Jean-Marc Neefs - Academia.edu (original) (raw)

Papers by Jean-Marc Neefs

Nucleic Acids Research, 1990

Eukaryotic small ribosomal subunit RNAs contain an area of variable structure, V4, which comprise... more Eukaryotic small ribosomal subunit RNAs contain an area of variable structure, V4, which comprises about 250 nucleotides in most species, whereas the corresponding area in bacterial small ribosomal subunit RNAs consists of about 64 nucleotides folded into a single hairpin. There is no consensus on the secondary structure of area V4 in eukaryotes, about 10 different models having been proposed. The prediction of a model on a comparative basis poses special problems because, due to the variability of the area in length as well as sequence, a dependable alignment is very difficult to achieve. A new model was derived by systematic examination of all combinations of helices that have been hitherto proposed, plus some new ones. The following properties of the helices were examined: transposability to all presently known sequences, presence of compensating substitutions, and thermodynamic stability. A model was selected by ranking all possible combinations of transposable helices according to the number of compensating substitutions scored. The optimal model comprises a pseudoknot and four hairpin structures. Certain species contain additional hairpins inserted between these structural elements, while in others the structure is partially or entirely deleted.

Journal of Molecular Evolution, 1990

A tree was constructed from a structurally conserved area in an alignment of 83 small ribosomal s... more A tree was constructed from a structurally conserved area in an alignment of 83 small ribosomal subunit sequences of eukaryotic, archaebacterial, eubacterial, plastidial, and mitochondrial origin. The algorithm involved computation and optimization of a dissimilarity matrix. According to the tree, only plant mitochondria belong to the eubacterial primary kingdom, whereas animal, fungal, algal, and ciliate mitochondria branch off from an internal node situated between the three primary kingdoms. This result is at variance with a parsimony tree of similar size published by Cedergren et al. (J Mol Evol 28:98-112, 1988), which postulates the mitochondria to be monophyletic and to belong to the eubacterial primary kingdom. The discrepancy does not follow from the use of conflicting sequence alignments, hence it must be due to the use of different treeing algorithms. We tested our algorithm on a set of sequences resulting from a simulated evolution and found it capable of faithfully reconstructing a branching topology that involved very unequal evolutionary rates. The use of more limited or more extended areas of the complete sequence alignment, comprising only very conserved or also more variable portions of the small ribosomal subunit structure, does have some influence on the tree topology. In all cases, however, the nonplant mitochondria seem to branch off before the emergence ofeubacteria, and the differences are limited to the branching pattern among different types of mitochondria.

FEBS Letters, 1990

Evolutionary trees based on partial small ribosomal subunit RNA sequences of 22 metaxoa species h... more Evolutionary trees based on partial small ribosomal subunit RNA sequences of 22 metaxoa species have been published [( 1988) Science 239, 748-7531. In these trees, cnidarians (Radiata) seemed to have evolved independently from the Bilateria, which is in contradiction with the general evolutionary view. In order to further investigate this problem, the complete srRNA sequence of the sea anemone Anemoniu sulcuta was determined and evolutionary trees were constructed using a matrix optimization method. In the tree thus obtained the sea anemone and Bilateria together form a monophyletic cluster, with the sea anemone forming the first line of descent of the metaxoan group.

BMC Bioinformatics, 2010

Numbers and data mining are easy. Our numerical system counts 10 digits, any combination is possi... more Numbers and data mining are easy. Our numerical system counts 10 digits, any combination is possible, and every measured value can be captured in a number. Large quantities of measures can be analysed efficiently using incredibly powerful calculators, and resulting information can be shown is simple clear graphs.

