Impact of bidirectional relationships between streptococcus anginosus group and host tissue matrix components on cellular activity: Role in establishment of infection

This paper investigates pathogenic mechanisms of the Streptococcus anginosus group (SAG) of bacteria which influence the biological activity of periodontal ligament (PDL) cells, endothelial cells and also how matrix proteins produced by these host cells influence bacterial virulence factors. Isolates of SAG species, designated S. anginosus, S. constellatus and S. intermedius, were derived from healthy commensal and clinical pathogenic infection sites. SAG culture supernatants contained multiple protein components which differed between isolates. All SAG supernatants increased cellular proliferation and decreased decorin synthesis and collagen assembly by PDL cells and reduced endothelial cell migration. SAG isolates responded differently to extracellular matrix (ECM) components synthesised by PDL cells, but there was an overall notable increase in hydrolytic enzyme activity and in the production of the cytotoxin intermedilysin by S. intermedius. Collectively, the results indicate that both commensal and pathogenic SAG isolates were capable of impairing the ability of PDL cells and endothelial cells to make functional vascularised tissue. Reduced decorin synthesis is likely to have a major impact on cell signalling, angiogenesis and matrix assembly. Furthermore, ECM components produced by PDL cells were differentially capable of moderately increasing SAG enzymic activity, leading to subtle ECM modifications. The impact this bidirectional effect has on the tissue remodelling process is discussed

Two essential light chains regulate the MyoA lever arm to promote Toxoplasma gliding motility

Key to the virulence of apicomplexan parasites is their ability to move through tissue and to invade and egress from host cells. Apicomplexan motility requires the activity of the glideosome, a multicomponent molecular motor composed of a type XIV myosin, MyoA. Here we identify a novel glideosome component, essential light chain 2 (ELC2), and functionally characterize the two essential light chains (ELC1 and ELC2) of MyoA in Toxoplasma. We show that these proteins are functionally redundant but are important for invasion, egress, and motility. Molecular simulations of the MyoA lever arm identify a role for Ca2+ in promoting intermolecular contacts between the ELCs and the adjacent MLC1 light chain to stabilize this domain. Using point mutations predicted to ablate either the interaction with Ca2+ or the interface between the two light chains, we demonstrate their contribution to the quality, displacement, and speed of gliding Toxoplasma parasites. Our work therefore delineates the importance of the MyoA lever arm and highlights a mechanism by which this domain could be stabilized in order to promote invasion, egress, and gliding motility in apicomplexan parasites

Automated Fourier space region-recognition filtering for off-axis digital holographic microscopy

Automated label-free quantitative imaging of biological samples can greatly benefit high throughput diseases diagnosis. Digital holographic microscopy (DHM) is a powerful quantitative label-free imaging tool that retrieves structural details of cellular samples non-invasively. In off-axis DHM, a proper spatial filtering window in Fourier space is crucial to the quality of reconstructed phase image. Here we describe a region-recognition approach that combines shape recognition with an iterative thresholding to extracts the optimal shape of frequency components. The region recognition technique offers fully automated adaptive filtering that can operate with a variety of samples and imaging conditions. When imaging through optically scattering biological hydrogel matrix, the technique surpasses previous histogram thresholding techniques without requiring any manual intervention. Finally, we automate the extraction of the statistical difference of optical height between malaria parasite infected and uninfected red blood cells. The method described here pave way to greater autonomy in automated DHM imaging for imaging live cell in thick cell cultures

Association between childhood adversities and long-term suicidality among South Africans from the results of the South African Stress and Health study: a cross-sectional study

