Problems concerning the operation of high productivity biomass fermentations using volatile liquid hydrocarbon feedstocks

The possibilities of using liquefied petroleum gas (LPG) heavy ends, predominantly volatile liquid n-alkanes (a location-specific hydrocarbon feedstock) for single-cell protein (SCP) production are examined against criteria established to define potentially attractive SCP production processes. The factors discussed include the use of the heat of vaporization for fermentor cooling, the efficiency of conversion of nalkane vapors, problems of maintaining constant composition substrates when feeding volatile liquid n-alkane vapors to laboratory fermentors, the possible solvent effect of liquid n-alkanes, and the possibilities of competitive inhibition. The study confirms that mixed volatile n-alkane feedstocks will introduce major physical and biological problems for both product and process research and development. Even when the technical problems are solved, the economic question of whether a direct production route using the feedstock as the fermentation substrate or an indirect route involving the conversion of the feedstock, by chemical means, into methanol, which can then be used as the fermentation substrate, needs careful examination.     

Kindlin Is Mechanosensitive: Force-Induced Conformational Switch Mediates Cross-Talk among Integrins

Mechanical stresses directly regulate the function of several proteins of the integrin-mediated focal adhesion complex as they experience intra- and extracellular forces. Kindlin is a largely overlooked member of the focal adhesion complex whose roles in cellular mechanotransduction are only recently being identified. Recent crystallographic experiments have revealed that kindlins can form dimers that bind simultaneously to two integrins, providing a mechanistic explanation of how kindlins may promote integrin activation and clustering. In this study, using the newly identified molecular structure, we modeled the response of the kindlin2 dimer in complex with integrin β1 to mechanical cytoskeletal forces on integrins. Using molecular dynamics simulations, we show that forces on integrins are directly transmitted to the kindlin2 dimerization site, resulting in a shift in an R577-S550/E553 interaction network at this site. Under force, R577 on one protomer switches from interacting with S550 to forming new hydrogen bonds with E553 on the neighboring protomer, resulting in the strengthening of the kindlin2 dimer in complex with integrin β1. This force-induced strengthening is similar to the catch-bond mechanisms that have previously been observed in other adhesion molecules. Based on our results, we propose that the kindlin2 dimer is mechanosensitive and can strengthen integrin-mediated focal adhesions under force by shifting the interactions at its dimerization sites.     

Novel pyrrolopyrimidine derivatives: design,synthesis, molecular docking,molecular simulations and biological evaluations as antioxidant and anti-inflammatory agents

Current medical approaches to control the Covid-19 pandemic are either to directly target the SARS-CoV-2 via innovate a defined drug and a safe vaccine or indirectly target the medical complications of the virus. One of the indirect strategies for fighting this virus has been mainly dependent on using anti‐inflammatory drugs to control cytokines storm responsible for severe health complications. We revealed the discovery of novel fused pyrrolopyrimidine derivatives as promising antioxidant and anti-inflammatory agents. The newly synthesised compounds were evaluated for their in vitro anti-inflammatory activity using RAW264.7 cells after stimulation with lipopolysaccharides (LPS). The results revealed that 3a, 4b, and 8e were the most potent analogues. Molecular docking and simulations of these compounds against COX-2, TLR-2 and TLR-4 respectively was performed. The former results were in line with the biological data and proved that 3a, 4b and 8e have potential antioxidant and anti-inflammatory effects.     

Fourfold paralogy regions on human HOX-bearing chromosomes: Role of ancient segmental duplications in the evolution of vertebrate genome

BackgroundSusumu Ohno’s idea that modern vertebrates are degenerate polyploids (concept referred as 2R hypothesis) has been the subject of intense debate for past four decades. It was proposed that intra-genomic synteny regions (paralogons) in human genome are remains of ancient polyploidization events that occurred early in the vertebrate history. The quadruplicated paralogon centered on human HOX clusters is taken as evidence that human HOX-bearing chromosomes were structured by two rounds of whole genome duplication (WGD) events.ResultsEvolutionary history of human HOX-bearing chromosomes (chromosomes 2/7/12/17) was evaluated by the phylogenetic analysis of multigene families with triplicated or quadruplicated distribution on these chromosomes. Topology comparison approach categorized the members of 44 families into four distinct co-duplicated groups. Distinct gene families belonging to a particular co-duplicated group, exhibit similar evolutionary history and hence have duplicated simultaneously, whereas genes of two distinct co-duplicated groups do not share their evolutionary history and have not duplicated in concert with each other.ConclusionThe recovery of co-duplicated groups suggests that “ancient segmental duplications and rearrangements” is the most rational model of evolutionary events that have generated the triplicated and quadruplicated paralogy regions seen on the human HOX-bearing chromosomes.     