British journal of cancer, 2000

We have cloned a human Hevin cDNA from omental adipose tissue of different patients by reverse tr... more We have cloned a human Hevin cDNA from omental adipose tissue of different patients by reverse transcription polymerase chain reaction and shown a sequence variation due to a possible polymorphism at amino acid position 161 (E/G). Hevin protein expressed in vitro showed molecular weights of approximately 75 kDa and 150 kDa, suggesting that Hevin may form a homodimer in vitro. Using Northern blots and a human expressed sequence tAg database analysis, Hevin was shown to be widely expressed in human normal or non-neoplastic diseased tissues with various levels. In contrast to this, its expression was strongly down-regulated in most neoplastic cells or tissues tested. However, neither the mechanism nor the physiological meaning of this down-regulation is known. As an initial step towards investigating the functional role of Hevin in cell growth and differentiation, we transiently or stably expressed this gene in cancer cells (HeLa 3S) that are devoid of endogenous Hevin and measured DNA...

Systematic and Applied Microbiology, 1993

ABSTRACT 16S and 23S ribosomal RNA (rRNA) genes from campylobacteria were studied by polymerase c... more ABSTRACT 16S and 23S ribosomal RNA (rRNA) genes from campylobacteria were studied by polymerase chain reaction and DNA sequence analysis using universally conserved oligonucleotide primers. In the 16S rRNA gene sequences of all C. sputorum strains tested, an insertion of about 250 bp was found that was not present in the 16S rRNA genes of other Campylobacter species. This insertion was not present on the rRNA level in C. sputorum, and the 16S rRNA was found to be fragmented in this organism. From the length of the fragments, it could be concluded that the insertion is an internal transcribed spacer, which is probably excised during rRNA maturation. Similar internal transcribed spacers were also found in the 23S rRNA genes from several Campylobacter strains. On the basis of partial 23S rRNA gene sequences about 875 bp in length and comprising some of the most variable helices, phylogenetic analysis was performed on 17 Campylobacter strains. The results of this analysis were compared to a phylogenetic tree based on complete 16S rRNA sequences.

Systematic and Applied Microbiology, 1994

Nature Communications, 2014

Bedaquiline (BDQ), an ATP synthase inhibitor, is the first drug to be approved for treatment of m... more Bedaquiline (BDQ), an ATP synthase inhibitor, is the first drug to be approved for treatment of multidrug-resistant tuberculosis in decades. Though BDQ has shown excellent efficacy in clinical trials, its early bactericidal activity during the first week of chemotherapy is minimal. Here, using microfluidic devices and time-lapse microscopy of Mycobacterium tuberculosis, we confirm the absence of significant bacteriolytic activity during the first 3-4 days of exposure to BDQ. BDQ-induced inhibition of ATP synthesis leads to bacteriostasis within hours after drug addition. Transcriptional and proteomic analyses reveal that M. tuberculosis responds to BDQ by induction of the dormancy regulon and activation of ATP-generating pathways, thereby maintaining bacterial viability during initial drug exposure. BDQ-induced bacterial killing is significantly enhanced when the mycobacteria are grown on non-fermentable energy sources such as lipids (impeding ATP synthesis via glycolysis). Our results show that BDQ exposure triggers a metabolic remodelling in mycobacteria, thereby enabling transient bacterial survival. Figure 1 | Delayed killing of M. tuberculosis by BDQ. (a) Kill kinetics of BDQ for M. tuberculosis over a period of 18 days and (b) initial 5 days of the BDQ kill kinetics. The bacteria were grown in liquid culture (Middlebrook 7H9 medium) in the presence of the indicated concentrations of BDQ or the front-line anti-TB drug isoniazid as a control. (c) Decrease of cellular ATP levels in M. tuberculosis during 18 days of BDQ treatment. (d) Cellular ATP levels during the initial 48 h of BDQ treatment. Inset: cellular ATP levels in the BDQ-resistant M. tuberculosis strain. ATP levels were determined using the bioluminescence method and are displayed as relative luminescence units (RLUs). Representative results from two experiments are shown. NATURE COMMUNICATIONS |

