Periodontal therapy increases neutrophil extracellular trap degradation

In periodontitis, polymorphonuclear leucocytes (PMNs) are activated. They entrap and eliminate pathogens by releasing neutrophil extracellular traps (NETs). Abnormal NET degradation is part of a pro-inflammatory status, affecting co-morbidities such as cardiovascular disease. We aimed to investigate the ex vivo NET degradation capacity of plasma from periodontitis patients compared to controls (part 1) and to quantify NET degradation before and after periodontal therapy (part 2). Fresh NETs were obtained by stimulating blood-derived PMNs with phorbol 12-myristate 13-acetate. Plasma samples from untreated periodontitis patients and controls were incubated for 3 h onto freshly generated NETs (part 1). Similarly, for part 2, NET degradation was studied for 91 patients before and 3, 6 and 12 mo after non-surgical periodontal therapy with and without adjunctive systemic antibiotics. Finally, NET degradation was fluorospectrometrically quantified. NET degradation levels did not differ between periodontitis patients and controls, irrespective of subject-related background characteristics. NET degradation significantly increased from 65.6 ± 1.7% before periodontal treatment to 75.7 ± 1.2% at 3 mo post periodontal therapy, and this improvement was maintained at 6 and 12 mo, irrespective of systemic usage of antibiotics. Improved NET degradation after periodontitis treatment is another systemic biomarker reflecting a decreased pro-inflammatory status, which also contributes to an improved cardiovascular condition.     

Interactive effects of APOE haplotype, sex, and exercise on postheparin plasma lipase activities

Hepatic lipase (HL) and lipoprotein lipase (LPL) activities (HLA, LPLA) modify lipoproteins and facilitate their binding to hepatic receptors. Apolipoprotein E (APOE) physically interacts with the lipases, and the three common haplotypes of the APOE gene (ε2, ε3, and ε4) yield protein isoforms (E2, E3, and E4, respectively) that are functionally different. Lipase activities themselves differ by sex and exercise training status. The interaction of APOE genotype, exercise training, and sex effects on lipase activities has not been studied. We measured postheparin plasma lipase activities in normolipidemic men and women with the three most common APOE genotypes, which are the haplotype combinations ε2/ε3 (n = 53 ), ε3/ε3 (n = 62), and ε4/ε3 (n = 52), enrolled in 6 mo of aerobic exercise training. These haplotype combinations comprise an estimated 11.6, 62.3, and 21.3% of the population, respectively. Baseline HLA was 35% lower in women than in men (P < 0.0001). In men but not women, HLA was higher in ε2/ε3 group compared with ε4/ε3 (P = 0.01) and ε3/ε3 (P = 0.05). Neither sex nor APOE genotype affected baseline LPLA. Training decreased HLA by 5.2% (P = 0.018) with no APOE effect. The apparent increase in LPLA following exercise was significant and APOE dependent only when corrected for baseline insulin (P < 0.05). Exercise decreased LPLA by 0.8 μmol free fatty acid (FFA)·ml?1·h?1 (-6%) in ε3/ε3 compared with the combined increases of 6.6% in ε2/ε3 and 12% in ε4/ε3 (P = 0.018 vs. ε3/ε3). However, these differences were statistically significant only after correcting for baseline insulin. We conclude that common APOE genotypes interact with 1) sex to modulate HLA regardless of training status, with ε2/ε3 men demonstrating higher HLA than ε3/ε3 or ε4/ε3 men, and 2) aerobic training to modulate LPLA, regardless of sex, with ε3/ε3 subjects showing a significant decrease compared with an increase in ε2/ε3 and ε3/ε4 after controlling for baseline insulin.     

Adverse environmental conditions influence age-related innate immune responsiveness

Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder that belongs to a group of conditions called laminopathies which affect nuclear lamins. Mutations in two genes, LMNA and ZMPSTE24, have been found in patients with HGPS. The p.G608G LMNA mutation is the most commonly reported mutation. The aim of this work was to compile a comprehensive literature review of the clinical features and genetic mutations and mechanisms of this syndrome as a contribution to health care workers. This review shows the necessity of a more detailed clinical identification of Hutchinson-Gilford progeria syndrome and the need for more studies on the pharmacologic and pharmacogenomic approach to this syndrome.     

