Recent developments in bioreactor scale production of bacterial polyhydroxyalkanoates

Bioprocess and Biosystems Engineering - Polyhydroxyalkanoates (PHAs) are biological plastics that are sustainable alternative to synthetic ones. Numerous microorganisms have been identified as PHAs...     

Changes in presynaptic calcium signalling accompany age‐related deficits in hippocampal LTP and cognitive impairment

The loss of cognitive function accompanying healthy aging is not associated with extensive or characteristic patterns of cell death, suggesting it is caused by more subtle changes in synaptic properties. In the hippocampal CA1 region, long‐term potentiation requires stronger stimulation for induction in aged rats and mice and long‐term depression becomes more prevalent. An age‐dependent impairment of postsynaptic calcium homeostasis may underpin these effects. We have examined changes in presynaptic calcium signalling in aged mice using a transgenic mouse line (SyG37) that expresses a genetically encoded calcium sensor in presynaptic terminals. SyG37 mice showed an age‐dependent decline in cognitive abilities in behavioural tasks that require hippocampal processing including the Barnes maze, T‐maze and object location but not recognition tests. The incidence of LTP was significantly impaired in animals over 18 months of age. These effects of aging were accompanied by a persistent increase in resting presynaptic calcium, an increase in the presynaptic calcium signal following Schaffer collateral fibre stimulation, an increase in postsynaptic fEPSP slope and a reduction in paired‐pulse facilitation. These effects were not caused by synapse proliferation and were of presynaptic origin since they were evident in single presynaptic boutons. Aged synapses behaved like younger ones when the extracellular calcium concentration was reduced. Raising extracellular calcium had little effect on aged synapses but altered the properties of young synapses into those of their aged counterparts. These effects can be readily explained by an age‐dependent change in the properties or numbers of presynaptic calcium channels.     

Size and time-dependent induction of proinflammatory cytokines expression in brains of mice treated with gold nanoparticles

Gold nanoparticles (GNPs) are among the ideal nano-sized materials for medical applications such as imaging and drug delivery. Considering the significance of recent reports on acute phase induction of inflammatory mediators by GNPs, we studied the effect of GNPs on proinflammatory cytokines gene expression in mouse brain. Group 1 served as control whereas groups 2–4 were given only one intraperitoneal dose of 5, 20 and 50?nm GNPs, respectively and sacrificed after 24?h. The animals in groups 5–7 also received the same treatment but sacrificed after 7?days. Groups 8–10 received two injections of GNPs (5, 20 and 50?nm, respectively), first at the beginning of study and second on day 6, and sacrificed on day 7. Total RNA was extracted from the cerebral tissue and analyzed for the gene expressions of IL-1β, IL-6 and TNF-α. A single injection of 5?nm diameter GNPs significantly increased the mRNA expression of IL-1β and IL-6 in mouse brain on day 7, which was not augmented by the second dose of the same GNPs. Larger size GNPs (20?nm and 50?nm) did not cause any significant change in the expression of proinflammatory cytokines in mouse brain. In conclusion, systemic administration of small sized GNPs (5?nm) induced a proinflammatory cascade in mouse brain indicating a crucial role of GNPs size on immune response. It is important to use the right sized GNPs in order to avoid an acute phase inflammatory response that could be cytotoxic or interfere with the bioavailability of nanomaterials.     

Toxicological impact of butralin,glyphosate-isopropylammonium and pendimethalin herbicides on physiological parameters of Biomphalaria alexandrina snails

ABSTRACT

Biomphalaria alexandrina snails have been used as bioindicators for freshwater qaulity and the effects of some herbicides such as butralin, glyphosate-isopropylammonium and pendimethalin). In the present study the effect of these three herbicides on snail biochemistry was examined. The results indicated that the herbicides increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the haemolymph of B. alexandrina snails and significantly decreased total protein and albumin content. Light microscopical examinations of haemocytes monolayers of B. alexandrina snails showed three different cell types (small cells, granulocytes and hyalinocytes). All three herbicides caused abnormalities in cell shapes. Flow cytometric analysis of haemocytes from B. alexandrina demonstrated that circulating haemocyte populations could be divided into two main subtypes differing in their granularity (granulocytes or hyalinocytes) and size (large and small cells). In addition, the flow cytometric analysis showed that the total number of dead haemocytes in the haemolymph was significantly increased in treated groups compared to the control group. Phagocytosis in groups treated with the herbicides was highly significantly increased compared to the control indicating a very strong response of the treated snails. The results of the alkaline comet assay of DNA damage demonstrated that these herbicides have a genotoxic effect.     

