Representation of Coarse-grained Potentials for Polymer Simulations

In order to be able to simulate long time and large space scale properties of polymer melts one has to resort to coarse grained models, for example by subdividing all polymers into parts and restricting attention to the center of mass positions and velocities of these parts. The dynamics of these variables is governed by Langevin equations in which the free energy obtained by integrating the remaining variables provides the potential of the conservative forces. In general this leads to many particle interactions on the coarse-grained level. Methods suggested in the literature to represent these many particle interactions by effective two body interactions are reviewed and a new method, based on the Gibbs-Bogoliubov inequality, is proposed. The reason why none of these methods is able to reproduce the pressure of the underlying atomistic model is discussed.     

Vitreous TIMP-1 levels associate with neovascularization and TGF-β2 levels but not with fibrosis in the clinical course of proliferative diabetic retinopathy

In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and CCN2 (connective tissue growth factor; CTGF) cause blindness by neovascularization and subsequent fibrosis. This angio-fibrotic switch is associated with a shift in the balance between vitreous levels of CCN2 and VEGF in the eye. Here, we investigated the possible involvement of other important mediators of fibrosis, tissue inhibitor of metalloproteinases (TIMP)-1 and transforming growth factor (TGF)-β2, and of the matrix metalloproteinases (MMP)-2 and MMP-9, in the natural course of PDR. TIMP-1, activated TGF-β2, CCN2 and VEGF levels were measured by ELISA in 78 vitreous samples of patients with PDR (n = 28), diabetic patients without PDR (n = 24), and patients with the diabetes-unrelated retinal conditions macular hole (n = 10) or macular pucker (n = 16), and were related to MMP-2 and MMP-9 activity on zymograms and to clinical data, including degree of intra-ocular neovascularization and fibrosis. TIMP-1, CCN2 and VEGF levels, but not activated TGF-β2 levels, were significantly increased in the vitreous of diabetic patients, with the highest levels in PDR patients. CCN2 and the CCN2/VEGF ratio were the strongest predictors of degree of fibrosis. In diabetic patients with or without PDR, activated TGF-β2 levels correlated with TIMP-1 levels, whereas in PDR patients, TIMP-1 levels, MMP-2 and proMMP-9 were associated with degree of neovascularization, like VEGF levels, but not with fibrosis. We confirm here our previous findings that retinal fibrosis in PDR patients is significantly correlated with vitreous CCN2 levels and the CCN2/VEGF ratio. In contrast, TIMP-1, MMP-2 and MMP-9 appear to have a role in the angiogenic phase rather than in the fibrotic phase of PDR.     

Superiority of Trans-Oral over Trans-Nasal Sampling in Detecting Streptococcus pneumoniae Colonization in Adults

The human nasopharynx is the main reservoir for Streptococcus pneumoniae. We applied conventional and molecular methods to determine the prevalence of S. pneumoniae nasopharyngeal colonization in adults. Paired trans-orally and trans-nasally obtained nasopharyngeal samples from 268 parents of 24-month-old children were assessed for pneumococcal presence. Parents were classified as colonized when live pneumococci were recovered from either sample cultured on medium selective for S. pneumoniae. Of the 52 (19%) colonized parents 49 (18%) were culture-positive in trans-nasal and 10 (4%) in trans-oral samples. Bacterial growth was harvested from these cultures, DNA isolated and tested by quantitative-PCR (qPCR) targeting lytA and piaA genes specific for S. pneumoniae. A sample was considered positive if signals for both genes were detected. Altogether 105 (39%) individuals were classified as positive for pneumococcus by qPCR including 50 (19%) in trans-nasal and 94 (35%) in trans-oral settings. Although significantly more trans-nasal compared to trans-oral samples were culture-positive for S. pneumoniae at the primary diagnostic step (p<0.001) the opposite was observed in qPCR results (p<0.001). To confirm the presence of live pneumococcus in samples positive by qPCR but negative at the initial diagnostic step, we serially-diluted cell harvests, re-cultured and carefully examined for S. pneumoniae presence. Live pneumococci were recovered from an additional 43 parents including 42 positive in trans-oral and 4 in trans-nasal samples increasing the number of individuals culture- and qPCR-positive to 93 (35%) and positive by either of two methods to 107 (40%). There were significantly more trans-oral than trans-nasal samples positive for pneumococcus by both culture and qPCR (n = 71; 27%; vs. n = 50; 19%; p<0.05). Our data suggest that pneumococcal colonization is more common in adults than previously estimated and point towards the superiority of a trans-oral over a trans-nasal approach when testing adults for colonization with S. pneumoniae.     

Identification of a Huperzine A-producing endophytic fungus from Phlegmariurus taxifolius

Molecular Biology Reports - Highly prized huperzine A (Hup A), a natural alkaloid formerly isolated from the Chinese medicinal plant Huperzia serrata, has been widely used for the treatment of...     

Urogenital Chlamydia trachomatis Infections among Ethnic Groups in Paramaribo,Suriname; Determinants and Ethnic Sexual Mixing Patterns

Background

Little is known about the epidemiology of urogenital Chlamydia trachomatis infection (chlamydia) in Suriname. Suriname is a society composed of many ethnic groups, such as Creoles, Maroons, Hindustani, Javanese, Chinese, Caucasians, and indigenous Amerindians. We estimated determinants for chlamydia, including the role of ethnicity, and identified transmission patterns and ethnic sexual networks among clients of two clinics in Paramaribo, Suriname.

Methods

Participants were recruited at two sites a sexually transmitted infections (STI) clinic and a family planning (FP) clinic in Paramaribo. Urine samples from men and nurse-collected vaginal swabs were obtained for nucleic acid amplification testing. Logistic regression analysis was used to identify determinants of chlamydia. Multilocus sequence typing (MLST) was performed to genotype C. trachomatis. To identify transmission patterns and sexual networks, a minimum spanning tree was created, using full MLST profiles. Clusters in the minimum spanning tree were compared for ethnic composition.

