Towards National Integration in Kenya: Beyond Ethno-Centricism and Class Conflict

This paper presents a vital view of a contemporary perspective on dealing with historical challenges to national integration in Kenya. It bases its discussions behind three ideas emanating from the backdrop of both a historical ethno-political society and globalization pull-factors with emphasis on social media. There are three key objectives herein each of which is resultant on a domestic society to harness national cohesion and reconciliation in Kenya. These are; examine the relevance of inter-ethnic marriages; assess the contributions of the youth and social media in promoting unity; and examine the contribution of a university environment in promoting political socialization in transforming future political culture in Kenya. This study works on the finding that the contemporary political intolerance in Kenya is based on an underlying ideology of ethnic nationalism unconsciously or consciously promoted by ‘the politician’ therefore the persistence of both social-economic conflicts along ethnic factions. The working methodology is primarily from a qualitative angle that looked at existing literature topical issues as; national integration, cohesion, ethnic conflict and peace transformation in national politics from relevant secondary sources. The analysis emanates from a theoretical framework that triangulates the Marxist and Wallersteinian class conflicts as a conceptualization and contextual interpretation of the case in point. The paper gives two recommendations to relevant stakeholders in harnessing unity and cohesion in Kenya. It suggests on the importance of putting emphasis on the positive utilization of the social media by youth as well as building capacity on youth transformation by embracing the culture of inter-ethnic marriages as a way to demystify ethnocentric hegemony. Keywords: National Integration, Ethnicity, Class, Conflict and Politic

Social-Legal Environment and Women Participation in the Securities Market in Kenya

Securities markets are essential vehicles of raising capital, portfolio diversification and liquidity management among investors. Investors aim to generate extra returns while keeping their risk at manageable levels. Active participation of women in stock markets in Kenya is key in ensuring a level playing field for both men and women in matters development and investment. In Kenya the concentration of women investors in the Securities market has been increasing with the aim of bridging the gender gap among stockholders gradually. As at June 2020, women comprised 34% of the total investors in the Nairobi securities exchange. This reflects an increase in the number of investors to 513,063 from 273,234 in the year 2010. However, despite this increase the number of women investors was lower than male investors; women only held investment worth ksh 2.4 Billion (25%)  as compared to Ksh 7.1 billion (75%) held by men. This clearly indicates that there is a myriad of gender related issues that prevent participation of women in stock market. This study investigated the social- legal factors that affect women participation in the stock market. The study adopted a positivist research philosophy, and a descriptive correlation design. STATA software tool was used to analyze data and the findings were presented in tables, graphs and charts. The study findings were; financial literacy levels among women in Kenya is low, some cultures in Kenya undermine women and condemn them to household chores and  various family responsibilities, traditional beliefs and practices hinder women from participating in the stock market and the matrimonial property and land laws in Kenya are biased against women. The study recommends that learning institutions should incorporate financial literacy programs directed at women to help in bringing change in attitude towards participation in the securities market, younger generation of women in the society should be mentored by those who have carved out a niche for themselves in the securities market, there is need also to establish clear legal and regulatory frameworks and gender-disaggregated data gathering measures to guarantee women’s secure rights to land, including the right to inherit, own, access, control, and participate in land governance. Keywords: Securities market, social legal environment, women participation, financial literacy DOI: 10.7176/EJBM/13-20-14 Publication date:October 31st 202

Effect of Determinants of Lending Interest Rate Fluctuations on the Profitability of Commercial Banks in Kenya

Volatility in lending interest rates represents one of the key forms of financial risk faced by commercial banks in Kenya. The aim of this research project was to identify and assess the effect that the determinants of lending interest rate volatility have on the profit levels realized by commercial banks in Kenya for the period 2010-2015.  This study used profitability measured by Net Interest Margin as the dependent variable, while the independent variables were Borrowers’ Default Rate, Central Bank of Kenya Liquidity Ratio, Central Bank Kenya Cash Reserve Ratio, Inflation Rate and Maturity Mismatch. The study population was the total 42 commercial banks that were in operation as at the end of 2015, with a sample size of 20 banks. The study used secondary data collected from individual commercial banks, among them audited financial statements, published bank supervision reports by Central Bank of Kenya, data on inflation was obtained from Kenya National Bureau of Statistics. Data analysis involved both descriptive and inferential statistics; with descriptive statistics involving the use of mean, standard deviation, minimum and maximum values of data collected, while the inferential statistics comprising the use of regression coefficients to test the hypotheses ywith values generated using the Statistical Package for Social Sciences software. The findings of the study revealed that Borrower’s Default Rate, Inflation Rate and Maturity Mismatch Risk would impact negatively on the profitability of banks, whereas Cash Reserve Ratio and Liquidity Ratio would impact positively on the profitability of commercial banks in Kenya. The study therefore concluded that commercial banks should work in tandem with Central Bank of Kenya in order to constantly monitor the Cash Reserve Ratio and Liquidity levels to avoid cases of instability; the Inflation Rate should be watched as well in order to know and study the borrowing culture of the various bank clientele, and that both Maturity Mismatch and Borrowers Default Rate levels should be contained to avoid growth in Non-Performing Loans and to keep the banks’ loan book open and in constant flow. Key words: interest rate fluctuation, Default Rate, Liquidity Ratio, Cash Reserve Ratio DOI: 10.7176/RJFA/10-8-21 Publication date: April 30th 201

Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy

AbstractBCL-2 family proteins are central regulators of mitochondrial apoptosis and validated anti-cancer targets. Using small cell lung cancer (SCLC) as a model, we demonstrated the presence of differential addiction of cancer cells to anti-apoptotic BCL-2, BCL-XL or MCL-1, which correlated with the respective protein expression ratio. ABT-263 (navitoclax), a BCL-2/BCL-XL inhibitor, prevented BCL-XL from sequestering activator BH3-only molecules (BH3s) and BAX but not BAK. Consequently, ABT-263 failed to kill BCL-XL-addicted cells with low activator BH3s and BCL-XL overabundance conferred resistance to ABT-263. High-throughput screening identified anthracyclines including doxorubicin and CDK9 inhibitors including dinaciclib that synergized with ABT-263 through downregulation of MCL-1. As doxorubicin and dinaciclib also reduced BCL-XL, the combinations of BCL-2 inhibitor ABT-199 (venetoclax) with doxorubicin or dinaciclib provided effective therapeutic strategies for SCLC. Altogether, our study highlights the need for mechanism-guided targeting of anti-apoptotic BCL-2 proteins to effectively activate the mitochondrial cell death programme to kill cancer cells.</jats:p

Androgen Deprivation Therapy Potentiates the Efficacy of Vascular Targeted Photodynamic Therapy of Prostate Cancer Xenografts

WST11 vascular targeted photodynamic therapy (VTP) is a local ablation approach relying upon rapid, free radical-mediated destruction of tumor vasculature. A phase III trial showed that VTP significantly reduced disease progression when compared with active surveillance in patients with low-risk prostate cancer. The aim of this study was to identify a druggable pathway that could be combined with VTP to improve its efficacy and applicability to higher risk prostate cancer tumors. Transcriptome analysis of VTP-treated tumors (LNCaP-AR xenografts) was used to identify a candidate pathway for combination therapy. The efficacy of the combination therapy was assessed in mice bearing LNCaP-AR or VCaP tumors. Gene set enrichment analysis identifies the enrichment of androgen-responsive gene sets within hours after VTP treatment, suggesting that the androgen receptor (AR) may be a viable target in combination with VTP. We tested this hypothesis in mice bearing LNCaP-AR xenograft tumors by using androgen deprivation therapy (ADT), degarelix, in combination with VTP. Compared with either ADT or VTP alone, a single dose of degarelix in concert with VTP significantly inhibited tumor growth. A sharp decline in serum prostate-specific antigen (PSA) confirmed AR inhibition in this group. Tumors treated by VTP and degarelix displayed intense terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining 7 days after treatment, supporting an increased apoptotic frequency underlying the effect on tumor inhibition. Improvement of local tumor control following androgen deprivation combined with VTP provides the rationale and preliminary protocol parameters for clinical trials in patients presented with locally advanced prostate cancer.

Plasmodium berghei calcium dependent protein kinase 1 is not required for host cell invasion.

Plasmodium Calcium Dependent Protein Kinase (CDPK1) is required for the development of sexual stages in the mosquito. In addition, it is proposed to play an essential role in the parasite's invasive stages possibly through the regulation of the actinomyosin motor and micronemal secretion. We demonstrate that Plasmodium berghei CDPK1 is dispensable in the parasite's erythrocytic and pre-erythrocytic stages. We successfully disrupted P. berghei CDPK1 (PbCDPK1) by homologous recombination. The recovery of erythrocytic stage parasites lacking PbCDPK1 (PbCDPK1-) demonstrated that PbCDPK1 is not essential for erythrocytic invasion or intra-erythrocytic development. To study PbCDPK1's role in sporozoites and liver stage parasites, we generated a conditional mutant (CDPK1 cKO). Phenotypic characterization of CDPK1 cKO sporozoites demonstrated that CDPK1 is redundant or dispensable for the invasion of mammalian hepatocytes, the egress of parasites from infected hepatocytes and through the subsequent erythrocytic cycle. We conclude that P. berghei CDPK1 plays an essential role only in the mosquito sexual stages

Conditional mutagenesis of PbCDPK1.

