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| 1 | Antimicrobial peptides: new hope in the war against multidrug resistance显示文摘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. | James Mwangi Xue Hao Ren Lai Zhi-Ye Zhang | 2019 | Zoological Research2019，40，6： | 23 |
| 2 | Purification and characterization of a novel anti-coagulant from the leech Hirudinaria manillensis显示文摘Protease inhibitors have been reported rarely from the leech Hirudinaria manillensis.In this study,we purified a novel protease inhibitor(bdellin-HM-2)with anticoagulant properties from H.manillensis.With 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 theC-terminus.cDNAcloning 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 plasmin.Bdellin-HM-2 showed anticoagulant effects by proIonging the activated partial thromboplastin time(aPTT),indicating a role in enabling H.manillensis to obtain a blood meal from its host.Our 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. | Ruo-Mei Cheng Xiao-Peng Tang Ai-Lin Long James Mwangi Ren Lai Rui-Pu Sun Cheng-Bo Long Zhen-Qing Zhang | 2019 | Zoological Research2019，40，3： | 5 |
| 3 | Immunogenetic factors driving formation of ultralong VH CDR3 in Bos taurus antibodies显示文摘The antibody repertoire of Bos taurus is characterized by a subset of variable heavy(VH)chain regions with ultralong third complementarity determining regions(CDR3)which,compared to other species,can provide a potent response to challenging antigens like HIV env.These unusual CDR3 can range to over seventy highly diverse amino acids in length and form uniqueβ-ribbon‘stalk’and disulfide bonded‘knob’structures,far from the typical antigen binding site.The genetic components and processes for forming these unusual cattle antibody VH CDR3 are not well understood.Here we analyze sequences of Bos taurus antibody VH domains and find that the subset with ultralong CDR3 exclusively uses a single variable gene,IGHV1-7(VHBUL)rearranged to the longest diversity gene,IGHD8-2.An eight nucleotide duplication at the 3′end of IGHV1-7 encodes a longer V-region producing an extended Fβ-strand that contributes to the stalk in a rearranged CDR3.A low amino acid variability was observed in CDR1 and CDR2,suggesting that antigen binding for this subset most likely only depends on the CDR3.Importantly a novel,potentially AID mediated,deletional diversification mechanism of the B.taurus VH ultralong CDR3 knob was discovered,in which interior codons of the IGHD8-2 region are removed while maintaining integral structural components of the knob and descending strand of the stalk in place.These deletions serve to further diversify cysteine positions,and thus disulfide bonded loops.Hence,both germline and somatic genetic factors and processes appear to be involved in diversification of this structurally unusual cattle VH ultralong CDR3 repertoire. | Thaddeus C Deiss Melissa Vadnais Feng Wang Patricia L Chen Ali Torkamani Waithaka Mwangi Marie-Paule Lefranc Michael F Criscitiello Vaughn V Smider | 2019 | Cellular & Molecular Immunology2019，16，1： | 4 |
| 4 | Antimicrobial peptide LL-37 forms complex with bacterial DNA to facilitate blood translocation of bacterial DNA and aggravate ulcerative colitis显示文摘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'. | 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 | 2018 | Science Bulletin2018，63，20： | 4 |
| 5 | Transferrin plays a central role in coagulation balance by interacting with clotting factors显示文摘Coagulation balance is maintained through fine-tuned interactions among clotting factors,whose physiological concentrations vary substantially.In particular,the concentrations of coagulation proteases(pM to nM)are much lower than their natural inactivator antithrombin(AT,〜3μM),suggesting the existence of other coordinators.In the current study,we found that transferrin(norm plasma concentration〜40 μM)interacts with fibrinogen,thrombin,factor Xlla(FXlla),and AT with different affinity to maintain coagulation balance.Normally,transferrin is sequestered by binding with fibrinogen(normal plasma