Cell migration plays a vital role in both health and disease. It is driven by reorganization of the actin cytoskeleton, which is regulated by actin-binding proteins cofilin and profilin. Stress-inducible phosphoprotein 1 (STIP1) is a well-described co-chaperone of the Hsp90 chaperone system, and our findings identify a potential regulatory role of STIP1 in actin dynamics. We show that STIP1 can be isolated in complex with actin and Hsp90 from HEK293T cells and directly interacts with actin in vitro via the C-terminal TPR2AB-DP2 domain of STIP1, potentially due to a region spanning two putative actin-binding motifs. We found that STIP1 could stimulate the in vitro ATPase activity of actin, suggesting a potential role in the modulation of F-actin formation. Interestingly, while STIP1 depletion in HEK293T cells had no major effect on total actin levels, it led to increased nuclear accumulation of actin, disorganization of F-actin structures, and an increase and decrease in cofilin and profilin levels, respectively. This study suggests that STIP1 regulates the cytoskeleton by interacting with actin, or via regulating the ratio of proteins known to affect actin dynamics.
Background and objectives Kigelia africana is a medicinal plant growing naturally in many parts of Africa. In Kenya, a water concoction of the plant is used to treat breast and prostate cancers. Laboratory data on its anti-cancer activity and active principles is limited, hence no scientific rationale for its medicinal use. This study reports on in-vitro toxic activities of dichloromethane and methanol extracts of the plant against human breast cancer cells and phytochemical screening of the two extracts. Methodology Plant extracts were obtained by sequential solvent extraction of dry plant material (stem bark) using analytical grade dichloromethane: methanol (1:1) and methanol (Sigma Aldrich). In-vitro anti-cancer activities of the extracts were determined using the suphorhodamine (SRB) assay against a human breast cancer cell line (HCC 1937). Preliminary Thin layer chromatography of plant extracts was done using POLYGRAM® SIL G/UV 254 plates (Merck) to establish presence of different classes of secondary metabolites. Results In-vitro cytotoxic activities of the two extracts were significantly different ( P = 0.05). The methanol extract exhibited higher activity (IC 50 = 26.02 μg/ml) compared to that of dichloromethane: methanol (1:1) (IC 50 = 55.01 μg/ml). Phyto-chemical screening of the two extracts revealed the presence of terpenoids, phenols, steroids and flavonoids. Conclusion The high in-vitro anti-cancer activities of solvent extracts of Kigelia africana justify its use in traditional medicine to manage breast cancer. Phytochemical analysis of the extracts reveal similar profiles hence the differences in their anti-cancer activities can be attributed to quantitative variations of various classes of secondary metabolites.
Lipids are hydrocarbons comprised of long‐chain fatty acids and are found in all living things. In the environment, microorganisms degrade them to obtain energy using esterases and lipases. These enzymes are nowadays used in different industrial applications. We report isolation of 24 bacteria with esteresic and lipolytic activity from Lake Magadi, Kenya. The isolates were characterised using morphological, biochemical, and molecular methods. Isolates grew at an optimum salt concentration of 5–8% (w/v), pH range of 8.0–9.0, and temperature range of 35–40°C. The isolates were positive for esterase and lipase assay as well as other extracellular enzymes. Phylogenetic analysis of the 16S ribosomal RNA gene showed that the isolates were affiliated to the genus Bacillus, Alkalibacterium, Staphylococcus, Micrococcus, Halomonas, and Alkalilimnicola. None of the bacterial isolates produced antimicrobial agents, and all of them were resistant to trimethoprim and nalidixic acid but susceptible to streptomycin, amoxillin, chloramphenicol, and cefotaxime. Growth at elevated pH, salt, and temperature is an indicator that the enzymes from these organisms could function well under haloalkaline conditions. Therefore, Lake Magadi could be a good source of isolates with the potential to produce unique biocatalysts for the biotechnology industry.
