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Molecular phylogeny of fig wasps Agaonidae are not monophyletic.

According to the present classification, the family Agaonidae contains all fig pollinators as well as five subfamilies of non-pollinating fig wasps. The molecular phylogeny of the family was reconstructed using partial sequences of the 28S rRNA (D1 and D2 domains). Our results show that the family Agaonidae is not monophyletic. As a consequence, we restrict the famiy to the pollinator clade, and assign the non-pollinating subfamilies to various chalcid families. Sycoecinae, Otitesellinae and Sycoryctinae are included in Pteromalidae, whereas Sycophaginae and Epichrysomallinae are left unclassified and will require more in-depth morphological studies. Moreover, we proved that the fig pollination syndrome evolved only once, early in group history. The resource due to the fig-pollinator mutualism has secondarily been colonized independently by different Chalcid lineages.

Animals↗

Classification of some active HIV-1 protease inhibitors and their inactive analogues using some uncorrelated three-dimensional molecular descriptors and a fuzzy c-means algorithm.

A fuzzy c-means algorithm was used to classify some 3D convex hull descriptors computed for 345 active HIV-1 protease inhibitors collected from literature and 437 inactive analogues searched from the MDL/ISIS database. The number of descriptors used to represent each compound was from 4 to 8, and they were uncorrelated using the principal component analysis. These uncorrelated descriptors were then divided into two groups and classified by the fuzzy c-means algorithm. The classification produced a clear-cut switch in membership functions computed for each uncorrelated descriptor at the group boundary. Compounds with nonswitching membership functions computed were treated as outliers, and they were counted for estimating the accuracy of the classification. The averaged accuracy of classification for the active inhibitor set was about 80% which was better than that directly classified by a linear discriminant function on the original 3D convex hull descriptors. The whole classification scheme was also applied to several sets of some conventional descriptors computed for each compound, but the averaged accuracy was around 58%. Further classification using some 3D convex hull descriptors searched from comparing the distribution of these descriptors was performed on a new data set composed of 289 outliers-deducted active inhibitors and 63 outliers identified from the inactive analogues through previous classification. This final classification identified 19 inactive analogues which were similar in structural and topological features to those of some highly active inhibitors classified together with them.

Algorithms↗

[Vascular abnormalities].

Formerly, if one would decide to get some interest in vascular anomalies, one would be abashed by the multiplicity of classifications, the empiricism of treatments but mainly by the poverty of fundamental research due to the lack of animal models. Today progress in molecular Biology and imaging allow to establish a coherent classification of vascular anomalies. Thanks to the development of quantum physics, pulsed dye laser is very efficacious in the treatment of capillary malformations (port-wine stains). Plastic surgery and reconstructive microsurgery allow wide resection of venous and arteriovenous malformations in collaboration with interventional radiology. Finally, recent discoveries in molecular genetic will allow the creation of transgenic mice with vascular anomalies phenotypically similar to human malformations. So, in the near future, we will be able to test experimentally new therapeutic approaches but especially set up research protocols directed to a better understanding of the pathogenic mechanisms of these vascular anomalies.

Animals↗

Structure, specificity and function of cyclomaltodextrinase, a multispecific enzyme of the alpha-amylase family.

Cyclomaltodextrinase (CDase, EC 3.2.1.54), maltogenic amylase (EC 3. 2.1.133), and neopullulanase (EC 3.2.1.135) are reported to be capable of hydrolyzing all or two of the following three types of substrates: cyclomaltodextrins (CDs); pullulan; and starch. These enzymes hydrolyze CDs and starch to maltose and pullulan to panose by cleavage of alpha-1,4 glycosidic bonds whereas alpha-amylases essentially lack activity on CDs and pullulan. They also catalyze transglycosylation of oligosaccharides to the C3-, C4- or C6-hydroxyl groups of various acceptor sugar molecules. The present review surveys the biochemical, enzymatic, and structural properties of three types of such enzymes as defined based on the substrate specificity toward the CDs: type I, cyclomaltodextrinase and maltogenic amylase that hydrolyze CDs much faster than pullulan and starch; type II, Thermoactinomyces vulgaris amylase II (TVA II) that hydrolyzes CDs much less efficiently than pullulan; and type III, neopullulanase that hydrolyzes pullulan efficiently, but remains to be reported to hydrolyze CDs. These three types of enzymes exhibit 40-60% amino acid sequence identity. They occur in the cytoplasm of bacteria and have molecular masses from 62 to 90 kDa which are slightly larger than those of most alpha-amylases. Multiple amino acid sequence alignment and crystal structures of maltogenic amylase and TVA II reveal the presence of an N-terminal extension of approximately 130 residues not found in alpha-amylases. This unique N-terminal domain as seen in the crystal structures apparently contributes to the active site structure leading to the distinct substrate specificity through a dimer formation. In aqueous solution, most of these enzymes show a monomer-dimer equilibrium. The present review discusses the multiple specificity in the light of the oligomerization and the molecular structures arriving at a clarified enzyme classification. Finally, a physiological role of the enzymes is proposed.

