A5052988670- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Insect symbiosis and bacterial influences
- Helminth infection and control
- Biochemical and Molecular Research
- Parasites and Host Interactions
- Synthesis and Biological Evaluation
- Chemical Synthesis and Analysis
- Fatty Acid Research and Health
- Protein Kinase Regulation and GTPase Signaling
- Face recognition and analysis
- Synthetic Organic Chemistry Methods
- Parasitic Diseases Research and Treatment
- Cancer Treatment and Pharmacology
- Anesthesia and Neurotoxicity Research
- Bipolar Disorder and Treatment
- Parasitic Infections and Diagnostics
- Viral gastroenteritis research and epidemiology
- Cardiac Arrest and Resuscitation
- Traumatic Brain Injury and Neurovascular Disturbances
- Face and Expression Recognition
- Clinical Nutrition and Gastroenterology
- Emotion and Mood Recognition
- Cancer-related Molecular Pathways
- Vector-borne infectious diseases
London School of Hygiene & Tropical Medicine
2015-2024
University of Warwick
2024
University of London
2014-2023
Nazarbayev University
2020-2023
Education and Research Institute
2014-2021
National Institute of Allergy and Infectious Diseases
2016-2020
National Institutes of Health
2017
Eisai (United States)
1993-2015
Edward P. Evans Foundation
2015
University of the West Indies
2015
Chronic Trypanosoma cruzi infections lead to cardiomyopathy in 20-30% of cases.A causal link between cardiac infection and pathology has been difficult establish because a lack robust methods detect scarce, focally distributed parasites within tissues.We developed highly sensitive bioluminescence imaging system based on T. expressing novel luciferase that emits tissue-penetrating orange-red light.This enabled long-term serial evaluation parasite burdens individual mice with an vivo limit...
It has recently been reported that Ki-Ras protein can be modified in vitro by farnesylation or geranylgeranylation. However, a previous analysis of prenylationin vivo found only farnesylated Ki-Ras. In this report it is shown under normal conditions, and when cells are treated with the farnesyl transferase inhibitors B956 B957, inhibited becomes geranylgeranylated dose dependent manner. These results have strong implications design anticancer drugs based on inhibition prenylation....
Shock due to Gram-negative bacterial sepsis is a consequence of acute inflammatory response lipopolysaccharide (LPS) or endotoxin released from bacteria. LPS major constituent the outer membrane bacteria, and its terminal disaccharide phospholipid (lipid A) portion contains key structural features responsible for toxic activity. Based on proposed structure nontoxic Rhodobacter capsulatus lipid A, fully stabilized antagonist E5531 has been synthesized. In vitro, demonstrated potent antagonism...
Background Epidemiological and clinical studies suggest that increased intake of eicosapentaenoic acid (EPA) alleviates unipolar depression. Aims To examine the efficacy EPA in treating depression bipolar disorder. Method In a 12-week, double-blind study individuals with were randomly assigned to adjunctive treatment placebo ( n =26) or 1g/day =24) 2 g/day =25) ethyl-EPA. Primary was assessed by Hamilton Rating Scale for Depression (HRSD), changes Young Mania Clinical Global Impression (CGI)...
The ras protooncogene is involved in regulation of cell growth. Mutations that activate the protein result uncontrolled Ras undergoes a series posttranslational processing events, first which, farnesylation, crucial for function protein. Inhibitors farnesyltransferase enzyme are therefore potential candidates development anticancer drugs. Tetrapeptides have been reported to be good inhibitors this vitro. We synthesized analogs tetrapeptide Cys-Val-Phe-Met by replacement amino-terminal amide...
Trypanosoma cruzi is the most important parasitic infection in Latin America and also genetically highly diverse, with at least six discrete typing units (DTUs) reported: Tc I, IIa, IIb, IIc, IId, IIe. However, current six-genotype classification likely to be a poor reflection of total genetic diversity present this undeniably ancient parasite. To determine whether epidemiologically information “hidden” sub-DTU level, we developed 48-marker panel polymorphic microsatellite loci investigate...
Background.Traveler's diarrhea in Thailand is frequently caused by Campylobacter jejuni. Rates of fluoroquinolone (FQ) resistance organisms have exceeded 85% recent years, and reduced efficacy has been observed.
Trypanosoma cruzi is the causative agent of Chagas disease, which affects more than 9 million people in Latin America. We have generated a draft genome sequence TcI strain Sylvio X10/1 and compared it to TcVI reference CL Brener identify lineage-specific features. found virtually no differences core gene content by presence/absence analysis, but 6 open reading frames from were missing X10/1. Several multicopy families, including DGF, mucin, MASP GP63 contain substantially fewer genes X10/1,...
