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Peter Nyasulu,1,2 Simon Sikwese,2,3 Tobias Chirwa,2 Chandra Makanjee,4 Madalitso Mmanga,5 Joseph Omoniyi Babalola,6 James Mpunga,7 Hastings T Banda,8 Adamson S Muula,9,10 Alister C Munthali11 1Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 2School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 3Pakachere Institute of Health and Development Communication, Blantyre, Malawi; 4Department of Medical Radiation Sciences, University of Canberra, Canberra, WA, Australia; 5District TB Office, Department of Environmental Health, District Health Office, Ntcheu, Malawi; 6Division of Community Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 7National Tuberculosis Control Program, Community Health Sciences Unit, Ministry of Health, Lilongwe, 8Research for Equity and Community Health (REACH) Trust, Lilongwe, 9Department of Community Health, College of Medicine, University of Malawi, Blantyre, 10African Centre of Excellence in Public Health and Herbal Medicine, College of Medicine, University of Malawi, Blantyre, 11Centre for Social Research, University of Malawi, Zomba, Malawi Introduction: The global burden of tuberculosis (TB) remains significantly high, with overreliance on biomedical interventions and inadequate exploration of the socioeconomic and cultural context of the infected population. A desired reduction in disease burden can be enhanced through a broader theoretical understanding of people’s health beliefs and concerns about TB. In this qualitative study, we explore the knowledge, beliefs, and perceptions of community members and people diagnosed with TB toward TB in Ntcheu district, Malawi. Methods: Using a qualitative phenomenological study design, data were obtained from eight focus-group discussions and 16 individual in-depth interviews. The community’s experiences and perceptions of TB were captured without using any preconceived framework. Adult participants who had had or never had a diagnosis of TB were purposively selected by sex and age and enrolled for the study. Discussions and individual interviews lasting about 60 minutes each were audiotaped, transcribed, and translated into English and analyzed using MaxQDA 10 software for qualitative analysis. Results: Most participants believed that TB was curable and would go for diagnosis if they had symptoms suggestive of the disease. However, based on their beliefs, individuals expressed some apprehension about the spread of TB and the social implications of being diagnosed with the disease. This perception affected participants’ responses about seeking diagnosis and treatment. Conclusion: A supportive and collective approach consisting of a combination of mass media, interactive communication campaigns, emphasizing TB symptoms, transmission, and stigma could be useful in addressing barriers to early diagnosis and care-seeking behavior. Keywords: tuberculosis, knowledge, perception of TB, beliefs, Ntcheu, Malawi

The articles in this Special Issue were selected from responses to a call for abstracts on the theme “Generation of African Scholars and the Intellectual Legacies”. The idea was originally conceived by the late Professor Michael Cross, pioneer Director of the Ali Mazrui Centre for Higher Education Studies (AMCHES), University of Johannesburg, South Africa, to be a flagship project of the budding centre. It aimed to bring together, outstanding scholars from diverse disciplinary backgrounds and perspectives to critically investigate, analyse and document the intellectual legacies of African scholars, leaders, and institutions. Its central objective was to analyse the nature of African scholars’ contributions to knowledge production with the specific goal of influencing and/or shaping the higher education landscape, discourses, policies, and practices in Africa.

The use of medicinal plants as an alternative mean of treating various diseases has drawn the attention of several researchers. The desire to find lasting solutions to epilepsy among humans increases every day. Thus, this work was aimed at investigating the potential capacity of the studied phytochemicals in Alsophila spinulosa against human 4-aminobutyrate-aminotransferase as well as to predict the nonbonding interactions involved in the studied complexes. In this work, ten compounds with biological activities were selected and studied using molecular docking method. The molecules selected obtained from A. spinulosa leaves were optimized and various descriptors that described the anti-4-aminobutyrate-aminotransferase features were obtained. More so, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(((2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-4H-chromen-4-one (compound 9) with highest binding affinity proved to have greater strength to inhibit 4-aminobutyrate-aminotransferase thereby downregulating epilepsy than other studied compounds and the reference drug (clobazam). The ADMET features of both compound 9 and clobazam were explored and reported.

As former colonies of Western imperial powers, virtually all aspects of African life have been invaded by forces of Western hegemony. Colonial mentality is the blind assimilation or internalisation of the colonial powers’ socio-cultural forms resulting in the destructive and disruptive abandonment of the ways of life of the colonies. As it applies to Africa, colonial mentality is a product of African cultural invasion in which, having been exposed to colonial experience for a long time, an average African has internalised foreign ideas and ideals—so much so that she has lost the authentic African ways of life in the process. Using philosophical methods of argumentation and critical engagements, this paper contends that a connection exists between colonial mentality and the observed failure of African universities to efficiently effectuate their relevance as Africa’s development partners. The paper identifies four key areas in which colonial mentality plays out most profoundly in African universities, namely, the nature of knowledge produced, the mode of certification, the language of instruction, and research funding. The paper argues that the incursion of colonial mentality in these vital areas continues to impede African universities’ capacity to substantively contribute to African development drives and aspirations. Given this close nexus, the paper maintains that African universities may never realise their potential as a critical sector in African development discourse. This qualitative research is based on critical inquiry through a process of identifying, questioning and assessing deeply held assumptions about Western hegemony. The paper concludes that decolonisation in learning spaces can only be a feasible project if it is accorded the seriousness that it deserves by all stakeholders both within and outside the university.

