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Search Results: 1 - 10 of 12725 matches for " Ahmed Ahmed equal contributor "
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Mycetoma Medical Therapy
Oliverio Welsh equal contributor ,Hail Mater Al-Abdely equal contributor,Mario Cesar Salinas-Carmona equal contributor,Ahmed Hassan Fahal equal contributor
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0003218
Abstract: Medical treatment of mycetoma depends on its fungal or bacterial etiology. Clinically, these entities share similar features that can confuse diagnosis, causing a lack of therapeutic response due to inappropriate treatment. This review evaluates the response to available antimicrobial agents in actinomycetoma and the current status of antifungal drugs for treatment of eumycetoma.
Autozygome Sequencing Expands the Horizon of Human Knockout Research and Provides Novel Insights into Human Phenotypic Variation
Ahmed B. Alsalem equal contributor,Anason S. Halees equal contributor,Shamsa Anazi,Shomoukh Alshamekh,Fowzan S. Alkuraya
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1004030
Abstract: The use of autozygosity as a mapping tool in the search for autosomal recessive disease genes is well established. We hypothesized that autozygosity not only unmasks the recessiveness of disease causing variants, but can also reveal natural knockouts of genes with less obvious phenotypic consequences. To test this hypothesis, we exome sequenced 77 well phenotyped individuals born to first cousin parents in search of genes that are biallelically inactivated. Using a very conservative estimate, we show that each of these individuals carries biallelic inactivation of 22.8 genes on average. For many of the 169 genes that appear to be biallelically inactivated, available data support involvement in modulating metabolism, immunity, perception, external appearance and other phenotypic aspects, and appear therefore to contribute to human phenotypic variation. Other genes with biallelic inactivation may contribute in yet unknown mechanisms or may be on their way to conversion into pseudogenes due to true recent dispensability. We conclude that sequencing the autozygome is an efficient way to map the contribution of genes to human phenotypic variation that goes beyond the classical definition of disease.
The ESAT-6 Protein of Mycobacterium tuberculosis Interacts with Beta-2-Microglobulin (β2M) Affecting Antigen Presentation Function of Macrophage
Gopalkrishna Sreejit equal contributor,Asma Ahmed equal contributor,Nazia Parveen,Vishwanath Jha,Vijaya Lakshmi Valluri,Sudip Ghosh,Sangita Mukhopadhyay
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004446
Abstract: ESAT-6, an abundantly secreted protein of Mycobacterium tuberculosis (M. tuberculosis) is an important virulence factor, inactivation of which leads to reduced virulence of M. tuberculosis. ESAT-6 alone, or in complex with its chaperone CFP-10 (ESAT-6:CFP-10), is known to modulate host immune responses; however, the detailed mechanisms are not well understood. The structure of ESAT-6 or ESAT-6:CFP-10 complex does not suggest presence of enzymatic or DNA-binding activities. Therefore, we hypothesized that the crucial role played by ESAT-6 in the virulence of mycobacteria could be due to its interaction with some host cellular factors. Using a yeast two-hybrid screening, we identified that ESAT-6 interacts with the host protein beta-2-microglobulin (β2M), which was further confirmed by other assays, like GST pull down, co-immunoprecipitation and surface plasmon resonance. The C-terminal six amino acid residues (90–95) of ESAT-6 were found to be essential for this interaction. ESAT-6, in complex with CFP-10, also interacts with β2M. We found that ESAT-6/ESAT-6:CFP-10 can enter into the endoplasmic reticulum where it sequesters β2M to inhibit cell surface expression of MHC-I-β2M complexes, resulting in downregulation of class I-mediated antigen presentation. Interestingly, the ESAT-6:β2M complex could be detected in pleural biopsies of individuals suffering from pleural tuberculosis. Our data highlight a novel mechanism by which M. tuberculosis may undermine the host adaptive immune responses to establish a successful infection. Identification of such novel interactions may help us in designing small molecule inhibitors as well as effective vaccine design against tuberculosis.