Objective: Suicide and suicidal behaviours are significant public health problems and a leading cause of death worldwide and in South Africa. We examined the association between childhood adversities and suicidal behaviour over the life course. Methods: A national probability sample of 4351 South African adult participants (aged 18 years and older) in the South African Stress and Health (SASH) study was interviewed as part of the World Mental Health Surveys initiative. Respondents provided sociodemographic and diagnostic information, as well as an account of suicide-related thoughts and behaviours. Suicidality or suicidal behaviour were defined as were defined as suicide attempts and suicidal ideation in the total sample, and suicide plans and attempts among ideators. Childhood adversities included physical abuse, sexual abuse, parental death, parental divorce, other parental loss, family violence, physical illness and financial adversity. The association between suicidality and childhood adversities was examined using discrete-time survival models. Results: More than a third of the respondents with suicidal behaviour experienced at least one childhood adversity, with physical abuse, parental death and parental divorce being the most prevalent adversities. Physical abuse, sexual abuse and parental divorce were identified as significant risk markers for lifetime suicide attempts, while physical abuse and parental divorce were significantly correlated with suicidal ideation. Two or more childhood adversities were associated with a twofold higher risk of lifetime suicide attempts. Sexual abuse (OR 9.3), parental divorce (OR 3.1) and childhood physical abuse (OR 2.2) had the strongest associations with lifetime suicide attempts. The effect of childhood adversities on suicidal tendencies varied over the life course. For example, sexual abuse was significantly associated with suicide attempts during childhood and teen years, but not during young and later adulthood. Conclusions: Childhood adversities, especially sexual abuse, physical abuse and parental divorce, are important risk factors for the onset and persistence of suicidal behaviour, with this risk being greatest in childhood and adolescence

Masters of the Universe: Bid Rigging by Private Equity Firms in Multibillion Dollar LBOs

In the first successful case of its kind, a class action alleging widespread collusion in the market for leveraged buyouts, some of the world’s largest private equity firms settled Dahl v. Bain Capital Partners, LLC for $590.5 million. The case was unique not only for its size and the fact that it involved complex financial transactions instead of a typical commodity, but also because the claimants used auction theory to demonstrate both the “plus” factors required to prove antitrust injury and the resulting damages. Economic analyses show that the cost to shareholders of collusion in the eight litigated multi-billion dollar leveraged buyout transactions approached$12 billion. The use of empirical economic analysis in antitrust litigation is now de rigueur. Courts expect it, and litigants have an array of econometricians available who understand both how to work with data and antitrust doctrine. In “ordinary” commodities price fixing cases, plaintiffs and defendants are expected to engage experts who gather transaction data and apply regression theory and other economic analyses to contest whether it is possible to demonstrate injury, impact, and damages. Dahl was not an ordinary case in that it involved neither a commodity nor a sellers’ cartel. Instead, it involved a buyers’ cartel which, Plaintiffs alleged, conspired to drive down the price of a number of unique, large LBOs during the mid-2000s. Additionally, the case was notable because of the Plaintiffs’ decision to use the auction theory to demonstrate the existence of antitrust violations and the extent of damage

Collagen-induced arthritis in C57BL/6 mice is associated with a robust and sustained T-cell response to type II collagen

Many genetically modified mouse strains are now available on a C57BL/6 (H-2b) background, a strain that is relatively resistant to collagen-induced arthritis. To facilitate the molecular understanding of autoimmune arthritis, we characterised the induction of arthritis in C57BL/6 mice and then validated the disease as a relevant pre-clinical model for rheumatoid arthritis

Gastric Helicobacter infection induces iron deficiency in the INS-GAS mouse

There is increasing evidence from clinical and population studies for a role of H. pylori infection in the aetiology of iron deficiency. Rodent models of Helicobacter infection are helpful for investigating any causal links and mechanisms of iron deficiency in the host. The aim of this study was to investigate the effects of gastric Helicobacter infection on iron deficiency and host iron metabolism/transport gene expression in hypergastrinemic INS-GAS mice. INS-GAS mice were infected with Helicobacter felis for 3, 6 and 9 months. At post mortem, blood was taken for assessment of iron status and gastric mucosa for pathology, immunohistology and analysis of gene expression. Chronic Helicobacter infection of INS- GAS mice resulted in decreased serum iron, transferrin saturation and hypoferritinemia and increased Total iron binding capacity (TIBC). Decreased serum iron concentrations were associated with a concomitant reduction in the number of parietal cells, strengthening the association between hypochlorhydria and gastric Helicobacter-induced iron deficiency. Infection with H. felis for nine months was associated with decreased gastric expression of iron metabolism regulators hepcidin, Bmp4 and Bmp6 but increased expression of Ferroportin 1, the iron efflux protein, iron absorption genes such as Divalent metal transporter 1, Transferrin receptor 1 and also Lcn2 a siderophore-binding protein. The INS-GAS mouse is therefore a useful model for studying Helicobacter-induced iron deficiency. Furthermore, the marked changes in expression of gastric iron transporters following Helicobacter infection may be relevant to the more rapid development of carcinogenesis in the Helicobacter infected INS-GAS model

