Rethinking Pan-Africanism and Nationalism in Africa: The Dilemma of Nation-Building in Nigeria

After over fifty years of independence, many African states are steeped in the crisis of nation-building. Many have either witnessed sectarian violent conflict or are currently going through one. This has impacted negatively on socio-economic development across the continent. With many African states either failing or at the verge of failing, the future of nation-building in Africa appears not only bleak but also gravitating towards a justification of the thesis of colonisation that Africans are incapable of developing state systems without the intervention of the outsider – the West. Some scholars have blamed territorial nationalism for the nation-building deficit in Africa. Nigeria, the most populous nation of blacks in the world, is a typical illustration of a state currently steeped in the crisis of nation-building in Africa. This study interrogates her nation-building experience with a view to locating the roots of the problem and suggesting possible ways of fixing it. It finds that at the heart of the crisis of nation-building is the absence of an enabling political ideology. The study argues that the ideologies of nationalism and Pan-Africanism are not necessarily antithetical but mutually reinforcing. Consequently, the failure of nation-building in Africa as illustrated by the existential reality of Nigeria is the failure to realize the complementarities of nationalism and Pan-Africanism as ideologies of nation-building. It is recommended therefore that Nigeria and other African states should adopt Pan-Africanism as their political ideology as a way out of the crisis of nation-building in the twenty-first century. Keywords: Pan-Africanism, nationalism, ideology, nation-building, Nigeria, Afric

Estimating entropies from molecular dynamics simulations

The methods to compute the excess entropy and the entropy of solvation using liquid water as a test system were studied. The accuracy and convergence behavior of five methods based on thermodynamic integration and perturbation techniques was evaluated. Through the thermodynamic integration accurate entropy differences were obtained in which many copies of a solute were desolvated. Only two methods yield useful results, the calculation of solute-solvent entropy through thermodynamic integration and the calculation of solvation entropy through the temperature derivative of the corresponding free-energy difference, when one solute molecule is involved

Effects of Mega Dose Micronutrient Supplementation On Serum Zinc, Retinol and Immune Status of Adult Males and Females Diagnosed with and Without HIV, Malaria and TB in Western Kenya – An Unpublished Perspective as at The Year 2004

Background: The role of micronutrients in management of HIV/AIDS, malaria and TB remains poorly understood worldwide. Objectives: To assess differences in mega dose nutritional management between HIV-seronegative and seropositive adult males and females diagnosed with HIV at Voluntary Testing and Counseling Centers (VCT) in Western Kenya. Methods: This was a randomized controlled study in which 90 subjects were recruited on the basis of an HIV-seropositive result from a voluntary and counseling center (VCT) using rapid HIV test kits. They were evaluated at baseline and every 4 weeks for 3 months to establish their clinical, biochemical and immunological status. After 12 weeks, 74 clients were still in the study, 9 were lost to follow-up while 7 had died. Of the 74 who completed the study, confirmation of baseline HIV status by ELIZA revealed that 63 were HIV-seropositive while 11 were HIV-seronegative despite losing spouses to HIV/AIDS. Correlations between parameters at baseline, during and after intervention were determined; Spearman’s Rho Coefficients indicating the level of significance. Group means were used to compare continuous data while categorical data was compared using Chi-Square. Results: Significant reductions in the clinical manifestation of disease were noted in the cohort after intervention for 12 weeks. Despite the large and different micronutrient dosages used between the two study arms, the only difference by arm of intervention was in the serum vitamin E level at 4 weeks which was much higher in arm 1 than it was in arm 2 of the study (p = 0.005). This might have been occasioned by the significant repletion of zinc in both arms, probably because use of citric acid in both arms improved zinc up-take from the supplements, food and/or reserves enabling other nutrients to be appropriately restored in both arms, these supporting the decision to pool the study arms and compare differences by HIV-seronegative and seropositive, notwithstanding the small sample sizes recruited but which nonetheless were our study limitation. Independent of the intervention arms, reduction of viral load by more than 0.5 log10 copies/ml correlated with higher baseline optical densities of HIV antibodies (P = 0.016) and higher baseline viral loads (p = 0.0001). A lower optical density of HIV antibodies at baseline correlated with higher serum zinc levels at 12 weeks (p = 0.008) and a lower Body Mass Index (BMI) at baseline (p = 0.029). Independent of the arm of study, a significant increase in CD4 cells counts post intervention correlated with lower baseline viral loads (p = 0.010), lower baseline NK cell counts (p = 0.007

Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress:A Pilot Study

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS). In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman’s method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710, p < 0.001) and inversely associated with CRP (St. β = −0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042). This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation

Distinct amyloid-beta and tau-associated microglia profiles in Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent form of dementia and is characterized by abnormal extracellular aggregates of amyloid-beta and intraneuronal hyperphosphorylated tau tangles and neuropil threads. Microglia, the tissue-resident macrophages of the central nervous system (CNS), are important for CNS homeostasis and implicated in AD pathology. In amyloid mouse models, a phagocytic/activated microglia phenotype has been identified. How increasing levels of amyloid-beta and tau pathology affect human microglia transcriptional profiles is unknown. Here, we performed snRNAseq on 482,472 nuclei from non-demented control brains and AD brains containing only amyloid-beta plaques or both amyloid-beta plaques and tau pathology. Within the microglia population, distinct expression profiles were identified of which two were AD pathology-associated. The phagocytic/activated AD1-microglia population abundance strongly correlated with tissue amyloid-beta load and localized to amyloid-beta plaques. The AD2-microglia abundance strongly correlated with tissue phospho-tau load and these microglia were more abundant in samples with overt tau pathology. This full characterization of human disease-associated microglia phenotypes provides new insights in the pathophysiological role of microglia in AD and offers new targets for microglia-state-specific therapeutic strategies

Small Hydrophobic Protein of Human Metapneumovirus Does Not Affect Virus Replication and Host Gene Expression In Vitro

Human metapneumovirus (HMPV) encodes a small hydrophobic (SH) protein of unknown function. HMPV from which the SH open reading frame was deleted (HMPVΔSH) was viable and displayed similar replication kinetics, cytopathic effect and plaque size compared with wild type HMPV in several cell-lines. In addition, no differences were observed in infection efficiency or cell-to-cell spreading in human primary bronchial epithelial cells (HPBEC) cultured at an air-liquid interphase. Host gene expression was analyzed in A549 cells infected with HMPV or HMPVΔSH using microarrays and mass spectrometry (MS) based techniques at multiple time points post infection. Only minor differences were observed in mRNA or protein expression levels. A possible function of HMPV SH as apoptosis blocker, as proposed for several members of the family Paramyxoviridae, was rejected based on this analysis. So far, a clear phenotype of HMPV SH deletion mutants in vitro at the virus and host levels is absent

COVID-19:immunopathology, pathophysiological mechanisms, and treatment options

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally despite the worldwide implementation of preventive measures to combat the disease. Although most COVID-19 cases are characterised by a mild, self-limiting disease course, a considerable subset of patients develop a more severe condition, varying from pneumonia and acute respiratory distress syndrome (ARDS) to multi-organ failure (MOF). Progression of COVID-19 is thought to occur as a result of a complex interplay between multiple pathophysiological mechanisms, all of which may orchestrate SARS-CoV-2 infection and contribute to organ-specific tissue damage. In this respect, dissecting currently available knowledge of COVID-19 immunopathogenesis is crucially important, not only to improve our understanding of its pathophysiology but also to fuel the rationale of both novel and repurposed treatment modalities. Various immune-mediated pathways during SARS-CoV-2 infection are relevant in this context, which relate to innate immunity, adaptive immunity, and autoimmunity. Pathological findings in tissue specimens of patients with COVID-19 provide valuable information with regard to our understanding of pathophysiology as well as the development of evidence-based treatment regimens. This review provides an updated overview of the main pathological changes observed in COVID-19 within the most commonly affected organ systems, with special emphasis on immunopathology. Current management strategies for COVID-19 include supportive care and the use of repurposed or symptomatic drugs, such as dexamethasone, remdesivir, and anticoagulants. Ultimately, prevention is key to combat COVID-19, and this requires appropriate measures to attenuate its spread and, above all, the development and implementation of effective vaccines.</p

Catalysis of iron core formation in Pyrococcus furiosus ferritin

The hollow sphere-shaped 24-meric ferritin can store large amounts of iron as a ferrihydrite-like mineral core. In all subunits of homomeric ferritins and in catalytically active subunits of heteromeric ferritins a diiron binding site is found that is commonly addressed as the ferroxidase center (FC). The FC is involved in the catalytic Fe(II) oxidation by the protein; however, structural differences among different ferritins may be linked to different mechanisms of iron oxidation. Non-heme ferritins are generally believed to operate by the so-called substrate FC model in which the FC cycles by filling with Fe(II), oxidizing the iron, and donating labile Fe(III)–O–Fe(III) units to the cavity. In contrast, the heme-containing bacterial ferritin from Escherichia coli has been proposed to carry a stable FC that indirectly catalyzes Fe(II) oxidation by electron transfer from a core that oxidizes Fe(II). Here, we put forth yet another mechanism for the non-heme archaeal 24-meric ferritin from Pyrococcus furiosus in which a stable iron-containing FC acts as a catalytic center for the oxidation of Fe(II), which is subsequently transferred to a core that is not involved in Fe(II)-oxidation catalysis. The proposal is based on optical spectroscopy and steady-state kinetic measurements of iron oxidation and dioxygen consumption by apoferritin and by ferritin preloaded with different amounts of iron. Oxidation of the first 48 Fe(II) added to apoferritin is spectrally and kinetically different from subsequent iron oxidation and this is interpreted to reflect FC building followed by FC-catalyzed core formation