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Dive into the research topics where Jacob Souopgui is active.

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Featured researches published by Jacob Souopgui.


Human Molecular Genetics | 2008

Atypical Mowat–Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NuRD corepressor complex

Griet Verstappen; Leonardus Van Grunsven; Christine Michiels; Tom Van de Putte; Jacob Souopgui; Jozef Van Damme; Eric Bellefroid; Joël Vandekerckhove; Danny Huylebroeck

Mutations in ZFHX1B cause Mowat-Wilson syndrome (MWS) but the precise mechanisms underlying the aberrant functions of mutant ZFHX1B proteins (also named Smad-interacting protein-1, SIP1) in patients are unknown. Using mass spectrometry analysis, we identified subunits of the NuRD corepressor complex in affinity-purified Zfhx1b complexes. We find that Zfhx1b associates with NuRD through its N-terminal domain, which contains a previously postulated NuRD interacting motif. Interestingly, this motif is substituted by an unrelated sequence in a recently described MWS patient. We show here that such aberrant ZFHX1B protein is unable to recruit NuRD subunits and displays reduced transcriptional repression activity on the XBMP4 gene promoter, a target of Zfhx1b. We further demonstrate that the NuRD component Mi-2beta is involved in repression of the Zfhx1b target gene E-cadherin as well as in Zfhx1b-induced neural induction in animal caps from Xenopus embryos. Thus, NuRD and Zfhx1b functionally interact, and defective NuRD recruitment by mutant human ZFHX1B can be a MWS-causing mechanism. This is the first study providing mechanistic insight into the aberrant function of a single domain of the multi-domain protein ZFHX1B/SIP1 in human disease.


Cellular and Molecular Life Sciences | 2013

The ZIC gene family encodes multi-functional proteins essential for patterning and morphogenesis

Rob Houtmeyers; Jacob Souopgui; Sabine Tejpar; Ruth M. Arkell

The zinc finger of the cerebellum gene (ZIC) discovered in Drosophila melanogaster (odd-paired) has five homologs in Xenopus, chicken, mice, and humans, and seven in zebrafish. This pattern of gene copy expansion is accompanied by a divergence in gene and protein structure, suggesting that Zic family members share some, but not all, functions. ZIC genes are implicated in neuroectodermal development and neural crest cell induction. All share conserved regions encoding zinc finger domains, however their heterogeneity and specification remain unexplained. In this review, the evolution, structure, and expression patterns of the ZIC homologs are described; specific functions attributable to individual family members are supported. A review of data from functional studies in Xenopus and murine models suggest that ZIC genes encode multifunctional proteins operating in a context-specific manner to drive critical events during embryogenesis. The identification of ZIC mutations in congenital syndromes highlights the relevance of these genes in human development.


Developmental Biology | 2008

Hairy2-Id3 interactions play an essential role in Xenopus neural crest progenitor specification.

Massimo Nichane; Noémie de Crozé; Xi Ren; Jacob Souopgui; Anne H. Monsoro-Burq; Eric Bellefroid

Loss of function studies have shown that the Xenopus helix-loop-helix transcription factor Hairy2 is essential for neural crest formation and maintains cells in a mitotic undifferentiated state. However, its position in the genetic cascade regulating neural crest formation and its relationship with other neural crest regulators remain largely unknown. Here we find that Hairy2 is regulated by BMP, FGF and Wnt and that it is only required downstream of BMP and FGF for neural crest formation. We show that Hairy2 overexpression represses neural crest and upregulates neural border genes at early stages while it expands a subset of them in later embryos. We show that Hairy2 downregulates Id3, another essential HLH neural crest regulator, through attenuation of BMP signaling. Knockdown and rescue experiments indicate that Id3 protein, which physically interacts with Hairy2, negatively regulates Hairy2 activity. However, Id3 is required to allow Hairy2 to promote neural crest formation. Together, our results provide evidence that Hairy2 acts downstream of FGF and BMP signals at the neural border to maintain cells in an undifferentiated state, and that Hairy2-Id3 interactions play an essential role in neural crest progenitor specification.


Human Molecular Genetics | 2016

Zic2 mutation causes holoprosencephaly via disruption of NODAL signalling.

