Differential Regulation of Cysteinyl Leukotriene Receptor Signaling by Protein Kinase C in Human Mast Cells

Cysteinyl leukotrienes (cys-LTs) are a group of lipid mediators that are potent bronchoconstrictors, powerful inducers of vascular leakage and potentiators of airway hyperresponsiveness. Cys-LTs play an essential role in asthma and are synthesized as well as activated in mast cells (MCs). Cys-LTs relay their effects mainly through two known GPCRs, CysLT₁R and CysLT₂R. Although protein kinase C (PKC) isoforms are implicated in the regulation of CysLT₁R function, neither the role of PKCs in cys-LT-dependent MC inflammatory signaling nor the involvement of specific isoforms in MC function are known. Here, we show that PKC inhibition augmented LTD₄ and LTE₄-induced calcium influx through CysLT₁R in MCs. In contrast, inhibition of PKCs suppressed c-fos expression as well MIP1β generation by cys-LTs. Interestingly, cys-LTs activated both PKCα and PKCε isoforms in MC. However, knockdown of PKCα augmented cys-LT mediated calcium flux, while knockdown of PKCε attenuated cys-LT induced c-fos expression and MIP1β generation. Taken together, these results demonstrate for the first time that cys-LT signaling downstream of CysLT₁R in MCs is differentially regulated by two distinct PKCs which modulate inflammatory signals that have significant pathobiologic implications in allergic reactions and asthma pathology.     

Patterns of liana community diversity and structure in a tropical rainforest reserve,Ghana: effects of human disturbance

Most studies have concluded that liana diversity and structure increase with disturbance. However, a contradictory pattern has emerged recently calling for more research in the area. Liana diversity and structure were investigated in three forest types that differ in disturbance intensity (nondisturbed, moderately disturbed and heavily disturbed forest: NDF, MDF and HDF, respectively) in the Atewa Range Forest Reserve, Ghana. In each forest type, 10 square plots of 0.25 ha were demarcated. Lianas with diameter ≥1 cm located on trees with diameter ≥10 cm were enumerated. A total of 429 individuals representing 40 species, 29 genera and seventeen families were identified in the study. Shannon diversity and species richness of lianas were significantly lower in the HDF (P < 0.05). Liana density and basal area differed significantly across all forest types (P < 0.0001). The importance value index (IVI) of most liana species varied greatly across the forest types. The current study has provided evidence to support the pattern of decreasing liana diversity and structure with disturbance in some tropical forests. Further studies are recommended to gain more understanding of the factors that are responsible for the divergent liana responses to disturbance in tropical forests.     

Variants of the <Emphasis Type="Italic">EAAT2</Emphasis> Glutamate Transporter Gene Promoter Are Associated with Cerebral Palsy in Preterm Infants

Preterm delivery is associated with neurodevelopmental impairment caused by environmental and genetic factors. Dysfunction of the excitatory amino acid transporter 2 (EAAT2) and the resultant impaired glutamate uptake can lead to neurological disorders. In this study, we investigated the role of single nucleotide polymorphisms (SNPs; g.-200C>A and g.-181A>C) in the EAAT2 promoter in susceptibility to brain injury and neurodisability in very preterm infants born at or before 32-week gestation. DNA isolated from newborns’ dried blood spots were used for pyrosequencing to detect both SNPs. Association between EAAT2 genotypes and cerebral palsy, cystic periventricular leukomalacia and a low developmental score was then assessed. The two SNPs were concordant in 89.4% of infants resulting in three common genotypes all carrying two C and two A alleles in different combinations. However, in 10.6% of cases, non-concordance was found, generating six additional rare genotypes. The A alleles at both loci appeared to be detrimental and consequently, the risk of developing cerebral palsy increased four- and sixfold for each additional detrimental allele at -200 and -181 bp, respectively. The two SNPs altered the regulation of the EAAT2 promoter activity and glutamate homeostasis. This study highlights the significance of glutamate in the pathogenesis of preterm brain injury and subsequent development of cerebral palsy and neurodevelopmental disabilities. Furthermore, the described EAAT2 SNPs may be an early biomarker of vulnerability to neurodisability and may aid the development of targeted treatment strategies.     