Amino Acid Sequence↗

Molecular analysis of nematode diversity and the evolution of parasitism.

A thorough and coherent classification of the phylum Nematoda is essential if the evolution of countless phenotypes is to be understood. Here, Mark Dorris, Paul De Ley and Mark Blaxter discuss how the application of molecular phylogenetics is helping to resolve some of the inconsistencies in morphological classification and phylogeny by establishing relationships between free-living and parasitic groups, showing possible patterns underlying the origins of parasitism and placing key nematode species in an evolutionary context for comparative study.

Animals↗

[The molecular genetics of meningiomas and genotypic/phenotypic correlations].

The WHO classification divides meningiomas in three grades. In grade 1 tumors, by far the most common (90 p. cent), inactivation of the NF2 gene (associated to the loss of chromosome 22) is the most frequent alteration. However, a subset of grade 1 meningiomas does not involve the NF2 gene and is less likely to evolve towards higher grade tumors. After NF2 inactivation, additional events may occur and are related to greater aggressiveness, such as loss of 1p, 14q, 10 q and 9p chromosomes, reactivation of telomerase, inactivation of the p16/CDKN2A gene. All these alterations are much more frequent in grades 2 (atypical) and 3 (malignant) of the WHO classification. In addition to reviewing the available literature, we pooled together the individual cases in order to refine the correlation between genotype and phenotype (histological grading, location) and to propose a model for tumoral progression of meningiomas.

Disease Progression↗

[Highest level of division in classification of organisms. 3. Monodermata and Didermata].

The deepening our knowledge and embrassing the larger array of the investigated organisms leads to replacement of typological classifications with phylogenetic ones. This process seems to be the main stream of modern systematics. But typological classifications have not lost the value, remaining the important tool of the description of phylogeny. It is especially obvious today when molecular reconstructions are using so widely. However resulted phylogenetic classifications are difficult for understandable interpretation. Therefore phylogeneticist is interested in elaboration of typological classifications that can help to explain the results. As an example the phylogenetic classifications of organisms proposed recently by Cavalier-Smith (1998, 2002) and Gupta (1998, 2000) are considered. The modified system of Gupta is the most adequate description of organism phylogeny. Basal clostridia and togobacteria have to the greatest degree kept features of a common ancestor of organisms. From this common ancestor evolution spread by two phyletic lines. One of them included Gram-negative bacteria. The main groups of them have branched of from a common ancestor in the following order: (Deinococci, Chloroflexi) --> (Cyanobacteria) --> (Chlamydia, CFB, Fibrobacteria, Chlorobia) --> (Aquificae) --> --> (Epsilonproteobacteria, Deltaproteobacteria) --> (Alfaproteobacteria) --> (Betaproteobacteria) --> --> (Gammaproteobacteria). In other phyletic line the main groups were separated in the following order: (Thermotogae) --> (Clostridia, Fusobacteria) --> (Bacillae) --> (Actinobacteria). Exact position of archaebacteria and eukaryotes related to this line remains unclear. Typological division of organisms into Didermata and Monodermata (Gupta, 1998) corresponds to these two branches of a cladogram. The cell of the diderm organisms is covered with two membranes, plasmatic and outer. The cell of the monoderm organisms has only one plasmatic membrane. Development of the cellular organization at the earliest stages of evolution of a life went through use of non-lamellar (non-bilayer) lipids which could give a cell with one membrane (not two membranes as in the scenario of Cavalier-Smith (2001)). Membranes appeared at the earliest stages of the evolution of life. Therefore their distinction is quite logical to take as a principle the first typological division of organisms. At the same time the typological classifications considered beyond the framework of phylogenetics, have no independent value. Typological classifications do not give monothetic division into groups. Always there are exceptions. So, among Monodermata there are Gram-negative forms (Acidaminococcaceae, Syntrophomonadaceae, some Thermoanaerobacteriaceae), which are didermic.

Bacteria↗

Occupational exposure to immunologically active agents and risk for lymphoma.