concentration〜10 μM)at a molar ratio of 4:1.In atherosclerosis,abnormally up-regulated transferrin interacts with and potentiates thrombin/FXlla and blocks ATs inactivation effect on coagulation proteases by binding to AT,thus inducing hypercoagulability.In the mouse model,transferrin overexpression aggravated atherosclerosis,whereas transferrin inhibition via shRNA knockdown or treatment with antitransferrin antibody or designed peptides interfering with transferrin-thrombin/FXlla interactions alleviated atherosclerosis.Collectively,these findings identify that transferrin is an important clotting regulator and an adjuster in the maintenance of coagulation balance and modifies the coagulation cascade. | Xiaopeng Tang Zhiye Zhang Mingqian Fang Yajun Han Gan Wang Sheng Wang Min Xue Yaxiong Li Li Zhang Jian Wu Biqing Yang James Mwangi Qiumin Lu Xiaoping Du Ren Lai | 2020 | Cell Research2020，30，2： | 2 |
| 6 | Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya显示文摘 | Wendy P O'Meara Phillip Bejon Tabitha W Mwangi Emelda A Okiro Norbert Peshu Robert W Snow Charles RJC Newton Kevin Marsh | 2008 | The Lancet2008，，9649： | 2 |
| 7 | The Structure and Outcomes of a HIV Post exposure Prophylaxis Program in a High HIV Prevalence Setup in Western Kenya显示文摘 | Siika AM Nyandiko WM Mwangi A | 2009 | Acquir Immune Defic Syndr2009，51，1： | 1 |
| 8 | Heritability of malaria in Africa显示文摘 | Mackinnon MJ Mwangi TW Snow RW | 2005 | PLoS Med2005，2，12： | 1 |
| 9 | Genetic and genomic ap-proaches for the discovery of parasite genes involved in antima-larial drug resistance显示文摘 | Mwangi JM Ranford-Cartwright LC | 2013 | Parasitology2013，，： | 1 |
| 10 | Learning to solve compare word problems: The effect of example format and generating self-explanations 显示文摘 | Mwangi W Sweller J | 1998 | Cognition and Instruction1998，16，2： | 1 |
| 11 | Argi- nine and glutamine supplementation to culture media improves the performance of various channel catfish immune cells 显示文摘 | Pohlenz C Buentello J A Mwangie W | 2012 | Fish I: Shellfish Immunol2012，32，5： | 1 |
| 12 | Field -derived Schiztosoma manoni and Biomphalaria pfeifferi in Kenya: a compatible association characterized by lack of strong local adaptation, and presence of some snails able to per- sistently produce cercariae for over a year显示文摘 | Mutuku MW Dweni CK Mwangi M | 2014 | Parasit Vec- tors2014，26，7： | 1 |
| 13 | The haptoglobin 2-2 genotype is associated with a reduced incidence of Plasmodium falciparum malaria in chil?dren on the coast of Kenya显示文摘 | Atkinson SH Mwangi TW Uyoga SM | 2007 | Clin Infect Dis2007，44，6： | 1 |
| 14 | Challenges of the maize seed industry in eastern and southern Africa: A compelling case for private–public intervention to promote growth显示文摘 | Augustine S. Langyintuo Wilfred Mwangi Alpha O. Diallo John MacRobert John Dixon Marianne B?nziger | 2010 | Food Policy2010，，4： | 1 |
| 15 | Diagnosis of acute bacte- rial meningitis at distant hospital in sub-saharan African 显示文摘 | Berkley JA Mwangi I Ngetsd C J | 2001 | Lancet2001，357，9270： | 1 |
| 16 | Assessment of energy performance and air pollutant emis- sions in a diesel engine generator fueled with water-contai- ning ethanol-biodiesel-diesel blend of fuels 显示文摘 | Wen-Jhy Lee Yi-Cheng Liu Francis Kimani Mwangi | 2011 | Energy2011，36，9： | 1 |
| 17 | A review of feature ex- tration techniques in neuroimaging 显示文摘 | Mwangi B Tian T S Soares J C | 2014 | Neuroinformat- ics2014，12，2： | 1 |
| 18 | Diagnosis of acute bacterial meningitis at a district hospital in subSaharan African显示文摘 | Berkley JA Mwangi I Ngetsd CJ | 2001 | Lancet2001，357，9270： | 1 |
| 19 | Indicators of acute bacterial meningitis in children at a rural Kenyan district hospital显示文摘 | Berkley JA Versteeg AC Mwangi I | 2004 | Pediatrics2004，114，6： | 1 |
| 20 | Diagnosis of acute bacterial meningitis in children at a district hospital in sub-Saharan Africa显示文摘 | James A Berkley Isiah Mwangi Caroline J Ngetsa Salim Mwarumba Brett S Lowe Kevin Marsh Charles RJC Newton | 2001 | The Lancet2001，，9270： | 1 |
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