Comparison of Two Multilocus Sequence Based Genotyping Schemes for Leptospira Species
Ahmed Ahmed equal contributor ,Janjira Thaipadungpanit equal contributor,Siriphan Boonsilp,Vanaporn Wuthiekanun,Kishore Nalam,Brian G. Spratt,David M. Aanensen,Lee D. Smythe,Niyaz Ahmed,Edward J. Feil,Rudy A. Hartskeerl,Sharon J. Peacock
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001374
Abstract: Background Several sequence based genotyping schemes have been developed for Leptospira spp. The objective of this study was to genotype a collection of clinical and reference isolates using the two most commonly used schemes and compare and contrast the results. Methods and Findings A total of 48 isolates consisting of L. interrogans (n = 40) and L. kirschneri (n = 8) were typed by the 7 locus MLST scheme described by Thaipadungpanit et al., and the 6 locus genotyping scheme described by Ahmed et al., (termed 7L and 6L, respectively). Two L. interrogans isolates were not typed using 6L because of a deletion of three nucleotides in lipL32. The remaining 46 isolates were resolved into 21 sequence types (STs) by 7L, and 30 genotypes by 6L. Overall nucleotide diversity (based on concatenated sequence) was 3.6% and 2.3% for 7L and 6L, respectively. The D value (discriminatory ability) of 7L and 6L were comparable, i.e. 92.0 (95% CI 87.5–96.5) vs. 93.5 (95% CI 88.6–98.4). The dN/dS ratios calculated for each locus indicated that none were under positive selection. Neighbor joining trees were reconstructed based on the concatenated sequences for each scheme. Both trees showed two distinct groups corresponding to L. interrogans and L. kirschneri, and both identified two clones containing 10 and 7 clinical isolates, respectively. There were six instances in which 6L split single STs as defined by 7L into closely related clusters. We noted two discrepancies between the trees in which the genetic relatedness between two pairs of strains were more closely related by 7L than by 6L. Conclusions This genetic analysis indicates that the two schemes are comparable. We discuss their practical advantages and disadvantages.
Human Cellular Immune Response to the Saliva of Phlebotomus papatasi Is Mediated by IL-10-Producing CD8+ T Cells and Th1-Polarized CD4+ Lymphocytes
Maha Abdeladhim equal contributor,Mélika Ben Ahmed equal contributor ,Soumaya Marzouki,Nadia Belhadj Hmida,Thouraya Boussoffara,Nabil Belhaj Hamida,Afif Ben Salah,Hechmi Louzir
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001345
Abstract: Background The saliva of sand flies strongly enhances the infectivity of Leishmania in mice. Additionally, pre-exposure to saliva can protect mice from disease progression probably through the induction of a cellular immune response. Methodology/Principal Findings We analysed the cellular immune response against the saliva of Phlebotomus papatasi in humans and defined the phenotypic characteristics and cytokine production pattern of specific lymphocytes by flow cytometry. Additionally, proliferation and IFN-γ production of activated cells were analysed in magnetically separated CD4+ and CD8+ T cells. A proliferative response of peripheral blood mononuclear cells against the saliva of Phlebotomus papatasi was demonstrated in nearly 30% of naturally exposed individuals. Salivary extracts did not induce any secretion of IFN-γ but triggered the production of IL-10 primarily by CD8+ lymphocytes. In magnetically separated lymphocytes, the saliva induced the proliferation of both CD4+ and CD8+ T cells which was further enhanced after IL-10 blockage. Interestingly, when activated CD4+ lymphocytes were separated from CD8+ cells, they produced high amounts of IFN-γ. Conclusion Herein, we demonstrated that the overall effect of Phlebotomus papatasi saliva was dominated by the activation of IL-10-producing CD8+ cells suggesting a possible detrimental effect of pre-exposure to saliva on human leishmaniasis outcome. However, the activation of Th1 lymphocytes by the saliva provides the rationale to better define the nature of the salivary antigens that could be used for vaccine development.