Robert Bellah’s article “Community Properly Understood…” is critical of the conventional conception of community as a product of consensus established by shared values and goals among people of common social reality. The need for such a critical approach is arguably encouraged by the rather imprecise deployment of the notion of community in the vast communitarian literature, a deployment which truly raises issues of concern over what the term ‘community’ really means. Bellah’s article is one of the numerous responses to this quest. This paper challenges Bellah’s view on community and offers some arguments to demonstrate why his conception of community may not be adequate. While the uniqueness of his argument is not in doubt, the paper argues that Bellah commits a straw man fallacy by conflating a normative question, “what ought we to do to achieve a working and progressive community?” with the descriptive question, “what is community?” The paper argues that an adequate conception of community must be such that its conception is acceptable to both the liberals and the communitarians. To achieve this, the paper introduces the notion of shared spaces to the conceptualization of the concept of community, and thereby arrives at the definition of community in terms with which both sides of the debate can relate. The paper concludes that with an appropriate concept of community, it would be obvious, contrary to the popular opinion, that liberals and communitarians are both committed to the survival of the community, and that they only differ in their respective approaches to achieving this common goal.

In this study, Ti6Al4V-ZrO2-Si3N4 ternary composites were fabricated using a novel spark plasma sintering technique at different temperatures between 950-1200 °C, the pressure of 50 MPa, sintering rate of 100 °C/min, and a holding time of 10 min to determine the effect of sintering temperature on the consolidated composites. The microstructures of the fabricated composites were examined by the scanning electron microscope (SEM-EDX). The distinct phases and the nano-mechanical properties of the composite were determined by the X-ray diffractometer and nanoindenter. The results show a non-linear response. At elevated temperatures from the composite sample, CT1-950 °C to the composite sample, CT2-1100 °C, the densification, and nanomechanical properties experienced an increase, and when the temperature is elevated to 1200 °C, composite CT3 declines in values. However, the relative density of all fabricated composites was above 95%, which suggests an overall good densification via the spark plasma sintering technique. The ternary composite fabricated at 1100 °C, (CT2) attained maximum values of Vickers hardness, elastic modulus, and nano hardness at 7380 MPa, 177.91 GPa, and 60.06 GPa, respectively, while composite CT3 declines at 1200 °C.

The place of the world in the life of individual human being cannot be underestimated. This fact has culminated in the high esteem in which the concept of the world is held in the existentialist thinking. Using the Sartrean existentialist methodological approach, the paper critically examines the notion of the world (ayé) in the existentialist thinking of the Yoruba people of Nigeria. The paper argues that although humans find themselves thrown into the world (ayé) amidst situations that are not of their own making, sometimes amidst untoward circumstances, the right mark of an authentic existence is ṣíṣe ayé which literally means “doing the world”, rather than mere gbígbé ayé, that is, living in the world. The paper concludes that the hallmark of authentic existence is to be found in the act of “doing the world” rather than just living in it.

To develop a semiconductor interface with enhanced spatial separation of carriers under visible light irradiation for the photoelectrochemical (PEC) oxidation process, we explored the fabrication of a Bi 2 O 2 S/NiTiO 3 heterojunction photoanode for the removal of sulfamethoxazole in water. The Bi 2 O 2 S/NiTiO 3 photoanode was synthesized via an in situ hydrothermal process, and it exhibited better light absorption and charge separation, as well as a reduced rate of recombination of photoexcited charge species compared to pristine Bi 2 O 2 S and NiTiO 3. The improved photoelectrocatalytic performance was attributed to the synergistic interaction between Bi 2 O 2 S and NiTiO 3 and the presence of an S-O bond at the heterojunction interface, thus resulting in Z-scheme heterojunction formation. Various characterization methods such as XPS, UV-DRS, electrochemical impedance spectroscopy, photoluminescence, FESEM, TEM, and photocurrent response measurements were explored to explain the optical and electrochemical properties of the semiconductor heterojunction. The PEC degradation process was optimized, demonstrating a degradation efficiency removal of 80% for 5 mg/L sulfamethoxazole in water, with a TOC removal of 45.5%. A Z-scheme heterojunction formation mechanism was proposed to explain the enhanced photoelectrocatalytic activity of the photoanode. This work generally contributes to the development of efficient and sustainable photoanodes for environmental remediation.

