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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.

Toll-like and Interleukin-1/18 receptor resistance (TIR) domain-containing proteins function as important signaling and immune regulatory molecules. TIR domain-containing proteins identified in eukaryotic and prokaryotic species also exhibit NAD+ hydrolase activity in select bacteria, plants, and mammalian cells. We report the crystal structure of theAcinetobacter baumanniiTIR domain protein (AbTir-TIR) with confirmed NAD+hydrolysis and map the conformational effects of its interaction with NAD+using HDX-MS. NAD+results in mild decreases in deuterium uptake at the dimeric interface. In addition, AbTir-TIR exhibits EX1 kinetics indicative of large cooperative conformational changes which are slowed down upon substrate binding. Additionally, we have developed label-free imaging using 2pFLIM which shows differences in bacteria expressing native and mutant NAD+ hydrolase-inactivated AbTir-TIREAprotein. Our observations are consistent with substrate-induced conformational changes reported in other TIR model systems with NAD+ hydrolase activity. These studies provide further insight into bacterial TIR protein mechanisms and their varying roles in biology.

In rural areas where measuring scales are expensive and unavailable, linear body measurements can be used as predictors of body weight. Breast girth (BG), body length (BL), wing span (WS), wing length (WL), and thigh length (TL) of Nigerian local turkeys are the best discriminating variables in differentiating the birds, according to recent studies. There are also significant physical differences between the sexes, as well as differences in trait associations within each sex. Genetic differences may account for the majority of morphological differences in turkeys. In developing and underdeveloped countries, discriminant analysis provides a practical analytical framework for characterizing and managing turkey's genetic resources. To fully understand the genetic variation among indigenous, crossbred, and exotic turkeys, this study should be followed up with molecular approaches. The ability to distinguish the growth traits of indigenous or native, exotic and crossbred turkeys in Nigeria using multivariate discriminant analysis could aid in the implementation of a conservation and improvement strategy for indigenous turkeys, ensuring the long-term development of animals using their genetic merits. Dans les zones rurales où les échelles de mesure sont chères et indisponibles, les mesures corporelles linéaires peuvent être utilisées comme prédicteurs du poids corporel. La circonférence de la poitrine (CP), la longueur du corps (LC), l'envergure des ailes (EA), la longueur des ailes (LA) et la longueur des cuisses (LC) des dindes locales nigérianes sont les meilleures variables discriminantes pour différencier les oiseaux, selon des études récentes. Il existe également des différences physiques significatives entre les sexes, ainsi que des différences dans les associations de traits au sein de chaque sexe. Les différences génétiques peuvent expliquer la majorité des différences morphologiques chez les dindes. Dans les pays en développement et sous-développés, l'analyse discriminante fournit un cadre analytique pratique pour caractériser et gérer les ressources génétiques de la dinde. Pour bien comprendre la variation génétique parmi les dindes indigènes, croisées et exotiques, cette étude devrait être suivie d'approches moléculaires. La capacité de distinguer les traits de croissance des dindes indigènes ou indigènes, exotiques et croisées au Nigeria à l'aide d'une analyse discriminante multivariée pourrait aider à la mise en œuvre d'une stratégie de conservation et d'amélioration des dindes indigènes, assurant le développement à long terme des animaux en utilisant leurs mérites génétiques.

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

Some aspiring African students prefer to travel “abroad” or overseas for example, the United States, Canada, Germany, France, and other developed countries to further their careers. This was a common practice for well-to-do families. To be more specific, some rich families in Nigeria tend to overlook higher institutions in their country. In my case, my dad inspired me, many decades ago, about travelling overseas to study. I was probably 12 years old when he hinted to me that his wish was for me to study overseas even though he did not mention any particular country. Ever since my dad indicated that desire, I accepted his wish until it came into fruition 20 years later. Specifically, in August 1979, I began my journey to the United States of America. However, while in the foreign land many African students confront multidimensional problems that range from prejudicial perceptions to illusory generalizations. For many Africans, problems include difficulty adjusting to a new cultural environment, xenophobia, misrepresentation, and miscategorization. Despite such problems, they are able to succeed and excel in their chosen professions. In this article, I discuss my experiences while maneuvering the treacherous terrain of America’s Colleges/School of Education.

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.

Recent demographic changes in the United States have shown that we live in a multicultural society. However, for some reason, colleges and universities are still floundering in mediocrity when it comes to multiculturalism. What we see in higher education is multiculturalism that is fraudulent and unaccountable and the fact that individuals from culturally and linguistically diverse (CLD) and vulnerable backgrounds consistently endure White supremacy, racism, discrimination, and xenophobia, to say the least. In addition, we consistently see that proactive and measurable efforts are not made in the recruitment, retention, graduation, continuation, tenure, and promotion of students, faculty, staff, and leaders from CLD, immigrant, and vulnerable backgrounds. While there are well-written and documented policies, mission and vision statements, and goals and objectives in institutions of higher learning, there appears to be deficits in applicability and accountability measures of equity, diversity, quality, goodness, and fairness. Most strategies seem to be feel-good, look-good, fake, bandaid, and fraudulent approaches that are divorced from realities. How do we reverse these moves while respecting the traditional roles of higher education? This article responds to this critical question.

