Measures,Gaps, and Mitigation Strategies in Bangladesh’s COVID-19 Response

EcoHealth - The Coronavirus Disease 2019 (COVID-19) spread rapidly from China to most other countries around the world in early 2020 killing millions of people. To prevent virus spread, world...     

Nicotinic Receptor Subunit α5 Modifies Assembly,Up-regulation,and Response to Pro-inflammatory Cytokines

In the mammalian brain high affinity nicotine-binding sites are composed of at least the α4 and β2 subunits. Additional nicotinic acetylcholine receptor subunits that are often co-expressed with α4+β2 include α5. The introduction of α5 into 293 cells expressing α4+β2 strongly favors assembly of α4+α5+β2 receptors, increases constitutive ligand binding density as measured using [³H]epibatidine, but reduces the magnitude of up-regulation in response to chronic nicotine. In contrast, when β4 is substituted for β2, α5 interferes with the assembly of these receptors, demonstrating an important role for the β subunit in this process. When cells co-express α4+α5+β2+β4, over 50% of the subunit associations include all four subunits, but they fail to be detected using [³H]epibatidine binding. However, complexes of α4+α5+β2 do preferentially emerge from these subunit mixtures, and these mixtures bind ligand. In previous studies of α4+β2+β4 co-expression by 293 cells, the inflammatory cytokines IL-1β and TNFα influenced the outcome of receptor assembly (Gahring, L. C., Days, E. L., Kaasch, T., González de Mendoza, M., Owen, L., Persiyanov, K., and Rogers, S. W. (2005) J. Neuroimmunol. 166, 88–101). When α5 is included in this subunit mixture, and cells are exposed to either inflammatory cytokine, subunit association is no longer altered. These findings suggest that α5 is an influential modulator of α4+β2 nicotinic acetylcholine receptor assembly and stabilizes their expression in response to fluctuations in external conditions.     

“Pleiotypic Response”

A hypothesis has been developed to relate stringent control in bacteria to a set of interactions involved in the regulation of growth of transformed and untransformed mammalian cells.     

Response of β-Glucosidase to Fungal Infections in Seed, Ovary and Fruit

Localization and changes in the activity of -glucosidase were investigated in wheat caryopsis and glumes infected with Stagonospora nodorum as well as in lily ovaries and harvested tomato fruits both inoculated with Botrytis cinerea. It was established that the pathogen invasion caused splitting of wheat seed coat, xylem blocking in lily carpel and decay in tomato fruits. B. cinerea invasion evoked disorders of the embryogenesis accompanied by a decreased activity of -glucosidase in all ovules. The activity of the enzyme was not changed considerably in wheat seeds as the infection occurred in the late embryonal stages and the embryonal processes were not affected. In the seeds of harvested tomatoes distant from the invaded area the enzyme activity was not changed as well.     

PARP-1 Inhibitor,DPQ, Attenuates LPS-Induced Acute Lung Injury through Inhibiting NF-κB-Mediated Inflammatory Response

Acute lung injury (ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Poly (ADP-ribose) polymerase-1 has been demonstrated to be involved in tissue inflammation and one of its inhibitors, 3, 4-Dihydro-5[4-(1-piperindinyl)butoxy]-1(2H)-isoquinoline (DPQ), exerts anti-inflammatory effect. However, it is still unclear whether the DPQ possesses the protective effect on ALI and what mechanisms are involved. In this study, we tested the effect of DPQ on the lung inflammation induced by lipopolysaccharide (LPS) challenge in mice. We found that 6 h-LPS challenge induced significant lung inflammation and vascular leakage in mice. Treatment with DPQ at the dose of 10 μg/kg markedly reduced the neutrophil infiltration, myeloperoxidase activity and up-regulation of pro-inflammatory mediators and cytokines. LPS-elevated vascular permeability was decreased by DPQ treatment, accompanied by the inhibition of apoptotic cell death in mice lungs. In addition, we isolated mice peritoneal macrophages and showed pretreatment with DPQ at 10 μM inhibited the production of cytokines in the macrophages following LPS stimulation. DPQ treatment also inhibited the phosphorylation and degradation of IκB-α, subsequently blocked the activation of nuclear factor (NF)-κB induced by LPS in vivo and in vitro. Taken together, our results show that DPQ treatment inhibits NF-κB signaling in macrophages and protects mice against ALI induced by LPS, suggesting inhibition of Poly (ADP-ribose) polymerase-1 may be a potential and effective approach to resolve inflammation for the treatment of ALI.     

Synthetic Peptide TPLVTLFK,a Selective Agonist of Nonopioid β-Endorphin Receptor,Reduces the Corticotropin and Corticosterone Response

