Crossing the Line: Selection and Evolution of Virulence Traits

The evolution of pathogens presents a paradox. Pathogenic species are often absolutely dependent on their host species for their propagation through evolutionary time, yet the pathogenic lifestyle requires that the host be damaged during this dependence. It is clear that pathogenic strategies are successful in evolutionary terms because a diverse array of pathogens exists in nature. Pathogens also evolve using a broad range of molecular mechanisms to acquire and modulate existing virulence traits in order to achieve this success. Detailing the benefit of enhanced selection derived through virulence and understanding the mechanisms through which virulence evolves are important to understanding the natural world and both have implications for human health

An integrative model of lateral epicondylalgia

Tennis elbow or lateral epicondylalgia is a diagnosis familiar to many within the general community and presents with an uncomplicated clinical picture in most cases. However, the underlying pathophysiology presents a more complex state and its management has not been conclusively determined. Research on this topic extends across anatomical, biomechanical and clinical literature; however, integration of findings is lacking. We propose that the current understanding of the underlying pathophysiology of lateral epicondylalgia can be conceptualised as encompassing three interrelated components: (i) the local tendon pathology, (ii) changes in the pain system, and (iii) motor system impairments. This paper presents a model that integrates these components on the basis of a literature review with the express aim of assisting in the targeting of specific treatments or combinations thereof to individual patients

Psychological factors not strength deficits are associated with severity of gluteal tendinopathy: a cross-sectional study

Gluteal tendinopathy is the most common lower limb tendinopathy presenting to general practice. It has a high prevalence amongst middle-aged women and impacts on daily activities, work participation and quality of life. The aim was to compare physical and psychological characteristics between subgroups of severity of pain and disability.A multicentre cross-sectional cohort of 204 participants (mean age 55\ua0years, 82% female) who had a clinical diagnosis of gluteal tendinopathy with magnetic resonance imaging confirmation were assessed. A range of physical and psychosocial characteristics were recorded. Pain and disability were measured with the VISA-G questionnaire. A cluster analysis was used to identify mild, moderate and severe subgroups based on total VISA-G scores. Between-group differences were then evaluated with a MANCOVA, including sex and study site as covariates, followed by a Bonferroni post hoc test. Significance was set at 0.05.There were significantly higher pain catastrophizing and depression scores in the more severe subgroups. Lower pain self-efficacy scores were found in the severe group compared to the moderate and mild groups. Greater waist girth and body mass index (BMI), lower activity levels and poorer quality of life were reported in the severe group compared to the mild group. Hip abductor muscle strength and hip circumference did not differ between subgroups of severity.Individuals with severe gluteal tendinopathy present with psychological distress, poorer quality of life, greater BMI and waist girth. Given these features, the consideration of psychological factors in more severe patients may be important to optimize patient outcomes and reduce healthcare utilization.Patients with severe gluteal tendinopathy exhibit greater psychological distress, poorer quality of life and greater waist girth and BMI when compared to less severe cases. This implies that clinicians ought to consider psychological factors in the management of more severe gluteal tendinopathy

Detection of HER2 amplification in circulating free DNA in patients with breast cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is amplified and overexpressed in 20-25% of breast cancers. This study investigated circulating free DNA (cfDNA) for detection of HER2 gene amplification in patients with breast cancer. METHODS: Circulating free DNA was extracted from plasma of unselected patients with primary breast cancer (22 before surgery and 68 following treatment), 30 metastatic patients and 98 female controls using the QIAamp Blood DNA Mini Kit (Qiagen). The ratio of HER2 to an unamplified reference gene (contactin-associated protein 1 (CNTNAP1)) was measured in cfDNA samples by quantitative PCR (qPCR) using SK-BR-3 cell line DNA as a positive control. RESULTS: We validated the qPCR assay with DNA extracted from 23 HER2 3+ and 40 HER2-negative tumour tissue samples; the results agreed for 60 of 63 (95.2%) tumours. Amplification was detected in cfDNA for 8 of 68 patients following primary breast cancer treatment and 5 of 30 metastatic patients, but was undetected in 22 patients with primary breast cancer and 98 healthy female controls. Of the patients with amplification in cfDNA, 10 had HER2 3+ tumour status by immunohistochemistry. CONCLUSIONS: The results demonstrate for the first time the existence of amplified HER2 in cfDNA in the follow-up of breast cancer patients who are otherwise disease free. This approach could potentially provide a marker in patients with HER2-positive breast cancer