In this study, a new Schiff base, 3-(5-(4-hydroxybenzylideneamino)naphthalen-1-yliminomethyl)phenol, has been synthesized via one-pot two-step condensation of benzaldehyde derivatives with 1,5-diaminonaphthalene. The Schiff base was characterized using nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectrophotometry and mass spectrometry. Photophysical and optical properties of the imine system were investigated using Ultraviolet–Visible (UV–Vis) and fluorescence spectrophotometry, and computational calculation. Quantum chemical investigations of the excited state energies, energy gap (ΔE), light harvesting efficiency (LHE), polarizability (α), first hyperpolarizability (β) and second hyperpolarizability (γ) at time-dependent density functional theory (TD-)DFT/B3LYP/6–311 + + G(d,p) level were conducted in vacuum, cyclohexane and ethanol. The hyperpolarizabilities were compared with those of urea (standard nonlinear optical (NLO) material). The UV–Vis result shows a low-energy absorption edge and an appreciable fluorescence quantum yield (Φf = 0.45). Large Stokes shift (59 nm) and high LHE (85%) were obtained in cyclohexane. Calculated quantum chemical parameters were solvent-sensitive and suggested that the molecule is reactive and kinetically less stable. Low ΔE (3.25 eV) was observed which suggests semiconducting potential of the material. The first and second hyperpolarizabilities are about fifteen times and ninety times larger than those of urea, respectively, indicating its good potentials as NLO and photonic materials.

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.

Inclusive and equitable education is the ultimate tool to develop students, communities, and the general society. And, special education is an added tool to help atypical and vulnerable students to be productive citizens in a thriving society. Ceteris paribus, for many culturally and linguistically diverse (CLD) students with disabilities, being educated in an inclusive environment should be the ideal policy. However, it is not! Inclusion has continued to be debatable, challenged, and controversial, making this ideal goal implausible and unrealistic. Coupled with their disabilities, CLD students experience the loaded problems of discrimination, racism, and xenophobia in the multidimensional forms of misidentification, misassessment, mislabeling/miscategorization, misplacement, and misinstruction. These multiple problems make it easy for general and special education professionals and service providers to (a) view placement as instruction, (b) focus on unidimensional and narrow confines, and (b) intentionally, unintentionally, or inaccurately judge CLD students’ capabilities and willingness to maximize their fullest potential. The question then is, since the goal is to increase “normalcy” in the lives of CLD students with disabilities, is it not important to equitably educate them with their “normal” peers in inclusive settings? This article responds to this question.

Metals used in industries are exposed to several processes such as acid cleaning, pickling, and descaling, which leads to corrosion. A good measure of corrosion control has been achieved by reducin...

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

Objective To investigate the perception of sister professional groups in Nigeria towards radiography profession. Methods: Questionnaires were used to survey the opinions of 160 healthcare professionals from five professional groups. The respondents scored radiographers on some characteristics of professional occupations. Results: Only in education was radiography scored 70.0 % and above by respondents. The range of scores in other areas was 55 – 65 %. Conclusion: Nigerian radiographers need to strive harder to improve public perception on many indices.

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

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, pre-differentiation (myoblasts) and post-differentiation (myotubes), as well as from acutely stimulated myotubes (1hr @ 14V, C-Pace EM, IonOptix) using total exosome isolation reagent (TEI, ThermoFisher, referred to as extracellular particles [EPs]) and differential ultracentrifugation (dUC; EVs). Myotube-EPs (~98 nm) were 41% smaller than myoblast-EPs (~167 nm, pvs. myoblast-EPs (pvs. myoblast EVs (pvs. post-skeletal muscle differentiation. There was no effect of acute stimulation on biophysical profile or protein markers in EPs. Acute stimulation-derived EPs did not alter mitochondrial mass nor cell count/viability. Further investigation into the effects of chronic contractile activity on the biophysical characteristics and cargo of skeletal muscle-specific EVs are warranted.

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.

Assessment is used to describe the process of gathering information to make judgments about how well someone has performed, how much progress has been made, and how much potential someone has. In other words, gathering information and forming judgments are both indispensable to good teaching. Educational institutions, government agencies, and professional associations are placing increasing emphasis on assessing performance in relevant areas of their domains. In this chapter, several issues important to the establishment of appropriate assessment procedures and the potential uses of both traditional and innovative assessment techniques are discussed. Finally, the limitations of traditional assessment techniques are considered, followed by the future perspectives on assessment techniques.

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.

Nations’ human and material resources are unevenly endowed, distributed and developed. This allows flow of labor, raw materials, capital and finished products across national boundaries and markets; thus resulting in “mercantilism” as the earliest international economic system that proposes massive and aggressive export over import to accumulate wealth, to have favorable balance of payment and trade and to be still relevant in today’s economy. Game theory and Global Strategic Rivalry theory were used in analyzing various innovations and discoveries (industrial, technological, colonial, imperial, liberalism and globalization) as the economic strategies are offshoots of mercantilist evolvement. Hence, mercantilism never died nor was it buried as claimed by many scholars.

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