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Deficiency in blood coagulation factor VIII (FVIII) results in life-threating bleeding (hemophilia A) treated by infusions of FVIII concentrates. To improve disease treatment, FVIII has been modified to increase its plasma half-life, which requires understanding mechanisms of FVIII catabolism. An important catabolic actor is hepatic low density lipoprotein receptor-related protein 1 (LRP1), which also regulates many other clinically significant processes. Previous studies showed complexity of FVIII site for binding LRP1.To characterize binding sites between FVIII and LRP1 and suggest a model of the interaction.A series of recombinant ligand-binding complement-type repeat (CR) fragments of LRP1 including mutated variants was generated in a baculovirus system and tested for FVIII interaction using surface plasmon resonance, tissue culture model, hydrogen-deuterium exchange mass spectrometry, and in silico.Multiple CR doublets within LRP1 clusters II and IV were identified as alternative FVIII-binding sites. These interactions follow the canonical binding mode providing major binding energy, and additional weak interactions are contributed by adjacent CR domains. A representative CR doublet was shown to have multiple contact sites on FVIII.FVIII and LRP1 interact via formation of multiple complex contacts involving both canonical and non-canonical binding combinations. We propose that FVIII-LRP1 interaction occurs via switching such alternative binding combinations in a dynamic mode, and that this mechanism is relevant to other ligand interactions of the low-density lipoprotein receptor family members including LRP1.

The effects of cadmium alone and that of cadmium plus aqueous extract of the calyx of Hibiscus sabdariffa Linn on organ gravimetry and lipid profile of the African catfish (Clarias gariepinus) have been examined. The treatments did not alter the brain-, gill- and liver- body weight ratios when compared to the cadmium and extract- free group, the control. Relative to the control group, brain and gill homogenates‘ total- and LDL-cholesterol concentrations were significantly (P < 0.05) decreased in the group of fish exposed to cadmium alone. Exposure to cadmium alone also caused significant (P < 0.05) increase in liver triacylglycerol relative to the control. When compared to the group exposed to cadmium only fish exposed to cadmium and 0.25% aqueous extract of Hibiscus sabdariffa Linn calyx had significantly (P < 0.05) higher, brain total – and LDL-cholesterol levels. The latter treatment, combination of cadmium and extract did not alter the levels of triacylglycerol in the three organs examined relative to the cadmium only group. The aqueous extract of Hibiscus sabdariffa calyx therefore offers protection against cadmium-induced decrease in brain total-and LDL-cholesterol of the catfish, Clarias gariepinus.

In this study, the effects of sun-dried and charcoal-broiled beef compounded diets and their vitamin A supplemented versions on vitamin A and ?-carotene levels in rat liver and serum were examined. The rats were in five experimental groups; the sun-dried beef compounded diet only, the charcoal-broiled beef compounded diet only, growers mash plus vitamin A, sun-dried beef compounded diet plus vitamin A supplements, and charcoal-broiled beef compounded diet plus vitamin A supplements. The rats were given 0.8 g feed/g average group body weight in terms of feed for 14 days. The vitamin A supplements were administered to the rats by gavage at a dose of 400 IU units daily for 14 days. After 14 days, relative to rats given sun-dried beef compounded diet only, the rats given charcoal-broiled beef compounded diet only had a statistically significant decrease in ?-carotene and vitamin A levels in the liver, although there was a significant increase in ?-carotene levels in the serum. Administering vitamin A supplements to the compounded diets led to a significant (P < 0.05) increase in ?-carotene in the rat liver and serum compared to the rats given just the corresponding compounded diets only. The results presented here show that regular consumption of broiled beef leads to the production of bioactive metabolites or compounds which reduces vitamin A and ?-carotene levels in the serum and liver

The ability of Hibiscus sabdariffa Linn calyx extract to act as anti-stress agent has been investigated by using its effect on stress-induced changes in serum cholesterol and cortisol levels in the rabbit as a measure of anti-stress action. Relative to zero time serum (zero time post stress) cholesterol value, the 120 minutes value of stressed rabbits treated with water was not significantly changed (67.40 ± 2.32 mg/dL (zero time); 46.80 ± 4.15 mg/dL (120 minutes). However, relative to zero time serum cholesterol value, the 120 minutes value of stressed rabbits treated with Hibiscus sabdariffa Linn calyx extract was significantly (P0.05) different from the 120 minutes value, though the latter was lower in value (9.16 ± 1.76ug/dL (zero time); 5.90 ± 1.52 ?g/dL (120 minutes). These data suggest that Hibiscus sabdariffa Linn calyx extract protects against stress-induced changes in serum cholesterol and so possesses anti-stress ability. The apparent inability of the extract to produce significant reduction in serum cortisol status of stressed and extract treated rabbits is discussed.

