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Antimicrobial peptides: new hope in the war against multidrug resistance

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Zoological Research 2019年第6期40卷 488-505页

作者： James mwangi Xue Hao Ren Lai Zhi-Ye Zhang Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming Yunnan 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming Yunnan 650204China Sino-African Joint Research Center Kunming Institute of ZoologyChinese Academy of SciencesKunming Yunnan 650223China Institutes for Drug Discovery and Development Chinese Academy of SciencesShanghai 201203China KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunming Yunnan 650223China Center for Biosafety Mega-Science Chinese Academy of SciencesWuhan Hubei 430071China

The discovery of antibiotics marked a golden age in the revolution of human medicine. However,decades later, bacterial infections remain a global healthcare threat, and a return to the pre-antibiotic era seems inevitable if stringent measures are not adopted to curb the rapid emergence and spread of multidrug resistance and the indiscriminate use of antibiotics. In hospital settings, multidrug resistant(MDR) pathogens, including carbapenem-resistant Pseudomonas aeruginosa, vancomycin-resistant enterococci(VRE), methicillin-resistant Staphylococcus aureus(MRSA), and extendedspectrum β-lactamases(ESBL) bearing Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae are amongst the most problematic due to the paucity of treatment options,increased hospital stay, and exorbitant medical costs. Antimicrobial peptides(AMPs) provide an excellent potential strategy for combating these threats. Compared to empirical antibiotics, they show low tendency to select for resistance, rapid killing action, broad-spectrum activity, and extraordinary clinical efficacy against several MDR strains. Therefore, this review highlights multidrug resistance among nosocomial bacterial pathogens and its implications and reiterates the importance of AMPs as next-generation antibiotics for combating MDR superbugs.

关键词： Multidrug resistance Nosocomial infections Antimicrobial peptide Antibiotic alternatives

Design methods for antimicrobial peptides with improved performance

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Zoological Research 2023年第6期44卷 1095-1114页

作者： James mwangi Peter Muiruri Kamau Rebecca Caroline Thuku Ren Lai Key Laboratory of Bioactive Peptides of Yunnan Province Engineering Laboratory of Peptides of Chinese Academy of SciencesKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Centre for Non-Human PrimatesKunming Primate Research CentreNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Sino-African Joint Research CentreNew Cornerstone Science InstituteKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China Centre for Evolution and Conservation Biology Southern Marine Science and Engineering Guangdong LaboratoryGuangzhouGuangdong 511458China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China

The recalcitrance of pathogens to traditional antibiotics has made treating and eradicating bacterial infections more *** this regard,developing new antimicrobial agents to combat antibiotic-resistant strains has become a top *** peptides(AMPs),a ubiquitous class of naturally occurring compounds with broadspectrum antipathogenic activity,hold significant promise as an effective solution to the current antimicrobial resistance(AMR)*** AMPs have been identified and evaluated for their therapeutic application,with many already in the drug development *** distinct properties,such as high target specificity,potency,and ability to bypass microbial resistance mechanisms,make AMPs a promising alternative to traditional ***,several challenges,such as high toxicity,lability to proteolytic degradation,low stability,poor pharmacokinetics,and high production costs,continue to hamper their clinical ***,recent research has focused on optimizing the properties of AMPs to improve their *** understanding the physicochemical properties of AMPs that correspond to their activity,such as amphipathicity,hydrophobicity,structural conformation,amino acid distribution,and composition,researchers can design AMPs with desired and improved *** this review,we highlight some of the key strategies used to optimize the performance of AMPs,including rational design and de novo *** also discuss the growing role of predictive computational tools,utilizing artificial intelligence and machine learning,in the design and synthesis of highly efficacious lead drug candidates.

关键词： Antimicrobial resistance Antimicrobial peptides Design methods Peptidomimetics Artificial intelligence

Bacterial Sample Concentration and Culture Monitoring Using a PEG-Based Osmotic System with Inline Impedance and Voltammetry Measurements

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Journal of Analysis and Testing 2019年第2期3卷 166-174页

作者： Martin K.Kimani John mwangi Edgar D.Goluch Department of Chemical Engineering Northeastern UniversityBostonMA 02115USA Department of Bioengineering Northeastern UniversityBostonMA 02115USA

Impedance measurements using graphite electrodes were used to detect the increase in culture medium conductivity due to bacteria growth in real time along with simultaneous voltammetric monitoring of pyocyanin *** methods were compared to conventional continuous monitoring of bacterial cultures using turbidity measurement at an optical density of 600 nm(OD600).A practical osmotic system was further designed for concentrating bacterial cultures during growth to enable earlier detection using the electrochemical *** cultures,starting from an initial culture density of 1×10^(8) cells/mL,were grown inside a sealed cellulose ester dialysis membrane,while polyethylene glycol in LB medium was used as the draw solution outside the membrane to gradually concentrate the growing cultures.0.7-mm-diameter graphite for mechanical pencils was utilized as working and counter electrodes with a platinum wire reference electrode for electrochemical measurements with and without the osmotic *** the absence of forward osmosis,impedance meas-urements detected culture growth~1 h faster than conventional *** osmosis showed a twofold decrease in the time to detect pyocyanin production as an indicator for bacterial *** impedance monitoring,removal of water by osmosis was conflated with the impedance decrease due to cell growth;however,the results show a promising ability to detect bacteria growth via an observed shift in osmotic impedance profile when bacteria are present in a *** monitoring the deviation in the impedance profile,a threefold improvement in detection time was achieved when compared to conventional OD600 measurements.