The first description of a disease resembling dengue fever (DF) was in the 15th century slave trade era by Spanish sailors visiting the Tanzania coast. The disease, then associated with evil spirits is now known to be caused by four serotypes of dengue virus (DENV1-4) that are transmitted by Aedes mosquitoes. Kenya has experienced multiple outbreaks, mostly associated with DENV-2. In this study, plasma samples obtained from 37 febrile patients during a DF outbreak at Kenya’s south coast in March 2019 were screened for DENV. Total RNA was extracted and screened for the alpha- and flavi-viruses by real-time polymerase chain reaction (qPCR). DENV-3 was the only virus detected. Shotgun metagenomics and targeted sequencing were used to obtain DENV whole genomes and the complete envelope genes (E gene) respectively. Sequences were used to infer phylogenies and time-scaled genealogies. Following Maximum likelihood and Bayesian phylogenetic analysis, two DENV-3 genotypes (III, n = 15 and V, n = 2) were found. We determined that the two genotypes had been in circulation since 2015, and that both had been introduced independently. Genotype III’s origin was estimated to have been from Pakistan. Although the origin of genotype V could not be ascertained due to rarity of these sequences globally, it was most related to a 2006 Brazilian isolate. Unlike genotype III that has been described in East and West Africa multiple times, this was the second description of genotype V in Kenya. Of note, there was marked amino acid variances in the E gene between study samples and the Thailand DENV-3 strain used in the approved Dengvaxia vaccine. It remains to be seen whether these variances negatively impact the efficacy of the Dengvaxia or future vaccines.
Genus Eucalyptus belongs to the family Myrtaceae and consists of more than 900 species, various hybrids and varieties. The major species that are grown in Kenya are Eucalyptus grandis, E. globulus, E. saligna and E. camaldulensis. Most Eucalyptus species are highly dependent on rainfall and this is challenged by climatic changes owing to global warming making it difficult to effectively match the availability of mature trees and the market demand especially for use as power transmission poles. With the widespread availability of other naturally occurring Eucalyptus species such as E. camaldulensis and E. globulus, it becomes important to determine the genetic diversity and to analyze the phenotypic traits of these species for suitability as power transmission poles in order to counter the overdependence on E. grandis. Phenotypic traits investigated included measuring total tree height and diameter at breast height (DBH), while molecular data were obtained from sequencing MatK, rbcL and TrnL-F genes from selected species and evolutionary analyses such as nucleotide substitution rates, base composition disparity indices, evolutionary divergence, nucleotide diversity indices and phylogeny construction were conducted in MEGA 11. Significant differences in DBH and height among Eucalyptus species were observed when the phenotypic data were subjected to ANOVA. In this study, E. robusta, E. paniculata, E. maculata, E. dunnii, E. camaldulensis and E. citriodora are fit to be used as power transmission poles but they are limited by their short height. However, E. tereticornis and E. glaucina have the desired DBH and height and hence can be used as substitutes for E.grandis. Generally, the molecular phylogeny study has shown that the studied Eucalyptus species are closely related and form various monophyletic clades which can be attributed to the short genetic distances, low substitution rates, low nucleotide bias disparity indices and low diversity scores. Further phylogenetic and gene expression studies involving more Eucalyptus species are needed to better understand Eucalyptus phylogeny, and diversity and identify species with similar genetic make-up to that of E. grandis which has been used extensively for the provision of electricity transmission poles.
Covid-19 was first reported in Wuhan China but has now spread globally with overwhelming impacts on human health and health systems. The disease is caused by the SARs-Cov-2 which is related to the SARs-Cov-1 that causes SARs. There is evidence suggesting that the virus originated from the Rhinolophilid bats and has subsequently undergone recombination to allow for a natural selection for a human host and it is thought that the recombination might have occurred either prior or upon infection of the human host. These events of natural selection are presumed to have hastened human to human transmission. However, analyses of sequences from Covid-19 isolates from China and across the globe point to a unique case scenario that may suggest selection and evolution of the virus upon infection of the human host. In this paper we have examined the role of the human ACE-2 receptor in determining the predisposition to Covid-19 and analyzed Covid-19 sequences deposited in the virus database from around the globe to provide evidence that the disease burden is different across regions and among individuals as determined by the genetics of the virus and that the virus is rapidly evolving across regions and populations. Our phylogenetics data confirms that all strains circulating around the globe are related to the strains from China, the origin of the virus and further depicts varying degrees of similarity and disparity which suggests that the virus is mutating. While the USA has already been shown to have sequences closely related to the Wuhan sequences, here we report that the sequences from Spain and Africa are distantly related to the Wuhan sequences. Owing to the unique presentation of the disease in regions across the globe, the summary presented here informs of the need to tailor the management of the disease as dictated by viral and host genetic factors and the observed regional burden of the disease.
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