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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

Purification and characterization of a novel anti-coagulant from the leech Hirudinaria manillensis

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Zoological Research 2019年第3期40卷 205-210页

作者： Ruo-Mei Cheng Xiao-Peng Tang Ai-Lin Long james mwangi Ren Lai Rui-Pu Sun Cheng-Bo Long Zhen-Qing Zhang Department of Pharmaceutical Sciences College of Pharmaceutical SciencesSoocbow UniversitySuzhou Jiangsu 215123China Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyKunming Yunnan 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming Yunnan 650204China Jiangxi Medical College Nanchang UniversityNanchang Jiangxi 330006China

Protease inhibitors have been reported rarely from the leech Hirudinaria *** this study,we purified a novel protease inhibitor(bdellin-HM-2)with anticoagulant properties from *** a molecular weight of 1.4x104,bdellin-HM-2 was also characterized with three intra?molecular disulfide bridges at the N-terminus and multiple HHXDD and HXDD motifs at *** revealed that the putative nucleotide-encoding protein of bdellin-HM-2 contained 132 ami no acids and was encoded by a 399 bp open reading frame(ORF).Sequence alignment showed that bdellin-HM-2 shared similarity with the“non-classical"Kazal-type serine protease inhibitors,but had no inhibitory effect on trypsin,elastase,chymotrypsin,kallikrein,factor Xlla(FXIIa),factor Xia(FXIa),factor Xa(FXa),thrombin,or ***-HM-2 showed anticoagulant effects by proIonging the activated partial thromboplastin time(aPTT),indicating a role in enabling *** to obtain a blood meal from its *** results suggest that bdellin-HM丒2 may play a crucial role in blood-sucking in this leech species and may be a pote ntial can didate for the development of clinical anti-thrombotic drugs.

关键词： Hirudinaria manillensis Bdellin-HM-2 "Non-classical"Kazal inhibitors Blood sucking Anticoagulant Anti-thrombotic drugs

Prediction of Client Support on Contractor Performance as a Critical Success Factor

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Journal of Building Construction and Planning Research 2021年第1期9卷 77-89页

作者： Johnson Matu Augustine mwangi Gatotoh james Mushori Open Distance and eLearning Campus University of Nairobi Nairobi Kenya

The aim of this study was to assess the influence of client support on performance of contractors within the road construction industry in Kenya. The study adopted descriptive survey research design and correlation research design. The target population was 156 selected from road contractors, engineers working in road authorities, technical auditors and consultants in the road sector. Stratified and proportionate sampling techniques were employed in coming up with a sample size of 62 respondents drawn from a target population of 156. From the simple linear regression conducted, the findings revealed that client support influences the performance of contractors in the road construction sector. Thus, we recommend that client support is highly needed to avoid issues such as delayed payment that would adversely affect performance of contractors in the road construction industry. This will subsequently lead to timely completion of roads, achieving cost effective and quality road projects.

关键词： Client Support Road Contractors Contractor Performance

Characterization of Forest Degradation beyond Canopy Cover Change in Mau Forest, Kenya

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Open Journal of Forestry 2022年第4期12卷 393-407页

作者： Merceline Awuor Ojwala Felix Mutua mwangi james Kinyanjui Department of Geomatic Engineering and Geospatial Information Systems Jommo Kenyatta University of Agriculture and Technology Nairobi Kenya Directorate of Resource Surveys and Remote Sensing Nairobi Kenya School of Natural Resources and Environmental Studies Karatina University Karatina Kenya

Monitoring Forest degradation is evidence enough to show a country’s commitment to monitor the forest trend both for national and local decision-making and international reporting processes. Unlike deforestation which is easier to point out, monitoring forest degradation is quite a challenge since there is no universal definition and thus no clear monitoring methods apart from the canopy cover change. This research, therefore, sought to look at the degradation trends in the Mau forest complex between 1995-2020 with the aim of finding out whether monitoring canopy density changes over time and quantifying these changes in terms of biomass loss could be a good approach in monitoring forest degradation. Forest Canopy Density (FCD) model was adopted focusing on using vegetation indices describing biophysical conditions of Vegetation, Shadow and Bareness to monitor changes in canopy density as a parameter for describing forest degradation in the forest blocks of Maasai Mau and Olpusimoru in Mau forest complex. Results indicated how different vegetation indices responded to changes in the vegetation density and eventually changes in the canopy density values which were converted in terms of biomass loss. The forest Canopy Density model proved to be a good tool for monitoring forest degradation since it combines different biophysical indices with different characteristics capturing what is happening below the canopy.