Production of hand-made cloned buffalo (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>) embryos from non-viable somatic cells

Use of non-viable somatic cells for hand-made cloning (HMC) can enable production of cloned animals from tissues obtained from elite or endangered dead animals. Buffalo skin fibroblast cells were rendered non-viable by heat treatment and used for HMC. Although fusion (93.6 ± 1.72 vs 67.1 ± 2.83%) and cleavage (90.3 ± 1.79 vs 65.8 ± 1.56%) rate was lower (P < 0.001) than that for controls, blastocysts could be successfully produced. However, blastocyst rate (34.1 ± 2.43 vs 6.9 ± 2.18%, P < 0.001) and total cell number of blastocysts (TCN, 221.3 ± 25.14 vs 151.1 ± 21.69, P < 0.05) were lower and apoptotic index (4.8 ± 1.06 vs 10.9 ± 1.21) was higher (P < 0.001) than that of controls. In another experiment, ear tissue of slaughterhouse buffaloes was preserved in mustard oil at room temperature for 48 h following which somatic cells were harvested by enzymatic digestion and used for HMC. Although fusion (96.8 ± 1.48 vs 84.2 ± 3.19%), cleavage (89.6 ± 3.59 vs 77.2 ± 3.99%), and blastocyst rate (36.9 ± 7.45 vs 13.1 ± 6.87%) were lower (P < 0.01), TCN (223.0 ± 27.89 vs 213.3 ± 28.21) and apoptotic index (3.97 ± 0.67 vs 5.22 ± 0.51) of blastocysts were similar to those of controls. In conclusion, HMC can be successfully used for production of blastocysts from non-viable cells and from cells obtained from freshly slaughtered buffaloes. This can pave the way for the restoration of farm or wild animals by HMC if somatic cells could be obtained within a few hours after their death.     

Forest biomass,productivity and carbon cycling along a rainfall gradient in West Africa

Net Primary Productivity (NPP) is one of the most important parameters in describing the functioning of any ecosystem and yet it arguably remains a poorly quantified and understood component of carbon cycling in tropical forests, especially outside of the Americas. We provide the first comprehensive analysis of NPP and its carbon allocation to woody, canopy and root growth components at contrasting lowland West African forests spanning a rainfall gradient. Using a standardized methodology to study evergreen (EF), semi‐deciduous (SDF), dry forests (DF) and woody savanna (WS), we find that (i) climate is more closely related with above and belowground C stocks than with NPP (ii) total NPP is highest in the SDF site, then the EF followed by the DF and WS and that (iii) different forest types have distinct carbon allocation patterns whereby SDF allocate in excess of 50% to canopy production and the DF and WS sites allocate 40%–50% to woody production. Furthermore, we find that (iv) compared with canopy and root growth rates the woody growth rate of these forests is a poor proxy for their overall productivity and that (v) residence time is the primary driver in the productivity‐allocation‐turnover chain for the observed spatial differences in woody, leaf and root biomass across the rainfall gradient. Through a systematic assessment of forest productivity we demonstrate the importance of directly measuring the main components of above and belowground NPP and encourage the establishment of more permanent carbon intensive monitoring plots across the tropics.     

Malaria Infection,Poor Nutrition and Indoor Air Pollution Mediate Socioeconomic Differences in Adverse Pregnancy Outcomes in Cape Coast,Ghana

Background

The epidemiological evidence linking socioeconomic deprivation with adverse pregnancy outcomes has been conflicting mainly due to poor measurement of socioeconomic status (SES). Studies have also failed to evaluate the plausible pathways through which socioeconomic disadvantage impacts on pregnancy outcomes. We investigated the importance of maternal SES as determinant of birth weight and gestational duration in an urban area and evaluated main causal pathways for the influence of SES.