Results

Between March 2008 and July 2010, 415 men and 274 women were included at the STI clinic and 819 women at the FP clinic. Overall chlamydia prevalence was 15% (224/1508). Age, ethnicity, and recruitment site were significantly associated with chlamydia in multivariable analysis. Participants of Creole and Javanese ethnicity were more frequently infected with urogenital chlamydia. Although sexual mixing with other ethnic groups did differ significantly per ethnicity, this mixing was not independently significantly associated with chlamydia. We typed 170 C. trachomatis-positive samples (76%) and identified three large C. trachomatis clusters. Although the proportion from various ethnic groups differed significantly between the clusters (P = 0.003), all five major ethnic groups were represented in all three clusters.

Conclusion

Chlamydia prevalence in Suriname is high and targeted prevention measures are required. Although ethnic sexual mixing differed between ethnic groups, differences in prevalence between ethnic groups could not be explained by sexual mixing.     

COMPASS II: extended coverage for polymer and drug-like molecule databases

The COMPASS II force field has been developed by extending the coverage of the COMPASS force field (J Phys Chem B 102(38):7338–7364, 1998) to polymer and drug-like molecules found in popular databases. Using a fragmentation method to systematically construct small molecules that exhibit key functional groups found in these databases, parameters applicable to database compounds were efficiently obtained. Based on the same parameterization paradigm as used in the development of the COMPASS force field, new parameters were derived by a combination of fits to quantum mechanical data for valence parameters and experimental liquid and crystal data for nonbond parameters. To preserve the quality of the original COMPASS parameters, a quality assurance suite was used and updated to ensure that additional atom-types and parameters do not interfere with the existing ones. Validation against molecular properties, liquid and crystal densities, and enthalpies, demonstrates that the quality of COMPASS is preserved and the same quality of prediction is achieved for the additional coverage.     

Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients

Bacterial pneumonia is a major cause of morbidity and mortality in elderly. We hypothesize that dysbiosis between regular residents of the upper respiratory tract (URT) microbiome, that is balance between commensals and potential pathogens, is involved in pathogen overgrowth and consequently disease. We compared oropharyngeal microbiota of elderly pneumonia patients (n=100) with healthy elderly (n=91) by 16S-rRNA-based sequencing and verified our findings in young adult pneumonia patients (n=27) and young healthy adults (n=187). Microbiota profiles differed significantly between elderly pneumonia patients and healthy elderly (PERMANOVA, P<0.0005). Highly similar differences were observed between microbiota profiles of young adult pneumonia patients and their healthy controls. Clustering resulted in 11 (sub)clusters including 95% (386/405) of samples. We observed three microbiota profiles strongly associated with pneumonia (P<0.05) and either dominated by lactobacilli (n=11), Rothia (n=51) or Streptococcus (pseudo)pneumoniae (n=42). In contrast, three other microbiota clusters (in total n=183) were correlated with health (P<0.05) and were all characterized by more diverse profiles containing higher abundances of especially Prevotella melaninogenica, Veillonella and Leptotrichia. For the remaining clusters (n=99), the association with health or disease was less clear. A decision tree model based on the relative abundance of five bacterial community members in URT microbiota showed high specificity of 95% and sensitivity of 84% (89% and 73%, respectively, after cross-validation) for differentiating pneumonia patients from healthy individuals. These results suggest that pneumonia in elderly and young adults is associated with dysbiosis of the URT microbiome with bacterial overgrowth of single species and absence of distinct anaerobic bacteria. Whether the observed microbiome changes are a cause or a consequence of the development of pneumonia or merely coincide with disease status remains a question for future research.     

Molecular insights into cell toxicity of a novel familial amyloidogenic variant of β2‐microglobulin

The first genetic variant of β₂‐microglobulin (b2M) associated with a familial form of systemic amyloidosis has been recently described. The mutated protein, carrying a substitution of Asp at position 76 with an Asn (D76N b2M), exhibits a strongly enhanced amyloidogenic tendency to aggregate with respect to the wild‐type protein. In this study, we characterized the D76N b2M aggregation path and performed an unprecedented analysis of the biochemical mechanisms underlying aggregate cytotoxicity. We showed that, contrarily to what expected from other amyloid studies, early aggregates of the mutant are not the most toxic species, despite their higher surface hydrophobicity. By modulating ganglioside GM1 content in cell membrane or synthetic lipid bilayers, we confirmed the pivotal role of this lipid as aggregate recruiter favouring their cytotoxicity. We finally observed that the aggregates bind to the cell membrane inducing an alteration of its elasticity (with possible functional unbalance and cytotoxicity) in GM1‐enriched domains only, thus establishing a link between aggregate‐membrane contact and cell damage.     

Competition and predation in simple food webs: intermediately strong trade-offs maximize coexistence

Competition and predation are fundamental interactions structuring food webs. However, rather than always following these neat theoretical categories, mixed interactions are ubiquitous in nature. Of particular importance are omnivorous species, such as intra-guild predators that can both compete with and predate on their prey. Here, we examine trade-offs between competitive and predatory capacities by analysing the entire continuum of food web configurations existing between purely predator-prey and purely competitive interactions of two consumers subsisting on a single resource. Our results show that the range of conditions allowing for coexistence of the consumers is maximized at intermediately strong trade-offs. Even though coexistence under weak trade-offs and under very strong trade-offs is also possible, it occurs under much more restrictive conditions. We explain these findings by an intricate interplay between energy acquisition and interaction strength.