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Biomedical subjects

F Francis

Publications and source records attributed to F Francis.

At least 19 recordsLinked to original sources

Outcome of imported liver allografts and impact on patient access to liver transplantation.

Liver allografts declined by local transplant centers are then offered regionally or nationally as imported grafts. Most of these grafts are declined because of poor donor quality. We retrospectively reviewed the medical records of patients who underwent liver transplantation between January 2004 and December 2005. There were 102 liver transplants in 98 recipients. They were divided into two groups: imported graft recipients (n = 37) and locally procured grafts recipients (n = 61). Eighty-six percent (32 of 37) of imported grafts were obtained from extended criteria donors defined as subjects treated with high doses of ionotropes with elevated liver enzymes, donor age over 70 years, macrosteatosis above 25%, positive hepatitis C or hepatitis B core antibody serology, systemic disease, history of cancer, hypernatremia, or with infection. The remaining grafts were declined due to unavailability of suitable recipients or social history. Recipient age and etiology of liver disease were similar for both groups. The mean MELD score was 22.1 +/- .9 among the imported graft recipients and 26.1 +/- 1 for the locally procured graft recipients (P < .01). There was no difference in blood loss or postoperative complications. Postoperative mean peak total bilirubin was similar in both groups. However, imported graft recipients had significantly higher mean peak AST (2436 +/- 282 vs 1380 +/- 165 U/L, P < .001) and ALT (1098 +/- 114 vs 803 +/- 87 U/L, P < .05). Primary graft nonfunction as well as 30 day and 1-year patient and graft survivals were similar for both groups. In conclusion, imported grafts can be transplanted in selected patients with outcomes comparable to locally procured grafts.

Hepatitis C↗

So-called 'cryptogenic' partial seizures resulting from a subtle cortical dysgenesis due to a doublecortin gene mutation.

We report the case of a female suffering from resistant partial seizures, which were related to 'cryptogenic' epilepsy, as the cerebral cortex was considered normal on the initial MRI images. As her son is mentally retarded and has a pachygyria, the doublecortin gene, usually involved in band heterotopia or lissencephaly, was screened for mutations. A missense mutation was identified, shared by both the son and his mother, and a subtle discontinuous subcortical heterotopia was subsequently detected on the mother's MRI. The pathophysiology of epilepsy in this woman is discussed in the light of the role of doublecortin, not only in neuronal migration, but also in axonal growth and dendritic connectivity.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Impact of close habitat on the entomological diversity and abundance in carrot open fields.

Vegetable open fields areas have been increasing for the last decade in Wallonia (South part of Belgium), mainly in Hesbaye. To be in accordance with quality standards, especially in terms of agrochemical residues (R.M.L.), biological pest control was developed and reduces the insecticide use, leading to have safer fresh products. Carrot represents an important cultivated species in Wallonia. To asses the impact of close habitat on both pest (mainly aphids) and beneficial insects, carrot fields were investigated during all the production duration in 2000. Twelve fields between Waremme and Hannut were visited weekly from June to October. Insects were caught using yellow traps and determined to the family level. Approximately 90,000 insects belonging to 109 families were identified. Significant differences linked to field closed habitat were observed on 31 families. An increase of biodiversity in term of family number near set-asides and woody borders was observed. Evaluation of pest and beneficial diversity and density in vegetable crops was discussed to promote future IPM program.

Animals↗

Doublecortin interacts with mu subunits of clathrin adaptor complexes in the developing nervous system.

Doublecortin is a microtubule-associated protein required for normal corticogenesis in the developing brain. We carried out a yeast two-hybrid screen to identify interacting proteins. One of the isolated clones encodes the mu1 subunit of the adaptor complex AP-1 involved in clathrin-dependent protein sorting. We found that Doublecortin also interacts in yeast with mu2 from the AP-2 complex. Mutagenesis and pull-down experiments showed that these interactions were mediated through a tyrosine-based sorting signal (YLPL) in the C-terminal part of Doublecortin. The functional relevance of these interactions was suggested by the coimmunoprecipitation of Doublecortin with AP-1 and AP-2 from mouse brain extracts. This interaction was further supported by RNA in situ hybridization and immunofluorescence studies. Taken together these data indicate that a certain proportion of Doublecortin interacts with AP-1 and/or AP-2 in vivo and are consistent with a potential involvement of Doublecortin in protein sorting or vesicular trafficking.

Adaptor Protein Complex 1↗

Glutathione S-transferases of Aulacorthum solani and Acyrthosiphon pisum: partial purification and characterization.

