Platelet-activating factor-induced chemokine gene expression requires NF-kappaB activation and Ca2+/calcineurin signaling pathways. Inhibition by receptor phosphorylation and beta-arrestin recruitment

Previously, we reported that platelet-activating factor (PAF) stimulates higher G protein activation and a more robust Ca2+ mobilization in RBL-2H3 cells expressing carboxyl terminus deletion, phosphorylation-deficient mutant of PAF receptor (mPAFR) when compared with the wild-type receptor (PAFR). However, PAF did not provide sufficient signal for CC chemokine receptor ligand 2 (CCL2) production in cells expressing mPAFR. Based on these findings, we hypothesized that receptor phosphorylation provides a G protein-independent signal that synergizes with Ca2+ mobilization to induce CCL2 production. Here, we show that a mutant of PAFR (D289A), which does not couple to G proteins, was resistant to agonist-induced receptor phosphorylation. Unexpectedly, we found that when this mutant was coexpressed with mPAFR, it restored NF-kappaB activation and CCL2 production. PAF caused translocation of beta-arrestin from the cytoplasm to the membrane in cells expressing PAFR but not a phosphorylation-deficient mutant in which all Ser/Thr residues were replaced with Ala (DeltaST-PAFR). Interestingly, PAF induced significantly higher NF-kappaB and nuclear factor of activated T cells (NFAT)-luciferase activity as well as CCL2 production in cells expressing DeltaST-PAFR than those expressing PAFR. Furthermore, a Ca2+/calcineurin inhibitor completely inhibited PAF-induced NFAT activation and CCL2 production but not NF-kappaB activation. These findings suggest that the carboxyl terminus of PAFR provides a G protein-independent signal for NF-kappaB activation, which synergizes with G protein-mediated Ca2+/calcineurin activation to induce CCL2 production. However, receptor phosphorylation and beta-arrestin recruitment inhibit CCL2 production by blocking both NF-kappaB activation and Ca2+/calcineurin-dependent signaling pathways.     

A mass mortality of fishes caused by receding water levels in the vegetated littoral zone of the West Kleinemonde Estuary,South Africa

On 15 November 2017 the mouth of the West Kleinemonde Estuary breached following heavy catchment rains and increased river flow. The water level in the estuary following mouth opening decreased by 1.65 m within 24 h, resulting in an almost complete draining of the littoral zone where large beds of the aquatic macrophyte Ruppia cirrhosa and mats of the associated filamentous algae were present. As the water depth within the plant beds decreased, the macrophytes, together with the algal filaments, created an increasingly dense mat, trapping fish that were resident, foraging or passing through the littoral zone. By 16 November 2017 large numbers of fishes belonging to at least 20 species were trapped in pools and depressions within the littoral, as well as within the R. cirrhosa beds and filamentous algal mats in the lower reaches of this system. Other affected taxa included crustaceans, especially isopods, and large numbers of small bivalves attached to macrophyte vegetation. Beneficiaries of the fish kill, in terms of unexpected food availability, included a variety of piscivorous bird species and the Cape clawless otter Aonyx capensis. This is the first documented account of a diverse species fish kill associated with estuary mouth breaching.     

Length‐weight and length‐length relationships of two gobiid fishes Eleotris fusca (Forster, 1801) and Odontamblyopus rubicundus (Hamilton, 1822) from the Payra River,southern Bangladesh

The present study provides the estimates of length‐weight relationships (LWRs) and length‐length relationships (LLRs) of two gobiid fishes Eleotris fusca and Odontamblyopus rubicundus from the Payra River, southern Bangladesh. Fish samples were collected from the set bagnet (mesh size <2 mm) fishers of the Payra River in July 2016. Allometric coefficient (b) values were 2.95 for E. fusca and 2.76 for O. rubicundus. Additionally, the LLRs were highly significant with r² ≥ .955. While the estimate of the LWR for O. rubicundus includes a substantial larger sample size and thus provides a more reliable LWR than the one published so far, the LWR for E. fusca must be considered as tentative because the sample includes only juveniles for a fish that reaches a maximum standard length more than three times as much. Additional studies are needed to further improve our LWR knowledge base for these fish species.     

Trends in Malaria in Odisha,India—An Analysis of the 2003–2013 Time-Series Data from the National Vector Borne Disease Control Program

Background

Although Odisha is the largest contributor to the malaria burden in India, no systematic study has examined its malaria trends. Hence, the spatio-temporal trends in malaria in Odisha were assessed against the backdrop of the various anti-malaria strategies implemented in the state.

Methods

Using the district-wise malaria incidence and blood examination data (2003–2013) from the National Vector Borne Disease Control Program, blood examination-adjusted time-trends in malaria incidence were estimated and predicted for 2003–2013 and 2014–2016, respectively. An interrupted time series analysis using segmented regression was conducted to compare the disease trends between the pre (2003–2007) and post-intensification (2009–2013) periods. Key-informant interviews of state stakeholders were used to collect the information on the various anti-malaria strategies adopted in the state.