Freshwater crayfish invasions in South Africa: past,present and potential future

Freshwater crayfish invasions have been studied around the world, but less so in Africa, a continent devoid of native freshwater crayfish. The present study reviews historical and current information on alien freshwater crayfish species introduced into South Africa and aims to indicate which areas are at risk from invasion. As is the case elsewhere, South Africans have shown a keen interest in both farming and keeping freshwater crayfish as pets, which has resulted in Cherax cainii, Cherax destructor, Cherax quadricarinatus and Procambarus clarkii being introduced to the country. There is evidence of successful establishment in the wild for C. quadricarinatus and P. clarkii in different parts of the country. Species distribution models suggest that the eastern part of the country and parts of the Eastern and Western Cape are at higher risk of invasion. At present, illegal translocations represent the most likely pathway of crayfish spread in South Africa. A continued risk of invasion by freshwater crayfish species in South Africa is highlighted, which reinforces the need for more research, as well as for strong mitigation measures, such as stronger policing of existing regulations, management or eradication where feasible and public education.     

The PagN protein of <Emphasis Type="Italic">Salmonella enterica</Emphasis> serovar Typhimurium is an adhesin and invasin

Background  

The pagN gene of Salmonella enterica serovar Typhimurium is a PhoP-regulated gene that is up-regulated during growth within macrophages and in vivo in murine models of infection. The PagN protein displays similarity to the Hek and Tia invasins/adhesins of Escherichia coli. Thus far no function has been ascribed to the PagN protein.     

Dimerization of Receptor Protein-Tyrosine Phosphatase alpha in living cells

Background  

Dimerization is an important regulatory mechanism of single membrane-spanning receptors. For instance, activation of receptor protein-tyrosine kinases (RPTKs) involves dimerization. Structural, functional and biochemical studies suggested that the enzymatic counterparts of RPTKs, the receptor protein-tyrosine phosphatases (RPTPs), are inhibited by dimerization, but whether RPTPs actually dimerize in living cells remained to be determined.     

The laminin β1-competing peptide YIGSR induces a hypercontractile,hypoproliferative airway smooth muscle phenotype in an animal model of allergic asthma

Background

Fibroproliferative airway remodelling, including increased airway smooth muscle (ASM) mass and contractility, contributes to airway hyperresponsiveness in asthma. In vitro studies have shown that maturation of ASM cells to a (hyper)contractile phenotype is dependent on laminin, which can be inhibited by the laminin-competing peptide Tyr-Ile-Gly-Ser-Arg (YIGSR). The role of laminins in ASM remodelling in chronic asthma in vivo, however, has not yet been established.

Methods

Using an established guinea pig model of allergic asthma, we investigated the effects of topical treatment of the airways with YIGSR on features of airway remodelling induced by repeated allergen challenge, including ASM hyperplasia and hypercontractility, inflammation and fibrosis. Human ASM cells were used to investigate the direct effects of YIGSR on ASM proliferation in vitro.

Results

Topical administration of YIGSR attenuated allergen-induced ASM hyperplasia and pulmonary expression of the proliferative marker proliferating cell nuclear antigen (PCNA). Treatment with YIGSR also increased both the expression of sm-MHC and ASM contractility in saline- and allergen-challenged animals; this suggests that treatment with the laminin-competing peptide YIGSR mimics rather than inhibits laminin function in vivo. In addition, treatment with YIGSR increased allergen-induced fibrosis and submucosal eosinophilia. Immobilized YIGSR concentration-dependently reduced PDGF-induced proliferation of cultured ASM to a similar extent as laminin-coated culture plates. Notably, the effects of both immobilized YIGSR and laminin were antagonized by soluble YIGSR.

Conclusion

These results indicate that the laminin-competing peptide YIGSR promotes a contractile, hypoproliferative ASM phenotype in vivo, an effect that appears to be linked to the microenvironment in which the cells are exposed to the peptide.     

MalariaSphere: A greenhouse-enclosed simulation of a natural Anopheles gambiae (Diptera: Culicidae) ecosystem in western Kenya

Background  

The development and implementation of innovative vector control strategies for malaria control in Africa requires in-depth ecological studies in contained semi-field environments. This particularly applies to the development and release of genetically-engineered vectors that are refractory to Plasmodium infection. Here we describe a modified greenhouse, designed to simulate a natural Anopheles gambiae Giles ecosystem, and the first successful trials to complete the life-cycle of this mosquito vector therein.