Objective: Lately, various scientists have been paying a lot of consideration to the design of operational antimicrobial agents due to the rise of multiple drug-resistant strains. Therefore, this work is aimed at discovering the biochemical behavior of the analyzed polypeptides in relation to glutamine amidotransferase GatD (pdb id: 5n9m) for gram positive bacteria and beta-lactamase class A (pdb id: 5fqq) for gram negative bacteria. Additionally, this study aims to identify the specific atoms involved in the observed biochemical interactions between the studied complexes using computational methods., Methods: In this work, five polypeptides were studied using insilico approach via Spartan 14 software, molecular operating environment, ADMETSar, and Gromacs., Results: The descriptors obtained revealed the activities of the studied compounds, the molecular interaction between the studied ligands as well as glutamine amidotransferase GatD (pdb id: 5n9m) and beta-lactamase class A (pdb id: 5fqq) which thereby exposed compound 1 and 5 to be the compounds with greatest ability to inhibit the studied targets among other studied compounds., Conclusion: Our discoveries may open door for the design of collection of proficient polypeptide-based drug-like compounds as potential anti-microbial agents., Competing Interests: None., (IJBMB Copyright © 2024.)

In this work, the biochemical activities of seven cyclic peptides were investigated using the insilico approach. The materials used in this work were Spartan 14 for quantum chemical analysis, molecular operating environment software for molecular docking and ADMETSAR 2.0 for pharmacokinetic investigation. The calculated features obtained for each compound were explored and it was observed that the molecules used in this research have potential anti-human insulin-degrading enzyme activities. Also, (3S,6S,9S)-9-(( R )-1-(benzyloxy)ethyl)-6-methyl-3-(4-methylphenethyl)-1,4,7,10-tetraazacyclododecane-2,5,8,11-tetraone (compound 2) with highest binding affinity (-7.95349026 kcal/mol) possess utmost ability to inhibit human insulin-degrading enzyme (PDB id: 2g56) than other investigated compounds and acarbose (referenced compound). The pharmacokinetic analysis for compound 2 was examined and compared to the predicted report for the referenced compound., (© 2024 The Author(s).)

The anti-NS2B-NS3 proteases activities of Azadirachta indica L. were investigated via the data obtained from selected bioactive compounds from Azadirachta indica L. The work was investigated using insilico approach and the series of computational software were used to execute the task. The software used were Spartan 14, material studio, Padel, Pymol, Autodock tool, Autodock vina and discovery studio. The obtained descriptors from 2D and 3D of the optimized compounds were screened and they were used to develop QSAR model using material studio software. Also, biological interaction between the selected bioactive compounds from Azadirachta indica L. and NS2B-NS3 proteases (PDB ID: 2fom) were accomplished using docking method and the calculated binding affinity as well as the residues involved in the interaction were reported. More so, the ADMET features for [(5 S ,6 R ,7 S ,8 R ,9 S ,10 R ,11 S ,12 R ,13 S ,17 R )-17-(2,5-dihydroxy-2,5-dihydrofuran-3-yl)-11,12-dihydroxy-6‑methoxy-4,4,8,10,13-pentamethyl-1,16-dioxo-6,7,9,11,12,17-hexahydro-5 H -cyclopenta[ a ]phenanthren-7-yl] 3-methylbut-2-enoate ( Compound 6) and (10 R ,13 S ,14 S ,17 S )-17-[1-(3,4-dihydroxy-5,5-dimethyloxolan-2-yl)ethyl]-4,4,10,13,14-pentamethyl-1,2,5,6,9,11,12,15,16,17-decahydrocyclopenta[a]phenanthren-3-one ( compound 12 ) with lowest binding affinity were investigated and reported., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2023 The Author(s).)

Membrane proteins can be examined in near-native lipid-bilayer environments with the advent of polymer-encapsulated nanodiscs. These nanodiscs self-assemble directly from cellular membranes, allowing in vitro probing of membrane proteins with techniques that have previously been restricted to soluble or detergent-solubilized proteins. Often, however, the high charge densities of existing polymers obstruct bioanalytical and preparative techniques. Thus, the authors aim to fabricate electroneutral-yet water-soluble-polymer nanodiscs. By attaching a sulfobetaine group to the commercial polymers DIBMA and SMA(2:1), these polyanionic polymers are converted to the electroneutral maleimide derivatives, Sulfo-DIBMA and Sulfo-SMA(2:1). Sulfo-DIBMA and Sulfo-SMA(2:1) readily extract proteins and phospholipids from artificial and cellular membranes to form nanodiscs. Crucially, the electroneutral nanodiscs avert unspecific interactions, thereby enabling new insights into protein-lipid interactions through lab-on-a-chip detection and in vitro translation of membrane proteins. Finally, the authors create a library comprising thousands of human membrane proteins and use proteome profiling by mass spectrometry to show that protein complexes are preserved in electroneutral nanodiscs., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