The effects of anthocyanin-free aqueous extract of Hibiscus sabdariffa petal on body weight gain, organ/body weight ratio and selected toxicological indices in cadmium intoxicated male rats were examined. When compared to cadmium-free and extract-free control ,cadmium caused significant (P < 0.05) decreases in prostate/body weight and testis/body weight ratios .Prostatic acid phosphatase activity (only in prostate) and catalase activities in the prostate and testis were also significantly ( P < 0.05 ) increased. It was also found to have increased malondialdehyde (MDA) concentrations significantly (P < 0.05) relative to the cadmium-free and extract- free control rats. Pretreatment of rats with anthocyanin-free aqueous extract of H. sabdariffa offered 51.8 and 32.7% protection to the prostate and testis respectively against cadmium-induced decreases in prostate/body weight and testis/body weight ratios relative to rats exposed to cadmium alone. The extract also caused 55.0% decrease in cadmium – mediated inhibition of prostatic acid phosphatase activity in the prostate and 81.8% decrease in its enhancement of superoxide dismutase activity in prostate relative to rats exposed to cadmium alone. Prior exposure of rats to the extract before cadmium significantly (p < 0.05) reduced superoxide dismutase activity in the prostate when compared to the rats exposed to cadmium only. Anthocyanin-free extract of the aqueous extract H. sabdariffa petal therefore offers partial, protection against cadmium – induced changes in prostate and testes

Poor strength and workability often result in low quality concrete that can cause structural failures. This research work was conducted to improve the strength and workability of concrete at reduced amount of water due to the addition of super plasticizer by replacing partially the concrete materials: cement, with fly ash at 0%, 5%, 10% and 15%; fine aggregate, with quarry dust at 0% and 15%; and the addition of sulphonated Naphthalene Formaldehyde Condensate (SNFC) super plasticizer at 0% and 0.6% by weight of cement content reducing the amount of water to 0.45 w/c from the conventional 0.6 and 0.55 w/c ratio. Concrete cube specimens were prepared with these inclusions using grade M20 concrete and nominal mix proportion of 1:2:4. Sieve analysis test, specific gravity test, fineness test were carried out on the concrete materials, workability test was carried out on each concrete specimen, a compressive strength test and weight density test was done at 7days and 28days curing. The compressive strength of concrete made with fly ash, quarry dust and SNFC at 28days ranges from 19.58N/mm2 to 30.23N/mm2. These results were higher compared to those of conventional concrete. A combination of fly ash, quarry dust and SNFC was then recommended for solving problems of low-strength concrete.

Accurate prediction of the natural gas consumption in Nigeria is crucial to Gas management. This study utilizes the improved Grey model (MGM(1,1,⊗b)), which is an improvement of the modified Grey model (MGM(1,1)), to forecast the natural gas consumption of Nigeria for the year 2021 to 2025. A secondary data retrieved from the NNPC 2019 annual statistics bulletin was used to build a model for this prediction. Noting that MGM(1,1) model uses the Grey action quantity as a unique real number which do not reflect the uncertainty nature of Grey systems. A model (MGM(1,1,⊗b)) was developed such that it extends the MGM(1,1) model to retain the uncertainty nature of Grey systems. The new modified Grey model (MGM(1,1,⊗b)) was used to make prediction of the natural gas consumption of Nigeria and the results shows that the (MGM(1,1,⊗b)) model gives a prediction interval which the actual value is bracketed. This implies that natural gas consumption of Nigeria for 2021 to 2025 lies within the (MGM(1,1,⊗b)) model prediction values for the same year.

