by genotypes 1 (58.8% of infected patients) and 3 (35.6%). Percentages of patients infected with subtypes 1b and 1a were 37.4% and 13.1%, respectively. Genotypes 2 and 4 were present in a very low percentage of patients (2.2% and 3.4%, respectively) while genotypes 5 and 6 were not detected. Analysis of regional differences in the distribution of HCV genotypes revealed similar percentages of subtype 3a and 1b infections in the Split region while the majority of infections in other regions were caused by subtype 1b. Infections with genotypes 2 and 4 were present in less than 5% of patients in all geographic regions. Analysis of an association between risk factors for infection and distribution of genotypes and subtypes in a subset of patients from the Split region confirmed the association between IVDU and subtype 3a. We conclude that the prevalence of HCV genotypes and subtypes follows the pattern of other Southern and Eastern European Countries with the predominance of subtypes 1b, 3a and 1a.