Molecular and Cellular Endocrinology, 2000

The authors previously reported that one of the cAMP-response elements (CREs) of the human beta3-... more The authors previously reported that one of the cAMP-response elements (CREs) of the human beta3-AR gene, beta3CRE2, interacts with a nuclear factor which is distinct from CREB/ATF family. We named this factor WATSF-1 (white adipose tissue specific factor-1) since it is preferentially expressed in WAT. In this work, we have shown the absence of DNA binding or transcriptional activity of this factor in several non-adipose cells tested. By computer analysis, beta3CRE2 was found to constitute an octameric element that is highly homologous to the binding site for some members of the nuclear hormone receptor superfamily. Using the response elements of other adipocyte-specific nuclear receptors as competitors, a 'cross-talk' between WATSF-1 and these response elements has been demonstrated. However, the affinity of WATSF-1 for these response elements differs from that for beta3CRE2 (self), implying that WATSF-1 is distinct from these adipocyte-specific nuclear receptors. Furthermore the DNA-binding activity of WATSF-1 was shown to be enhanced by phosphatase treatment, suggesting that phosphorylation may play an important role in the functional modulation of this factor. In an effort to prove that it is indeed an adipocyte-specific factor, we used 3T3-L1 cells, a cellular model of WAT, that can undergo differentiation into adipocytes. The DNA binding and transcriptional activity of this factor appeared during differentiation of the cells. Taken together, these results demonstrate that WATSF-1 is a putative white adipocyte-specific nuclear orphan receptor induced during adipogenesis and is a transcriptional activator through one of the CREs of the human beta3-AR gene. Targeting this factor may be a novel therapeutic approach to stimulation of the beta3-AR signal transduction pathway in adipose tissues.

Journal of Biological Chemistry, 1999

Hydrolysis of the neuropeptide N-acetyl-L-aspartyl-Lglutamate (NAAG) by N-acetylated ␣-linked aci... more Hydrolysis of the neuropeptide N-acetyl-L-aspartyl-Lglutamate (NAAG) by N-acetylated ␣-linked acidic dipeptidase (NAALADase) to release glutamate may be important in a number of neurodegenerative disorders in which excitotoxic mechanisms are implicated. The gene coding for human prostate-specific membrane antigen, a marker of prostatic carcinomas, and its rat homologue glutamate carboxypeptidase II have recently been shown to possess such NAALADase activity. In contrast, a closely related member of this gene family, rat ileal 100-kDa protein, possesses a dipeptidyl peptidase IV activity. Here, we describe the cloning of human ileal 100-kDa protein, which we have called a NAALADase-"like" (NAALADase L) peptidase based on its sequence similarity to other members of this gene family, and its inability to hydrolyze NAAG in transient transfection experiments. Furthermore, we describe the cloning of a third novel member of this gene family, NAALADase II, which codes for a type II integral membrane protein and which we have localized to chromosome 11 by fluorescent in situ hybridization analysis. Transient transfection of NAALADase II cDNA confers both NAALADase and dipeptidyl peptidase IV activity to COS cells. Expression studies using reverse transcription-polymerase chain reaction and Northern blot hybridization show that NAALADase II is highly expressed in ovary and testis as well as within discrete brain areas.

The two text mining strategies: finding co-occurrences of biological entities within documents, a... more The two text mining strategies: finding co-occurrences of biological entities within documents, and finding relationships using Natural Language Processing, are often seen as competitors. Here we adopt a flexible approach where the techniques are adapted and combined to suit the nature of the document corpus, and the specific task. The approach was tested on three tasks relevant to cancer treatment: finding kinases associated with cancer, finding gene mutations, and finding interactions between proteins associated with cancer. The paper describes the use of entity disambiguation, cooccurrence and linguistic processing in these tasks, and provides an overview of the methodology and results.

selecting target genes or proteins for new drugs. We found the application of virtual reality to ... more selecting target genes or proteins for new drugs. We found the application of virtual reality to the field of genomics to be successfull.

The Biochemical journal, 1998

Histamine H1 receptor expression has been reported to change in disorders such as allergic rhinit... more Histamine H1 receptor expression has been reported to change in disorders such as allergic rhinitis, autoimmune myocarditis, rheumatoid arthritis and atherosclerosis. Here we report the isolation and characterization of genomic clones containing the 5' flanking (regulatory) region of the human histamine H1 receptor gene. An intron of approx. 5.8 kb was identified in the 5' untranslated region, which suggests that an entire subfamily of G-protein-coupled receptors may contain an intron immediately upstream of the start codon. The transcription initiation site was mapped by 5' rapid amplification of cDNA ends to a region 6.2 kb upstream of the start codon. Immediately upstream of the transcription start site a fragment of 1.85 kb was identified that showed promoter activity when placed upstream of a luciferase reporter gene and transiently transfected into cells expressing the histamine H1 receptor. The promoter sequence shares a number of characteristics with the promoter...