Trypanosoma cruzi, the agent of Chagas disease, can be subdivided into six discrete typing units (DTUs), TcI, TcIIa, TcIIb, TcIIc, TcIId or TcIIe, each having distinct epidemiologically important features. Dozens genetic markers are available to determine DTU which a T. cruzi isolate belongs, but there is no consensus on should used. We selected five assays: three polymerase chain reaction (PCR)-restriction fragment length polymorphisms based single nucleotide (SNPs) in HSP60, Histone H1,...
Trypanosoma cruzi, the etiological agent of Chagas disease, is highly genetically diverse. Numerous lines evidence point to existence six stable genetic lineages or DTUs: TcI, TcIIa, TcIIb, TcIIc, TcIId, and TcIIe. Molecular dating suggests that T. cruzi likely have been an endemic infection neotropical mammalian fauna for many millions years. Here we applied a panel 49 polymorphic microsatellite markers developed from online genome document diversity among 53 isolates belonging lineage so...
The single celled eukaryote Trypanosoma cruzi, a parasite transmitted by numerous species of triatomine bug in the Americas, causes Chagas disease humans. T. cruzi generally reproduces asexually and appears to have clonal population structure. However, two six major circulating genetic lineages, TcV TcVI, are TcII-TcIII inter-lineage hybrids that frequently isolated from humans regions where chronic is particularly severe. Nevertheless, prevalent view hybridisation events were evolutionarily...
ABSTRACT The antifungal drug posaconazole has shown significant activity against Trypanosoma cruzi in vitro and experimental murine models. Despite this, a recent clinical trial it displayed limited curative potential. Drug testing is problematic Chagas disease because of difficulties demonstrating sterile cure, particularly during the chronic stage infection when parasite burden extremely low tissue distribution ill defined. To better assess efficacy acute disease, we have exploited highly...
Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence tsetse fly as obligatory vector, and need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand molecular causes consequences of these differences, we sequenced genome akinetoplastic strain China compared it b. reference strain. The annotated shows extensive similarity reference, with 94.9% predicted coding sequences (CDS) having ortholog in evansi, 94.6%...
Background Mitochondrial DNA is a valuable taxonomic marker due to its relatively fast rate of evolution. In Trypanosoma cruzi, the causative agent Chagas disease, mitochondrial genome has unique structural organization consisting 20–50 maxicircles (∼20 kb) and thousands minicircles (0.5–10 kb). T. cruzi an early diverging protist displaying remarkable genetic heterogeneity recognized as complex six discrete typing units (DTUs). The majority infected humans are asymptomatic for life while...
Chagas' disease is responsible for significant mortality and morbidity in Latin America. Current treatments display variable efficacy have adverse side effects, hence more effective, better tolerated drugs are needed. However, recent efforts proved unsuccessful with failure of the ergosterol biosynthesis inhibitor posaconazole phase II clinical trials despite promising vitro vivo studies. The lack translation between laboratory experiments outcome a major issue further drug discovery...
Abstract The insect-transmitted protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, and infects 5–8 million people in Latin America. disease characterised by an acute phase, which partially resolved immune system, but then develops as a chronic life-long infection. There consensus that front-line drugs benznidazole nifurtimox are more effective against stage both clinical experimental settings. However, confirmative studies have been restricted difficulties...
Host and parasite diversity are suspected to be key factors in Chagas disease pathogenesis. Experimental investigation of underlying mechanisms is hampered by a lack tools detect scarce, pleiotropic infection foci. We developed sensitive imaging models track Trypanosoma cruzi dynamics quantify tissue-specific loads, with minimal sampling bias. used this technology investigate cardiomyopathy caused highly divergent strains BALB/c, C3H/HeN C57BL/6 mice. The gastrointestinal tract was...
Background Infection with Trypanosoma cruzi causes Chagas disease, a major public health problem throughout Latin America. There is no vaccine and the only drugs have severe side effects. Efforts to generate new therapies are hampered by limitations in our understanding of parasite biology disease pathogenesis. Studies compromised complexity long-term nature infection, fact that parasites barely detectable during chronic stage. In addition, functional dissection T. has been restricted...
We present SpeakingFaces as a publicly-available large-scale multimodal dataset developed to support machine learning research in contexts that utilize combination of thermal, visual, and audio data streams; examples include human–computer interaction, biometric authentication, recognition systems, domain transfer, speech recognition. is comprised aligned high-resolution thermal visual spectra image streams fully-framed faces synchronized with recordings each subject speaking approximately...