Amphiphilic copolymers that directly extract membrane proteins and lipids from cellular membranes to form nanodiscs combine the advantages of harsher membrane mimics with those of a native-like membrane environment. Among the few commercial polymers that are capable of forming nanodiscs, alternating diisobutylene/maleic acid (DIBMA) copolymers have gained considerable popularity as gentle and UV-transparent alternatives to aromatic polymers. However, their moderate hydrophobicities and high electric charge densities render all existing aliphatic copolymers rather inefficient under near-physiological conditions. Here, we introduce Glyco-DIBMA, a bioinspired glycopolymer that possesses increased hydrophobicity and reduced charge density but nevertheless retains excellent solubility in aqueous solutions. Glyco-DIBMA outperforms established aliphatic copolymers in that it solubilizes lipid vesicles of various compositions much more efficiently, thereby furnishing smaller, more narrowly distributed nanodiscs that preserve a bilayer architecture and exhibit rapid lipid exchange. We demonstrate the superior performance of Glyco-DIBMA in preparative and analytical applications by extracting a broad range of integral membrane proteins from cellular membranes and further by purifying a membrane-embedded voltage-gated K + channel, which was fluorescently labeled and analyzed with the aid of microfluidic diffusional sizing (MDS) directly within native-like lipid-bilayer nanodiscs.

Two new surfactants, F 5 OM and F 5 DM, were designed as partially fluorinated analogues of n -dodecyl-β-D-maltoside (DDM). The micellization properties and the morphologies of the aggregates formed by the two surfactants in water and phosphate buffer were evaluated by NMR spectroscopy, surface tension measurement, isothermal titration calorimetry, dynamic light scattering, small-angle X-ray scattering, and analytical ultracentrifugation. As expected, the critical micellar concentration (cmc) was found to decrease with chain length of the fluorinated tail from 2.1-2.5 mM for F 5 OM to 0.3-0.5 mM for F 5 DM, and micellization was mainly entropy-driven at 25 °C. Close to their respective cmc, the micelle sizes were similar for both surfactants, that is, 7 and 13 nm for F 5 OM and F 5 DM, respectively, and both increased with concentration forming 4 nm diameter rods with maximum dimensions of 50 and 70 nm, respectively, at a surfactant concentration of ∼30 mM. The surfactants were found to readily solubilize lipid vesicles and extract membrane proteins directly from Escherichia coli membranes. They were found more efficient than the commercial fluorinated detergent F 6 H 2 OM over a broad range of concentrations (1-10 mM) and even better than DDM at low concentrations (1-5 mM). When transferred into the two new surfactants, the thermal stability of the proteins bacteriorhodopsin (bR) and FhuA was higher than in the presence of their solubilization detergents and similar to that in DDM; furthermore, bR was stable over several months. The membrane enzymes SpNOX and BmrA were not as active as in DDM micelles but similarly active as in F 6 OM. Together, these findings indicate both extracting and stabilizing properties of the new maltose-based fluorinated surfactants, making them promising tools in MP applications.

We report the preparation and application of a heterostructured photoelectrocatalyst comprising carbon nanoparticles (CNPs) and boron codoped BiVO 4 and WO 3 for the removal of an organic dye pollutant in water. The materials, synthesized by hydrothermal method, were characterized by X-ray diffraction, diffuse reflectance UV-visible spectroscopy, energy-dispersive X-ray spectroscopy, and electron microscopy. The catalysts were immobilized on treated titanium sheets by drop-casting. The fabricated electrodes were characterized by linear sweep voltammetry (LSV) and chronoamperometry. Diffuse reflectance spectroscopy of the catalysts reveals that the incorporation of CNPs and B into the structure of monoclinic BiVO 4 enhanced its optical absorption in both UV and visible regions. The LSV measurements carried out in 0.1 M Na 2 SO 4 showed that the BiVO 4 - and WO 3 -based photoelectrode demonstrated significant photoactivity. CNP/B-BiVO 4 and CNP/B-BiVO4/WO 3 photoanodes gave photocurrent densities of approximately 0.83 and 1.79 mA/cm 2 , respectively, at 1.2 V (vs 3 M Ag/AgCl). The performance of the electrodes toward degradation of orange II dye was in the order BiVO 4 < B-BiVO 4 < WO 3 < CNP-BiVO 4 < CNP/B-BiVO 4 < CNP/B-BiVO 4 /WO 3 , and the apparent rate constants obtained by fitting the experimental data into the Langmuir Hinshelwood kinetic model are 0.0924, 0.1812, 0.254, and 0.845 h -1 for BiVO 4 , WO 3 , CNP/B-BiVO 4 , and CNP/B-BiVO 4 /WO 3 , respectively. The chemical oxygen demand abatement after 3 h of electrolysis at the best performing photoanode was 58%. The study showed that BiVO 4 and WO 3 are promising anodic materials for photoelectrocatalytic water treatment plant., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Introduction: sustained viral suppression using antiretroviral treatment (ART) occurs with adherence to treatment of at least 95%. Non-adherence promotes the development of drug-resistance and treatment failure in individuals infected with Human Immunodeficiency Virus. In Limpopo Province, the adherence rate is approximately 61%, but the prevalence and the factors associated with adherence at Letaba hospital HIV clinic are not well established. Therefore, the aim of this study was to identify the factors associated with adherence among HIV-infected young adults, aged 18-35 years, attending the clinic., Methods: a cross-sectional survey was conducted in Letaba HIV clinic among young adults of 18-35 years old. Logistic regression analysis was performed to determine factors associated with ART adherence. We reported odds ratios with the corresponding 95% confidence intervals and p-values. A p-value < 0.1 was considered as statistically significant. ART adherence was defined as taking more than 95% of the prescribed treatment, 3 days prior to completion of the questionnaire., Results: a total of 281 participants were enrolled with 163 (58.0%) females and more than three quarter, 222 (79.0%) between the ages of 18 and 29 years. The overall ART adherence stood at (87.2%) (95% CI: 63.0%-89.0%) representing 245 participants. Non-adherers to treatment, 36 (12.8%): patients reported no reason (3.9%), forgetting (3.2%), feeling good (3.2%), fear and running out of treatment (2.5%) as some of the reasons for not taking treatment within the three days prior to data collection. The following factors: tertiary education (p = 0.07), age (30-35; p-value: 0.07), drug availability (p-value: 0.07), were only marginally significantly associated with ART adherence., Conclusion: the study found unsatisfactory ART adherence among our participants. Our study suggests that factors other than sociodemographic and clinical factors might better explain differences in adherence. This highlights the need for a more complex study that would look at the entire system in which these patients are navigating as well as their mental models., Competing Interests: The authors declare no competing interests.

