Borrelia burgdorferi protein interactions critical for microbial persistence in mammals

Borrelia burgdorferi is the causative agent of Lyme disease that persists in a complex enzootic life cycle, involving Ixodes ticks and vertebrate hosts. The microbe invades ticks and vertebrate hosts in spite of active immune surveillance and potent microbicidal responses, and establishes long‐term infection utilising mechanisms that are yet to be unravelled. The pathogen can cause multi‐system disorders when transmitted to susceptible mammalian hosts, including in humans. In the past decades, several studies identified a limited number of B. burgdorferi gene‐products critical for pathogen persistence, transmission between the vectors and the host, and host–pathogen interactions. This review will focus on the interactions between B. burgdorferi proteins, as well as between microbial proteins and host components, protein and non‐protein components, highlighting their roles in pathogen persistence in the mammalian host. A better understanding of the contributions of protein interactions in the microbial virulence and persistence of B. burgdorferi would support development of novel therapeutics against the infection.     

Effectiveness of Antenatal Clinics to Deliver Intermittent Preventive Treatment and Insecticide Treated Nets for the Control of Malaria in Pregnancy in Kenya

Background

Malaria in pregnancy can have devastating consequences for mother and baby. Coverage with the WHO prevention strategy for sub-Saharan Africa of intermittent-preventive-treatment (IPTp) with two doses of sulphadoxine-pyrimethamine (SP) and insecticide-treated-nets (ITNs) in pregnancy is low. We analysed household survey data to evaluate the effectiveness of antenatal clinics (ANC) to deliver IPTp and ITNs to pregnant women in Nyando district, Kenya.

Methods

We assessed the systems effectiveness of ANC to deliver IPTp and ITNs to pregnant women and the impact on low birthweight (LBW). Logistic regression was used to identify predictors of receipt of IPTp and ITN use during pregnancy.

Results

Among 89% of recently pregnant women who attended ANC at least once between 4–9 months gestation, 59% reported receiving one dose of SP and 90% attended ANC again, of whom 57% received a second dose, resulting in a cumulative effectiveness for IPTp of 27%, most of whom used an ITN (96%). Overall ITN use was 89%, and ANC the main source (76%). Women were less likely to receive IPTp if they had low malaria knowledge (0.26, 95% CI 0.08–0.83), had a child who had died (OR 0.36, 95% CI 0.14–0.95), or if they first attended ANC late (OR 0.20, 95% CI 0.06–0.67). Women who experienced side effects to SP (OR 0.18, CI 0.03–0.90) or had low malaria knowledge (OR 0.78, 95% CI 0.11–5.43) were less likely to receive IPTp by directly observed therapy. Ineffective delivery of IPTp reduced its potential impact by 231 LBW cases averted (95% CI 64–359) per 10,000 pregnant women.

Conclusion

IPTp presents greater challenges to deliver through ANC than ITNs in this setting. The reduction in public health impact on LBW resulting from ineffective delivery of IPTp is estimated to be substantial. Urgent efforts are required to improve service delivery of this important intervention.     

Possible rheumatoid arthritis subtypes in terms of rheumatoid factor,depression, diagnostic delay and emotional expression: an exploratory case-control study

Introduction

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathology of rheumatoid arthritis (RA), particularly as vulnerable personality types are exposed to chronic stress. Emotions are powerful modulators of stress responses. However, little is known about whether patients with RA process emotions differently to matched controls. In this study we: 1) assessed whether the trait emotional intelligence (trait EI) scores of patients with RA differ from healthy controls at the facet level; 2) explored any subgroups in RA, in terms of trait EI and common risk factors.

Methods

A total of 637 patients with RA were compared to 496 controls on the trait EI Questionnaire (TEIQue). RA subgroups were explored in terms of trait EI, rheumatoid factor status (RF+/-), depression and time from onset of symptoms until diagnosis (diagnostic delay).

Results

The RA group rated themselves lower on Adaptability, Stress-management, Emotion management, Self-esteem, Sociability, Assertiveness, Impulsiveness and Well-being, and higher on Empathy and Relationships than healthy controls. The RF- subtype reported more time with depression (25.2 vs. 11.3 months), a longer diagnostic delay (3.0 vs. 1.7 years), and greater emotional expression (5.15 vs. 4.72), than the RF+ subtype. These differences were significant at the P <0.05 level, but not following strict Bonferroni corrections and should therefore be treated as indicative only. RF- patients with a longer diagnostic delay reported depression lasting three times longer (42.7 months), when compared to three other subtypes (11.0 to 12.7 months).