Evolutionary trees based on small ribosomal subunit RNA sequences yield a new perspective on euka... more Evolutionary trees based on small ribosomal subunit RNA sequences yield a new perspective on eukaryote evolution. In agreement with classical views regarding evolution, animals, green plants, and fungi form monophyletic groups which seem to have originated nearly simultaneously. The evolution of these organisms took place in a relatively short time interval and is characterized by a massive diversification of life forms. In contrast, the dissimilarity among protoctist small ribosomal subunit RNA sequences is huge and exceeds the diversity seen in the entire prokaryotic world. Furthermore, some Protoctista branch off very soon in eukaryote evolution, while others diverge much later. Based on these ribosomal RNA data, Protoctista should be regarded as a collection of independent evolutionary lineages. Because the evolutionary distance between the different groups of Protoctista is, in several cases, larger than the evolutionary distance between plants, fungi and animals, the classification of eukaryotes into four kingdoms seems to be artificial and may not reflect true evolutionary relationships.

Drug Discovery Today, 2015

The explored kinome was extended with broad profiling using the DiscoveRx and Millipore assay pan... more The explored kinome was extended with broad profiling using the DiscoveRx and Millipore assay panels. The analysis of the profiling of 3368 selected inhibitors on 456 kinases in the DiscoveRx format delivered several insights. First, the coverage depended on the threshold of the selectivity parameter. Second, the relation between hit confirmation rates and inhibitor selectivity showed unexpectedly that higher selectivity can increase the likelihood of false positives. Third, comparing the coverage of a focused to that of a random library showed that the design based on a maximum number of scaffolds was superior to a limited number of scaffolds. Therefore, selective compounds can be used in target validation, enable the jumpstarting of new kinase drug discovery projects, and chart new biological space via phenotypic screening.

Systematic and Applied Microbiology, 1993

ABSTRACT The primary structure of the small ribosomal subunit RNA (SSU rRNA) was determined for 1... more ABSTRACT The primary structure of the small ribosomal subunit RNA (SSU rRNA) was determined for 13 species belonging to 10 ascomycete families and for the basidiomycetous anamorphic yeast Rhodotorula glutinis. The sequences were fitted into an alignment of all hitherto published complete or nearly complete eukaryotic small subunit rRNA sequences. The evolutionary relationships within the fungi were examined by construction of a tree from 87 SSU rRNA sequences, corresponding to 71 different species, by means of a distance matrix method and bootstrap analysis. It confirms the early divergence of the zygomycetes and the classical division of the higher fungi into basidiomycetes and ascomycetes. The basidiomycetes are divided into true basidiomycetes and ustomycetes. Within the ascomycetes, the major subdivisions hemiascomycetes and euascomycetes can be recognized. However, Schizosaccharomyces pombe does not belong to the cluster of the hemiascomycetes, to which it is assigned in classical taxonomic schemes, but forms a distinct lineage. Among the euascomycetes, the plectomycetes and the pyrenomycetes can be distinguished. Within the hemiascomycetes, the polyphyly of genera like Pichia or Candida and of families like the Dipodascaceae and the Saccharomycetaceae can be observed.

Systematic and Applied Microbiology, 1994

... van de Peer 1 ,; Jean-Marc Neefs 1 ,; Peter de Rijk 1 ,; Paul de Vos 2 ,; Rupert de Wachter 1... more ... van de Peer 1 ,; Jean-Marc Neefs 1 ,; Peter de Rijk 1 ,; Paul de Vos 2 ,; Rupert de Wachter 1 , Corresponding author contact information , a. 1 Departement Biochemie, Universiteit Antwerpen (UIA), Antwerpen, Belgium; 2 Laboratorium voor Microbiologie, Universiteit Gent, Gent, ...