Bromodomain-containing proteins are often part of chromatin-modifying complexes, and their activity can lead to altered expression of genes that drive cancer, inflammation and neurological disorders in humans. Bromodomain-PHD finger protein 1 (BRPF1) is part of the MOZ (monocytic leukemic zinc-finger protein) HAT (histone acetyltransferase) complex, which is associated with chromosomal translocations known to contribute to the development of acute myeloid leukemia (AML). BRPF1 contains a unique combination of chromatin reader domains including two plant homeodomain (PHD) fingers separated by a zinc knuckle (PZP domain), a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. BRPF1 is known to recruit the MOZ HAT complex to chromatin by recognizing acetylated lysine residues on the N-terminal histone tail region through its bromodomain. However, histone proteins can contain several acetylation modifications on their N-terminus, and it is unknown how additional marks influence bromodomain recruitment to chromatin. Here, we identify the BRPF1 bromodomain as a selective reader of di-acetyllysine modifications on histone H4. We used ITC assays to characterize di-acetylated histone ligands bound to the BRPF1 bromodomain and found that the domain binds preferentially to histone peptides H4K5acK8ac and H4K5acK12ac. Analytical ultracentrifugation (AUC) experiments revealed that the monomeric state of the BRPF1 bromodomain coordinates di-acetylated histone ligands. NMR chemical shift perturbation studies, along with binding and mutational analysis, revealed non-canonical regions of the bromodomain-binding pocket that are important for histone tail recognition. Together, our findings provide critical information on how the combinatorial action of post-translational modifications can modulate BRPF1 bromodomain binding and specificity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/948091v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1ab89deorg.highwire.dtl.DTLVardef@e855dborg.highwire.dtl.DTLVardef@15cc13borg.highwire.dtl.DTLVardef@9228fc_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIHistone post-translational modifications recruit bromodomain-containing proteins such as BRPF1 to chromatin, but it is unknown how multiple modifications modulate acetyllysine binding. C_LIO_LIThe BRPF1 bromodomain preferentially binds to di-acetyllysine modifications on the histone H4 tail. C_LIO_LIDi-acetyllysine recognition is coordinated by functional monomers of the BRPF1 bromodomain using amino acids near the canonical bromodomain binding pocket. C_LIO_LIAdjacent phosphorylation and methylation modifications on the histone tail inhibit the BRPF1 bromodomain interaction with acetyllysine. C_LIO_LICross-talk between multiple modifications on the histone tails is likely an important mechanism for regulating bromodomain interactions with chromatin. C_LI

Extracellular vesicles (EVs) are small lipid membrane-bound structures that are secreted by all cells, and play a central role in cellular communication. EVs are released from skeletal muscle during exercise, but the effects of contractile activity on skeletal muscle-derived EVs (Skm-EVs) are poorly understood due to the challenges in distinguishing Skm-EVs derived from exercising muscle in vivo. To specifically characterize Skm-EVs, C2C12 myoblasts were differentiated into myotubes, and electrically paced (3h/day x 4days @14V, C-PACE EM, IonOptix) to mimic chronic exercise in vitro. EVs were isolated from conditioned media from control and stimulated myotubes using differential ultracentrifugation. Isolated EVs were characterized biophysically (size, zeta potential, yield, protein markers and by transmission electron microscopy; TEM). Chronic stimulation increased markers of mitochondrial biogenesis such as MitoTracker Red staining, cytochrome c oxidase activity and expression of cytochrome c (pvs. non-stimulated myotubes. The average size of EVs from chronically stimulated myotubes (CS-EVs, 132 nm) was 26% smaller than control (CON-EVs, 178 nm) (pvs. CON-EVs (pvs. CON-EVs (p

Exercise is associated with health benefits, including the prevention and management of obesity. However, heterogeneity in the adaptive response to exercise training exists. Our objective was to evaluate if changes in extracellular vesicles (EVs) after acute aerobic exercise were associated with the responder phenotype following 6-weeks of resistance training (RT).This is a secondary analysis of plasma samples from the EXIT trial (clinical trial#02204670). Eleven sedentary youth with obesity (15.7 ± 0.5 yrs, BMI ≥95th percentile) underwent acute exercise (60% HRR, 45 min). Blood was collected at baseline [AT0 min], during [AT15-45 min], and 75 min post-recovery [AT120], and EVs purified using size exclusion chromatography from extracted plasma. Afterward, youth participated in 6-weeks RT and were categorized into responders or non-responders based on changes in insulin sensitivity.We assessed EV biophysical profile (size, zeta potential, protein yield, and EV subtype protein expression) in a single-blind fashion. Overall, there was a general increase in EV production in both groups. Average EV size was larger in responders (~147 nm)Our data suggest that youth with obesity that respond to RT produce larger EVs that are TSG101+ and CD63+, with increased EV protein yield during acute exercise.

