Bounding wide composite vector resonances at the LHC

In composite Higgs models (CHMs), electroweak precision data generically push colourless composite vector resonances to a regime where they dominantly decay into pairs of light top partners. This greatly attenuates their traces in canonical collider searches, tailored for narrow resonances promptly decaying into Standard Model final states. By reinterpreting the CMS same-sign dilepton (SS2$\ell$) analysis at the Large Hadron Collider (LHC), originally designed to search for top partners with electric charge $5/3$, we demonstrate its significant coverage over this kinematical regime. We also show the reach of the 13 TeV run of the LHC, with various integrated luminosity options, for a possible upgrade of the SS2$\ell$ search. The top sector of CHMs is found to be more fine-tuned in the presence of colourless composite resonances in the few TeV range.Comment: 9 pages, 5 figures. Minor corrections for publication in JHE

Comparison of contact patterns relevant for transmission of respiratory pathogens in Thailand and the Netherlands using respondent-driven sampling

Understanding infection dynamics of respiratory diseases requires the identification and quantification of behavioural, social and environmental factors that permit the transmission of these infections between humans. Little empirical information is available about contact patterns within real-world social networks, let alone on differences in these contact networks between populations that differ considerably on a socio-cultural level. Here we compared contact network data that were collected in the Netherlands and Thailand using a similar online respondent-driven method. By asking participants to recruit contact persons we studied network links relevant for the transmission of respiratory infections. We studied correlations between recruiter and recruited contacts to investigate mixing patterns in the observed social network components. In both countries, mixing patterns were assortative by demographic variables and random by total numbers of contacts. However, in Thailand participants reported overall more contacts which resulted in higher effective contact rates. Our findings provide new insights on numbers of contacts and mixing patterns in two different populations. These data could be used to improve parameterisation of mathematical models used to design control strategies. Although the spread of infections through populations depends on more factors, found similarities suggest that spread may be similar in the Netherlands and Thailand

The Conserved Tarp Actin Binding Domain Is Important for Chlamydial Invasion

The translocated actin recruiting phosphoprotein (Tarp) is conserved among all pathogenic chlamydial species. Previous reports identified single C. trachomatis Tarp actin binding and proline rich domains required for Tarp mediated actin nucleation. A peptide antiserum specific for the Tarp actin binding domain was generated and inhibited actin polymerization in vitro and C. trachomatis entry in vivo, indicating an essential role for Tarp in chlamydial pathogenesis. Sequence analysis of Tarp orthologs from additional chlamydial species and C. trachomatis serovars indicated multiple putative actin binding sites. In order to determine whether the identified actin binding domains are functionally conserved, GST-Tarp fusions from multiple chlamydial species were examined for their ability to bind and nucleate actin. Chlamydial Tarps harbored variable numbers of actin binding sites and promoted actin nucleation as determined by in vitro polymerization assays. Our findings indicate that Tarp mediated actin binding and nucleation is a conserved feature among diverse chlamydial species and this function plays a critical role in bacterial invasion of host cells

PheMaDB: A solution for storage, retrieval, and analysis of high throughput phenotype data

<p>Abstract</p> <p>Background</p> <p>OmniLog™ phenotype microarrays (PMs) have the capability to measure and compare the growth responses of biological samples upon exposure to hundreds of growth conditions such as different metabolites and antibiotics over a time course of hours to days. In order to manage the large amount of data produced from the OmniLog™ instrument, PheMaDB (Phenotype Microarray DataBase), a web-based relational database, was designed. PheMaDB enables efficient storage, retrieval and rapid analysis of the OmniLog™ PM data.</p> <p>Description</p> <p>PheMaDB allows the user to quickly identify records of interest for data analysis by filtering with a hierarchical ordering of Project, Strain, Phenotype, Replicate, and Temperature. PheMaDB then provides various statistical analysis options to identify specific growth pattern characteristics of the experimental strains, such as: outlier analysis, negative controls analysis (signal/background calibration), bar plots, pearson's correlation matrix, growth curve profile search, <it>k</it>-means clustering, and a heat map plot. This web-based database management system allows for both easy data sharing among multiple users and robust tools to phenotype organisms of interest.</p> <p>Conclusions</p> <p>PheMaDB is an open source system standardized for OmniLog™ PM data. PheMaDB could facilitate the banking and sharing of phenotype data. The source code is available for download at <url>http://phemadb.sourceforge.net</url>.</p