Membrane proteins usually need to be extracted from their native environment and separated from other membrane components for in-depth in vitro characterization. The use of styrene/maleic acid (SMA) copolymers to solubilize membrane proteins and their surrounding lipids into bilayer nanodiscs is an attractive approach toward this goal. We have recently shown that a diisobutylene/maleic acid (DIBMA) copolymer similarly solubilizes model and cellular membranes but, unlike SMA(3:1), has a mild impact on lipid acyl-chain order and thermotropic phase behavior. Here, we used fluorescence spectroscopy, small-angle X-ray scattering, size-exclusion chromatography, dynamic light scattering, and 31 P nuclear magnetic resonance spectroscopy to examine the self-association of DIBMA and its membrane-solubilization properties against lipids differing in acyl-chain length and saturation. Although DIBMA is less hydrophobic than commonly used SMA(3:1) and SMA(2:1) copolymers, it efficiently formed lipid-bilayer nanodiscs that decreased in size with increasing polymer/lipid ratio while maintaining the overall thickness of the membrane. DIBMA fractions of different molar masses were similarly efficient in solubilizing a saturated lipid. Coulomb screening at elevated ionic strength or reduced charge density on the polymer at low pH enhanced the solubilization efficiency of DIBMA. The free-energy penalty for transferring phospholipids from vesicular bilayers into nanodiscs became more unfavorable with increasing acyl-chain length and unsaturation. Altogether, these findings provide a rational framework for using DIBMA in membrane-protein research by shedding light on the effects of polymer and lipid properties as well as experimental conditions on membrane solubilization.

Once removed from their natural environment, membrane proteins depend on membrane-mimetic systems to retain their native structures and functions. To this end, lipid-bilayer nanodiscs that are bounded by scaffold proteins or amphiphilic polymers such as styrene/maleic acid (SMA) copolymers have been introduced as alternatives to detergent micelles and liposomes for in vitro membrane-protein research. Herein, we show that an alternating diisobutylene/maleic acid (DIBMA) copolymer shows equal performance to SMA in solubilizing phospholipids, stabilizes an integral membrane enzyme in functional bilayer nanodiscs, and extracts proteins of various sizes directly from cellular membranes. Unlike aromatic SMA, aliphatic DIBMA has only a mild effect on lipid acyl-chain order, does not interfere with optical spectroscopy in the far-UV range, and does not precipitate in the presence of low millimolar concentrations of divalent cations., (© 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