The synthetic peptide octarphin (TPLVTLFK) corresponding to the sequence 12–19 of β-endorphin, a selective agonist of nonopioid β-endorphin receptor, was labeled with tritium to specific activity of 29 Ci/mmol. The analysis of the specific binding of [³H]octarphin to anterior pituitary membranes obtained from rats before and after the lipopolysaccharide (LPS)-injection showed that 2 h after LPS administration the value of maximal binding capacity of the membranes (B_max) was increased by 1.6 times (B_max 12.3 ± 0.8 and 20.0 ± 1.9 pmol/mg of protein, respectively), while the binding affinity was not changed (K _d 5.8 ± 0.3 and 5.5 ± 0.4 nM, respectively). At the same time, LPS did not have a significant effect on the characteristics of the labeled peptide binding to adrenal cortex membranes. Intranasal injection of octarphin at doses of 10–30 μg/rat was found to reduce the LPS-induced corticotropin and corticosterone response. The effect of the peptide was dose-dependent with a maximum at a dose 20 μg/rat. Aminoguanidine (AG 100 mg/kg i.p.), a selective inducible nitric oxide synthase (iNOS) inhibitor, completely abolished the inhibitory effect of the peptide on the LPS-induced corticotropin and corticosterone response. At the same time, octarphin in vitro stimulated in a time- and concentration-dependent manner the anterior pituitary iNOS expression of rats injected with LPS (1 mg/kg i.p.). The maximum level of the iNOS expression was observed at a peptide concentration of 10 nM after 2 h cultivation. These results indicate that the inhibitory effect of octarphin on LPS-induced secretion of corticotropin and corticosterone due to the ability of the peptide to stimulate the expression of iNOS in the anterior pituitary.     

Activity Change in Response to Bad Air Quality,National Health and Nutrition Examination Survey, 2007–2010

Air pollution contributes to poor respiratory and cardiovascular health. Susceptible individuals may be advised to mitigate effects of air pollution through actions such as reducing outdoor physical activity on days with high pollution. Our analysis identifies the extent to which susceptible individuals changed activities due to bad air quality. This cross-sectional study included 10,898 adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Participants reported if they did something differently when air quality was bad. Susceptible categories included respiratory conditions, cardiovascular conditions and older age (≥65 years). Analyses accounted for complex survey design; logistic regression models controlled for gender, race, education, smoking, and body mass index. 1305 individuals reported doing something differently (12.0%, 95% confidence interval (CI): 10.9, 13.1). This percentage was 14.2% (95% CI: 11.6, 16.8), 25.1% (95% CI: 21.7, 28.6), and 15.5% (95% CI: 12.2, 18.9) among older adults, those with a respiratory condition, and those with a cardiovascular condition, respectively. In adjusted regression models the following were significantly more likely to have changed activity compared to those who did not belong to any susceptible group: respiratory conditions (adjusted odds ratio (aOR): 2.61, 95% CI: 2.03, 3.35); respiratory and cardiovascular conditions (aOR: 4.36, 95% CI: 2.47, 7.69); respiratory conditions and older age (aOR: 3.83; 95% CI: 2.47, 5.96); or all three groups (aOR: 3.52; 95% CI: (2.33, 5.32). Having cardiovascular conditions alone was not statistically significant. Some individuals, especially those with a respiratory condition, reported changing activities due to poor air quality. However, efforts should continue to educate the public about air quality and health.     

Response of thirsty rats to absence of water: Frustration,disinhibition or compensation?

Water-deprived rats were allowed to drink in an experimental chamber during a series of training trials, and were then presented with an empty water spout during a single test trial. Their initial response to absence of water was to bite, sniff and paw at the empty spout (spout-directed behaviour), after which they engaged in activities such as eating, grooming and exploration of the chamber. By comparison with control animals that had no expectation of water, experimental rats performed these latter activities in a bizarre ‘speeded-up’ manner, which was quantifiable as an increase in local rate. Both the occurrence of spout-directed behaviour and the increase in local rate of other activities were enhanced by increasing the prior level of water deprivation and by offering a more palatable fluid during training. The results are discussed in relation to current models of behavioural switching.     

An Adaptive Immune Response in Drosophila?

The ability to mount an adaptive immune response is thought to be an attribute restricted to vertebrates. A new study conducted in Drosophila demonstrates that invertebrate immunity can adapt to an immune challenge and mount a specific immune response.     

Adaptive Response to DNA-Damaging Agents in Natural Saccharomyces cerevisiae Populations from “Evolution Canyon”, Mt. Carmel,Israel

Background

Natural populations of most organisms, especially unicellular microorganisms, are constantly exposed to harsh environmental factors which affect their growth. UV radiation is one of the most important physical parameters which influences yeast growth in nature. Here we used 46 natural strains of Saccharomyces cerevisiae isolated from several natural populations at the “Evolution Canyon” microsite (Nahal Oren, Mt. Carmel, Israel). The opposing slopes of this canyon share the same geology, soil, and macroclimate, but they differ in microclimatic conditions. The interslope differences in solar radiation (200%–800% more on the “African” slope) caused the development of two distinct biomes. The south-facing slope is sunnier and has xeric, savannoid “African” environment while the north-facing slope is represented by temperate, “European” forested environment. Here we studied the phenotypic response of the S. cerevisiae strains to UVA and UVC radiations and to methyl methanesulfonate (MMS) in order to evaluate the interslope effect on the strains'' ability to withstand DNA-damaging agents.

Methodology/Principal Findings

We exposed our strains to the different DNA-damaging agents and measured survival by counting colony forming units. The strains from the “African” slope were more resilient to both UVA and MMS than the strains from the “European” slope. In contrast, we found that there was almost no difference between strains (with similar ploidy) from the opposite slopes, in their sensitivity to UVC radiation. These results suggest that the “African” strains are more adapted to higher solar radiation than the “European” strains. We also found that the tetraploids strains were more tolerant to all DNA-damaging agents than their neighboring diploid strains, which suggest that high ploidy level might be a mechanism of adaptation to high solar radiation.

Conclusions/Significance

Our results and the results of parallel studies with several other organisms, suggest that natural selection appears to select, at a microscale, for adaptive complexes that can tolerate the higher UV radiation on the “African” slope.