Risk Factors Associated with the Development of Atopic Sensitization in Indonesia

Background

The prevalence of allergic diseases has increased not only in high income but also in low-to-middle income countries. However, risk factors for their development are still not well established, particularly in the latter.

Objective

To assess prevalence and identify risk factors for sensitization to two major inhalant allergens among children from semi-urban and rural areas in Indonesia.

Method

A cross-sectional survey was performed among 1,674 school children aged 5–15 years old. Information on potential risk factors and reported allergic symptoms were obtained by questionnaire. Helminth infections were assessed. Skin prick tests (SPT) were performed, total IgE as well as allergen-specific IgE for house dust mite (HDM) and cockroach were measured.

Result

The prevalence of allergic skin sensitization to both aeroallergens was significantly higher in the semi-urban than in the rural area. However, serum IgE against HDM and cockroach as well as total IgE were significantly lower in semi-urban than in rural children. In the semi-urban area, there was a significant positive association between SPT to HDM and higher paternal education but a negative one with hookworm infection. The risk factors linked to cockroach sensitization were different: being of a farmer offspring and lacking access to piped water were associated with an increased risk for a positive SPT to cockroach. No significant associations between measured risk factors and having a positive SPT were found in the rural area.

Conclusion

Sensitization to HDM and cockroach is common in Indonesia, more often translating into a positive SPT in the semi-urban than in the rural setting. Whereas high paternal education and low hookworm infection were associated with increased risk of SPT to HDM, we were surprised to find parameters of lower SES were identified as risk factor for cockroach SPT.     

Periostin Deficiency Increases Bone Damage and Impairs Injury Response to Fatigue Loading in Adult Mice

Bone damage removal and callus formation in response to fatigue loading are essential to prevent fractures. Periostin (Postn) is a matricellular protein that mediates adaptive response of cortical bone to loading. Whether and how periostin influences damage and the injury response to fatigue remains unknown. We investigated the skeletal response of Postn ^-/- and Postn ^+/+ mice after fatigue stimulus by axial compression of their tibia. In Postn ^+/+ mice, cracks number and surface (CsNb, CsS) increased 1h after fatigue, with a decrease in strength compared to non-fatigued tibia. At 15 days, CsNb had started to decline, while CtTV and CtBV increased in fatigued vs non-fatigued tibia, reflecting a woven bone response that was present in 75% of the fatigued bones. Cortical porosity and remodelling also prominently increased in the fatigued tibia of Postn ^+/+ mice. At 30 days, paralleling a continuous removal of cortical damage, strength of the fatigued tibia was similar to the non-fatigue tibia. In Postn ^-/- mice, cracks were detectable even in the absence of fatigue, while the amount of collagen crosslinks and tissue hardness was decreased compared to Postn ^+/+. Fatigue significantly increased CsNb and CsS in Postn ^-/-, but was not associated with changes in CtTV and CtBV, as only 16% of the fatigued bones formed some woven bone. Cortical porosity and remodelling did not increase either after fatigue in Postn ^-/- , and the level of damage remained high even after 30 days. As a result, strength remained compromised in Postn ^-/- mice. Contrary to Postn ^+/+ , which osteocytic lacunae showed a change in the degree of anisotropy (DA) after fatigue, Postn^-/- showed no DA change. Hence periostin appears to influence bone materials properties, damage accumulation and repair, including local modeling/remodeling processes in response to fatigue. These observations suggest that the level of periostin expression could influence the propensity to fatigue fractures.     