Lecture Notes in Computer Science, 2014

Nucleic Acids Research, 1990

Eukaryotic small ribosomal subunit RNAs contain an area of variable structure, V4, which comprise... more Eukaryotic small ribosomal subunit RNAs contain an area of variable structure, V4, which comprises about 250 nucleotides in most species, whereas the corresponding area in bacterial small ribosomal subunit RNAs consists of about 64 nucleotides folded into a single hairpin. There is no consensus on the secondary structure of area V4 in eukaryotes, about 10 different models having been proposed. The prediction of a model on a comparative basis poses special problems because, due to the variability of the area in length as well as sequence, a dependable alignment is very difficult to achieve. A new model was derived by systematic examination of all combinations of helices that have been hitherto proposed, plus some new ones. The following properties of the helices were examined: transposability to all presently known sequences, presence of compensating substitutions, and thermodynamic stability. A model was selected by ranking all possible combinations of transposable helices according to the number of compensating substitutions scored. The optimal model comprises a pseudoknot and four hairpin structures. Certain species contain additional hairpins inserted between these structural elements, while in others the structure is partially or entirely deleted.

Journal of Molecular Evolution, 1990

A tree was constructed from a structurally conserved area in an alignment of 83 small ribosomal s... more A tree was constructed from a structurally conserved area in an alignment of 83 small ribosomal subunit sequences of eukaryotic, archaebacterial, eubacterial, plastidial, and mitochondrial origin. The algorithm involved computation and optimization of a dissimilarity matrix. According to the tree, only plant mitochondria belong to the eubacterial primary kingdom, whereas animal, fungal, algal, and ciliate mitochondria branch off from an internal node situated between the three primary kingdoms. This result is at variance with a parsimony tree of similar size published by Cedergren et al. (J Mol Evol 28:98-112, 1988), which postulates the mitochondria to be monophyletic and to belong to the eubacterial primary kingdom. The discrepancy does not follow from the use of conflicting sequence alignments, hence it must be due to the use of different treeing algorithms. We tested our algorithm on a set of sequences resulting from a simulated evolution and found it capable of faithfully reconstructing a branching topology that involved very unequal evolutionary rates. The use of more limited or more extended areas of the complete sequence alignment, comprising only very conserved or also more variable portions of the small ribosomal subunit structure, does have some influence on the tree topology. In all cases, however, the nonplant mitochondria seem to branch off before the emergence ofeubacteria, and the differences are limited to the branching pattern among different types of mitochondria.

FEBS Letters, 1990

Evolutionary trees based on partial small ribosomal subunit RNA sequences of 22 metaxoa species h... more Evolutionary trees based on partial small ribosomal subunit RNA sequences of 22 metaxoa species have been published [( 1988) Science 239, 748-7531. In these trees, cnidarians (Radiata) seemed to have evolved independently from the Bilateria, which is in contradiction with the general evolutionary view. In order to further investigate this problem, the complete srRNA sequence of the sea anemone Anemoniu sulcuta was determined and evolutionary trees were constructed using a matrix optimization method. In the tree thus obtained the sea anemone and Bilateria together form a monophyletic cluster, with the sea anemone forming the first line of descent of the metaxoan group.

BMC Bioinformatics, 2010

Numbers and data mining are easy. Our numerical system counts 10 digits, any combination is possi... more Numbers and data mining are easy. Our numerical system counts 10 digits, any combination is possible, and every measured value can be captured in a number. Large quantities of measures can be analysed efficiently using incredibly powerful calculators, and resulting information can be shown is simple clear graphs.

British journal of cancer, 2000

We have cloned a human Hevin cDNA from omental adipose tissue of different patients by reverse tr... more We have cloned a human Hevin cDNA from omental adipose tissue of different patients by reverse transcription polymerase chain reaction and shown a sequence variation due to a possible polymorphism at amino acid position 161 (E/G). Hevin protein expressed in vitro showed molecular weights of approximately 75 kDa and 150 kDa, suggesting that Hevin may form a homodimer in vitro. Using Northern blots and a human expressed sequence tAg database analysis, Hevin was shown to be widely expressed in human normal or non-neoplastic diseased tissues with various levels. In contrast to this, its expression was strongly down-regulated in most neoplastic cells or tissues tested. However, neither the mechanism nor the physiological meaning of this down-regulation is known. As an initial step towards investigating the functional role of Hevin in cell growth and differentiation, we transiently or stably expressed this gene in cancer cells (HeLa 3S) that are devoid of endogenous Hevin and measured DNA...