Exosomal release pathway and autophagy together maintain homeostasis and survival of cells under stressful conditions. Autophagy is a catabolic process through which cell entities, such as malformed biomacromolecules and damaged organelles, are degraded and recycled via the lysosomal-dependent pathway. Exosomes, a sub-type of extracellular vesicles (EVs) formed by the inward budding of multivesicular bodies (MVBs), are mostly involved in mediating communication between cells. The unfolded protein response (UPR) is an adaptive response that is activated to sustain survival in the cells faced with the endoplasmic reticulum (ER) stress through a complex network that involves protein synthesis, exosomes secretion and autophagy. Disruption of the critical crosstalk between EVs, UPR and autophagy may be implicated in various human diseases, including cancers and neurodegenerative diseases, yet the molecular mechanism(s) behind the coordination of these communication pathways remains obscure. Here, we review the available information on the mechanisms that control autophagy, ER stress and EV pathways, with the view that a better understanding of their crosstalk and balance may improve our knowledge on the pathogenesis and treatment of human diseases, where these pathways are dysregulated.

International audience; Iron is an essential element for nearly all organisms, and under anoxic and/or reducing conditions, Fe2+ is the dominant form of iron available to bacteria. The ferrous iron transport (Feo) system is the primary prokaryotic Fe2+ import machinery, and two constituent proteins (FeoA and FeoB) are conserved across most bacterial species. However, how FeoA and FeoB function relative to one another remains enigmatic. In this work, we explored the distribution of feoAB operons encoding a fusion of FeoA tethered to the N-terminal, G-protein domain of FeoB via a connecting linker region. We hypothesized that this fusion poises FeoA to interact with FeoB to affect function. To test this hypothesis, we characterized the soluble NFeoAB fusion protein from Bacteroides fragilis, a commensal organism implicated in drug-resistant infections. Using X-ray crystallography, we determined the 1.50-Å resolution structure of BfFeoA, which adopts an SH3-like fold implicated in protein–protein interactions. Using a combination of structural modeling, small-angle X-ray scattering, and hydrogen–deuterium exchange mass spectrometry, we show that FeoA and NFeoB interact in a nucleotide-dependent manner, and we mapped the protein–protein interaction interface. Finally, using guanosine triphosphate (GTP) hydrolysis assays, we demonstrate that BfNFeoAB exhibits one of the slowest known rates of Feo-mediated GTP hydrolysis that is not potassium-stimulated. Importantly, truncation of FeoA from this fusion demonstrates that FeoA–NFeoB interactions function to stabilize the GTP-bound form of FeoB. Taken together, our work reveals a role for FeoA function in the fused FeoAB system and suggests a function for FeoA among prokaryotes.

Iron is an essential element for nearly all organisms, and under anoxic and/or reducing conditions, Fe2+ is the dominant form of iron available to bacteria. The ferrous iron transport (Feo) system has been identified as the primary prokaryotic Fe2+ import machinery, and two proteins (FeoA and FeoB) are conserved across most bacterial species. However, how FeoA and FeoB function relative to one another remained enigmatic. In this work we explored the distribution of feoAB operons predicted to encode for a fusion of FeoA tethered to the soluble N-terminal, G-protein domain of FeoB via a connecting linker region. We hypothesized that this fusion might poise FeoA to interact with FeoB in order to affect function. To test this hypothesis, we cloned, expressed, purified, and biochemically characterized the soluble NFeoAB fusion protein from Bacteroides fragilis, a commensal organism implicated in drug-resistant peritoneal infections. Using X-ray crystallography, we determined to 1.50 Å resolution the structure of BfFeoA, which adopts an SH3-like fold implicated in protein-protein interactions. In combination with structural modeling, small-angle X-ray scattering, and hydrogen-deuterium exchange mass spectrometry, we show that FeoA and NFeoB indeed interact in a nucleotide-dependent manner, and we have mapped the protein-protein interaction interface. Finally, using GTP hydrolysis assays, we demonstrate that BfNFeoAB exhibits one of the slowest known rates of Feo-mediated GTP hydrolysis and is not potassium-stimulated, indicating that FeoA-NFeoB interactions may function to stabilize the GTP-bound form of FeoB. Our work thus reveals a role for FeoA function in the fused FeoAB systems and suggests a broader role for FeoA function amongst prokaryotes.