关键词： Osmotic concentration Pseudomonas aeruginosa Bacterial growth detection Impedance electrochemical monitoring Forward osmosis

Structure of the 40S ribosomal subunit of Plasmodium falciparum by homology and de novo modeling

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Acta Pharmaceutica Sinica B 2017年第1期7卷 97-105页

作者： Harrison Ndung'u mwangi Peter Wagacha Peterson Mathenge Fredrick Sijenyi Francis Mulaa Center for Biotechnology and Bioinformatics Chiromo CampusUniversity of Nairobi.HEP Bioinformatics Consultants Ltd. Department of Computing Informatics University of Nairobi DNA Software Inc. Department of Biochemistry Riverside DriveChiromo CampusUniversity of Nairobi

Generation of three dimensional structures of macromolecules using in silico structural modeling technologies such as homology and de novo modeling has improved dramatically and increased the speed by which tertiary structures of organisms can be generated. This is especially the case if a homologous crystal structure is already available. High-resolution structures can be rapidly created using only their sequence information as input, a process that has the potential to increase the speed of scientific discovery. In this study, homology modeling and structure prediction tools such as RNA123 and SWISS–MODEL were used to generate the 40 S ribosomal subunit from Plasmodium falciparum. This structure was modeled using the published crystal structure from Tetrahymena thermophila, a homologous eukaryote. In the absence of the Plasmodium falciparum 40 S ribosomal crystal structure, the model accurately depicts a global topology, secondary and tertiary connections, and gives an overall root mean square deviation(RMSD) value of 3.9 ? relative to the template's crystal structure. Deviations are somewhat larger in areas with no homology between the templates. These results demonstrate that this approach has the power to identify motifs of interest in RNA and identify potential drug targets for macromolecules whose crystal structures are unknown. The results also show the utility of RNA homology modeling software for structure determination and lay the groundwork for applying thisapproach to larger and more complex eukaryotic ribosomes and other RNA-protein complexes. Structures generated from this study can be used in in silico screening experiments and lead to the determination of structures for targets/hit complexes.

关键词： Ribosome 40S subunit RNA structure Plasmodium falciparum 3D modeling De novo Homology

Effect of Head Position Angles on the Blood Flow in the Jugular Vein of Giraffes

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World Journal of Mechanics 2021年第8期11卷 165-175页

作者： Rogers Omboga Amenya Johanna Kibet Sigey geoffrey Moriaso Ole Maloiy David mwangi Theuri Department of Mathematics and Physical Sciences Dedan Kimathi University of Technology Nyeri Kenya Department of Pure and Applied Mathematics Jomo Kenyatta University of Agriculture and Technology Juja Kenya Department of Animal Physiology and Biotechnology University of Nairobi Nairobi Kenya

The study investigated the effect of the angular position of the head on the blood flow in the jugular vein of giraffes. The vein considered is elastic and collapsible such that its cross-sectional area is not uniform. Transmural pressure causes the blood to move along the vein. Mathematical equations describing the flow were developed, and the vein was considered to be inclined at an angle φ to the horizontal. A finite-difference scheme was used to solve the equations of motion for the flow. The results are presented via relevant tables and plots. Our findings show that a change in the position of the head causes variation in the external pressure, which in turn causes variation in the cross-sectional area of the vein. Moreover, a drop (or increase) in the inertial pressure of the blood may cause the vein to collapse (or distend), which again triggers a change in the pressure.