Systematic and Applied Microbiology, 1993

ABSTRACT 16S and 23S ribosomal RNA (rRNA) genes from campylobacteria were studied by polymerase c... more ABSTRACT 16S and 23S ribosomal RNA (rRNA) genes from campylobacteria were studied by polymerase chain reaction and DNA sequence analysis using universally conserved oligonucleotide primers. In the 16S rRNA gene sequences of all C. sputorum strains tested, an insertion of about 250 bp was found that was not present in the 16S rRNA genes of other Campylobacter species. This insertion was not present on the rRNA level in C. sputorum, and the 16S rRNA was found to be fragmented in this organism. From the length of the fragments, it could be concluded that the insertion is an internal transcribed spacer, which is probably excised during rRNA maturation. Similar internal transcribed spacers were also found in the 23S rRNA genes from several Campylobacter strains. On the basis of partial 23S rRNA gene sequences about 875 bp in length and comprising some of the most variable helices, phylogenetic analysis was performed on 17 Campylobacter strains. The results of this analysis were compared to a phylogenetic tree based on complete 16S rRNA sequences.

Systematic and Applied Microbiology, 1994

Nature Communications, 2014

Bedaquiline (BDQ), an ATP synthase inhibitor, is the first drug to be approved for treatment of m... more Bedaquiline (BDQ), an ATP synthase inhibitor, is the first drug to be approved for treatment of multidrug-resistant tuberculosis in decades. Though BDQ has shown excellent efficacy in clinical trials, its early bactericidal activity during the first week of chemotherapy is minimal. Here, using microfluidic devices and time-lapse microscopy of Mycobacterium tuberculosis, we confirm the absence of significant bacteriolytic activity during the first 3-4 days of exposure to BDQ. BDQ-induced inhibition of ATP synthesis leads to bacteriostasis within hours after drug addition. Transcriptional and proteomic analyses reveal that M. tuberculosis responds to BDQ by induction of the dormancy regulon and activation of ATP-generating pathways, thereby maintaining bacterial viability during initial drug exposure. BDQ-induced bacterial killing is significantly enhanced when the mycobacteria are grown on non-fermentable energy sources such as lipids (impeding ATP synthesis via glycolysis). Our results show that BDQ exposure triggers a metabolic remodelling in mycobacteria, thereby enabling transient bacterial survival. Figure 1 | Delayed killing of M. tuberculosis by BDQ. (a) Kill kinetics of BDQ for M. tuberculosis over a period of 18 days and (b) initial 5 days of the BDQ kill kinetics. The bacteria were grown in liquid culture (Middlebrook 7H9 medium) in the presence of the indicated concentrations of BDQ or the front-line anti-TB drug isoniazid as a control. (c) Decrease of cellular ATP levels in M. tuberculosis during 18 days of BDQ treatment. (d) Cellular ATP levels during the initial 48 h of BDQ treatment. Inset: cellular ATP levels in the BDQ-resistant M. tuberculosis strain. ATP levels were determined using the bioluminescence method and are displayed as relative luminescence units (RLUs). Representative results from two experiments are shown. NATURE COMMUNICATIONS |