Respiratory pathogen colonisation of dental plaque, the lower airways and endotracheal tube biofilms during mechanical ventilation

Purpose In mechanically ventilated patients, the endotracheal tube is an essential interface between the patient and ventilator, but inadvertently, it also facilitates the development of ventilator-associated pneumonia (VAP) by subverting pulmonary host defenses. A number of investigations suggest that bacteria colonizing the oral cavity may be important in the etiology of VAP. The present study evaluated microbial changes that occurred in dental plaque and lower airways of 107 critically ill mechanically ventilated patients. Materials and Methods Dental plaque and lower airways fluid was collected during the course of mechanical ventilation, with additional samples of dental plaque obtained during the entirety of patients' hospital stay. Results A “microbial shift” occurred in dental plaque, with colonization by potential VAP pathogens, namely, Staphylococcus aureus and Pseudomonas aeruginosa in 35 patients. Post-extubation analyses revealed that 70% and 55% of patients whose dental plaque included S aureus and P aeruginosa, respectively, reverted back to having a predominantly normal oral microbiota. Respiratory pathogens were also isolated from the lower airways and within the endotracheal tube biofilms. Conclusions To the best of our knowledge, this is the largest study to date exploring oral microbial changes during both mechanical ventilation and after recovery from critical illness. Based on these findings, it was apparent that during mechanical ventilation, dental plaque represents a source of potential VAP pathogens

Porous metal–organic frameworks for enhanced performance silicon anodes in lithium-ion batteries

Maintaining the physical integrity of electrode microstructures in Li-ion batteries is critical to significantly extend their cycle life. This is especially important for high-capacity anode materials such as silicon, whose operational volume expansion exerts huge internal stress within the anode, resulting in electrode destruction and capacity fade. In this study, we demonstrate that by incorporating metal–organic frameworks (MOFs) with carboxylate organic linkers into Si-based anodes, a stable and flexible pore network is generated to maximize and maintain Li-ion flux throughout the electrode’s architecture. We show that the zirconium carboxylate MOF UiO-67 is a versatile comaterial to boost performance and mitigate the rate of anode degradation that presently limits the lifetime of Si anodes. The cage-like pores in UiO-67 and flexural properties of the 4,4′-biphenyldicarboxylate organic linker are proposed to create robust “ionophores” in the anode film to enhance longer term durability and performance

Parkinson’s disease: an inquiry into the etiology and treatment

Parkinson’s disease affects over one million people in the United States. Although there have been remarkable advances in uncovering the pathogenesis of this disabling disorder, the etiology is speculative. Medical treatment and operative procedures provide symptomatic relief only. Compression of the cerebral peduncle of the midbrain by the posterior cerebral artery in a patient with Parkinson’s Disease (Parkinson’s Disease) was noted on magnetic resonance imaging (MRI) scan and at operation in a patient with trigeminal neuralgia. Following the vascular decompression of the trigeminal nerve, the midbrain was decompressed by mobilizing and repositioning the posterior cerebral artery The patient's Parkinson's signs disappeared over a 48-hour period. They returned 18 months later with contralateral peduncle compression. A blinded evaluation of MRI scans of Parkinson's patients and controls was performed. MRI scans in 20 Parkinson's patients and 20 age and sex matched controls were evaluated in blinded fashion looking for the presence and degree of arterial compression of the cerebral peduncle. The MRI study showed that 73.7 percent of Parkinson's Disease patients had visible arterial compression of the cerebral peduncle. This was seen in only 10 percent of control patients (two patients, one of whom subsequently developed Parkinson’s Disease); thus 5 percent. Vascular compression of the cerebral peduncle by the posterior cerebral artery may be associated with Parkinson’s Disease in some patients. Microva-scular decompression of that artery away from the peduncle may be considered for treatment of Parkinson’s Disease in some patients