关键词： Forest Degradation Canopy Density Vegetation Indices Biomass Loss Monitoring

Antimicrobial peptide LL-37 forms complex with bacterial DNA to facilitate blood translocation of bacterial DNA and aggravate ulcerative colitis

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Science Bulletin 2018年第20期63卷 1364-1375页

作者： Zilei Duan Yaqun Fang Yang Sun Ning Luan Xue Chen Mengrou Chen Yajun Han Yizhu Yin james mwangi Junkun Niu Kunhua Wang Yinglei Miao Zhiye Zhang Ren Lai Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute .of ZoologyKunming 650223China Life Sciences College of Nanjing Agricultural University Nanjing 210095China Department of Gastroenterology The First Affiliated Hospital of Kunming Medical UniversityKunming 650032China Department of General Surgery The First Affiliated Hospital of Kunming Medical UniversityKunming 650032China Kunming College of Life Science University of Chinese Academy of SciencesKunming 650204China Sino-African Joint Research Center Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China

Bacterial DNA(bacDNA) is frequently found in serum of patient with ulcerative colitis(UC) and Crohn's disease, even blood bacterial culture is negative. How bacDNA evades immune elimination and is translocated into blood remain unclear. Here, we showed that bacDNA avoids elimination and disables bacteriakilling function of antimicrobial peptide LL-37(Cramp in mice) by forming complex with LL-37, which is inducible after culture with bacteria or bacterial products. Elevated LL-37-bacDNA complex was found in plasma and lesions of patients with UC. LL-37-bacDNA promoted inflammation by inducing Th1, Th2 and Th17 differentiation and activating toll-like receptor-9(TLR9). The complex also increased paracellular permeability, which possibly combines its inflammatory effects to promote local damage and bacDNA translocation into blood. Cramp-bacDNA aggravated mouse colitis severity while interference with the complex ameliorated the disease. The study identifies that inflammatogenic bacDNA utilizes LL-37 as a vehicle for blood translocation and to evade immune elimination. Additionally, bacteria may make a milieu by releasing bacDNA to utilize and resist host antimicrobial peptides as a ‘trojan horse'.

关键词： Ulcerative colitis Bacterial DNA LL-37 Immune elimination Chronic inflammation

Mixture Ratio Estimators Using Multi-Auxiliary Variables and Attributes for Two-Phase Sampling

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Open Journal of Statistics 2014年第9期4卷 776-788页

作者： Paul mwangi Waweru John Kung’u james Kahiri Department of Statistics and Actuarial Science Kenyatta University Nairobi Kenya

In this paper, we have proposed three classes of mixture ratio estimators for estimating population mean by using information on auxiliary variables and attributes simultaneously in two-phase sampling under full, partial and no information cases and analyzed the properties of the estimators. A simulated study was carried out to compare the performance of the proposed estimators with the existing estimators of finite population mean. It has been found that the mixture ratio estimator in full information case using multiple auxiliary variables and attributes is more efficient than mean per unit, ratio estimator using one auxiliary variable and one attribute, ratio estimator using multiple auxiliary variable and multiple auxiliary attributes and mixture ratio estimators in both partial and no information case in two-phase sampling. A mixture ratio estimator in partial information case is more efficient than mixture ratio estimators in no information case.