Dengue is the most prevalent arthropod-borne viral disease worldwide and affects approximately 2.5 billion people living in over 100 countries. Increasing geographic expansion of Aedes aegypti mosquitoes (which transmit the virus) has made dengue a global health concern. There are currently no approved antivirals available to treat dengue, and the only approved vaccine used in some countries is limited to seropositive patients. Treatment of dengue, therefore, remains largely supportive to date; hence, research efforts are being intensified for the development of antivirals. The nonstructural proteins, 3 and 5 (NS3 and NS5), have been the major targets for dengue antiviral development due to their indispensable enzymatic and biological functions in the viral replication process. NS5 is the largest and most conserved nonstructural protein encoded by flaviviruses. Its multifunctionality makes it an attractive target for antiviral development, but research efforts have, this far, not resulted in the successful development of an antiviral targeting NS5. Increase in structural insights into the dengue NS5 protein will accelerate drug discovery efforts focused on NS5 as an antiviral target. In this review, we will give an overview of the current state of therapeutic development, with a focus on NS5 as a therapeutic target against dengue.

The effect of Annona muricata methanol leaf extract (AMELE) on colon antioxidant status and ketone bodies in blood and urine of cycas treated rats was investigated. Seventy male Wistar albino rats were randomly assigned into seven groups of ten experimental animals in a study that lasted for twenty-eight days. After 28 days, using standard methods, serum and urinary ketone bodies were assayed. Malondialdehyde (MDA), antioxidants enzymes in the colon and histopathological analysis were assayed. The results showed ketogenic diet had significant (p

The adsorptive removal of total dissolved solids by activated coal using response surface methodology was investigated. A four-variable central composite experimental design was applied to correlate the adsorption variables (effluent pH, adsorbent dosage, contact time, and adsorption temperature). The adsorption variables were optimized based on the removal of total dissolved solids from fibre cement industry effluent. Three-dimensional surface plots were generated to estimate the effect of the combinations of the independent variables on the adsorption efficiency. The results of the model validation gave experimental yield 96.2%, predicted yield 96.5% obtained at effluent pH 6.27, adsorbent dosage 27.60 mg L−1, contact time 48.00 min, and adsorption temperature of 31.00 °C. The good agreement found between observed and predicted values supports the suitability of the applied model to predict the adsorption treatment.

Although there are several provisions within the Nigerian legal framework that, however, address the issue of church attack, the state capacity to implement effective constitutional sanctioning on perpetrators of this heinous crime has always been found wanting or completely absent, leading to countless religious attacks on churches with seeming state consent. This study employs semi-structured interviews to draw data from affected families from Benue and Enugu States, Nigeria. The article explored their experiences. The study participants were recruited through snowball sampling technique, and data were analysed thematically. The respondents stated that church killings or killing of Christians is rising because of the fact that perpetrators stand lower risk of detection and apprehension than other crimes. Also respondents interrogated that justification for the crime is land acquisition and religious intolerance. On the persistence of the challenge, all the 13 respondents stated that the crime seems to have state approval that has made it seemly impossible to tackle. The article calls for continuous inter-religious dialogue and intentional governmental responsibility in protecting lives of all persons living within the geographical enclave of Nigeria which is necessary for the common good. Closer understanding of other faiths and religions will help build bridges of peace and tolerance. The article also calls for the need to promote African traditional values, such as the value of sacredness of life, human respect and good neighbourliness. Contribution: This study initiated the discussions that will help the public understand the reason for continuous church attacks in Nigeria, what church crime connotes in the Nigerian context and its uniqueness from other crimes. These discussions sit quite well within the transdisciplinary religious perspective of this journal.

Extracellular vesicles (EVs), released from all cells, are essential to cellular communication and contain biomolecular cargo that can affect recipient cell function. Studies on the effects of contractile activity (exercise) on EVs usually rely on plasma/serum-based assessments, which contain EVs from many different cells. To specifically characterize skeletal muscle–derived vesicles and the effect of acute contractile activity, we used an in vitro model where C2C12 mouse myoblasts were differentiated to form myotubes. EVs were isolated from conditioned media from muscle cells at pre-differentiation (myoblasts) and post-differentiation (myotubes) and also from acutely stimulated myotubes (1 h @ 14 V, C-Pace EM, IonOptix, Westwood, MA, USA) using total exosome isolation reagent (TEI, ThermoFisher (Waltham, MA, USA), referred to as extracellular particles [EPs]) and differential ultracentrifugation (dUC; EVs). Myotube-EPs (~98 nm) were 41% smaller than myoblast-EPs (~167 nm, p < 0.001, n = 8–10). Two-way ANOVA showed a significant main effect for the size distribution of myotube vs. myoblast-EPs (p < 0.01, n = 10–13). In comparison, myoblast-EPs displayed a bimodal size distribution profile with peaks at

Exercise is associated with various health benefits, including the prevention and management of obesity and cardiometabolic risk factors. However, a strong heterogeneity in the adaptive response to exercise training exists. The objective of this study was to evaluate if changes in extracellular vesicles (EVs) after acute aerobic exercise (AE) were associated with the responder phenotype following 6-weeks of resistance exercise training. This is a secondary analysis of plasma samples from the EXIT trial (clinical trial #02204670). Eleven sedentary youth with obesity (15.7±0.5 years, BMI ≥ 95th percentile) underwent an acute bout of AE (60% heart rate reserve, 45 min). Blood was collected before exercise [at time (AT) 0 min], during [AT15, 30, 45 min], and 75 min after exercise [AT120]. Afterward, youth participated in 6-week resistance training program, and were categorized into responders (RE) or non-responders (NRE) based on changes in insulin sensitivity as measured by the Matsuda Index. EVs were isolated using size exclusion chromatography (Izon®). The primary outcome variable was EV biophysical profile, which includes size, zeta potential, protein yield and expression of markers associated with EV subtypes. The variables were analyzed in a single-blind fashion. Overall, there was a general increase in EV production in both groups. Average EV size was larger in RE (~147 nm) vs. NRE (~124 nm; p

Extracellular vesicles (EVs) are membranous vesicles secreted by both prokaryotic and eukaryotic cells and play a vital role in intercellular communication. EVs are classified into several subtypes based on their origin, physical characteristics, and biomolecular makeup. Exosomes, a subtype of EVs, are released by the fusion of multivesicular bodies (MVB) with the plasma membrane of the cell. Several methods have been described in literature to isolate exosomes from biofluids including blood, urine, milk, and cell culture media, among others. While differential ultracentrifugation (dUC) has been widely used to isolate exosomes, other techniques including ultrafiltration, precipitating agents such as poly-ethylene glycol (PEG), immunoaffinity capture, microfluidics, and size-exclusion chromatography (SEC) have emerged as credible alternatives with pros and cons associated with each. In this review, we provide a summary of commonly used exosomal isolation techniques with a focus on SEC as an ideal methodology. We evaluate the efficacy of SEC to isolate exosomes from an array of biological fluids, with a particular focus on its application to adipose tissue-derived exosomes. We argue that exosomes isolated via SEC are relatively pure and functional, and that this methodology is reproducible, scalable, inexpensive, and does not require specialized equipment or user expertise. However, it must be noted that while SEC is a good candidate method to isolate exosomes, direct comparative studies are required to support this conclusion.

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.

The study assessed the value relevance of accounting information on deposit money banks in Nigeria during IFRS financial periods. Ex Post Facto design and time series data were used for the purpose of this research. This study made use of ten selected deposit money banks quoted on the Nigerian Stock Exchange. The study covered eight years annual reports and accounts of these deposit money banks. The data collected for the study were tested using Regression analysis and Chow test statistical and revealed that book value per share and earnings per share are value relevant in determining share price of deposit money banks in Nigeria after the adoption of IFRS. The study therefore recommended among others that since earnings have not been demonstrated to be value relevant in determining market price, banks should undertake investments that generate more earnings. &nbsp

The human CYP2C9 plays a crucial role in the metabolic clearance of a wide range of clinical therapeutics. The *2 allele is a prevalent genetic variation in CYP2C9 that is found in various populations. A marked reduction of catalytic activity toward many important drug substrates has been demonstrated by CYP2C9*2, which represents an amino acid variation at position 144 from arginine to cysteine. The crystal structure of CYP2C9*2 in complex with an antihypertensive drug losartan was solved using X-ray crystallography at 3.1-A resolution. The Arg144Cys variation in the *2 complex disrupts the hydrogen-bonding interactions that were observed between the side chain of arginine and neighboring residues in the losartan complex of CYP2C9 and the wild-type (WT) ligand-free structure. The conformation of several secondary structural elements is affected, thereby altering the binding and orientation of drug and important amino acid side chains in the distal active site cavity. The new structure revealed distinct interactions of losartan in the compact active site of CYP2C9*2 and differed in occupancy at the other binding sites previously identified in the WT-losartan complex. Furthermore, the binding studies in solution using losartan illustrated lower activity of the CYP2C9*2 compared with the WT. Together, the findings yield valuable insights into the decreased hydroxylation activity of losartan in patients carrying CYP2C9*2 allele and provide a useful framework to investigate the effect of a single-nucleotide polymorphism that leads to altered metabolism of diverse drug substrates. SIGNIFICANCE STATEMENT: The *2 allele of the human drug-metabolizing enzyme CYP2C9 is found in different populations and results in significantly reduced activity toward various drug substrates. How the CYP2C9*2 variant induces altered drug metabolism is poorly understood given that the Arg144Cys variation is located far away from the active site. This work yield insight into the effect of distal variation using multitude of techniques that include X-ray crystallography, isothermal titration calorimetry, enzymatic characterization, and computational studies.