Histone H2B Monoubiquitination Facilitates the Rapid Modulation of Gene Expression during Arabidopsis Photomorphogenesis
Clara Bourbousse equal contributor,Ikhlak Ahmed equal contributor,Fran?ois Roudier,Gérald Zabulon,Eddy Blondet,Sandrine Balzergue,Vincent Colot,Chris Bowler ,Fredy Barneche
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002825
Abstract: Profiling of DNA and histone modifications has recently allowed the establishment of reference epigenomes from several model organisms. This identified a major chromatin state for active genes that contains monoubiquitinated H2B (H2Bub), a mark linked to transcription elongation. However, assessment of dynamic chromatin changes during the reprogramming of gene expression in response to extrinsic or developmental signals has been more difficult. Here we used the major developmental switch that Arabidopsis thaliana plants undergo upon their initial perception of light, known as photomorphogenesis, as a paradigm to assess spatial and temporal dynamics of monoubiquitinated H2B (H2Bub) and its impact on transcriptional responses. The process involves rapid and extensive transcriptional reprogramming and represents a developmental window well suited to studying cell division–independent chromatin changes. Genome-wide H2Bub distribution was determined together with transcriptome profiles at three time points during early photomorphogenesis. This revealed de novo marking of 177 genes upon the first hour of illumination, illustrating the dynamic nature of H2Bub enrichment in a genomic context. Gene upregulation was associated with H2Bub enrichment, while H2Bub levels generally remained stable during gene downregulation. We further report that H2Bub influences the modulation of gene expression, as both gene up- and downregulation were globally weaker in hub1 mutant plants that lack H2Bub. H2Bub-dependent regulation notably impacted genes with fast and transient light induction, and several circadian clock components whose mRNA levels are tightly regulated by sharp oscillations. Based on these findings, we propose that H2B monoubiquitination is part of a transcription-coupled, chromatin-based mechanism to rapidly modulate gene expression.
The Caenorhabditis elegans Homolog of Gen1/Yen1 Resolvases Links DNA Damage Signaling to DNA Double-Strand Break Repair
Aymeric P. Bailly,Alasdair Freeman equal contributor,Julie Hall equal contributor,Anne-Cécile Déclais equal contributor,Arno Alpi,David M. J. Lilley,Shawn Ahmed,Anton Gartner
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1001025
Abstract: DNA double-strand breaks (DSBs) can be repaired by homologous recombination (HR), which can involve Holliday junction (HJ) intermediates that are ultimately resolved by nucleolytic enzymes. An N-terminal fragment of human GEN1 has recently been shown to act as a Holliday junction resolvase, but little is known about the role of GEN-1 in vivo. Holliday junction resolution signifies the completion of DNA repair, a step that may be coupled to signaling proteins that regulate cell cycle progression in response to DNA damage. Using forward genetic approaches, we identified a Caenorhabditis elegans dual function DNA double-strand break repair and DNA damage signaling protein orthologous to the human GEN1 Holliday junction resolving enzyme. GEN-1 has biochemical activities related to the human enzyme and facilitates repair of DNA double-strand breaks, but is not essential for DNA double-strand break repair during meiotic recombination. Mutational analysis reveals that the DNA damage-signaling function of GEN-1 is separable from its role in DNA repair. GEN-1 promotes germ cell cycle arrest and apoptosis via a pathway that acts in parallel to the canonical DNA damage response pathway mediated by RPA loading, CHK1 activation, and CEP-1/p53–mediated apoptosis induction. Furthermore, GEN-1 acts redundantly with the 9-1-1 complex to ensure genome stability. Our study suggests that GEN-1 might act as a dual function Holliday junction resolvase that may coordinate DNA damage signaling with a late step in DNA double-strand break repair.
The Velvet Family of Fungal Regulators Contains a DNA-Binding Domain Structurally Similar to NF-κB
Yasar Luqman Ahmed equal contributor,Jennifer Gerke equal contributor,Hee-Soo Park equal contributor,?zgür Bayram,Piotr Neumann,Min Ni,Achim Dickmanns,Sun Chang Kim,Jae-Hyuk Yu ,Gerhard H. Braus ,Ralf Ficner
PLOS Biology , 2013, DOI: 10.1371/journal.pbio.1001750
Abstract: Morphological development of fungi and their combined production of secondary metabolites are both acting in defence and protection. These processes are mainly coordinated by velvet regulators, which contain a yet functionally and structurally uncharacterized velvet domain. Here we demonstrate that the velvet domain of VosA is a novel DNA-binding motif that specifically recognizes an 11-nucleotide consensus sequence consisting of two motifs in the promoters of key developmental regulatory genes. The crystal structure analysis of the VosA velvet domain revealed an unforeseen structural similarity with the Rel homology domain (RHD) of the mammalian transcription factor NF-κB. Based on this structural similarity several conserved amino acid residues present in all velvet domains have been identified and shown to be essential for the DNA binding ability of VosA. The velvet domain is also involved in dimer formation as seen in the solved crystal structures of the VosA homodimer and the VosA-VelB heterodimer. These findings suggest that defence mechanisms of both fungi and animals might be governed by structurally related DNA-binding transcription factors.