<p>(A) Schematic representation of the conditional mutagenesis of the PbCDPK1. (B) Southern hybridization demonstrating modification of the PbCDPK1 locus through the addition of FRT sites in FlpL/TRAP parasites. (C) PCR analysis using oligos p1 and p2, demonstrates excision of PbCDPK1 in genomic DNA obtained from (1) WT erythrocytic stages (2) FlpL/TRAP erythrocytic stages used for mosquito feeding (3) FlpL/TRAP erythrocytic stages recovered through bite infection from infected mosquitoes (4) CDPK1 cKO erythrocytic stages used for mosquito feeding (5) CDPK1 cKO erythrocytic stages recovered through bite infection from infected mosquitoes. (D) Intrahepatic development of CDPK1 cKO and control FlpL/TRAP sporozoites in HepG2 cells. Intracellular liver stages were quantified at 40–44 h p.i. (D) Parasite egress from infected HepG2 cells was monitored by quantifying the number of extracellular merosomes 66–70 h p.i. (E) <i>In vivo</i> infection of CDPK1 cKO and control FlpL/TRAP sporozoites was monitored by the appearance of erythrocytic stage parasites in mice infected through sporozoite injection.</p

WST11 vascular targeted photodynamic therapy effect monitoring by multispectral optoacoustic tomography (MSOT) in mice.

Objective: Monitoring emerging vascular-targeted photodynamic therapy (VTP) and understanding the time-dynamics of treatment effects remains challenging. We interrogated whether handheld multispectral optoacoustic tomography (MSOT) could noninvasively monitor the effect of VTP using WST11, a vascular-acting photosensitizer, on tumor tissues over time using a renal cell cancer mouse model. We also investigated whether MSOT illumination can induce VTP, to implement a single-modality theranostic approach. Materials and Methods: Eight BalB/c mice were subcutaneously implanted with murine renal adenocarcinoma cells (RENCA) on the flank. Three weeks later VTP was performed (10 min continuous illumination at 753 nm following intravenous infusion) using WST11 or saline as control. Handheld MSOT images were collected prior to VTP administration and subsequently thereafter over the course of the first hour, at 24 and 48 h. Data collected were unmixed for blood oxygen saturation in tissue (SO 2 ) based on the spectral signatures of deoxy- and oxygenated hemoglobin. Changes in oxygen saturation over time, relative to baseline, were examined by paired t-test for statistical significance (p &lt; 0.05). In-vivo findings were corroborated by histological analyses of the tumor tissue. Results: MSOT is shown to prominently resolve changes in oxygen saturation in tumors within the first 20 min post WST11-VTP treatment. Within the first hour post-treatment, SO 2 decreased by more than 60% over baseline (p &lt; 0.05), whereas it remained unchanged (p &gt; 0.1) in the sham-treated group. Moreover, unlike in the control group, SO 2 in treated tumors further decreased over the course of 24 to 48 h post-treatment, concomitant with the propagation of profound central tumor necrosis present in histological analysis. We further show that pulsed MSOT illumination can activate WST11 as efficiently as the continuous wave irradiation employed for treatment. Conclusion: Handheld MSOT non-invasively monitored WST11-VTP effects based on the SO 2 signal and detected blood saturation changes within the first 20 min post-treatment. MSOT may potentially serve as a means for both VTP induction and real-time VTP monitoring in a theranostic approach

Invasion of hepatocytes by <i>Plasmodium</i> sporozoites requires cGMP-dependent protein kinase and calcium dependent protein kinase 4

Invasion of hepatocytes by sporozoites is essential for Plasmodium to initiate infection of the mammalian host. The parasite’s subsequent intracellular differentiation in the liver is the first developmental step of its mammalian cycle. Despite their biological significance, surprisingly little is known of the signalling pathways required for sporozoite invasion. We report that sporozoite invasion of hepatocytes requires signalling through two second-messengers – cGMP mediated by the parasite’s cGMP-dependent protein kinase (PKG), and Ca(2)(+), mediated by the parasite’s calcium-dependent protein kinase 4 (CDPK4). Sporozoites expressing a mutated form of Plasmodium berghei PKG or carrying a deletion of the CDPK4 gene are defective in invasion of hepatocytes. Using specific and potent inhibitors of Plasmodium PKG and CDPK4, we demonstrate that PKG and CDPK4 are required for sporozoite motility, and that PKG regulates the secretion of TRAP, an adhesin that is essential for motility. Chemical inhibition of PKG decreases parasite egress from hepatocytes by inhibiting either the formation or release of merosomes. In contrast, genetic inhibition of CDPK4 does not significantly decrease the number of merosomes. By revealing the requirement for PKG and CDPK4 in Plasmodium sporozoite invasion, our work enables a better understanding of kinase pathways that act in different Plasmodium stages