OBJECTIVES: We evaluated whether occupational exposure to high molecular weight agents that are associated with asthma and that act predominantly through an immunoglobulin E (IgE)-dependent hypersensitivity mechanism is also associated with risk for specific lymphoma types. METHODS: The Spanish lymphoma case-control study includes 519 newly diagnosed cases of lymphoid neoplasms and 554 hospital controls ages 20 to 80 years. Lymphomas were histologically or cytologically confirmed and classified according to the WHO classification. Lifetime occupational exposure to seven high molecular weight agents such as latex was evaluated through an asthma-specific job-exposure matrix and validated by an industrial hygienist. Odds ratios (OR) and 95% confidence intervals (95% CI) were adjusted for age, sex, hospital, and occupational exposures. RESULTS: Subjects exposed to high molecular weight agents had an increased risk for Hodgkin's lymphoma (OR, 2.27; 95% CI, 0.93-5.50), particularly nodular sclerosis (OR, 3.22; 95% CI, 1.14-9.09). ORs did not increase with duration of exposure to these agents. Exposure to high molecular weight agents was not associated with risk of other B-cell lymphomas; for most specific subcategories of B-cell lymphoma, ORs were below unity. A slightly increased OR (95% CI) was seen for mycosis fungoides [1.60 (0.53-4.84)], although overall there was no increased risk for T-cell lymphomas. CONCLUSIONS: Exposure to immunologically active agents among clinically immunocompetent subjects was associated with risk for Hodgkin's lymphoma.

Asthma↗

[Carrent state of molecular pathology of stomach carcinomas].

Gastric carcinoma is one of the commonly diagnosed malignancies and remains an important cause of mortality in the Western hemisphere. Various sequences of genetic alterations may be responsible for the development of gastric cancer, as there exist two histological types: well-differentiated or intestinal-type and poorly differentiated or diffuse-type gastric cancers. While new genetic findings open new perspectives on carcinogenesis and molecular biology of gastric cancer, they have not been widely applied in routine diagnostic procedures, classification systems, disease monitoring, or prognostic assessment. We discuss the mechanisms molecular pathology in relation to their potential clinical relevance.

Apoptosis↗

Molecular and cellular staging for the severity of chronic rhinosinusitis.

OBJECTIVES: To correlate objective and subjective clinical parameters with molecular, cellular, and histologic markers and to acknowledge the importance of these basic science parameters in a severity classification system for chronic rhinosinusitis (CRS). STUDY DESIGN: Retrospective analysis of prospectively collected data of consecutive patients undergoing endoscopic sinus surgery for CRS in an academic institution. METHODS: The preoperative computed tomography (CT) scans of all patients with CRS scheduled for surgery were graded according to Lund and Mackay. The patients completed a Sino-Nasal Outcome Test (SNOT)-20 questionnaire and had a preoperative nasal endoscopy performed, which was graded by assigning an endoscopy score according to Lanza and Kennedy. Subjects had a medical questionnaire regarding presence of aspirin sensitivity, allergic rhinitis, asthma, and medication usage. Subjects also underwent pulmonary function testing and had skin tests for allergies. At the time of surgery, blood was drawn to determine the level of peripheral eosinophilia and the degree of polymorphisms of the leukotriene C4 synthase gene. Sinus mucosal and polyp tissue was examined pathologically for the number of eosinophils per high-powered filed (HPF) and was stained for EG2 to determine the portion of activated eosinophils. Leukotriene C4 levels (pg/g of tissue) were determined using a sensitive competitive enzyme immunoassay. Endoscopy and SNOT-20 scores were reevaluated 1 year after surgery. Data were analyzed for disease-severity correlation to recommend a severity classification system for CRS that incorporates the contribution of clinical, molecular, cellular, and histologic parameters. RESULTS: The presence of polyps resulted in higher preoperative CT scores and higher preoperative and postoperative symptom scores. Average preoperative CT scores were significantly higher in asthmatics and allergy patients and correlated with endoscopy scores. Patients with more than five eosinophils/HPF of sinus tissue had higher frequency of polyps and asthma and higher CT and endoscopy scores than patients without sinus tissue eosinophilia (less than or equal to 5 cells/HPF sinus tissue). The subgroup of patients with eosinophilic nasal polyps (eosinophilic hyperplastic rhinosinusitis) had more severe disease by CT and endoscopy than the subgroup of patients with nasal polyps (hyperplastic rhinosinusitis) but without eosinophilia. Similarly, patients without polyps but with tissue eosinophilia had more severe disease than patients without polyps and without eosinophilia. Leukotriene C4 levels were elevated in all patient groups. Symptom scores did not correlate with any of the parameters. CONCLUSION: We suggest the following severity classification system for CRS: 1) eosinophilic chronic hyperplastic rhinosinusitis (ECHRS): patients with polyps and sinus tissue eosinophilia; 2) noneosinophilic chronic hyperplastic rhinosinusitis (NECHRS): patients with polyps but without sinus tissue eosinophilia; 3) eosinophilic chronic rhinosinusitis (ECRS): patients without polyps but with sinus tissue eosinophilia; 4) noneosinophilic chronic rhinosinusitis (NECRS): patients without polyps and without sinus tissue eosinophilia.