During endocytosis, membrane components move to intraluminal vesicles of the endolysosomal compartment for digestion. At the late endosomes, cholesterol is sorted out mainly by two sterol-binding proteins, Niemann-Pick protein type C (NPC)1 and NPC2. To study the NPC2-mediated intervesicular cholesterol transfer, we developed a liposomal assay system. (Abdul-Hammed, M., B. Breiden, M. A. Adebayo, J. O. Babalola, G. Schwarzmann, and K. Sandhoff. 2010. Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion. J. Lipid Res. 51: 1747-1760.) Anionic lipids stimulate cholesterol transfer between liposomes while SM inhibits it, even in the presence of anionic bis(monoacylglycero)phosphate (BMP). Preincubation of vesicles containing SM with acid sphingomyelinase (ASM) (SM phosphodiesterase, EC 3.1.4.12) results in hydrolysis of SM to ceramide (Cer), which enhances cholesterol transfer. Besides SM, ASM also cleaves liposomal phosphatidylcholine. Anionic phospholipids derived from the plasma membrane (phosphatidylglycerol and phosphatidic acid) stimulate SM and phosphatidylcholine hydrolysis by ASM more effectively than BMP, which is generated during endocytosis. ASM-mediated hydrolysis of liposomal SM was also stimulated by incorporation of diacylglycerol (DAG), Cer, and free fatty acids into the liposomal membranes. Conversely, phosphatidylcholine hydrolysis was inhibited by incorporation of cholesterol, Cer, DAG, monoacylglycerol, and fatty acids. Our data suggest that SM degradation by ASM is required for physiological secretion of cholesterol from the late endosomal compartment, and is a key regulator of endolysosomal lipid digestion., (Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.)

We have measured the affinity of the CysF9[93]β sulfhydryl group of human deoxyhemoglobin and oxyhemoglobin for 5,5'-dithiobis(2-nitrobenzoate), DTNB, between pH ≈5.6 and 9 in order to understand the basis of the reported reduction of the Bohr effect induced by chemical modification of the sulfhydryl. We analyzed the results quantitatively on the basis of published data indicating that the sulfhydryl exists in two conformations that are coupled to the transition between two tertiary structures of hemoglobin in dynamic equilibrium. Our analyses show that the ionizable groups linked to the DTNB reaction have lower pKas of ionization in deoxyhemoglobin compared to oxyhemoglobin. So these ionizable groups should make negative contributions to the Bohr effect. We identify these groups as HisNA2[2]β, HisEF1[77]β and HisH21[143]β. We provide explanations for the finding that hemoglobin, chemically modified at CysF9[93]β, has a lower Bohr effect and a higher oxygen affinity than unmodified hemoglobin., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This study is a first-hand report of the immobilization of Nauclea diderrichii seed waste biomass (ND) (an agro-waste) with eco-friendly mesoporous silica (MS) and graphene oxide-MS (GO + MS) nanoparticles, producing two new hybrid materials namely: MND adsorbent for agro-waste modified with MS and GND adsorbent for agro-waste modified with GO + MS nanoparticles showed improved surface area, pore size and pore volume over those of the agro-waste. The abstractive potential of the new hybrid materials was explored for uptake of Cr(III) and Pb(II) ions. Analysis of experimental data from these new hybrid materials showed increased initial sorption rate of Cr(III) and Pb(II) ions uptake. The amounts of Cr(III) and Pb(II) ions adsorbed by MND and GND adsorbents were greater than those of ND. Modification of N. diderrichii seed waste significantly improved its rate of adsorption and diffusion coefficient for Cr(III) and Pb(II) more than its adsorption capacity. The rate of adsorption of the heavy metal ions was higher with GO + MS nanoparticles than for other adsorbents. Kinetic data were found to fit well the pseudo-second-order and the diffusion-chemisorption kinetic models suggesting that the adsorption of Cr(III) and Pb(II) onto these adsorbents is mainly through chemisorption mechanism. Analysis of kinetic data with the homogeneous particle diffusion kinetic model suggests that particle diffusion (diffusion of ions through the adsorbent) is the rate-limiting step for the adsorption process.

Hemoglobin exhibits allosteric structural changes upon ligand binding due to the dynamic interactions between the ligand binding sites, the amino acids residues and some other solutes present under physiological conditions. In the present study, the dynamical and quaternary structural changes occurring in two unligated (deoxy-) T structures and two fully ligated (oxy-) R, R2 structures of adult human hemoglobin were investigated with molecular dynamics. It is shown that, in the submicrosecond time scale, there is no marked difference in the global dynamics of the amino acid residues in both the oxy- and the deoxy-forms of the individual structures. In addition, the R, R2 are relatively stable and do not present quaternary conformational changes within the time scale of our simulations, while the T structure is dynamically more flexible and exhibited the T → R quaternary conformational transition, which is propagated by the relative rotation of the residues at the α(1)β(2) and α(2)β(1) interface.