Salmonella Pathogenicity Island 2 Is Expressed Prior to Penetrating the Intestine

Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that causes disease in mice that resembles human typhoid. Typhoid pathogenesis consists of distinct phases in the intestine and a subsequent systemic phase in which bacteria replicate in macrophages of the liver and spleen. The type III secretion system encoded by Salmonella pathogenicity island 2 (SPI-2) is a major virulence factor contributing to the systemic phase of typhoid pathogenesis. Understanding how pathogens regulate virulence mechanisms in response to the environment, including different host tissues, is key to our understanding of pathogenesis. A recombinase-based in vivo expression technology system was developed to assess SPI-2 expression during murine typhoid. SPI-2 expression was detectable at very early times in bacteria that were resident in the lumen of the ileum and was independent of active bacterial invasion of the epithelium. We also provide direct evidence for the regulation of SPI-2 by the Salmonella transcription factors ompR and ssrB in vivo. Together these results demonstrate that SPI-2 expression precedes penetration of the intestinal epithelium. This induction of expression precedes any documented SPI-2-dependent phases of typhoid and may be involved in preparing Salmonella to successfully resist the antimicrobial environment encountered within macrophages

Democratization in a passive dendritic tree : an analytical investigation

One way to achieve amplification of distal synaptic inputs on a dendritic tree is to scale the amplitude and/or duration of the synaptic conductance with its distance from the soma. This is an example of what is often referred to as “dendritic democracy”. Although well studied experimentally, to date this phenomenon has not been thoroughly explored from a mathematical perspective. In this paper we adopt a passive model of a dendritic tree with distributed excitatory synaptic conductances and analyze a number of key measures of democracy. In particular, via moment methods we derive laws for the transport, from synapse to soma, of strength, characteristic time, and dispersion. These laws lead immediately to synaptic scalings that overcome attenuation with distance. We follow this with a Neumann approximation of Green’s representation that readily produces the synaptic scaling that democratizes the peak somatic voltage response. Results are obtained for both idealized geometries and for the more realistic geometry of a rat CA1 pyramidal cell. For each measure of democratization we produce and contrast the synaptic scaling associated with treating the synapse as either a conductance change or a current injection. We find that our respective scalings agree up to a critical distance from the soma and we reveal how this critical distance decreases with decreasing branch radius

A geometric network model of intrinsic grey-matter connectivity of the human brain

Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuro- science is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections

Serial dilution curve: a new method for analysis of reverse phase protein array data

Reverse phase protein arrays (RPPAs) are a powerful high-throughput tool for measuring protein concentrations in a large number of samples. In RPPA technology, the original samples are often diluted successively multiple times, forming dilution series to extend the dynamic range of the measurements and to increase confidence in quantitation. An RPPA experiment is equivalent to running multiple ELISA assays concurrently except that there is usually no known protein concentration from which one can construct a standard response curve. Here, we describe a new method called ‘serial dilution curve for RPPA data analysis’. Compared with the existing methods, the new method has the advantage of using fewer parameters and offering a simple way of visualizing the raw data. We showed how the method can be used to examine data quality and to obtain robust quantification of protein concentrations

Comparison of corticosteroid, autologous blood or sclerosant injections for chronic tennis elbow

Objectives To compare three different ultrasound-guided injections for chronic tennis elbow. Design Assessor-blinded, randomized controlled comparative trial. Methods 44 patients with clinically diagnosed tennis elbow, confirmed by Doppler ultrasound, received under ultrasound guidance, a single corticosteroid injection (n\ua0=\ua014), or two injections (separated by 4 weeks) of either autologous blood (n\ua0=\ua014) or polidocanol (n\ua0=\ua016). Clinical and ultrasound examination was performed at baseline, 4, 12 and 26 weeks. Results Complete recovery or much improvement was greater for corticosteroid injection than autologous blood and polidocanol at 4 weeks (p\ua

Thermodynamics of quantum Heisenberg spin chains

Thermodynamic properties of the quantum Heisenberg spin chains with S = 1/2, 1, and 3/2 are investigated using the transfer-matrix renormalization-group method. The temperature dependence of the magnetization, susceptibility, specific heat, spin-spin correlation length, and several other physical quantities in a zero or finite applied field are calculated and compared. Our data agree well with the Bethe ansatz, exact diagonalization, and quantum Monte Carlo results and provide further insight into the quantum effects in the antiferromagnetic Heisenberg spin chains.Comment: 9 pages, 10 figure