Results

The state annual malaria incidence declined from 10.82/1000 to 5.28/1000 during 2003–2013 (adjusted annual decline: -0.54/1000, 95% CI: -0.78 to -0.30). However, the annual blood examination rate remained almost unchanged from 11.25% to 11.77%. The keyinformants revealed that intensification of anti-malaria activities in 2008 led to a more rapid decline in malaria incidence during 2009–2013 as compared to that in 2003–2007 [adjusted decline: -0.83 (-1.30 to -0.37) and -0.27 (-0.41 to -0.13), respectively]. There was a significant difference in the two temporal slopes, i.e., -0.054 (-0.10 to -0.002, p = 0.04) per 1000 population per month, between these two periods, indicating almost a 200% greater decline in the post-intensification period. Although, the seven southern high-burden districts registered the highest decline, they continued to remain in that zone, thereby, making the achievement of malaria elimination (incidence <1/1000) unlikely by 2017.

Conclusion

The anti-malaria strategies in Odisha, especially their intensification since 2008, have helped improve its malaria situation in recent years. These successful measures need to be sustained and perhaps intensified further for eliminating malaria from Odisha.     

Multiple factors interact to produce responses resembling spectrum of human disease in Campylobacter jejuni infected C57BL/6 IL-10-/- mice

Background  

Campylobacter jejuni infection produces a spectrum of clinical presentations in humans - including asymptomatic carriage, watery diarrhea, and bloody diarrhea - and has been epidemiologically associated with subsequent autoimmune neuropathies. This microorganism is genetically variable and possesses genetic mechanisms that may contribute to variability in nature. However, relationships between genetic variation in the pathogen and variation in disease manifestation in the host are not understood. We took a comparative experimental approach to explore differences among different C. jejuni strains and studied the effect of diet on disease manifestation in an interleukin-10 deficient mouse model.     

Copper Oxide Nanoparticles Induced Mitochondria Mediated Apoptosis in Human Hepatocarcinoma Cells

Copper oxide nanoparticles (CuO NPs) are heavily utilized in semiconductor devices, gas sensor, batteries, solar energy converter, microelectronics and heat transfer fluids. It has been reported that liver is one of the target organs for nanoparticles after they gain entry into the body through any of the possible routes. Recent studies have shown cytotoxic response of CuO NPs in liver cells. However, the underlying mechanism of apoptosis in liver cells due to CuO NPs exposure is largely lacking. We explored the possible mechanisms of apoptosis induced by CuO NPs in human hepatocellular carcinoma HepG2 cells. Prepared CuO NPs were spherical in shape with a smooth surface and had an average diameter of 22 nm. CuO NPs (concentration range 2–50 µg/ml) were found to induce cytotoxicity in HepG2 cells in dose-dependent manner, which was likely to be mediated through reactive oxygen species generation and oxidative stress. Tumor suppressor gene p53 and apoptotic gene caspase-3 were up-regulated due to CuO NPs exposure. Decrease in mitochondrial membrane potential with a concomitant increase in the gene expression of bax/bcl2 ratio suggested that mitochondria mediated pathway involved in CuO NPs induced apoptosis. This study has provided valuable insights into the possible mechanism of apoptosis caused by CuO NPs at in vitro level. Underlying mechanism(s) of apoptosis due to CuO NPs exposure should be further invested at in vivo level.     

Biomimetic Synthesis of Selenium Nanospheres by Bacterial Strain JS-11 and Its Role as a Biosensor for Nanotoxicity Assessment: A Novel Se-Bioassay

Selenium nanoparticles (Se-NPs) were synthesized by green technology using the bacterial isolate Pseudomonas aeruginosa strain JS-11. The bacteria exhibited significant tolerance to selenite (SeO₃ ²⁻) up to 100 mM concentration with an EC₅₀ value of 140 mM. The spent medium (culture supernatant) contains the potential of reducing soluble and colorless SeO₃ ²⁻ to insoluble red elemental selenium (Se⁰) at 37°C. Characterization of red Se° product by use of UV-Vis spectroscopy, X-ray diffraction (XRD), atomic force microscopy (AFM) and transmission electron microscopy (TEM) with energy dispersive X-ray spectrum (EDX) analysis revealed the presence of stable, predominantly monodispersed and spherical selenium nanoparticles (Se-NPs) of an average size of 21 nm. Most likely, the metabolite phenazine-1-carboxylic acid (PCA) released by strain JS-11 in culture supernatant along with the known redox agents like NADH and NADH dependent reductases are responsible for biomimetic reduction of SeO₃ ²⁻ to Se° nanospheres. Based on the bioreduction of a colorless solution of SeO₃ ²⁻ to elemental red Se⁰, a high throughput colorimetric bioassay (Se-Assay) was developed for parallel detection and quantification of nanoparticles (NPs) cytotoxicity in a 96 well format. Thus, it has been concluded that the reducing power of the culture supernatant of strain JS-11 could be effectively exploited for developing a simple and environmental friendly method of Se-NPs synthesis. The results elucidated that the red colored Se° nanospheres may serve as a biosensor for nanotoxicity assessment, contemplating the inhibition of SeO₃ ²⁻ bioreduction process in NPs treated bacterial cell culture supernatant, as a toxicity end point.