This study reports the sequestration of Cd(II) and Hg(II) using a new biosorbent, Nauclea diderrichii seed biomass. Experimental data obtained were fitted into kinetic and thermodynamic models. Experimental data fitted best into pseudo-second order kinetic model among others. Results obtained kinetically revealed that the biosorption of Cd(II) and Hg(II) using N. diderrichii seed biosorbent increased with increase in temperature. At the highest temperature, which was 333 K, the highest amount of metal biosorbed, q(e), for Cd(II) and Hg(II) obtained were 6.30 and 6.15 mg/g respectively. The biosorption of Cd(II) was kinetically faster than that of Hg(II), the highest initial biosorption rates for Cd(II) and Hg(II) were 56.19 and 4.39 mg/g min respectively. Thermodynamic parameters obtained by Erying equation from this study revealed that the biosorption process was spontaneous, feasible, endothermic with a decrease in the degree of chaos in the biosorption system., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We examined the effect of Niemann-Pick disease type 2 (NPC2) protein and some late endosomal lipids [sphingomyelin, ceramide and bis(monoacylglycero)phosphate (BMP)] on cholesterol transfer and membrane fusion. Of all lipid-binding proteins tested, only NPC2 transferred cholesterol at a substantial rate, with no transfer of ceramide, GM3, galactosylceramide, sulfatide, phosphatidylethanolamine, or phosphatidylserine. Cholesterol transfer was greatly stimulated by BMP, little by ceramide, and strongly inhibited by sphingomyelin. Cholesterol and ceramide were also significantly transferred in the absence of protein. This spontaneous transfer of cholesterol was greatly enhanced by ceramide, slightly by BMP, and strongly inhibited by sphingomyelin. In our transfer assay, biotinylated donor liposomes were separated from fluorescent acceptor liposomes by streptavidin-coated magnetic beads. Thus, the loss of fluorescence indicated membrane fusion. Ceramide induced spontaneous fusion of lipid vesicles even at very low concentrations, while BMP and sphingomyelin did so at about 20 mol% and 10 mol% concentrations, respectively. In addition to transfer of cholesterol, NPC2 induced membrane fusion, although less than saposin-C. In this process, BMP and ceramide had a strong and mild stimulating effect, and sphingomyelin an inhibiting effect, respectively. Note that the effects of the lipids on cholesterol transfer mediated by NPC2 were similar to their effect on membrane fusion induced by NPC2 and saposin-C.

We have determined the second-order reverse rate constant, k(R), for the reaction of 5,5 -dithiobis(2-nitrobenzoate) - DTNB - with sheep hemoglobins as a function of pH from values of the second-order forward rate constant, k(F), and the equilibrium constant, K(equ), at 25 degrees C: k(R)=k(F)K(equ). We demonstrate that (i) inositol hexakisphosphate (inositol-P(6)) decreases k(F) and k(R) by increasing K(rt), the rright harpoon over left harpoont tertiary conformation transition constant; (ii) the conformation favored for both the forward and reverse reactions is the r conformation. For stripped hemoglobin we obtain from the k(F) data a t isomer population of 34.6% (+/-14) prior to reaction with DTNB; from the k(R) data we calculate a t isomer population of 44.8% (+/-4) following reaction with DTNB. In the presence of inositol-P(6) the latter value is increased to 79.5% (+/-2). These results demonstrate that an allosteric transition occurs on reaction with DTNB and on inositol-P(6) binding., (2009 Elsevier B.V. All rights reserved.)

The equilibrium constant (K(equ)) for the reaction of 5,5'-dithiobis(2-nitrobenzoate) - DTNB - with the CysF9[93]beta sulphydryl group of the haemoglobins of the sheep decreases by about two orders of magnitude between pH approximately 5.6 and 9.2: from a mean of 7.2+/-1 to a mean of 0.044+/-0.01. Calculations from the pH dependence of K(equ) show that in the r-t tertiary conformational transition of haemoglobin the t isomer population is 50.7 and 61.8% for the major and minor haemoglobins, respectively. In the presence of inositol hexakisphosphate (inositol-P(6)), K(equ) increases for both haemoglobins by about an order of magnitude through most of the pH range. The t isomer population also increases to 82.1 and 79.6% for the major and minor haemoglobins, respectively. These results indicate that inositol-P(6) increases the affinity of the sulphydryl for DTNB by increasing the population of the t isomer. It is highly probable that a minimum four-state model that includes the r-t transition is required for a full understanding of haemoglobin function.

Background: Postnatal growth monitoring is useful in assessing the health ofpreterm babies but their growth patterns have not been sufficiently studied in Africans., Aim: To describe the growth achievements ofpreterm, low birth weight, appropriately-sized, Nigerian infants., Study Design: The subjects were prospectively recruited from two centers Olabisi Onabanjo University Teaching Hospital (January 1994 to June 1995) and Havana Specialist Hospital (June 1995 to June 1997). The weight, length and occipito-frontal circumference of 89 preterm, low birth weight, appropriate-for-dates infants were monitored from birth until 53 post-conceptual weeks. Growth velocities were compared with 46 term infants., Results: Initial weight loss, age at regaining birth weight and growth rate in the early postnatal weeks were inversely related to gestational age. Subsequent weight gain was directly related to gestational age. Between birth and 40 weeks post conception, growth rates for different gestational age groups were 129 to 207 g/week (weight), 0.78 to 0.93 cm/week (length) and 0.62 to 0.65 cm/week (head circumference). After 40 weeks, the corresponding rates were 188 to 238 g/week, 0.86 to 0.96 cm week and 0.48 to 0.50 cm/week, respectively. Head growth demonstrated a faster catch-up than weight and body length in that order. The observed growth rates were slower in some respects than Caucasian figures but faster than reported for the Japanese., Conclusion: Study subjects had growth patterns within previously defined ranges. The better profile of western babies is probably related to better infrastructure while the advantage over Asian babies is probably racial.