ICEA of Mycoplasma agalactiae: a new family of self‐transmissible integrative elements that confers conjugative properties to the recipient strain

Horizontal gene transfer (HGT) is a major force of microbial evolution but was long thought to be marginal in mycoplasmas. In silico detection of exchanged regions and of loci encoding putative Integrative Conjugative Elements (ICE) in several mycoplasma genomes challenged this view, raising the prospect of these simple bacteria being able to conjugate. Using the model pathogen Mycoplasma agalactiae, we demonstrated for the first time that one of these elements, ICEA, is indeed self‐transmissible. As a hallmark of conjugative processes, ICEA transfers were DNase resistant and required viable cells. ICEA acquisition conferred ICE‐negative strains with the new ability to conjugate, allowing the spread of ICEA. Analysis of transfer‐deficient mutants indicated that this process requires an ICEA‐encoded lipoprotein of unknown function, CDS14. Formation of a circular extrachromosomal intermediate and the subsequent chromosomal integration of ICEA involved CDS22, an ICEA‐encoded product distantly related to the ISLre2 transposase family. Remarkably, ICEA has no specific or no preferential integration site, often resulting in gene disruptions. Occurrence of functional mycoplasma ICE offers these bacteria with a means for HGT, a phenomenon with far‐reaching implications given their minute‐size genome and the number of species that are pathogenic for a broad host‐range.     

TiO(2) nanocrystals electrochemiluminescence quenching by biological enlarged nanogold particles and its application for biosensing

Electrochemiluminescence (ECL) of TiO(2) nanocrystals with different crystal styles modified fluorine-doped tin oxide (FTO) electrode was investigated in H(2)O(2) solution. The amorphous TiO(2) nanospheres were facilely synthesized by the hydrothermal and condensation method. Crystal TiO(2), namely anatase and rutile, were prepared by calcination of the amorphous TiO(2) nanospheres at 450 and 800°C, respectively. The transmission electron microscope (TEM) and electron diffraction pattern were used to characterize the obtained TiO(2) nanoparticles morphology and the corresponding crystal styles. The electrochemical and ECL behaviors were investigated by cyclic voltammetry. The ECL quenching was observed by introduction of gold nanoparticles. Based on the quenching effect, a sensitive glucose ECL biosensor as a model was fabricated by in-situ growing-up gold seeds in AuCl(4)(-) solution induced by biologically generated H(2)O(2). The linear range to detect glucose is from 5.0×10(-7)M to 4.0×10(-3)M with the limit of detection of 2.5×10(-7)M.     

Phylogeography and niche modelling of the relict plant Amborella trichopoda (Amborellaceae) reveal multiple Pleistocene refugia in New Caledonia

Amborella trichopoda Baill. (Amborellaceae, Amborellales), the sole living member of the sister group to all other extant angiosperms, is endemic to New Caledonia. We addressed the intraspecific phylogeography of Amborella by investigating whether its present population genetic structure could be related to its current and past habitats. We found moderate range‐wide genetic diversity based on nuclear microsatellite data and detected four well‐differentiated, geographically distinct genetic groups using Bayesian clustering analyses. We modelled the ecological niche of Amborella based on the current climatic and environmental conditions. The predictive ability of the model was very good throughout the Central East mainland zone, but Amborella was predicted in the northern part of the island where this plant has not been reported. Furthermore, no significant barrier was detected based on habitat suitability that could explain the genetic differentiation across the area. Conversely, we found that the main genetic clusters could be related to the distribution of the suitable habitat at the last glacial maximum (LGM, c. 21 000 years BP), when Amborella experienced a dramatic 96.5% reduction in suitable area. At least two lineages survived in distinct putative refugia located in the Massif des Lèvres and in the vicinity of Mount Aoupinié. Our findings finally confirmed the importance of LGM rainforest refugia in shaping the current intra‐ and interspecific diversity in New Caledonian plants and revealed the possibility of an as yet unreported refugium. The combination of niche modelling and population genetics thereby offered novel insight into the biogeographical history of an emblematic taxon.     

Synthesis and evaluation of 5′-modified thymidines and 5-hydroxymethyl-2′-deoxyuridines as Mycobacterium tuberculosis thymidylate kinase inhibitors

We report the synthesis of 5′-modified thymidines (16, 18, 21, 23) and 5,5′-bis-substituted 2′-deoxyuridine analogues (30, 47) as inhibitors of thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt). These analogues were evaluated for their capacity to inhibit TMPKmt and solely two 5′-modified thymidines were found to possess moderate inhibitory activity. In addition, a feasibility study of protecting groups for the 5-CH₂OH moiety of 2′-deoxyuridines is described that enables to introduce the desired 5′-modification.     