Chronic Disease↗

Evolution of arginine deiminase (ADI) pathway genes.

We have analyzed the evolution of the three genes encoding structural enzymes of the arginine deiminase (ADI) pathway, arginine deiminase (ADI), ornithine transcarbamoylase (OTC), and carbamate kinase (CK) in a wide range of organisms, including Archaea, Bacteria, and Eukarya. This catabolic route was probably present in the last common ancestor to all the domains of life. The results obtained indicate that these genes have undergone a complex evolutionary history, including horizontal transfer events, duplications, and losses. Therefore, these genes are not adequate to infer organismal relationships at deep branching levels, but they provide an insight into how catabolic genes evolved and were assembled into metabolic pathways. Our results suggest that the three genes evolved independently and were later assembled into a single cluster with functional interdependence, thus, providing support for the gene recruitment hypothesis. Furthermore, the molecular phylogenetic analysis of OTC suggests a new classification of these genes into three subfamilies.

Amino Acid Sequence↗

5-HT receptor classification and nomenclature: towards a harmonization with the human genome.

Molecular biology has dramatically advanced our knowledge and understanding of receptors for 5-hydroxytryptamine (5-HT). The existence of multiple 5-HT receptors defined using traditional pharmacological and biochemical approaches has now been amply confirmed, but gene products encoding putative "new" 5-HT receptors have also been discovered. In some cases, the absence of suitably selective agonists and antagonists has hampered determination of a physiological role for these gene products. This makes their classification as formally recognised receptors premature.

Animals↗

Prenatal onset spinal muscular atrophy.

Five patients with severe spinal muscular atrophy (SMA) type I, all of whom presented with reduced fetal movements in utero, severe weakness at birth, and short survival time were assessed to attempt to determine whether their phenotype could be explained by their genotype. The diagnosis was confirmed by clinical, electrophysiological and histopathological features. Polymerase chain reaction assays were used to define the molecular diagnosis. A gene-dosage assay was used to assess the quantity of centromeric survival motor neuron gene (SMNc) present. In all cases the telomeric survival motor neuron gene (SMNt) was absent. The SMNc gene was present but in reduced copy number compared with a control group of children with less severe type I SMA, so may be important in determining severity. In the differential diagnosis of reduced fetal movements, SMA should be considered. The clinical classification may in future be clarified by molecular genetic findings.

Cell Survival↗

[Current state of molecular imaging research].

The recent years have seen significant advances in both molecular biology, allowing the identification of genes and pathways related to disease, and imaging technologies that allow for improved spatial and temporal resolution, enhanced sensitivity, better depth penetration, improved image processing, and beneficial combinations of different imaging modalities. These advances have led to a paradigm shift in the scope of diagnostic imaging. The traditional role of radiological diagnostic imaging is to define gross anatomy and structure in order to detect pathological abnormalities. Available contrast agents are mostly non-specific and can be used to image physiological processes such as changes in blood volume, flow, and perfusion but not to demonstrate pathological alterations at molecular levels. However, alterations at the anatomical-morphological level are relatively late manifestations of underlying molecular changes. Using molecular probes or markers that bind specifically to molecular targets allows for the non-invasive visualization and quantitation of biological processes such as gene expression, apoptosis, or angiogenesis at the molecular level within intact living organisms. This rapidly evolving, multidisciplinary approach, referred to as molecular imaging, promises to enable early diagnosis, can provide improved classification of stage and severity of disease, an objective assessment of treatment efficacy, and a reliable prognosis. Furthermore, molecular imaging is an important tool for the evaluation of physiological and pathophysiological processes, and for the development of new therapies. This article comprises a review of current technologies of molecular imaging, describes the development of contrast agents and various imaging modalities, new applications in specific disease models, and potential future developments.

Animals↗

Chronic pancreatitis: diagnosis, classification, and new genetic developments.