We demonstrate that 5,5'-dithiobis(2-nitrobenzoate) - DTNB - reacts with only CysF9[93]beta and CysB5[23]beta among the multiple sulfhydryl groups of the major and minor hemoglobins of the Japanese quail (Cortunix cortunix japonica). K(equ), the equilibrium constant for the reaction, does not differ very significantly between the two hemoglobins. It decreases 430-fold between pH approximately 5.6 and pH approximately 9: from a mean of 7+/-1 to a mean of 0.016+/-0.003. Quantitative analyses of the K(equ) data based on published X-ray and temperature-jump evidence for a tertiary structure transition in liganded hemoglobin enable the calculation of K(rt), the equilibrium constant for the r<---->t tertiary structure transition. K(rt) differs significantly between the two hemoglobins: 0.744+/-0.04 for the major, 0.401+/-0.01 for the minor hemoglobin. The mean pK(a)s of the two groups whose ionizations are coupled to the DTNB reaction are about the same as previously reported for mammalian hemoglobins.

Niemann-Pick type C disease is an inherited fatal disorder characterized by the accumulation of unesterified cholesterol and other lipids in the endosomal/lysosomal compartment. Two independent genes responsible for this neurodegenerative disorder have been identified, but the precise functions of the encoded Niemann-Pick C1 (NPC1) and C2 (NPC2) proteins are not yet known. We developed a cell-free assay for measuring intermembrane lipid transport and examined the ability of bovine NPC2 (bNPC2) for intermembrane cholesterol transfer. NPC2 specifically extracts cholesterol from phospholipid bilayers and catalyzes intermembrane transfer to acceptor vesicles in a dose- and time-dependent manner. This transfer activity is dependent on temperature, pH, ionic strength, lipid composition of the model membranes, and the ratio of donor to acceptor vesicles. In model membranes, the presence of the lysosomal anionic phospholipids bis(monooleoylglycero)phosphate and phosphatidyl inositol significantly stimulated cholesterol transfer by NPC2, whereas bis(monomyristoylglycero)phosphate, phosphatidyl serine, and phosphatidic acid had no effect. Moreover, ceramide stimulated cholesterol transfer slightly, whereas sphingomyelin reduced cholesterol transfer rates. With our assay system we identified for the first time the ability of other lysosomal proteins, most notably the GM2-activator protein, to mediate intermembrane cholesterol transfer. This assay system promises to be a valuable tool for further quantitative and mechanistic studies of protein-mediated lipid transfer.

The effect of association-dissociation on the sulphydryl reactivity of human hemoglobin A is reported. The reactivity of CysF9(93)beta towards the sulphydryl reagent, 5,5'-dithiobis(2-nitrobenzoate), is higher at lower concentrations of hemoglobin at all pH values. This is because hemoglobin dimers have higher sulphydryl reactivity than tetramers and it is known that the proportion of dimers increases as the hemoglobin concentration decreases. This study takes advantage of this observation to determine the tetramer-dimer dissociation constant, K(4,2), of hemoglobin A and subsequently the proton uptake and the proton release during this process. The concentration dependence profiles of the apparent second-order rate constants, k(app), show that (between 2 and 20 microM heme) k(app) decreases with increasing hemoglobin concentration. Above 30 M heme k(app) remains fairly constant for all hemoglobin derivatives (oxy, carbonmonoxy and aquomethemoglobin) used. The pH dependence of the negative logarithm of tetramer-dimer dissociation constant, pK(4,2), for oxy- (and for carbonmonoxy-) hemoglobin exhibits a biphasic character with a maximum near pH 7.4 (and 6.6). For aquomethemoglobin, pK(4,20 decreases with increasing pH. The tetramer-dimer dissociation of human oxyhemoglobin A at an ionic strength of 200 mM uptakes 0.87 +/- 0.09 mole of protons between pH 6.2 to 7.4 phase and releases 0.84 0.09 mole of protons between pH 7.4 and 9.0 phase. Under a similar condition carbonmonoxyhemoglobin uptakes 0.54 +/- 0.05 mole of protons between pH 5.8 and 6.6 phase and releases 0.48 +/- 0.05 mole of protons between pH 6.6 and 9.0 phase. Aquomethemoglobin has only a single phase, it releases 0.39 +/- 0.05 mole of protons during tetramer-dimer dissociation.