The Nigerian economy in the last two decades up until 2013 has been growing at an average of 6% and yet unemployment was equally growing in the region of 20% within the same period. This paradoxical situation has led to a flurry of studies and postulations aimed at providing explanation and solution to the phenomenon. This study making use of a regression model with annual data from 1980 to 2013, empirically determined the impact of public sector expenditures (CEXP and REXP) together with private sector investment (PINV) on unemployment (UNEMP) in Nigeria. Capital expenditure and private sector investment both in the medium to long-run were found to serve as catalyst towards reduction of unemployment, while recurrent expenditure was not statistically strong enough to do same. The R-2 (0.84) showed that greater proportion of the total variations in UNEMP was brought about by variations in the regressors. Further tests like autocorrelation, hetroscedasticity, specification error, and multicollinearity indicated respectively that there is no presence of autocorrelation hence the model produced a parsimonious result; the variance is constant over time; the link test confirmed by Ramsey reset test suggested there was no specification error; and lastly the variance inflation factor (VIF) of the variables implies that there is no evidence of multicollinearity. The study recommends, inter alia, that the proportion of capital expenditure in Nigerian budget profile should be systematically increased while the recurrent expenditure should be reduced; and there is need to stimulate competition among investors through removal of structural and institutional rigidities and government should design clear policy incentives to private sector investment.

The addition of biologically active natural products to [(1-5-η-2-MeOC 6 H 6 ) Fe(CO) 3 ][BF 4 ] afforded 1,3-diene substituted derivatives which on demetallation with Me 3 NO, gave new organic compounds with improved antimicrobial properties supported by quantum descriptors and QSAR measurements.

The electronic absorption spectra of acridine and 9-aminoacridine have been studied in various fluid solutions at room temperature. The modified Onsager–Abe–Iweibo reaction field model for a spherical molecule was employed to determine the oscillator strength, f , in vapour phase. The intensity enhancements for the forbidden transition observed are ascribed to perturbation forces between the solute and solvent molecules.

In this study, solvent dependence of electronic and nonlinear optical properties of a new Schiff base, 2-(((5-aminonaphthalen-1-yl)imino)methyl) phenol (DANOHB), has been investigated. Electronic and optical properties of the Schiff base studied using Uv-visible absorption and fluorescence spectroscopic techniques in solution show that the Schiff base exhibits fluorescence with a quantum yield of 0.21 and a Stokes shift of 39 nm. Quantum chemical calculations were performed on the Schiff base at time-dependent density functional level of theory using Becke-3-Lee-Yang-Parr method with 6-311++G(d,p) basis set. Solvent dependence of the excited state energies (EE), energy gap (ΔE), first-order (β) and second-order (γ) hyperpolarizabilities were studied in gas, cyclohexane and ethanol. The medium perturbed the energy levels which implies that the reactivity, activity and stability of the system are solvent sensitive. The γ is more than thirty times higher than urea (standard NLO material) and this property is further enhanced in less polar medium. Small ΔE and large hyperpolarizabilities obtained for this system suggest its good potential in photonics and nonlinear optical devices.