Glutathione S-transferases (GST) play an important role in the detoxification of many substances including allelochemicals from plants. Brassicaceae plants contain glucosinolates and emit volatile isothiocyanates which affect the GST system. A comparison of the GST of two aphid species, the generalist Aulacorthum solani found on Brassicaceae and the Fabaceae specialist Acyrthosiphon pisum, was made to try to explain their respective feeding behaviour. Differences of GST were determined among the two aphid species based on purification by affinity chromatography, SDS-PAGE and on kinetic studies. Purification yields using an epoxy-activated Sepharose 6B column were highly different for the two aphid species (18% and 34% for A. solani and A. pisum, respectively). These variations were confirmed by SDS-PAGE. While only a 27-kDa band was observed for A. pisum, two bands of approximately 25-kDa were visualized for the generalist aphid, A. solani. Considering the kinetic results, differences of Km and Vmax were observed following the aphid species when a range of substrates (CDNB and DCNB) and GSH concentrations were tested. Studies on the detoxification enzymes of generalist and specialist herbivores would be undertaken to determine accurately the effect of the host plant on the organisms eating them, particularly in terms of biochemical and ecological advantages.

Animals↗

Effects of allelochemicals from first (brassicaceae) and second (Myzus persicae and Brevicoryne brassicae) trophic levels on Adalia bipunctata.

Three Brassicaceae species, Brassica napus (low glucosinolate content), Brassica nigra (including sinigrin), and Sinapis alba (including sinalbin) were used as host plants for two aphid species: the generalist Myzus persicae and the specialist Brevicoryne brassicae. Each combination of aphid species and prey host plant was used to feed the polyphagous ladybird beetle, Adalia bipunctata. Experiments with Brassicaceae species including different amounts and kinds of glucosinolates (GLS) showed increased ladybird larval mortality at higher GLS concentrations. When reared on plants with higher GLS concentrations, the specialist aphid, B. brassicae, was found to be more toxic than M. persicae. Identification of GLS and related degradation products, mainly isothiocyanates (ITC), was investigated in the first two trophic levels, plant and aphid species, by high-performance liquid chromatography and gas chromatography-mass spectrometry, respectively. While only GLS were detected in M. persicae on each Brassicaceae species, high amounts of ITC were identified in B. brassicae samples (allyl-ITC and benzyl-ITC from B. nigra and S. alba, respectively) from all host plants. Biological effects of allelochemicals from plants on predators through aphid prey are discussed in relation to aphid species to emphasize the role of the crop plant in integrated pest management in terms of biological control efficacy.

Animals↗

Deletion of the cell-division inhibitor MinC results in lysis of Neisseria gonorrhoeae.

The minCDE genes involved in division site selection in Neisseria gonorrhoeae were identified using raw data from the N. gonorrhoeae genome project and are part of a cluster of 27 genes. When gonococcal min genes were heterologously expressed as a cluster in Escherichia coli, minicells and filaments were produced, indicating that gonococcal min genes disrupted cell division in other genera. The insertional inactivation of the minC gene of N. gonorrhoeae CH811 resulted in a strain (CSRC1) with decreased viability and grossly abnormal cell division as observed by phase-contrast and electron microscopy analysis. Western blot analysis of N. gonorrhoeae CSRC1 confirmed that MinC(Ng) was not produced. Complementation of CSRC1 by integrating a minC-6xHis tag fusion at the proAB locus by homologous recombination restored viability and 1.9 times wild-type levels of MinC(Ng) expression. This slight increase of expression caused a small percentage of the complemented cells to divide aberrantly. This suggested that the 6xHis tag has partially affected the stability of MinC, or that the chromosomal position of minC is critical to its regulation. Comparison of MinC proteins from different bacteria showed a homologous region corresponding to residues 135-230 with five conserved amino acids. Overexpression of MinC(Ng) in wild-type E. coli cells induced filamentation and an E. coli minC mutant was successfully complemented with minC(Ng). Therefore, the evidence indicates that MinC from N. gonorrhoeae acts as a cell-division inhibitor and that its role is essential in maintaining proper division in cocci.

Bacterial Proteins↗

Oviposition preferences of Episyrphus balteatus.