Rob Houtmeyers; Olive Tchouate Gainkam; Hannah A. Glanville-Jones; Ben Van den Bosch; Anna Chappell; Kristen S. Barratt; Jacob Souopgui; Sabine Tejpar; Ruth M. Arkell

The ZIC2 transcription factor is one of the genes most commonly mutated in Holoprosencephaly (HPE) probands. Studies in cultured cell lines and mice have shown a loss of ZIC2 function is the pathogenic mechanism but the molecular details of this ZIC2 requirement remain elusive. HPE arises when signals that direct morphological and fate changes in the developing brain and facial primordia are not sent or received. One critical signal is sent from the prechordal plate (PrCP) which develops beneath the ventral forebrain. An intact NODAL signal transduction pathway and functional ZIC2 are both required for PrCP establishment. We now show that ZIC2 acts downstream of the NODAL signal during PrCP development. ZIC2 physically interacts with SMAD2 and SMAD3, the receptor activated proteins that control transcription in a NODAL dependent manner. Together SMAD3 and ZIC2 regulate FOXA2 transcription in cultured cells and Zic2 also controls the foxA2 expression during Xenopus development. Variant forms of the ZIC2 protein, associated with HPE in man or mouse, are deficient in their ability to influence SMAD-dependent transcription. These findings reveal a new mechanism of NODAL signal transduction in the mammalian node and provide the first molecular explanation of how ZIC2 loss-of-function precipitates HPE.


Developmental Dynamics | 2009

Database of queryable gene expression patterns for Xenopus.

Michael J. Gilchrist; Mikkel Christensen; Odile Bronchain; Frédéric Brunet; Albert Chesneau; Ursula Fenger; Timothy J. Geach; Holly Ironfield; Ferdinand Kaya; Sadia Kricha; Robert W. Lea; Karine Massé; Isabelle Néant; Elodie Paillard; Karine Parain; Muriel Perron; Ludivine Sinzelle; Jacob Souopgui; Raphaël Thuret; Qods Ymlahi-Ouazzani; Nicolas Pollet

The precise localization of gene expression within the developing embryo, and how it changes over time, is one of the most important sources of information for elucidating gene function. As a searchable resource, this information has up until now been largely inaccessible to the Xenopus community. Here, we present a new database of Xenopus gene expression patterns, queryable by specific location or region in the embryo. Pattern matching can be driven either from an existing in situ image, or from a user‐defined pattern based on development stage schematic diagrams. The data are derived from the work of a group of 21 Xenopus researchers over a period of 4 days. We used a novel, rapid manual annotation tool, XenMARK, which exploits the ability of the human brain to make the necessary distortions in transferring data from the in situ images to the standard schematic geometry. Developmental Dynamics 238:1379–1388, 2009.


Parasites & Vectors | 2016

Still mesoendemic onchocerciasis in two Cameroonian community-directed treatment with ivermectin projects despite more than 15 years of mass treatment

Guy-Roger Kamga; Fanny Nadia Dissak-Delon; Hugues C. Nana-Djeunga; Benjamin D. Biholong; Stephen Mbigha-Ghogomu; Jacob Souopgui; Honorat G. M. Zouré; Michel Boussinesq; Joseph Kamgno; Annie Robert

BackgroundAfter more than a decade of community-directed treatment with ivermectin (CDTI) in Centre and Littoral Regions of Cameroon, onchocerciasis endemicity was still high in some communities according to the 2011 epidemiological evaluations. Some corrective measures were undertaken to improve the CDTI process and therefore reduce the burden of the disease. The objective of the present study was to assess the progress made towards the elimination of onchocerciasis in the Centre 1 and Littoral 2 CDTI projects where the worst performances were found in 2011. To this end, a cross-sectional survey was conducted in April 2015 in eight communities in two health districts (HD), Bafia in Centre 1 and Yabassi in Littoral 2, chosen because assessed at baseline and in 2011. All volunteers living for at least five years in the community, aged five years or more, underwent clinical and parasitological examinations. Individual compliance to ivermectin treatment was also assessed. Analyses of data were weighted proportionally to age and gender distribution in the population.ResultsIn the Bafia and Yabassi HD, 514 and 242 individuals were examined with a mean age of 35.1 (standard deviation, SD: 20.7) and 44.6 (SD: 16.3) years, respectively. In the Bafia HD, the weighted prevalences varied from 24.4 to 57.0 % for microfilaridermia and from 3.6 to 37.4 % for nodule presence across the surveyed communities. The community microfilarial load (CMFL), expressed in microfilariae/skin snip (mf/ss), significantly dropped from 20.84–114.50 mf/ss in 1991 to 0.31–1.62 mf/ss in 2015 in all the surveyed communities. In the Yabassi HD, the weighted prevalences varied from 12.3 to 59.3 % for microfilaridermia and from 1.5 to 3.7 % for nodule presence across the surveyed communities, while a significant drop was observed in CMFL, from 20.40–28.50 mf/ss in 1999 to 0.48–1.74 mf/ss in 2015. The 2014 weighted therapeutic coverage of participants varied from 65.8 % (95 % CI: 58.4–73.2) in Yabassi HD, to 68.0 % (95 % CI: 63.3–72.7) in Bafia HD, with important variations among communities.ConclusionsAfter more than 15 years of CDTI, onchocerciasis is still mesoendemic in the surveyed communities. Further studies targeting therapeutic coverage, socio-anthropological considerations of CDTI implementation and entomological studies would bring more insights to the persistence of the disease as observed in the present study.