Conclusions

RA patients and controls differ in their emotion-related personality traits, as operationalized by trait EI. These differences may make people with RA more susceptible to chronic stress and HPA-axis dysregulation. RA may be a highly heterogeneous illness where at least two subtypes may be characterized by personality, psychiatric and immunological differences. RF- status, as well as diagnostic delay and emotional expression, may predict future risk of depression. Research on the causes of RA could benefit from a systems science approach.     

Development of a new lacrimal drainage conduit using POSS nanocomposite

Lacrimal surgery in cases of severely obstructed or missing canalicular ducts is highly challenging. In these cases, the placement of a bypass tube is currently the only option to restore the drainage of tears into the nose and reduce the symptomatic watery eye. Different approaches to achieve functional drainage have been tried using blood vessels or artificial implants. The implantation of the rigid Lester Jones tube is, since its introduction in the late 1960s, the gold standard. The functional success is satisfactory. However, complication rates are high and remain, even with many modifications of the original design, a major problem. These complications include mainly the displacement and blockage of the tube, requiring regular checkups, as well as irritation of the surrounding tissue including the nose and the eye. The objective of this study was to develop a new lacrimal duct conduit (LDC) to restore structural and functional integrity of the lacrimal drainage system. The conduit is constructed with a novel polymer, polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane (POSS-PCU), that offers biocompatibility. We exploit nanotopography to evade the problems associated with current applications. A number of extrusion techniques were investigated for this purpose: ultrasonic atomization spraying, electrohydrodynamic atomization spraying/spinning, extrusion-coagulation, and high-pressure coagulation by autoclave and casting. Finally, the coagulation and cast technique were selected to construct an LDC superior to its predecessors, and its advantages highlighted.     

In situ endothelialization of intravascular stents from progenitor stem cells coated with nanocomposite and functionalized biomolecules

Owing to their noninvasive nature, coronary artery stents have become popular demand for patients undergoing percutaneous coronary intervention. Late restenosis, in-stent restenosis, and late thrombosis, all mediated by the denuded endothelium, represent the most recurrent failures of vascular stent induction. Higher patency rates of stents can be achieved by restoring the native internal environment of the vessel-an endothelium monolayer. This active organ inhibits the inflammatory reaction to injury responsible for thrombus and intimal hyperplasia, thereby providing a novel therapeutic option to combat the unacceptably high prevalence of restenosis. As the climax of the nanotechnology era approaches, tissue engineering is being explored by means of exploiting the multipotent abilities of stem cells and their adherence to bioactive surface nanocomposite polymers. The endothelium can be reconstructed from neighboring intact endothelium and adherence of circulating endothelium progenitor cells. The latter takes place via a series of signaling events: mobilization, adhesion, chemoattraction, migration, proliferation, and finally their differentiation in mature endothelial cells. A nanotopography surface can orchestrate endothelium formation, attributable to cellular interactions promoted by its nanosize. This review encompasses the prospect of in situ endothelialization, the mechanisms regulating the process, and the advantages of using a new generation of bioactive nanocomposite materials for coating metal stent scaffolds.     

A novel mechanism for the establishment of sister chromatid cohesion by the ECO1 acetyltransferase

Cohesin complex mediates cohesion between sister chromatids, which promotes high-fidelity chromosome segregation. Eco1p acetylates the cohesin subunit Smc3p during S phase to establish cohesion. The current model posits that this Eco1p-mediated acetylation promotes establishment by abrogating the ability of Wpl1p to destabilize cohesin binding to chromosomes. Here we present data from budding yeast that is incompatible with this Wpl1p-centric model. Two independent in vivo assays show that a wpl1∆ fails to suppress cohesion defects of eco1∆ cells. Moreover, a wpl1∆ also fails to suppress cohesion defects engendered by blocking just the essential Eco1p acetylation sites on Smc3p (K112, K113). Thus removing WPL1 inhibition is insufficient for generating cohesion without ECO1 activity. To elucidate how ECO1 promotes cohesion, we conducted a genetic screen and identified a cohesion activator mutation in the SMC3 head domain (D1189H). Smc3-D1189H partially restores cohesion in eco1∆ wpl1∆ or eco1 mutant cells but robustly restores cohesion in cells blocked for Smc3p K112 K113 acetylation. These data support two important conclusions. First, acetylation of the K112 K113 region by Eco1p promotes cohesion establishment by altering Smc3p head function independent of its ability to antagonize Wpl1p. Second, Eco1p targets other than Smc3p K112 K113 are necessary for efficient establishment.