Repeated evolution of queen parthenogenesis and social hybridogenesis in Cataglyphis desert ants

Over the last decade, genetic studies on social insects have revealed a remarkable diversity of unusual reproductive strategies, such as male clonality, female clonality, and social hybridogenesis. In this context, Cataglyphis desert ants are useful models because of their unique reproductive systems. In several species, queens conditionally use sexual reproduction and parthenogenesis to produce sterile workers and reproductive queens, respectively. In social hybridogenesis, two distinct genetic lineages coexist within a population, and workers result from mating between partners of different lineages; in contrast, queens and males are both produced asexually by parthenogenesis. Consequently, nonreproductive workers are all interlineage hybrids, whereas reproductives are all pure lineage individuals. Here, we characterized the reproductive systems of 11 species to investigate the distribution of the conditional use of sex and social hybridogenesis in Cataglyphis. We identified one new case in which sexual reproduction was conditionally used in the absence of dependent‐lineage reproduction. We also discovered five new instances of social hybridogenesis. Based on our phylogenetic analyses, we inferred that both the conditional use of sex and social hybridogenesis independently evolved multiple times in the genus Cataglyphis.     

Hotspots of stream tadpole diversity in forest and agricultural landscapes in Ranomafana,Madagascar

Landscape and Ecological Engineering - Logging and human-induced conversion of natural forests into agricultural areas are major drivers of biodiversity loss in the tropics. Anuran larvae can be...     

Nav1.5-dependent persistent Na+ influx activates CaMKII in rat ventricular myocytes and N1325S mice

Late Na(+) current (I(NaL)) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) are both increased in the diseased heart. Recently, CaMKII was found to phosphorylate the Na(+) channel 1.5 (Na(v)1.5), resulting in enhanced I(NaL). Conversely, an increase of I(NaL) would be expected to cause elevation of intracellular Ca(2+) and activation of CaMKII. However, a relationship between enhancement of I(NaL) and activation of CaMKII has yet to be demonstrated. We investigated whether Na(+) influx via Na(v)1.5 leads to CaMKII activation and explored the functional significance of this pathway. In neonatal rat ventricular myocytes (NRVM), treatment with the I(NaL) activators anemone toxin II (ATX-II) or veratridine increased CaMKII autophosphorylation and increased phosphorylation of CaMKII substrates phospholamban and ryanodine receptor 2. Knockdown of Na(v)1.5 (but not Na(v)1.1 or Na(v)1.2) prevented ATX-II-induced CaMKII phosphorylation, providing evidence for a specific role of Na(v)1.5 in CaMKII activation. In support of this view, CaMKII activity was also increased in hearts of transgenic mice overexpressing a gain-of-function Na(v)1.5 mutant (N(1325)S). The effects of both ATX-II and the N(1325)S mutation were reversed by either I(NaL) inhibition (with ranolazine or tetrodotoxin) or CaMKII inhibition (with KN93 or autocamtide 2-related inhibitory peptide). Furthermore, ATX-II treatment also induced CaMKII-Na(v)1.5 coimmunoprecipitation. The same association between CaMKII and Na(v)1.5 was also found in N(1325)S mice, suggesting a direct protein-protein interaction. Pharmacological inhibitions of either CaMKII or I(NaL) also prevented ATX-II-induced cell death in NRVM and reduced the incidence of polymorphic ventricular tachycardia induced by ATX-II in rat perfused hearts. Taken together, these results suggest that a Na(v)1.5-dependent increase in Na(+) influx leads to activation of CaMKII, which in turn phosphorylates Na(v)1.5, further promoting Na(+) influx. Pharmacological inhibition of either CaMKII or Na(v)1.5 can ameliorate cardiac dysfunction caused by excessive Na(+) influx.