关键词： Venous Flow Hemodynamics Collapsible Vein Blood Pressure Jugular Vein

Modeling Blood Flow in Veins of Uniform Properties (Giraffe Jugular Vein)

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Open Journal of Biophysics 2024年第2期14卷 132-153页

作者： Rogers Omboga Amenya Johanna Kibet Sigey geoffrey Moriaso Ole Maloiy David mwangi Theuri Department of Mathematics and Physical Sciences Dedan Kimathi University of Technology Nyeri Kenya Department of Pure and Applied Mathematics School of Mathematical Sciences Jomo Kenyatta Unversity of Agriculture and Technology Kisii Kenya Institute of Animal Physiology and Biotechnology Research University of Nairobi Nairobi Kenya

This paper models the giraffe’s jugular veins as a uniform collapsible tube from a rigid skull. The equations governing one-dimensional steady flow through such a tube for various conditions have been developed. The effects of inertial and inclination angles that have not been discussed previously have been included. It has been shown that different flows for a uniform tube (vein) are possible. However, this flow matches that of a jugular vein which is supercritical, and the steady solution has been given by the balance between the driving forces of gravity and the viscous resistance to the flow at the right atrium of the heart must be sub-critical for a fixed right-atrium pressure which means that an elastic jump is required to return the flow to sub-critical from the supercritical flow upstream this type of relationship gives rise to flow limitation at the same time given any right atrium fixed pressure there exists a maximum flow rate which when exceeded the boundary conditions of the flow do not hold boundary conditions at the right atrium are not satisfied hence making the steady flow impossible this mechanism of flow limitation is slightly different from the other one in that causes airways through forced expiration from the observation made it is clearly shown that there is an intravascular pressure difference with a change in height.

关键词： Blood Flow Jugular Vein Cross-Sectional Area Supercritical Subcritical Jump

Depressive Disorders Among Women Living in Resource Poor,Northern Kenya:The Role of Psycho-education

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Psychology Research 2018年第12期8卷 587-593页

作者： Gladys Kabura mwangi Africa International University NairobiKenya

This paper highlights the findings of a dissertation research which aimed to determine the effectiveness of a model of psycho-education(PE)developed for this study,in treating the symptoms of depressive disorders among Maasai women living in resource poor settings in Laikipia County,in Northern *** quasi-experimental research design with an experimental group(EG)and control group(CG)was adopted for this *** target population for this study were 686 female members of Conservation Enterprise Groups(CEG)operating in the area.A sample size of 200 was selected for the study;(EG,n=100)and(CG,n=100),at 80%power and 30%effective *** tool used to test for symptoms of depression was the Beck’s Depression Inventory(BDI).The PE was provided as an intervention treatment to the EG at the middle and end of the study,after which the respondents were tested for symptoms of *** prevalence of depression was established at 26.7%and statistical tests conducted throughout the studies showed that the PE treatment significantly improved depression symptoms(P<0.005).Data from the(CG)showed that if these symptoms were not treated using,they degenerated into severe *** was analysed using SPSS Version 21.0.

关键词： psycho-education treatment for depressive disorders Maasai women Northern Kenya

Depression&Anxiety Among Women in Northern Kenya:Sociodemographic Predictors

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Psychology Research 2024年第2期14卷 57-63页

作者： Gladys Kabura mwangi Johnson County Community College.Kansas USA

This article documents socio-demographic predictors of anxiety and depression among Maasai women in resource poor settings in Northern *** findings emerged from the findings of a dissertation research that aimed to establish the treatment effectiveness of an eclectic model of psychoeducation(PE)in treating depressive and anxiety symptoms among the *** study adopted a quasi-experimental research design which had an experimental group(EG)and control group(CG).The population for the study was 686 female members of Conservation Enterprise Groups(CEG)in Laikipia County,from which a sample of 200 were recruited for the study(EG,n=100 and CG,n=100),at 80%power and 30%effective *** Beck’s Depression Inventory(BDI)and Beck’s Anxiety Inventory(BAI)tools were used to assess the symptoms of depression and anxiety,*** PE was provided as an intervention treatment to the EG at the middle and end of the study,after which the respondents were tested for symptoms of *** study established the prevalence of depression as 26.7%and 31.3%for anxiety and disorders,among women in the *** was analyzed using SPSS Version 21.0.

关键词： sociodemographic anxiety depression predictors Maasai women Northern Kenya

Re-Testing in Batch Testing Model Based on Quality Control Process for Proportion Estimation

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Open Journal of Statistics 2021年第1期11卷 123-136页

作者： Ronald Waliaula Wanyonyi Olivia Wanjeri mwangi Charles Wambugu mwangi Department of Mathematics Egerton University Njoro Kenya Data Science Institute University of Delaware Newark DE USA Department of Mathematics and Actuarial Kabarak University Kabarak Kenya

The quality of products manufactured or procured by organizations is an important aspect of their survival in the global market. The quality control processes put in place by organizations can be resource-intensive but substantial savings can be realized by using acceptance sampling in conjunction with batch testing. This paper considers the batch testing model based on the quality control process where batches that test positive are re-tested. The results show that re-testing greatly improves the efficiency over one stage batch testing based on quality control. This is observed using Asymptotic Relative Efficiency (ARE), where for values of p computed ARE > 1 implying that our estimator has a smaller variance than the one-stage batch testing. Also, it was found that the model is more efficient than the classical two-stage batch testing for relatively high values of proportion.

关键词： Quality Control Batch Testing Cut Off Value Proportion Re-Testing