Multiple stressor effects on coral reef ecosystems

Global climate change has profound implications on species distributions and ecosystem functioning. In the coastal zone, ecological responses may be driven by various biogeochemical and physical environmental factors. Synergistic interactions can occur when the combined effects of stressors exceed their individual effects. The Red Sea, characterized by strong gradients in temperature, salinity, and nutrients along the latitudinal axis provides a unique opportunity to study ecological responses over a range of these environmental variables. Using multiple linear regression models integrating in situ, satellite and oceanographic data, we investigated the response of coral reef taxa to local stressors and recent climate variability. Taxa and functional groups responded to a combination of climate (temperature, salinity, air‐sea heat fluxes, irradiance, wind speed), fishing pressure and biogeochemical (chlorophyll a and nutrients ‐ phosphate, nitrate, nitrite) factors. The regression model for each species showed interactive effects of climate, fishing pressure and nutrient variables. The nature of the effects (antagonistic or synergistic) was dependent on the species and stressor pair. Variables consistently associated with the highest number of synergistic interactions included heat flux terms, temperature, and wind speed followed by fishing pressure. Hard corals and coralline algae abundance were sensitive to changing environmental conditions where synergistic interactions decreased their percentage cover. These synergistic interactions suggest that the negative effects of fishing pressure and eutrophication may exacerbate the impact of climate change on corals. A high number of interactions were also recorded for algae, however for this group, synergistic interactions increased algal abundance. This study is unique in applying regression analysis to multiple environmental variables simultaneously to understand stressor interactions in the field. The observed responses have important implications for understanding climate change impacts on marine ecosystems and whether managing local stressors, such as nutrient enrichment and fishing activities, may help mitigate global drivers of change.     

Expansion of Aedes africanus (Diptera: Culicidae), a sylvatic vector of arboviruses,into an urban environment of Abidjan,Côte d'Ivoire

In 2008, an outbreak of yellow fever occurred in Abidjan. The entomological investigations confirm that Abidjan is at risk of yellow fever with a suspicion of the National Park of Banco (NPB) forest as a likely area of re‐emergence. This study aims to assess the dispersion of sylvatic vectors of arboviruses from the NPB forest to the surrounding areas (Andokoi and Sagbé). The sampling was done in the rainy season using the WHO layer‐traps technique. Among the six species of Aedes sampled, Aedes aegypti and Aedes africanus were the potential vectors of arboviruses. Both species were collected in Sagbé but only Ae. aegypti in Andokoi. Only Ae. aegypti were present 400 and 800 m from NPB forest, but at 200 m, it showed respective proportions of 75.5% and 87.5% in Sagbé and Andokoi. In the NPB forest, however, Ae. africanus has been the predominant species. The study showed the presence of Ae. aegypti in Andokoi and Sagbé. However, Ae. africanus was found in the NPB forest and in the 200 m radius in Sagbé. The establishment of an entomological surveillance program in all areas would therefore be essential for the prevention of arboviruses outbreaks in Abidjan.     

Drug repurposing for SARS-CoV-2 main protease: Molecular docking and molecular dynamics investigations

The current novel corona virus illness (COVID-19) is a developing viral disease that was discovered in 2019. There is currently no viable therapeutic strategy for this illness management. Because traditional medication development and discovery has lagged behind the threat of emerging and re-emerging illnesses like Ebola, MERS-CoV, and, more recently, SARS-CoV-2. Drug developers began to consider drug repurposing (or repositioning) as a viable option to the more traditional drug development method. The goal of drug repurposing is to uncover new uses for an approved or investigational medicine that aren't related to its original use. The main benefits of this strategy are that there is less developmental risk and that it takes less time because the safety and pharmacologic requirements are met. The main protease (Mpro) of corona viruses is one of the well-studied and appealing therapeutic targets. As a result, the current research examines the molecular docking of Mpro (PDB ID: 5R81) conjugated repurposed drugs. 12,432 approved drugs were collected from ChEMBL and drugbank libraries, and docked separately into the receptor grid created on 5R81, using the three phases of molecular docking including high throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP). Based on docking scores and MM-GBSA binding free energy calculation, top three drugs (kanamycin, sulfinalol and carvedilol) were chosen for further analyses for molecular dynamic simulations.     

Kinetic analyses as a critical parameter in defining the side population (SP) phenotype

The side population (SP) phenotype has been reported as a method to identify hematopoietic stem cells in the bone marrow based upon differential staining with the fluorescent dye, Hoechst 33342. This technique has drawn great interest in the stem cell community, as it may provide a simple approach to the enrichment of progenitor cells from a variety of normal and malignant tissues. The frequency of these cells and their performance in functional assays has varied considerably within the literature. To investigate mechanisms that may contribute to the SP phenotype, we measured the fluorescence emission of Hoechst-stained bone marrow cells as a function of both time and dye concentration using a custom flow cytometer and data acquisition software. These measurements demonstrate that all nucleated cells within the bone marrow undergo an identical staining pattern at varying rates, even under conditions previously reported to abrogate the SP. Therefore, the SP phenotype is not unique to stem cells, but rather represents a transient feature of marrow cells exposed to Hoechst 33342 for varying amounts of time. We propose that heterogeneity of SP-defined populations may be a consequence of the rate at which differing cell populations accumulate Hoechst 33342. Further, we suggest that dye uptake kinetics will likely be an important factor for optimal use of Hoechst 33342 in isolating stem cells.