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Genotyping of Bacillus cereus Strains by Microarray-Based Resequencing

The ability to distinguish microbial pathogens from closely related but nonpathogenic strains is key to understanding the population biology of these organisms. In this regard, Bacillus anthracis, the bacterium that causes inhalational anthrax, is of interest because it is closely related and often difficult to distinguish from other members of the B. cereus group that can cause diverse diseases. We employed custom-designed resequencing arrays (RAs) based on the genome sequence of Bacillus anthracis to generate 422 kb of genomic sequence from a panel of 41 Bacillus cereus sensu lato strains. Here we show that RAs represent a “one reaction” genotyping technology with the ability to discriminate between highly similar B. anthracis isolates and more divergent strains of the B. cereus s.l. Clade 1. Our data show that RAs can be an efficient genotyping technology for pre-screening the genetic diversity of large strain collections to selected the best candidates for whole genome sequencing

cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

Mapping structural diversity in networks sharing a given degree distribution and global clustering: Adaptive resolution grid search evolution with Diophantine equation-based mutations

Methods that generate networks sharing a given degree distribution and global clustering can induce changes in structural properties other than that controlled for. Diversity in structural properties, in turn, can affect the outcomes of dynamical processes operating on those networks. Since exhaustive sampling is not possible, we propose a novel evolutionary framework for mapping this structural diversity. The three main features of this framework are: (a) subgraph-based encoding of networks, (b) exact mutations based on solving systems of Diophantine equations, and (c) heuristic diversity-driven mechanism to drive resolution changes in the MapElite algorithm.We show that our framework can elicit networks with diversity in their higher-order structure and that this diversity affects the behaviour of the complex contagion model. Through a comparison with state of the art clustered network generation methods, we demonstrate that our approach can uncover a comparably diverse range of networks without needing computationally unfeasible mixing times. Further, we suggest that the subgraph-based encoding provides greater confidence in the diversity of higher-order network structure for low numbers of samples and is the basis for explaining our results with complex contagion model. We believe that this framework could be applied to other complex landscapes that cannot be practically mapped via exhaustive sampling

Comparison of three methods for ascertainment of contact information relevant to respiratory pathogen transmission in encounter networks

<p>Abstract</p> <p>Background</p> <p>Mathematical models of infection that consider targeted interventions are exquisitely dependent on the assumed mixing patterns of the population. We report on a pilot study designed to assess three different methods (one retrospective, two prospective) for obtaining contact data relevant to the determination of these mixing patterns.</p> <p>Methods</p> <p>65 adults were asked to record their social encounters in each location visited during 6 study days using a novel method whereby a change in physical location of the study participant triggered data entry. Using a cross-over design, all participants recorded encounters on 3 days in a paper diary and 3 days using an electronic recording device (PDA). Participants were randomised to first prospective recording method.</p> <p>Results</p> <p>Both methods captured more contacts than a pre-study questionnaire, but ascertainment using the paper diary was superior to the PDA (mean difference: 4.52 (95% CI 0.28, 8.77). Paper diaries were found more acceptable to the participants compared with the PDA. Statistical analysis confirms that our results are broadly consistent with those reported from large-scale European based surveys. An association between household size (trend 0.14, 95% CI (0.06, 0.22), <it>P </it>< 0.001) and composition (presence of child 0.37, 95% CI (0.17, 0.56), <it>P </it>< 0.001) and the total number of reported contacts was observed, highlighting the importance of sampling study populations based on household characteristics as well as age. New contacts were still being recorded on the third study day, but compliance had declined, indicating that the optimal number of sample days represents a trade-off between completeness and quality of data for an individual.</p> <p>Conclusions</p> <p>The study's location-based reporting design allows greater scope compared to other methods for examining differences in the characteristics of encounters over a range of environments. Improved parameterisation of dynamic transmission models gained from work of this type will aid in the development of more robust decision support tools to assist health policy makers and planners.</p