This study investigated the potential of stevioside to prevent oxidative DNA damage in the liver and kidney of type 2 diabetes mellitus (T2DM) using high fat-low streptozocin rat model. Rats were treated daily with 12.5, 25 and 50 mg/kg stevioside orally for 21 days. Levels of biomarkers of T2DM, lipid profile and oxidative stress were assayed spectrophotometrically. The DNA ladder assay method was used to assess DNA fragmentation in the liver and kidney while computational analysis was used to predict the mechanisms of antidiabetic properties of stevioside. Stevioside significantly (p < 0.05) decreased the levels of plasma glucose, insulin, dipeptidyl peptidase IV and activities of kidney angiotensin converting enzyme. Stevioside significantly reduced oxidative stress by decreasing the levels of lipid peroxidation and nitric oxide in the liver and kidney; thereby, reducing the extent of DNA fragmentation in the liver and kidney of the diabetic rats. The in silico analysis showed that the ability of stevioside to exert these effects is linked to its inhibition of beta-adrenergic receptor kinase and G-protein-coupled receptor kinase. The results of this study suggest that the prevention of DNA fragmentation may be an additional benefit of the use of stevioside in the management of T2DM.

Network enabled capabilities (NEC) and electronic architectures in modern-day military vehicles fundamentally change the way in which the military conduct its operations. In-vehicle electronic (vetronics) architectures consist of the integration of a variety of safety-critical, deterministic and non-deterministic sub-systems through gateways and backbone networks. This assimilation provides the military with the required information superiority, battle space information integration and new capabilities. However, with this integration comes added security and safety risk. In essence, different communication nodes within the vehicle could be accessed with malicious intentions through NEC or by allowing tampered nodes to be part of the system during reconfiguration. Attacks on safety-critical sub-systems can affect the safety of the crew and also the completion of the military mission. This paper presents a novel integrated vetronics survivability architecture framework to protect and recover vehicle's vetronics from the growing threats of attacks. Architecture components are identified, and their behaviour is analysed to present an innovative vetronics survivability architectural framework. The paper proposes a framework for vetronics networks to protect them from cyber-attacksThe paper uses preventive and reactive mechanism to protect and recover from cyber threatsThe utilization of existing safety critical time triggered architectures is discussedThrough-life capability and cryptographic management is presentedThe framework is presented for open, modular, and scalable vetronics architecturesThe paper highlights applicability of the framework to current and future standards

The purpose of the study was to examine the extent to which royalties generated from forest resources contributed to community development in Boki Local Government area of Cross River State, Nigeria. The study used questionnaire survey of house-hold heads and Interview with focus groups to obtain data for this study. A total of 224 household heads representing 20 % of the available house-hold heads in the area was used for the study. The data collected were presented using tables and charts while an inferential statistics (Pearson’s Product Moment correlation) was employed to test the hypothesis of the study. The result of the analysis revealed that there exist a positive correlation coefficient of 0.911 which indicates a strong and positive relationship between royalties collected from forest resources and the number of developmental projects in the study area. Based on the findings of this study, it was recommended that more efforts be directed towards the monitoring and regulation of forest resource exploration activities in the area to ensure that royalties collected are directed towards the establishment of more developmental projects in the area so as to impact more positively on the living standard of the people.

The objective of this paper is to examine the relationship between the volatility of real exchange rate of own country and the G-3 countries (United States of America, Japan, and Germany/ or Euro zone) and the economic growth in developing countries. We draw a sample of African economies namely Nigeria, Kenya, Ghana, Malawi, Zambia and Mali and utilize quarterly data from the period 1980 -2013 which is divided into two periods 19802001 and 2002 – 2013. We apply the residual based cointegration test of Kao and Johansen –Fisher combined cointegration test to detect the long run relationships among the variables. Finally, we employ the Fully Modified Ordinary Least Squares of Philips and Hansen to estimate the long run coefficients of the model. The main results are: the long run relationships among the variables are strongly stable in the period 1980 – 2001 Original Research Article Onwuka and Obi; BJEMT, 6(1): 61-77, 2015; Article no.BJEMT.2015.043 62 but ambiguous in the period 2002 –2013. The financial system is underdeveloped and it negatively affects the economic growth in the selected African Countries. The own country’s real exchange rate volatility tends to depress the economic growth in both periods. The G-3 countries’ real exchange rate volatilities have mix results. While the Yen/Dollar and the Deutsche mark/Dollar improve economic growth, the Yen/Deutsche does not have any appreciable effect on economic growth in the developing African countries in the period 1980 2001. However, the period 2002 – 2013, the G-3 countries’ real exchange rate volatility tends to depress the economic growth in the developing African countries. These findings suggest that greater stability in international exchange rate system and lower G-3 currency volatility are desirable to promote higher growth in developing countries and which might reduce the possibility of occurrence of exchange rate crises.