A crucial aspect of predator oviposition behaviour is host plant choice, especially in hoverflies where the newly hatched offspring are unable to move a great distance to search for the appropriate prey. Such offspring must generally feed on the host plant aphids previously selected by the mother. Some factors involved in the selection of the oviposition site of Episyrphus balteatus De Geer include aphids associated to chemical stimuli, aphid colony size and host plant characteristics. Here we tested the hypothesis that there will not only be a rank order hierarchy of preference for aphid prey species reared on the same host plant but that a similar hierarchy of different host plant of one aphid species could be established. Therefore we compared the number of eggs laid on different combinations of host plant and aphid species. Vicia faba L., secondary metabolites free, Brassica napus L. and Sinapis alba L., containing low and high levels of glucosinolates respectively were used. The latter compounds are well known allelochemicals from Brassicaceae having a strong influence on specialist and generalist insects from both phytophagous and entomophagous levels. These experiments enhance the importance of tritrophic interactions in biological control of pests by underlining the host plant influence on aphidophagous predators, either directly or through the odours emitted by the phytophagous prey.

Animals↗

Evolution of aphidophagous ladybird populations in a vegetable crop and implications as biological agents.

Aphidophagous predators such as hoverfly and ladybird beetles are effective biological agents to control aphid pests in perennial and annual cultivated species. Introduction and conservation of beneficial insects are two ways to increase natural control of pests. Whether massive releases of entomophagous insects are expensive and time consuming, the preservation of predator natural populations can be expected by reducing and by adapting chemical treatments in crop fields. Vegetable cultivated areas increased in Belgium for several years, mainly Fabaceae species such as peas and beans. In this work, the evolution of ladybird species population was assessed from May to June in broad bean fields (Vicia faba L.) between Waremme and Hannut, in Hesbaye. Weekly, the aphid and aphidophagous beetle populations were collected from yellow traps and determined on plants by visual observations. Even if five ladybird species were identified, three of them represented more than 95% of the collected insects (Coccinella septempunctata L., Propylea quatuor-decimpunctata L. and Psyllobora vingintiduopunctata L.). Evolution of coccinellid populations during the cultivation season was discussed in relation to the presence of potential aphid preys and the agrochemical treatments which were applied. Integrated pest management in vegetable fields constitute a reliable way to increase the quality level of fresh vegetables in terms of pesticide residue limitations.

Animals↗

Effects of insecticide treatments on insect density and diversity in vegetable open fields.

Vegetable open field areas increased for 15 years in Wallonia, mainly in Hesbaye. To be in accordance with quality standards, especially in terms of agro-chimical residues (R.M.L.), biological pest control was developed and allowed to reduce the insecticide use, leading to have safer fresh products. Among cultivated species in Wallonia, leguminous crops represent more than 85% of the vegetable production. To assess the impact of insecticide treatment on both pests (mainly aphids) and beneficial insects (predators and parasitoïds), broad bean (Vicia faba L.) fields were investigated during all the production duration. Twelve fields between Waremme and Hannut were visited weakly from May to July. In each field, control untreated and treated plots were investigated. Insects were caught using yellow traps and determined until the family level. Approximately 90.000 insects belonging to 59 major families (99% of captures) and 64 minor families were identified. These results showed that biodiversity in terms of family numbers was significantly higher in unsprayed plots. In addition, biodiversity and biomass (insect density) increased gradually during the season. Evaluation of pest and beneficial diversity and density was discussed in relation to aphicid (lambda-cyhalothrin, pirimicarb) treatments and the development of I.P.M. program in vegetable crops.

Animals↗

Organization and transcription of the division cell wall (dcw) cluster in Neisseria gonorrhoeae.

A cluster of genes involved in cell division and cell wall (dcw) biosynthesis was identified in Neisseria gonorrhoeae using genomic analysis and through verification of gene order by polymerase chain reaction (PCR) analysis. The gonococcal dcw cluster consists of 17 genes, in the order 5'-mraZ-mraW-ftsI-murE-hyp1-murF- mraY-hyp2-murD-ftsW-murG-murC-ddl -ft sQ-ftsA-ftsZ-hyp3-3'. The gene organization of the dcw cluster of N. gonorrhoeae is more similar to that observed in Gram-negative rods such as Escherichia coli and Haemophilus influenzae than in Gram-positive bacteria. The cluster is characterized by several intergenic spaces. Compared with E. coli, two genes, ftsL and envA, are absent in the gonococcal dcw cluster and three hypothetical genes are novel to the cluster. The cluster is flanked by two transcriptional terminators consisting of paired neisserial uptake sequences and also includes four internal terminators, three of which are paired neisserial uptake sequences. We also found that a repeated sequence on the gonococcal genome, commonly called a Correia element, acts as the fourth transcriptional terminator. All termination sequences were shown to be fully functional by using reverse transcription PCR experiments. Transcriptional start sites upstream of ftsQ, ftsA and ftsZ were determined by primer extension and six promoters were identified; three promoters were located upstream of ftsZ in the intergenic space, two were upstream of ftsA within ftsQ and one was upstream of ftsQ within ddl. Some of these promoters were preferentially used under anaerobic conditions. The location of these promoters differed from those described in E. coli indicating dissimilar transcriptional regulation.