Improved Chiral SFC Screening for Analytical Method Development

In this study we describe the evaluation of a recently developed supercritical fluid chromatography (SFC) instrument for automated chiral SFC method development. The greatly improved gradient dwell volume and liquid flow control of the new instrument in combination with the use of shorter columns containing smaller stationary phase particles affords chiral SFC method development that is faster and more universal than previous systems. Chirality 25:799–804, 2013. © 2013 Wiley Periodicals, Inc.     

Effect of Lower Doses of Vanadate in Combination with Azadirachta indica Leaf Extract on Hepatic and Renal Antioxidant Enzymes in Streptozotocin-Induced Diabetic Rats

The present study was undertaken to investigate short-term (21 days) effects of oral administration of Azadirachta indica leaf extract and vanadate, separately and in combination, on the activities of antioxidant enzymes in streptozotocin-induced diabetic rats. Vanadate is a remarkable antidiabetic agent and shows insulin mimetic effect. However, severe toxicity is associated with vanadate when used in high concentration while at lower concentration the hypoglycemic property of vanadate is reduced. So, we used a low dose of vanadate in combination with A. indica leaf extract and evaluated their effect on the antioxidant defense system. Streptozotocin-diabetic rats were treated separately with insulin, vanadate (0.6 mg/ml), A. indica, and with combined dose of vanadate (0.2 mg/ml) and A. indica. At the end of the experiment, rats were sacrificed and serum glucose levels and activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were determined in cytosolic fraction of liver and kidney. Diabetic rats showed hyperglycemic condition and alteration in antioxidant enzyme activities. Treatment with antidiabetic compounds resulted in the reduction of glucose levels and restoration of enzyme activities to normal. Results showed that combined treatment of vanadate and A. indica leaf extract was the most effective in normalizing altered antioxidant enzyme system.     

Heliotherapy for Neonatal Hyperbilirubinemia in Southwest,Nigeria: A Baseline Pre-Intervention Study

Background

A novel filtered-sunlight phototherapy (FSPT) device has been demonstrated to be safe and efficacious for treating infants with neonatal jaundice in resource-constrained tropical settings. We set out to provide baseline data for evaluating the clinical impact of this device in a referral pediatric hospital.

Methods

We reviewed the medical records of infants admitted for neonatal hyperbilirubinemia in an inner-city Children’s Hospital in Lagos, between January 2012 and December 2014 to determine the pattern, treatment and outcomes during the pre-intervention period. Factors associated with adverse outcomes were identified through multivariable logistic regression.

Results

Of the 5,229 neonatal admissions over the period, a total of 1,153 (22.1%) were admitted for neonatal hyperbilirubinemia. Complete records for 1,118 infants were available for analysis. The incidence of acute bilirubin encephalopathy (ABE) and exchange transfusion (ET) were 17.0% (95% CI: 14.9%–19.3%) and 31.5% (95% CI: 28.8%–34.3%) respectively. A total of 61 (5.5%, 95% CI: 4.3%–6.9%) of the jaundiced infants died. Weight on admission, peak total serum bilirubin (TSB), sepsis and exposure to hemolytic products were predictive of ABE, while age on admission, peak TSB, ABO incompatibility and ABE were predictive of ET. Rhesus incompatibility, asphyxia, exposure to hemolytic substances and ABE were associated with elevated mortality risk, while ET was a protective factor. Lack of routine irradiance monitoring and steady energy supply were frequent challenges for conventional blue-light phototherapy.

Conclusions

Severe hyperbilirubinemia is associated with high rates of ABE and ET in this setting, and remains a significant contributor to neonatal admissions and mortality. To be impactful, FSPT, complemented with improved diagnostic facilities, should effectively curtail jaundice-related adverse outcomes in this and comparable settings.     

Soil microbes alter plant fitness under competition and drought

Plants exist across varying biotic and abiotic environments, including variation in the composition of soil microbial communities. The ecological effects of soil microbes on plant communities are well known, whereas less is known about their importance for plant evolutionary processes. In particular, the net effects of soil microbes on plant fitness may vary across environmental contexts and among plant genotypes, setting the stage for microbially mediated plant evolution. Here, we assess the effects of soil microbes on plant fitness and natural selection on flowering time in different environments. We performed two experiments in which we grew Arabidopsis thaliana genotypes replicated in either live or sterilized soil microbial treatments, and across varying levels of either competition (isolation, intraspecific competition or interspecific competition) or watering (well‐watered or drought). We found large effects of competition and watering on plant fitness as well as the expression and natural selection of flowering time. Soil microbes increased average plant fitness under interspecific competition and drought and shaped the response of individual plant genotypes to drought. Finally, plant tolerance to either competition or drought was uncorrelated between soil microbial treatments suggesting that the plant traits favoured under environmental stress may depend on the presence of soil microbes. In summary, our experiments demonstrate that soil microbes can have large effects on plant fitness, which depend on both the environment and individual plant genotype. Future work in natural systems is needed for a complete understanding of the evolutionary importance of interactions between plants and soil microorganisms.