Evidence for Circulation of the Rift Valley Fever Virus among Livestock in the Union of Comoros
Matthieu Roger equal contributor ,Marina Beral equal contributor,Séverine Licciardi equal contributor,Miradje Soulé,Abdourahime Faharoudine,Coralie Foray,Marie-Marie Olive,Marianne Maquart,Abdouroihamane Soulaimane,Ahmed Madi Kassim,Catherine Cêtre-Sossah,Eric Cardinale
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0003045
Abstract: Rift Valley fever virus (RVFV) is an arthropod-borne phlebovirus reported to be circulating in most parts of Africa. Since 2009, RVFV has been suspected of continuously circulating in the Union of Comoros. To estimate the incidence of RVFV antibody acquisition in the Comorian ruminant population, 191 young goats and cattle were selected in six distinct zones and sampled periodically from April 2010 to August 2011. We found an estimated incidence of RVFV antibody acquisition of 17.5% (95% confidence interval (CI): [8.9–26.1]) with a significant difference between islands (8.2% in Grande Comore, 72.3% in Moheli and 5.8% in Anjouan). Simultaneously, a longitudinal entomological survey was conducted and ruminant trade-related information was collected. No RVFV RNA was detected out of the 1,568 blood-sucking caught insects, including three potential vectors of RVFV mosquito species. Our trade survey suggests that there is a continuous flow of live animals from eastern Africa to the Union of Comoros and movements of ruminants between the three Comoro islands. Finally, a cross-sectional study was performed in August 2011 at the end of the follow-up. We found an estimated RVFV antibody prevalence of 19.3% (95% CI: [15.6%–23.0%]). Our findings suggest a complex RVFV epidemiological cycle in the Union of Comoros with probable inter-islands differences in RVFV circulation patterns. Moheli, and potentially Anjouan, appear to be acting as endemic reservoir of infection whereas RVFV persistence in Grande Comore could be correlated with trade in live animals with the eastern coast of Africa. More data are needed to estimate the real impact of the disease on human health and on the national economy.
Induction of Strain-Transcending Antibodies Against Group A PfEMP1 Surface Antigens from Virulent Malaria Parasites
Ashfaq Ghumra,Jean-Philippe Semblat equal contributor,Ricardo Ataide equal contributor,Carolyne Kifude equal contributor,Yvonne Adams equal contributor,Antoine Claessens,Damian N. Anong,Peter C. Bull,Clare Fennell,Monica Arman,Alfred Amambua-Ngwa,Michael Walther,David J. Conway,Lalla Kassambara,Ogobara K. Doumbo,Ahmed Raza,J. Alexandra Rowe
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002665
Abstract: Sequence diversity in pathogen antigens is an obstacle to the development of interventions against many infectious diseases. In malaria caused by Plasmodium falciparum, the PfEMP1 family of variant surface antigens encoded by var genes are adhesion molecules that play a pivotal role in malaria pathogenesis and clinical disease. PfEMP1 is a major target of protective immunity, however, development of drugs or vaccines based on PfEMP1 is problematic due to extensive sequence diversity within the PfEMP1 family. Here we identified the PfEMP1 variants transcribed by P. falciparum strains selected for a virulence-associated adhesion phenotype (IgM-positive rosetting). The parasites transcribed a subset of Group A PfEMP1 variants characterised by an unusual PfEMP1 architecture and a distinct N-terminal domain (either DBLα1.5 or DBLα1.8 type). Antibodies raised in rabbits against the N-terminal domains showed functional activity (surface reactivity with live infected erythrocytes (IEs), rosette inhibition and induction of phagocytosis of IEs) down to low concentrations (<10 μg/ml of total IgG) against homologous parasites. Furthermore, the antibodies showed broad cross-reactivity against heterologous parasite strains with the same rosetting phenotype, including clinical isolates from four sub-Saharan African countries that showed surface reactivity with either DBLα1.5 antibodies (variant HB3var6) or DBLα1.8 antibodies (variant TM284var1). These data show that parasites with a virulence-associated adhesion phenotype share IE surface epitopes that can be targeted by strain-transcending antibodies to PfEMP1. The existence of shared surface epitopes amongst functionally similar disease-associated P. falciparum parasite isolates suggests that development of therapeutic interventions to prevent severe malaria is a realistic goal.
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