Molecular and Cellular Endocrinology, 2000

The authors previously reported that one of the cAMP-response elements (CREs) of the human beta3-... more The authors previously reported that one of the cAMP-response elements (CREs) of the human beta3-AR gene, beta3CRE2, interacts with a nuclear factor which is distinct from CREB/ATF family. We named this factor WATSF-1 (white adipose tissue specific factor-1) since it is preferentially expressed in WAT. In this work, we have shown the absence of DNA binding or transcriptional activity of this factor in several non-adipose cells tested. By computer analysis, beta3CRE2 was found to constitute an octameric element that is highly homologous to the binding site for some members of the nuclear hormone receptor superfamily. Using the response elements of other adipocyte-specific nuclear receptors as competitors, a 'cross-talk' between WATSF-1 and these response elements has been demonstrated. However, the affinity of WATSF-1 for these response elements differs from that for beta3CRE2 (self), implying that WATSF-1 is distinct from these adipocyte-specific nuclear receptors. Furthermore the DNA-binding activity of WATSF-1 was shown to be enhanced by phosphatase treatment, suggesting that phosphorylation may play an important role in the functional modulation of this factor. In an effort to prove that it is indeed an adipocyte-specific factor, we used 3T3-L1 cells, a cellular model of WAT, that can undergo differentiation into adipocytes. The DNA binding and transcriptional activity of this factor appeared during differentiation of the cells. Taken together, these results demonstrate that WATSF-1 is a putative white adipocyte-specific nuclear orphan receptor induced during adipogenesis and is a transcriptional activator through one of the CREs of the human beta3-AR gene. Targeting this factor may be a novel therapeutic approach to stimulation of the beta3-AR signal transduction pathway in adipose tissues.

Journal of Biological Chemistry, 1999

Hydrolysis of the neuropeptide N-acetyl-L-aspartyl-Lglutamate (NAAG) by N-acetylated ␣-linked aci... more Hydrolysis of the neuropeptide N-acetyl-L-aspartyl-Lglutamate (NAAG) by N-acetylated ␣-linked acidic dipeptidase (NAALADase) to release glutamate may be important in a number of neurodegenerative disorders in which excitotoxic mechanisms are implicated. The gene coding for human prostate-specific membrane antigen, a marker of prostatic carcinomas, and its rat homologue glutamate carboxypeptidase II have recently been shown to possess such NAALADase activity. In contrast, a closely related member of this gene family, rat ileal 100-kDa protein, possesses a dipeptidyl peptidase IV activity. Here, we describe the cloning of human ileal 100-kDa protein, which we have called a NAALADase-"like" (NAALADase L) peptidase based on its sequence similarity to other members of this gene family, and its inability to hydrolyze NAAG in transient transfection experiments. Furthermore, we describe the cloning of a third novel member of this gene family, NAALADase II, which codes for a type II integral membrane protein and which we have localized to chromosome 11 by fluorescent in situ hybridization analysis. Transient transfection of NAALADase II cDNA confers both NAALADase and dipeptidyl peptidase IV activity to COS cells. Expression studies using reverse transcription-polymerase chain reaction and Northern blot hybridization show that NAALADase II is highly expressed in ovary and testis as well as within discrete brain areas.

The two text mining strategies: finding co-occurrences of biological entities within documents, a... more The two text mining strategies: finding co-occurrences of biological entities within documents, and finding relationships using Natural Language Processing, are often seen as competitors. Here we adopt a flexible approach where the techniques are adapted and combined to suit the nature of the document corpus, and the specific task. The approach was tested on three tasks relevant to cancer treatment: finding kinases associated with cancer, finding gene mutations, and finding interactions between proteins associated with cancer. The paper describes the use of entity disambiguation, cooccurrence and linguistic processing in these tasks, and provides an overview of the methodology and results.

selecting target genes or proteins for new drugs. We found the application of virtual reality to ... more selecting target genes or proteins for new drugs. We found the application of virtual reality to the field of genomics to be successfull.

The Biochemical journal, 1998

Histamine H1 receptor expression has been reported to change in disorders such as allergic rhinit... more Histamine H1 receptor expression has been reported to change in disorders such as allergic rhinitis, autoimmune myocarditis, rheumatoid arthritis and atherosclerosis. Here we report the isolation and characterization of genomic clones containing the 5' flanking (regulatory) region of the human histamine H1 receptor gene. An intron of approx. 5.8 kb was identified in the 5' untranslated region, which suggests that an entire subfamily of G-protein-coupled receptors may contain an intron immediately upstream of the start codon. The transcription initiation site was mapped by 5' rapid amplification of cDNA ends to a region 6.2 kb upstream of the start codon. Immediately upstream of the transcription start site a fragment of 1.85 kb was identified that showed promoter activity when placed upstream of a luciferase reporter gene and transiently transfected into cells expressing the histamine H1 receptor. The promoter sequence shares a number of characteristics with the promoter...