关键词： Ratio Estimator Multiple Auxiliary Variables Multiple Auxiliary Attributes Two-Phase Sampling Bi-Serial Correlation Coefficient

Effects of Sawdust, Forest Soil and Cow Dung Mixtures on Growth Characteristics of Blue Gum (<i>Eucalyptus saligna</i>) Seedlings in South Kinangop Forest, Nyandarua, Kenya

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Open Journal of Forestry 2017年第4期7卷 373-387页

作者： Fredrick Atanas Ashiono Hellen Kamiri Wangechi mwangi james Kinyanjui Kenya Forest Service South Kinangop Forest Station Nairobi Kenya School of Natural Resources and Environmental Studies Department of Natural Resources Karatina University Karatina Kenya School of Agriculture and Biotechnology Department of Crop Science Karatina University Karatina Kenya

Forestation programs, in Kenya have been hindered by, among others, high cost of tree seedling production and longtime seedlings stay in the nursery. This has been attributed to poor quality of forest soil and unavailability of alternative growth media. Study was carried out in South Kinangop forest station to evaluate the potential of mixing sawdust and cow dung with forest soil to form a nutrient rich growth media. Using forest soil;sawdust, cow dung and mixture of these components, this study sought to determine growth characteristics of Eucalyptus saligna seedlings under different conditions available in the nursery. The experiment was laid out in a Completely Randomized Design (CRD) with six treatments comprising of Saw dust alone (Tr 1), Forest soil alone (Tr 2);Sawdust: Cow dung mixture in the ratio of 1:1 (Tr 3);Forest soil to Sawdust-Cow dung mixture (1:1) in ratio of 1:1 by weight (Tr 4);Forest soil to Sawdust-Cow dung mixture (1:1) in ratio of 1:2 by weight (Tr 5) and Forest soil to Sawdust-Cow dung (1:1) in ratio of 1:3 by weight (Tr 6). Treatments were replicated three times and an experimental unit consisted of 110 seedlings of which 15 were tagged for height and root collar diameter measurement. The remaining 95 were used for biomass determination by destructive sampling. The results showed that Sawdust: Cow dung mixtures (Tr 3) had the highest measurements for height, root collar diameter and biomass at week 20 when compared to the rest of growth mixtures. Height measurements were significantly high (13.81 cm) for the Sawdust: Cow dung mixtures while the variation in root collar diameter and biomass were not significantly different among the treatments. Sawdust alone did not favor seedling growth and recorded the lowest measurements in height, root collar diameter and biomass. Nutrient release from the growth media during the experimental period was equally high for the Saw dust: Cow dung mixture (Tr 3) which was ideal media for raising tree seedling

关键词： CowDung Forest Soil Sawdust Tree Seedling

Estimation of Above Ground Biomass in Forests Using Alos Palsar Data in Kericho and Aberdare Ranges

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Open Journal of Forestry 2017年第2期7卷 79-96页

作者： Eunice Wamuyu Maina Patroba Achola Odera mwangi james Kinyanjui Department of Geomatic Engineering and Geospatial Information Systems Jomo Kenyatta University of Agriculture and Technology Nairobi Kenya Division of Geomatics School of Architecture Planning and Geomatics University of Cape Town Cape Town South Africa Department of Forestry School of Natural Resources and Environmental Studies Karatina University Karatina Kenya

Above Ground Biomass is one of the six pools identified in the inventory of forest resources and estimation of greenhouse gas emissions and sinks from the forestry sector. The pool varies by management practices in different agro-ecological or agro-climatic zones in forests. The quantification of above ground biomass (AGB) hence carbon sequestration in forests has been very difficult due to the immense costs required. This research was done to estimate AGB using ALOS PALSAR L band data (HH, HV polarisation) acquired in 2009 in relation with ground measurements data in Kericho and Aberdares ranges in Kenya. Tree data information was obtained from ground measurement of DBH and tree heights in 100 circular plots of 15 m radius, by use of random sampling technique. ALOS PALSAR image is advantageous for its active microwave sensor using L-band frequency to achieve cloud free imageries, and the ability of long wavelength cross-polarization to estimate AGB accurately for tropical forests. The variations result between Natural and plantation forest for measured and estimated biomass in Kericho HV band regression value was 0.880 and HH band was 0.520. In Aberdare ranges HV regression value of 0.708 and HH band regression value of 0.511 for measured and estimated biomass respectively. The variations can be explained by the influence of different management regimes induced human disturbances, forest stand age, density, species composition, and trees diameter distribution. However, further research is required to investigate how strong these factors affect relationship between AGB and Alos Palsar backscatters.

关键词： Above Ground Biomass Estimation Green House Gas Carbon Credits Alos Palsar Backscatter Cross-Polarization Regression Analysis