Methods

A population-based cross-sectional study was conducted among 559 mothers accessing postnatal services at the four main health facilities in Cape Coast, Ghana in 2011. Information on socioeconomic characteristics of the mothers was collected in a structured questionnaire.

Results

In multivariate linear regression adjusting for maternal age, parity and gender of newborn, low SES resulted in 292 g (95% CI: 440–145) reduction in birth weight. Important SES-related determinants were neighborhood poverty (221 g; 95% CI: 355–87), low education (187 g; 95% CI: 355–20), studentship during pregnancy (291 g; 95% CI: 506–76) and low income (147 g; 95% CI: 277–17). In causal pathway analysis, malaria infection (6–20%), poor nutrition (2–51%) and indoor air pollution (10–62%) mediated substantial proportions of the observed effects of socioeconomic deprivation on birth weight. Generalized linear models adjusting for confounders indicated a 218% (RR: 3.18; 95% CI: 1.41–7.21) risk increase of LBW and 83% (RR: 1.83; 95% CI: 1.31–2.56) of PTB among low income mothers. Low and middle SES was associated with 357% (RR: 4.57; 95% CI: 1.67–12.49) and 278% (RR: 3.78; 95% CI: 1.39–10.27) increased risk of LBW respectively. Malaria infection, poor nutrition and indoor air pollution respectively mediated 10–21%, 16–44% and 31–52% of the observed effects of socioeconomic disadvantage on LBW risk.

Conclusion

We provide evidence of the effects of socioeconomic deprivation, substantially mediated by malaria infection, poor nutrition and indoor air pollution, on pregnancy outcomes in a developing country setting.     

Achieving global mortality reduction targets and universal health coverage: The impact of COVID-19

Wenhui Mao and coauthors discuss possible implications of the COVID-19 pandemic for health aspirations in low- and middle-income countries.

Summary points

• The Coronavirus Disease 2019 (COVID-19) pandemic threatens progress toward a “grand convergence” in global health—universal reduction in deaths from infections and maternal and child health conditions to low levels—and toward achieving universal health coverage (UHC).
• Our analysis suggests that COVID-19 will exacerbate the difficulty of achieving grand convergence targets for tuberculosis (TB), maternal mortality, and, probably, for under-5 mortality. HIV targets are likely to be met.
• By 2035, our analysis suggests that the public sectors of low-income countries (LICs) would only be able to finance about a third of the costs of a package of 120 essential non-COVID-19 health interventions through domestic sources, unless the country increases significantly the priority assigned to the health sector; lower middle-income countries (LMICs) would likewise only be able to finance a little less than half.
• The likelihood of getting back on track for reaching grand convergence and UHC will depend on (i) how quickly COVID-19 vaccines can be deployed in LICs and LMICs; (ii) how much additional public sector health financing can be mobilized from external and domestic sources; and (iii) whether countries can rapidly strengthen and focus their health delivery systems.

     

The lack of effectiveness of (−)-epicatechin against alloxan induced diabetes in Wistar rats

(?)-Epicatechin, a naturally occurring flavonoid, has been reported to protect pancreatic beta cells from alloxan-induced diabetes (1) and to stimulate beta cell regeneration when given after alloxan administration (2,3). However, in the present study, we have not been able to confirm these findings. Administration of (?)-epicatechin (100 mg/kg/day for 15 days) beginning three days after alloxan administration (140 mg/kg) had no significant effect on blood glucose levels when compared to alloxan control animals. Another study which failed to demonstrate an antidiabetic effect of (?)-epicatechin (4) has been criticized for not using fresh solutions of (?)-epicatechin because of its instability in aqueous solution (5). We have found, however, that (?)-epicatechin is stable for at least five days based on thin-layer chromatographic analysis and optical rotation measurements.