Evolutionary trees based on small ribosomal subunit RNA sequences yield a new perspective on euka... more Evolutionary trees based on small ribosomal subunit RNA sequences yield a new perspective on eukaryote evolution. In agreement with classical views regarding evolution, animals, green plants, and fungi form monophyletic groups which seem to have originated nearly simultaneously. The evolution of these organisms took place in a relatively short time interval and is characterized by a massive diversification of life forms. In contrast, the dissimilarity among protoctist small ribosomal subunit RNA sequences is huge and exceeds the diversity seen in the entire prokaryotic world. Furthermore, some Protoctista branch off very soon in eukaryote evolution, while others diverge much later. Based on these ribosomal RNA data, Protoctista should be regarded as a collection of independent evolutionary lineages. Because the evolutionary distance between the different groups of Protoctista is, in several cases, larger than the evolutionary distance between plants, fungi and animals, the classification of eukaryotes into four kingdoms seems to be artificial and may not reflect true evolutionary relationships.

Drug Discovery Today, 2015

The explored kinome was extended with broad profiling using the DiscoveRx and Millipore assay pan... more The explored kinome was extended with broad profiling using the DiscoveRx and Millipore assay panels. The analysis of the profiling of 3368 selected inhibitors on 456 kinases in the DiscoveRx format delivered several insights. First, the coverage depended on the threshold of the selectivity parameter. Second, the relation between hit confirmation rates and inhibitor selectivity showed unexpectedly that higher selectivity can increase the likelihood of false positives. Third, comparing the coverage of a focused to that of a random library showed that the design based on a maximum number of scaffolds was superior to a limited number of scaffolds. Therefore, selective compounds can be used in target validation, enable the jumpstarting of new kinase drug discovery projects, and chart new biological space via phenotypic screening.

Systematic and Applied Microbiology, 1993

ABSTRACT The primary structure of the small ribosomal subunit RNA (SSU rRNA) was determined for 1... more ABSTRACT The primary structure of the small ribosomal subunit RNA (SSU rRNA) was determined for 13 species belonging to 10 ascomycete families and for the basidiomycetous anamorphic yeast Rhodotorula glutinis. The sequences were fitted into an alignment of all hitherto published complete or nearly complete eukaryotic small subunit rRNA sequences. The evolutionary relationships within the fungi were examined by construction of a tree from 87 SSU rRNA sequences, corresponding to 71 different species, by means of a distance matrix method and bootstrap analysis. It confirms the early divergence of the zygomycetes and the classical division of the higher fungi into basidiomycetes and ascomycetes. The basidiomycetes are divided into true basidiomycetes and ustomycetes. Within the ascomycetes, the major subdivisions hemiascomycetes and euascomycetes can be recognized. However, Schizosaccharomyces pombe does not belong to the cluster of the hemiascomycetes, to which it is assigned in classical taxonomic schemes, but forms a distinct lineage. Among the euascomycetes, the plectomycetes and the pyrenomycetes can be distinguished. Within the hemiascomycetes, the polyphyly of genera like Pichia or Candida and of families like the Dipodascaceae and the Saccharomycetaceae can be observed.

Systematic and Applied Microbiology, 1994

... van de Peer 1 ,; Jean-Marc Neefs 1 ,; Peter de Rijk 1 ,; Paul de Vos 2 ,; Rupert de Wachter 1... more ... van de Peer 1 ,; Jean-Marc Neefs 1 ,; Peter de Rijk 1 ,; Paul de Vos 2 ,; Rupert de Wachter 1 , Corresponding author contact information , a. 1 Departement Biochemie, Universiteit Antwerpen (UIA), Antwerpen, Belgium; 2 Laboratorium voor Microbiologie, Universiteit Gent, Gent, ...

Lecture Notes in Computer Science, 2014