Financing businesses in Africa : the role of microfinance

This paper evaluates how microfinance performed in providing business financing in 27 Sub-Saharan African countries. It uses data from the 2009 and 2010 Gallup World Poll, a nationally-representative survey of at least 1,000 individuals per country, conducted in up to 157 countries per year. The data, supported by rigorous statistical evidence in related literature on the use of microcredit around the world, demonstrate that economic gains from microcredit have been more modest than what was once believed. On the other hand, the analysis suggests that the poor save in order to start new businesses and that the introduction of formal products for small savings can be a key financial innovation. The authors also analyze the challenges the poor face in setting money aside to save, and discuss what policymakers can do to promote savings.Access to Finance,Banks&Banking Reform,Debt Markets,Financial Intermediation,Emerging Markets

The molecular basis of the interactions of copper metallochaperones

PhD ThesisCopper metallochaperones help prevent mis-metallation of proteins and ensure copper incorporation in specific Cu(I)-binding proteins by ligand-exchange reactions. The human copper metallochaperone (hCCS) for superoxide dismutase-1 (hSOD1) can interact via domain 1 with the carboxyl-terminal domain (CTD) of human β-secretase-1 (hBACE1). hBACE1 initiates the production of amyloid-β peptide (Aβ), the major constituent of senile plaques in Alzheimer’s disease (AD). One of the aims of this thesis was to identify the residues involved in mediating the interaction between hCCS and hBACE1 CTD and to investigate the role of copper in mediating this interaction using a yeast two-hybrid system. The data show that the Cys residues in the CXXC motifs of hCCS and hBACE1 CTD are essential for this interaction. The interaction is optimised by residues located close to the Cu(I)-binding sites. The hCCS/hBACE1 CTD interaction decreases in copper-deficient conditions. hBACE1 CTD was also shown to interact with the copper metallochaperone HAH1 involving the Cys residues in the CXXC motif of hBACE1 CTD. A model has been proposed based on the physiological implications of these data with respect to AD pathology. The interaction of hCCS with hSOD1 was also investigated using the yeast two-hybrid system. The mutation of the Cu(I)-binding residues in hCCS do not have a significant effect on the hSOD1/hCCS interaction. Interestingly, the hSOD1/hCCS interaction increases in copper-deficient conditions which can also have implications for AD pathology, as discussed in the proposed model. The yeast two-hybrid system was also used to study the interaction of the copper metallochaperone Atx1 from Synechocystis PCC 6803 (ScAtx1) with the metal-binding domains (MBDs) of the Cu(I)-transporting ATPases, CtaA (CtaAN) and PacS (PacSN). The data show that the residues on loop 5 of the ferredoxin-like fold of ScAtx1 (His61), CtaAN (Phe87) and PacSN (Tyr65) are important for mediating proteinprotein interactions. Swapping the loop 5 residue disrupted complex formation of ScAtx1 with CtaAN and PacSN. The mutation of ScAtx1 His61 to a charged residue or to a neutral Ala also weakens the interactions with the MBDs, demonstrating that His61 is the best choice of amino acid in this position to enable ScAtx1 to interact optimally with both of its target proteins. The possibility that ScAtx1 may form two structurally different complexes (side-to-side or head-to-head) with CtaAN and PacSN was also investigated. The data indicate that both CtaAN and PacSN can likely form a side-toside complex although the possibility that they can also form a head-to-head complex can not be excluded.The BBSRC

Biochemical Characterization of Enzyme Fidelity of Influenza A Virus RNA Polymerase Complex

It is widely accepted that the highly error prone replication process of influenza A virus (IAV), together with viral genome assortment, facilitates the efficient evolutionary capacity of IAV. Therefore, it has been logically assumed that the enzyme responsible for viral RNA replication process, influenza virus type A RNA polymerase (IAV Pol), is a highly error-prone polymerase which provides the genomic mutations necessary for viral evolution and host adaptation. Importantly, however, the actual enzyme fidelity of IAV RNA polymerase has never been characterized.Here we established new biochemical assay conditions that enabled us to assess both polymerase activity with physiological NTP pools and enzyme fidelity of IAV Pol. We report that IAV Pol displays highly active RNA-dependent RNA polymerase activity at unbiased physiological NTP substrate concentrations. With this robust enzyme activity, for the first time, we were able to compare the enzyme fidelity of IAV Pol complex with that of bacterial phage T7 RNA polymerase and the reverse transcriptases (RT) of human immunodeficiency virus (HIV-1) and murine leukemia virus (MuLV), which are known to be low and high fidelity enzymes, respectively. We observed that IAV Pol displayed significantly higher fidelity than HIV-1 RT and T7 RNA polymerase and equivalent or higher fidelity than MuLV RT. In addition, the IAV Pol complex showed increased fidelity at lower temperatures. Moreover, upon replacement of Mg(++) with Mn(++), IAV Pol displayed increased polymerase activity, but with significantly reduced processivity, and misincorporation was slightly elevated in the presence of Mn(++). Finally, when the IAV nucleoprotein (NP) was included in the reactions, the IAV Pol complex exhibited enhanced polymerase activity with increased fidelity.Our study indicates that IAV Pol is a high fidelity enzyme. We envision that the high fidelity nature of IAV Pol may be important to counter-balance the multiple rounds of IAV genome amplification per infection cycle, which provides IAV Pol with ample opportunities to generate and amplify genomic founder mutations, and thus achieve optimal viral mutagenesis for its evolution