Experimental Parasitology | 2002

Expression and characterization of Ov-47, a dominant antigen of Onchocerca volvulus

Stephen Mbigha Ghogomu; Jacob Souopgui; Roger Pelle; Vincent P.K. Titanji

The expression and characterization of a recombinant antigen termed Ov-47 are described. Ov-47 was identified and isolated from a lambda gt-11 cDNA expression library derived from adult female Onchocerca volvulus mRNA using rabbit antiserum raised against the surface proteins of O. volvulus female worms. The antiserum was earlier found to mediate, in vitro, cytoadherence and cytotoxicity reactions to microfilariae in the presence of heat-labile serum factors. The deduced amino acid sequence of the gene was assigned the EMBL GenBank Accession No. Y15993. The open reading frame (1077 bp) of the gene was then subcloned into pQE-60 and expressed in Escherichia coli JM109 cells. The gene encodes a protein with an apparent molecular weight of 47,000 Da as revealed by SDS-PAGE. Up to 100 micrograms/ml pure Ov-47 recombinant protein could be isolated from E. coli cultures by Ni-agarose affinity chromatography. The 47-kDa protein was recognized by sera from both infected and endemic normal subjects. The parent protein was found to have a molecular weight of 60 kDa. IgG3 subclass responses to Ov-47 were significantly higher in endemic normals than in infected subjects (P < 0.05). In contrast, IgG4 responses were higher in infected subjects than in endemic normals (P < 0.05). IgG2 response exhibited marked age dependency with lower responses in younger patients, which rose to higher levels in elderly patients. IgG1, IgG3, and IgG4 responses did not show any age dependency. This study clearly shows that Ov-47 is a dominant antigen of O. volvulus adult worms with an important role in the host-parasite-interplay.


PLOS Neglected Tropical Diseases | 2017

Adherence to ivermectin is more associated with perceptions of community directed treatment with ivermectin organization than with onchocerciasis beliefs

Fanny Nadia Dissak-Delon; Guy-Roger Kamga; Perrine Humblet; Annie Robert; Jacob Souopgui; Joseph Kamgno; Marie José Essi; Stephen Mbigha Ghogomu; Isabelle Godin

Background The fight against onchocerciasis in Africa has boomed thanks to the Community Directed Treatment with Ivermectin (CDTI) program. However, in Cameroon, after more than 15 years of mass treatment, onchocerciasis prevalence is still above the non-transmission threshold. This study aimed to explore a possible association between people’s beliefs/perceptions of onchocerciasis and of CDTI program, and their adherence to ivermectin in three regions of Cameroon. Methodology/Principal findings A cross sectional survey was carried out in three health districts with persistent high onchocerciasis prevalence. Participants were randomly selected in 30 clusters per district. Adherence to ivermectin was comparable between Bafang and Bafia (55.0% and 48.8%, respectively, p>0.05) and lower in Yabassi (40.7%). Among all factors related to program perceptions and disease representations that were studied, perceptions of the program are the ones that were most determinant in adherence to ivermectin. People who had a “not positive” opinion of ivermectin distribution campaigns were less compliant than those who had a positive opinion about the campaigns (40% vs 55% in Bafang, and 48% vs 62% in Bafia, p<0.01), as well as those who had a negative appreciation of community drug distributors’ commitment (22% vs 53% in Bafang, 33% vs 59% in Bafia, 27% vs 47% in Yabassi; p<0.01). The most common misconception about onchocerciasis transmission was the lack of hygiene, especially in Bafia and Yabassi. In Bafang, high proportions of people believed that onchocerciasis was due to high consumption of sugar (31% vs less than 5% in Bafia and Yabassi, p<0.001). Conclusion/Significance There are still frequent misconceptions about onchocerciasis transmission in Cameroon. Perceptions of ivermectin distribution campaigns are more strongly associated to adherence. In addition to education/sensitisation on onchocerciasis during the implementation of the CDTI program, local health authorities should strive to better involve communities and more encourage community distributors’ work.


Parasites & Vectors | 2018

Audit of the community-directed treatment with ivermectin (CDTI) for onchocerciasis and factors associated with adherence in three regions of Cameroon

Guy-Roger Kamga; Fanny Nadia Dissak-Delon; Hugues C. Nana-Djeunga; Benjamin D. Biholong; Stephen Mbigha Ghogomu; Jacob Souopgui; Joseph Kamgno; Annie Robert

BackgroundAfter more than 15 years of community-directed treatment with ivermectin (CDTI) in the Centre 1, Littoral 2 and West CDTI projects in Cameroon, the epidemiological evaluation conducted in 2011 revealed that onchocerciasis endemicity was still high in some communities. To investigate the potential reasons explaining this high endemicity, a cluster coverage survey was conducted in April-May 2015 in three health districts (HD), to assess the implementation of the CDTI, the 2014 therapeutic coverage and the five-year adherence to treatment. A two-stage cluster design was considered during analyses, with data weighted proportionally to age and gender distribution in the population.ResultsIn the three HDs, 69 community leaders, 762 heads of households, 83 community drug distributors (CDD) and 2942 household members were interviewed. The CDTI organization and the involvement of heads of households were in average weak, with 84.0% (95% CI: 81.2–86.4%) of them who had not participated in activities during the 2014 mass drug administration (MDA). On average, six of ten community leaders declared that the period of treatment was decided by the health personnel while the CDDs selection was made during a community meeting for only 43.4% of them. The 2014 weighted therapeutic coverage was 64.1% (95% CI: 56.8–70.9%), with no significant difference in the three HDs. The survey coverages were lower than the reported coverages with a significant difference varying from 14.1% to 22.0%. Among those aged 10 years and above, 57.8% (95% CI: 50.2–65.1%) declared having taken the treatment each time during the last five MDAs with no significant difference among HDs, while 9.8% (95% CI: 7.5–12.8%) declared that they had never taken the drug. In multivariate analysis, the most important factors associated with the five-year adherence to treatment were high involvement in CDTI and age (40+ years).ConclusionsDespite more than 15 years of CDTI, there was still weak community participation and ownership, a lower coverage than reported and an average five-year adherence in the surveyed HDs. The reinforcement of the community ownership by the Ministry of Public Health officials and the timely procurement of ivermectin as requested by the communities are some measures that should be implemented to improve the therapeutic coverage, adherence to treatment and hence achieve onchocerciasis elimination. Further anthropological and entomological studies would provide better insights into our understanding of the persistence of the disease in these three CDTI projects.


Journal of Ethnopharmacology | 2018

An ethnobotanical survey and inhibitory effects on NLRP3 inflammasomes/Caspase-1 of herbal recipes' extracts traditionally used in Rwanda for asthma treatment.

J.C. Tomani; Lea Olive Tchouate Gainkam; Samuel Nshutiyayesu; Marie Jeanne Mukazayire; Sofia Oliveira Ribeiro; Caroline Stevigny; Michel Frederich; Raymond Muganga; Jacob Souopgui

ETHNOPHARMACOLOGICAL RELEVANCE Respiratory diseases and asthma, in particular, are nowadays a global health problem. In Rwanda, some traditional healers claim to treat asthma with plant-based recipes, though there is no scientific proof so far. AIM OF THE STUDY Our study aimed at evaluating the toxicity and the anti-inflammatory effect of plant recipes used in Rwanda against asthma in order to select potential candidates for further characterization of the active compounds. MATERIALS AND METHODS Water (aqueous) and methanol-dichloromethane (organic) extracts from selected folkloric recipes were submitted for toxicity test on THP-1 derived macrophages using CellTiter-Glo Luminescent Cell Viability Assay. The evaluation of the anti-inflammatory effect of the plant extracts was carried out using the Caspase-Glo 1 Inflammasome assay on THP-1 -derived macrophages. RESULTS Most of both organic and aqueous extract showed more than 95% of cell viability up to 200 µg/ml, except for R03Cn organic extract that inhibited 25% of the cell viability. Plant extracts inhibited caspase-1 activation in THP-1 derived macrophages in a dose-dependent manner. Four extracts (R03Cn and R07Kn aqueous extracts, R10MK and R19Sz organic extracts) strongly downregulated the activation of caspase-1 (more than 70% at 50 µg/ml). In general, organic extracts exhibited better caspase-1 inhibitory effects than their aqueous counterparts. CONCLUSIONS The inhibition of inflammasome/caspase-1 is one of key mechanisms of action in asthma. Some traditional recipes are active on this mechanism and are thus strong candidates for the treatment of asthma and other inflammasome-mediated diseases. Further investigations are needed to characterize active molecules.

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Eric Bellefroid

Université libre de Bruxelles

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Elie Fokou

University of Yaoundé I

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Martin Fotso

University of Yaoundé I

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Roger Ponka

University of Yaoundé I

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Annie Robert

Université catholique de Louvain

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