The utilization of recent advances in molecular and genomic technologies and progress in pancreatic imaging techniques provided remarkable insight into genetic, environmental, immunologic, and pathobiological factors leading to chronic pancreatitis. Translation of these advances into clinical practice demands a reassessment of current approaches to diagnosis, classification, and staging. We conclude that an adequate pancreatic biopsy must be the gold standard against which all diagnostic approaches are judged. Although computed tomography remains the initial test of choice for the diagnosis of chronic pancreatitis, the roles of endoscopic retrograde pancreatography, endoscopic ultrasonography, and magnetic resonance imaging are considered. Once chronic pancreatitis is diagnosed, proper classification becomes important. Major predisposing risk factors to chronic pancreatitis may be categorized as either (1) toxic-metabolic, (2) idiopathic, (3) genetic, (4) autoimmune, (5) recurrent and severe acute pancreatitis, or (6) obstructive (TIGAR-O system). After classification, staging of pancreatic function, injury, and fibrosis becomes the next major concern. Further research is needed to determine the clinical and natural history of chronic pancreatitis developing in the context of various risk factors. New methods are needed for early diagnosis of chronic pancreatitis, and new therapies are needed to determine whether interventions will delay or prevent the progression of the irreversible damage characterizing end-stage chronic pancreatitis.

Chronic Disease↗

Molecular profiling of head and neck tumors.

PURPOSE OF REVIEW: Head and neck squamous cell carcinoma is the fifth most common cancer worldwide. Unfortunately, patients with the same diagnostic and prognostic profile can have markedly different clinical outcomes. This most likely results from the fact that the current taxonomy of head and neck squamous cell carcinoma groups molecularly different diseases with distinct clinical phenotypes into classifications based mainly on morphology. A combination of circumstances, including the advent of array-based technology and progress in the human genome initiative, now provides an ideal opportunity to begin performing comprehensive molecular and genetic profiling of head and neck squamous cell carcinoma. This article reviews recently reported studies that have used such approaches. RECENT FINDINGS: Comparison of gene expression profiles between head and neck squamous cell carcinoma and normal tissues showed altered expression levels of genes involved in the control of cell growth and differentiation, angiogenesis, apoptosis, cell cycle, and signaling, most of which have not been previously described in head and neck squamous cell carcinoma. Additionally, they revealed the implication of different signaling and metabolic pathways such wnt and noch, highlighting the potential role of these pathways in oral cancer development. Their results provide new insights into the carcinogenesis of head and neck squamous cell carcinoma as well as a source of potential prognostic and predictive markers and targets for its prevention and therapeutics. SUMMARY: Although the sample sizes of these studies were small and their findings therefore require further validation in larger trials, such preliminary results provide important clues to the understanding of the various gene networks implicated in oral carcinogenesis and may contribute to the selection of target genes for possible molecular diagnosis and therapy in the future.

Carcinoma, Squamous Cell↗

Advances in the diagnosis, molecular genetics, and treatment of pediatric embryonal CNS tumors.

Embryonal central nervous system (CNS) tumors are the most common group of malignant brain tumors in children. The diagnosis and classification of tumors belonging to this family have been controversial; however, utilization of molecular genetics is helping to refine traditional histopathologic and clinical classification schemes. Currently, this group of tumors includes medulloblastomas, supratentorial primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, ependymoblastomas, and medulloepitheliomas. While the survival of older children with nonmetastatic medulloblastomas has improved considerably within the past two decades, the outcomes for infants and for those with metastatic medulloblastomas or other high-risk embryonal CNS tumors remain poor. It is anticipated that the emerging field of molecular biology will greatly aid in the future stratification and therapy for pediatric patients with malignant embryonal tumors. In this review, recent advances in the diagnosis, molecular genetics, and treatment of the most common pediatric embryonal CNS tumors are discussed.

Central Nervous System Neoplasms↗

Analysis of the antibody response to an immunodominant epitope of the envelope glycoprotein of a lentivirus and its diagnostic potential.

The envelope glycoprotein of small ruminant lentiviruses (SRLV) is a major target of the humoral immune response and contains several linear B-cell epitopes. We amplified and sequenced the genomic segment encoding the SU5 antigenic site of the envelope glycoprotein of several SRLV field isolates. With synthetic peptides based on the deduced amino acid sequences of SU5 in an enzyme-linked immunosorbent assay (ELISA), we have (i) proved the immunodominance of this region regardless of its high variability, (ii) defined the epitopes encompassed by SU5, (iii) illustrated the rapid and peculiar kinetics of seroconversion to this antigenic site, and (iv) shown the rapid and strong maturation of the avidity of the anti-SU5 antibody. Finally, we demonstrated the modular diagnostic potential of SU5 peptides. Under Swiss field conditions, the SU5 ELISA was shown to detect the majority of infected animals and, when applied in a molecular epidemiological context, to permit rapid phylogenetic classification of the infecting virus.

Amino Acid Sequence↗