Base Sequence↗

The DNA sequence of human chromosome 21.

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

Base Sequence↗

Doublecortin mutations cluster in evolutionarily conserved functional domains.

Mutations in the X-linked gene doublecortin ( DCX ) result in lissencephaly in males or subcortical laminar heterotopia ('double cortex') in females. Various types of mutation were identified and the sequence differences included nonsense, splice site and missense mutations throughout the gene. Recently, we and others have demonstrated that DCX interacts and stabilizes microtubules. Here, we performed a detailed sequence analysis of DCX and DCX-like proteins from various organisms and defined an evolutionarily conserved Doublecortin (DC) domain. The domain typically appears in the N-terminus of proteins and consists of two tandemly repeated 80 amino acid regions. In the large majority of patients, missense mutations in DCX fall within the conserved regions. We hypothesized that these repeats may be important for microtubule binding. We expressed DCX or DCLK (KIAA0369) repeats in vitro and in vivo. Our results suggest that the first repeat binds tubulin but not microtubules and enhances microtubule polymerization. To study the functional consequences of DCX mutations, we overexpressed seven of the reported mutations in COS7 cells and examined their effect on the microtubule cytoskeleton. The results demonstrate that some of the mutations disrupt microtubules. The most severe effect was observed with a tyrosine to histidine mutation at amino acid 125 (Y125H). Produced as a recombinant protein, this mutation disrupts microtubules in vitro at high molar concentration. The positions of the different mutations are discussed according to the evolutionarily defined DC-repeat motif. The results from this study emphasize the importance of DCX-microtubule interaction during normal and abnormal brain development.

Amino Acid Sequence↗

Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia.

The chromosomal abnormality represented by an isodicentric X chromosome [idic(X)(q13)] is associated with a subset of acute myeloid leukemia (AML) and preleukemia observed in elderly females. A previous study localized the breakpoints of two acquired isodicentric X chromosomes associated with myelodysplasia to a 450-kb region proximal to the XIST gene. Here we report the construction and extensive characterization of a reliable 1-Mb P1 artificial chromosome and bacterial artificial chromosome contig covering a highly problematic region in Xq13 that includes the previously described isodicentric breakpoint region. In addition to mapping of the brain-specific gene (NAP1L2) and the phosphoglyceryl kinase alpha subunit 1 gene (PHKA1) and generation and mapping of a large number of STSs throughout the contig, we have mapped a putative transcriptional regulatory protein (HDACL1), and 35 ESTs. Sequencing data, Southern blot analysis, and fiber-FISH analysis have permitted characterization of extensive region-specific duplications and triplications in addition to an unusually high concentration of long interspersed repeat elements, both of which could be implicated in isodicentric chromosome formation and other Xq13 chromosome aberrations. FISH analysis of metaphase chromosomes from two previously unpublished AML patients and one preleukemic patient using cosmid clones and selected subclones allowed mapping of the idic(X)(q13) breakpoints to a 100-kb interval, consistent with the involvement of an X-linked gene in the genesis of this form of preleukemia, disruption of which may represent a preliminary step in progression to AML. Assembly and physical mapping of this complex 1-Mb contig establish a foundation for ongoing sequencing and gene identification projects in the region.

Acute Disease↗

A new gene involved in X-linked mental retardation identified by analysis of an X;2 balanced translocation.

X-linked forms of mental retardation (MR) affect approximately 1 in 600 males and are likely to be highly heterogeneous. They can be categorized into syndromic (MRXS) and nonspecific (MRX) forms. In MRX forms, affected patients have no distinctive clinical or biochemical features. At least five MRX genes have been identified by positional cloning, but each accounts for only 0.5%-1.0% of MRX cases. Here we show that the gene TM4SF2 at Xp11.4 is inactivated by the X breakpoint of an X;2 balanced translocation in a patient with MR. Further investigation led to identification of TM4SF2 mutations in 2 of 33 other MRX families. RNA in situ hybridization showed that TM4SF2 is highly expressed in the central nervous system, including the cerebral cortex and hippocampus. TM4SF2 encodes a member of the tetraspanin family of proteins, which are known to contribute in molecular complexes including beta-1 integrins. We speculate that through this interaction, TM4SF2 might have a role in the control of neurite outgrowth.

Amino Acid Sequence↗