COVID-19 market disruptions and food security: Evidence from households in rural Liberia and Malawi

We use data collected from panel phone surveys to document the changes in food security of households in rural Liberia and Malawi during the market disruptions associated with the COVID-19 lockdowns in 2020. We use two distinct empirical approaches in our analysis: (a) an event study around the date of the lockdowns (March to July 2020), and (b) a difference-in-differences analysis comparing the lockdown period in 2020 to the same months in 2021, in order to attempt to control for seasonality. In both countries, market activity was severely disrupted and we observe declines in expenditures. However, we find no evidence of declines in food security.1

Impact of an Educational Film on Parental Knowledge of Children with Cerebral Palsy

Parents of children with cerebral palsy (CP) must have knowledge about the disease and its management to improve the outcome. This uncontrolled interventional trial was carried out to evaluate the parental knowledge of CP and assess the impact of an educational programme on it. Preset questionnaires were filled before and 1 week after a single session educational programme using an educational film. Out of a total of 53 subjects, majority (75.5%) were from lower socioeconomic status. Initially, none knew the correct name of child’s illness; afterwards 45.3% could name it. When compared to previous status, there occurred significant improvement in the knowledge of parents after viewing the film with regard to knowing the cause of CP, knowing that motor involvement was predominant in CP, knowledge regarding curability of the disease, and knowledge about special schooling (P0.05). Majority (94.3%) found the film useful and 96.2% learned how they could help in the management of their children. Parental knowledge of CP is inadequate which can be improved by incorporating such educational programmes in special clinics to improve management

Identifying Molecular Signatures of Distinct Modes of Collective Migration in Response to the Microenvironment Using Three-Dimensional Breast Cancer Models

Collective cell migration is a key feature of transition of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) among many other cancers, yet the microenvironmental factors and underlying mechanisms that trigger collective migration remain poorly understood. Here, we investigated two microenvironmental factors, tumor-intrinsic hypoxia and tumor-secreted factors (secretome), as triggers of collective migration using three-dimensional (3D) discrete-sized microtumor models that recapitulate hallmarks of DCIS-IDC transition. Interestingly, the two factors induced two distinct modes of collective migration: directional and radial migration in the 3D microtumors generated from the same breast cancer cell line model, T47D. Without external stimulus, large (600 µm) T47D microtumors exhibited tumor-intrinsic hypoxia and directional migration, while small (150 µm), non-hypoxic microtumors exhibited radial migration only when exposed to the secretome of large microtumors. To investigate the mechanisms underlying hypoxia- and secretome-induced directional vs. radial migration modes, we performed differential gene expression analysis of hypoxia- and secretome-induced migratory microtumors compared with non-hypoxic, non-migratory small microtumors as controls. We propose unique gene signature sets related to tumor-intrinsic hypoxia, hypoxia-induced epithelial-mesenchymal transition (EMT), as well as hypoxia-induced directional migration and secretome-induced radial migration. Gene Set Enrichment Analysis (GSEA) and protein-protein interaction (PPI) network analysis revealed enrichment and potential interaction between hypoxia, EMT, and migration gene signatures for the hypoxia-induced directional migration. In contrast, hypoxia and EMT were not enriched in the secretome-induced radial migration, suggesting that complete EMT may not be required for radial migration. Survival analysis identified unique genes associated with low survival rate and poor prognosis in TCGA-breast invasive carcinoma dataset from our tumor-intrinsic hypoxia gene signature (CXCR4, FOXO3, LDH, NDRG1), hypoxia-induced EMT gene signature (EFEMP2, MGP), and directional migration gene signature (MAP3K3, PI3K3R3). NOS3 was common between hypoxia and migration gene signature. Survival analysis from secretome-induced radial migration identified ATM, KCNMA1 (hypoxia gene signature), and KLF4, IFITM1, EFNA1, TGFBR1 (migration gene signature) to be associated with poor survival rate. In conclusion, our unique 3D cultures with controlled microenvironments respond to different microenvironmental factors, tumor-intrinsic hypoxia, and secretome by adopting distinct collective migration modes and their gene expression analysis highlights the phenotypic heterogeneity and plasticity of epithelial cancer cells

Deficient IFN signaling by myeloid cells leads to MAVS-dependent virus-induced sepsis

The type I interferon (IFN) signaling response limits infection of many RNA and DNA viruses. To define key cell types that require type I IFN signaling to orchestrate immunity against West Nile virus (WNV), we infected mice with conditional deletions of the type I IFN receptor (IFNAR) gene. Deletion of the Ifnar gene in subsets of myeloid cells resulted in uncontrolled WNV replication, vasoactive cytokine production, sepsis, organ damage, and death that were remarkably similar to infection of Ifnar-/- mice completely lacking type I IFN signaling. In Mavs-/-×Ifnar-/- myeloid cells and mice lacking both Ifnar and the RIG-I-like receptor adaptor gene Mavs, cytokine production was muted despite high levels of WNV infection. Thus, in myeloid cells, viral infection triggers signaling through MAVS to induce proinflammatory cytokines that can result in sepsis and organ damage. Viral pathogenesis was caused in part by massive complement activation, as liver damage was minimized in animals lacking complement components C3 or factor B or treated with neutralizing anti-C5 antibodies. Disease in Ifnar-/- and CD11c Cre+Ifnarf/f mice also was facilitated by the proinflammatory cytokine TNF-α, as blocking antibodies diminished complement activation and prolonged survival without altering viral burden. Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury