History of burning mouth syndrome (1800-1950): A review.

This medical history historic literature review aims at understanding the evolution of the medical existence of burning mouth syndrome (BMS) over times. Three historic research tools were used (Medic@, IndexCat, Gallica) with several keywords, exploring the years 1800-1950. One hundred and fifty documents were obtained dating from 1803 to 1937, including 55 reviews, 44 original articles, 40 quotations, and 11 medical dictionaries. A total of 199 cases of BMS were reported which allowed for a narrative review of the early history of BMS (1800-1950). This review spans from the description of the first clinical cases by several authors in Europe to the creation of the syndrome by the French Academy of Medicine, its intellectual sponsorship by the emerging discipline of neuropsychiatry, to its subsequent evolution until the conceptual shift of the American authors. A better knowledge of the evolution of the nosology of BMS throughout history should bring a better understanding of current approaches for treating such an affection.

Neuropathic pain in the orofacial region: The role of pain history. A retrospective study.

INTRODUCTION: Orofacial neuropathic pain is often difficult to treat, mostly because of still unclear underlying mechanisms. The occurrence of such neuropathic pain varies depending on different factors, of which preexisting preoperative pain seems to be of high importance. The aim of this study was thus to test the hypothesis that prior history of pain could indeed be considered a risk factor for the development of orofacial neuropathic pain in the same region. METHODS: The study was performed in the dental department of the Groupe Hospitalier Pitié-Salpêtrière (GHPS) in Paris, France. We investigated the presence of prior inflammatory pain before development of orofacial neuropathic pain in 56 patients. For each patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain (at time of consultation); presence or absence of prior dental treatment; date and type of dental treatment received. RESULTS: 41 patients (73%) of orofacial neuropathic pain patients had a history of pain compatible with an inflammatory condition; 4% (n=2) did not report any prior pain and 23% (n=13) could not remember. Among the patients with documented history of pain prior to neuropathy, 88% (n=36) received surgical treatment; 61%, (n=25) endodontic treatment and 22%, (n=9) restorative treatment. All eventually received endodontic treatment or tooth extraction. These dental treatments are compatible with the hypothesis of prior inflammatory pain in these patients. CONCLUSION: These results support the hypothesis that prior inflammatory pain could favor the development of orofacial neuropathic pain. Prevention and treatment of inflammatory trigeminal pain may therefore play a key role in preventing future neuropathic pain development.

Taste function assessed by electrogustometry in burning mouth syndrome: a case-control study.

OBJECTIVE: Idiopathic burning mouth syndrome (iBMS) is characterized by oral persistent pain without any clinical or biological abnormality. The aim of this study was to evaluate taste function in iBMS subjects and healthy controls. MATERIAL AND METHODS: Electrogustometric thresholds (EGMt) were recorded in 21 iBMS patients and 21 paired-matched controls at nine loci of the tongue assessing fungiform and foliate gustatory papillae function. Comparison of EGMt was performed using the nonparametric Wilcoxon signed-rank test. A correlation between EGMt and self-perceived pain intensity assessed using a visual analogic scale (VAS) was analyzed with the Spearman coefficient. The level of significance was fixed at P < 0.05. RESULTS: Mean EGMt were significantly increased with iBMS for right side of the dorsum of the tongue and right lateral side of the tongue (P < 0.05). In the iBMS group, VAS scores were significantly correlated to EGMt at the tip of the tongue (r = -0.59; P < 0.05) and at the right and left lateral sides of the tongue (respectively, r = -0.49 and r = -0.47; P < 0.05). CONCLUSION: These data depicted impaired taste sensitivity in iBMS patients within fungiform and foliate taste bud fields and support potent gustatory/nociceptive interaction in iBMS.

Hedgehog Pathway-Mediated Vascular Alterations Following Trigeminal Nerve Injury.

Whereas neurovascular interactions in spinal neuropathic pain models have been well characterized, little attention has been given to such neurovascular interactions in orofacial neuropathic pain models. This study investigated in male Sprague-Dawley rats the vascular changes following chronic constriction injury (CCI) of the infraorbital nerve (IoN), a broadly validated preclinical model of orofacial neuropathic pain. Following IoN-CCI, an early downregulation of tight junction proteins Claudin-1 and Claudin-5 was observed within the endoneurium and perineurium, associated with increased local accumulation of sodium fluorescein (NaFlu) within the IoN parenchyma, as compared with sham animals. These events were evidence of local blood-nerve barrier disruption and increased vascular permeability. A significant upregulation of immunocytes (CD3, CD11b) and innate immunity (TLR2, TLR4) mRNA markers was also observed, suggestive of increased local inflammation. Finally, a significant downregulation of Hedgehog pathway readouts Patched-1 and Gli-1 was observed within the IoN after CCI and local injections of cyclopamine, a Hedgehog pathway inhibitor, replicated in naïve rats the molecular, vascular, and behavioral changes observed following IoN-CCI. These results suggest a major role of Hedgehog pathway inhibition in mediating local increased endoneurial and perineurial vascular permeability following trigeminal nerve injury, thus facilitating immunocytes infiltration, neuroinflammation development, and neuropathic pain-like aversive behavior.

Implication of the chemokine CCL2 in trigeminal nociception and traumatic neuropathic orofacial pain.

BACKGROUND: Chemokine (C-C motif) ligand 2 (CCL2) participates in different mechanisms contributing to the spinal cord inflammation and pain development after sciatic nerve injury. Recent data also support its role in orofacial thermal hypersensitivity, although its implication in different phases of trigeminal pain emergence is unclear. We assessed the importance of CCL2 signalling in biochemical and behavioural alterations during the early and late stages following chronic constriction injury of infraorbital nerve (ION-CCI), a model of peripheral traumatic trigeminal pain. METHODS: After evaluating the consequences of CCL2 intracisternal injection in naïve rats, we determined the expression changes for CCL2, inflammatory and glia activation markers in the somatosensory trigeminal complex (STC) and trigeminal ganglia (TG) after ION-CCI. The role of CCL2 signalling was assessed using pre-emptive or 'curative' intracisternal treatment with specific CCL2 receptor antagonist - INCB3344. RESULTS: Exogenous CCL2 evoked spontaneous behaviour reminiscent of orofacial pain and marked mechanical hypersensitivity, associated with increased expression of proinflammatory cytokines and glial markers in STC and TG. CCL2-evoked changes were prevented by the co-administration of INCB3344. Two weeks after ION-CCI, mRNA for CCL2, glial and inflammatory markers were up-regulated, and CCL2-immunoreactivity accumulated in central and ganglionic tissues. At this time, repeated intracisternal administration of INCB3344 did not attenuate the ION-CCI-associated behavioural nor biochemical changes. By contrast, pre-emptive INCB3344 treatment delayed the emergence of trigeminal mechanical allodynia and associated biochemical alterations. CONCLUSIONS: Our data suggest that CCL2 is involved principally in the early events accompanying the ION lesion rather than in long-term alterations and the maintenance of trigeminal mechanical hypersensitivity.

Dental afferents project onto gustatory neurons in the nucleus of the solitary tract.

The aim of this study was to investigate the inferior alveolar nerve (IAN) and chorda tympani (CT) projections onto gustatory neurons of the nucleus of the solitary tract (NST) in the rat by immunochemical and electrophysiological techniques. IAN afferents were retrogradely labeled. NST neurons were labeled either by retrograde tracer injection into the parabrachial nucleus (PBN) or by c-Fos mapping after CT activation. NST neurons responding to tastant stimulation were recorded in vivo before and after electrical stimulation of the IAN. Results from the immunolabeling approach showed IAN boutons "en passant" apposed to retrogradely labeled neurons from PBN and to CT-activated neurons in the NST. Recordings of single NST neurons showed that the electrical stimulation of the IAN significantly decreased CT gustatory responses. Analysis of these data provides an anatomical and physiological basis to support trigeminal dental and gustatory interactions within the brainstem.

[Radiographic study of the canal anatomy of mandibular premolars in a Senegalese population]. / Etude radiographique de l'anatomie canalaire des premolaires mandibulaires dans une population Senegalaise.

AIM: The purpose of this study was to assess the canal anatomy of mandiblar premolars in Senegalese population. MATERIALS AND METHODS: Retroalveolar radiographs of mandibular premolars of 208 patients in Senegal were obtained. Two experienced practitioners using a long cone tube and the parallel plane technique with angulators took the radiographs. The canal morphology of each tooth was determined in terms of the number of canals radiologically visible to the apex. Any anatomic structure emanating from the pulp chamber or the principal canal to the apex and measuring more than 3 millimetres was considered to be a supplementary canal. RESULTS: For the 208 patients studied, 412 first premolars were present and 4 were absent.Among the 412 teeth, 335 (81.3%) had a single canal, 62 (15.1%) 2 canals, and 17 (3.6%) 3 canals. For the second premolars 408 were present. Of the 408 teeth, 352 (86%) had one canal, 49 (12%) 2 canals, and 8 (2%) 3 canals. CONCLUSION: The prevalence of two or more canals in premolar mandibular from Senegalese patients was similar to that found in the others ethnic population.

[Prevalence of fixed prosthesis-related periodontitis in Senegal]. / Prévalence de la prothèse fixèe et des parodontites apicales associées au Sénégal.

The purpose of this study was to determine radiographically the prevalence of periapical periodontitis in teeth restored with crown in a Senegalese population. Full mouth periapical radiographs were obtained from 208 consecutive adult patients (6234 teeth) presenting as new patients to the Dental Service of the University. The presence of crown restorations, the periapical status and technical quality of root fillings associated were evaluated. 7.69% (n = 16) of patients had at least one tooth that was crowned. The total number of crowns assessed was 0.95% (n = 59). The molars were the teeth most crowned 40.67% (n = 24) followed by anterior teeth 30.50% (n = 18) and premolars 28.81% (n = 17). All the crowned teeth had previous root canal treatment of which only 16.94% (n = 10) were acceptable. 53 % (n = 32) of the teeth had apical periodontitis (PAI > 2). Unacceptable root fillings were associated with a higher prevalence of periapical disease (p < 0.05). Crown with a post extending more than 4 millimetres from the apex were associated with more periapical lesions 64.28% (p < 0.05). The results indicate a low prevalence of crowned teeth, an absence of vital preparation, a high prevalence of radiographic periapical disease and unacceptable root fillings associated.

Prevalence and technical quality of root fillings in Dakar, Senegal.

AIM: To examine the prevalence and technical quality of root fillings and the periapical status of root-filled teeth in a subpopulation of Dakar, Senegal. METHODOLOGY: Full-mouth periapical radiographs were obtained from 208 consecutive adults presenting as new patients to the Dental Service of the University. The occurrence and technical quality of root fillings were assessed for each root according to the apical extent of the root fillings and its density. The periapical status was evaluated using the Periapical Index Scoring System with a PAI > 2 indicating periapical disease. The presence of coronal restorations and posts was also noted. Statistical analysis was performed with the chi-square test with a significance level set at P < 0.05%. RESULTS: Of the 6234 teeth examined, 2.6% were root filled. A PAI > 2 was associated with 56.1% of the filled roots. Only 17.7% of the root fillings were technically acceptable and 26.2% of these were associated with a PAI > 2. In roots with unacceptable root fillings, 62.5% had a PAI > 2. Unacceptable root fillings were associated with a higher prevalence of periapical disease (P < 0.001). A post was seen in 18.9% of the filled roots with 66.2% associated with a PAI > 2. A permanent coronal restoration was present in 78.5% of the filled roots, of which 50.7% had a PAI > 2 vs 75.7% for no permanent restoration. At least one periapical lesion was seen in 59.6% of the subjects. CONCLUSION: The results indicate a low prevalence of teeth with radiographic periapical disease, a low prevalence of root-filled teeth and a high prevalence of unacceptable root fillings.

Use of chromosomal integron arrays as a phylogenetic typing system for Vibrio cholerae pandemic strains.

Approximately 200 serogroups of Vibrio cholerae exist, with only two, O1 and O139, responsible for epidemic and pandemic cholera. Strains from these serogroups have evolved from a common progenitor, with lateral gene transfer largely driving their emergence. These strains are so closely related that separation using single- or multi-locus phylogeny has proven difficult. V. cholerae strains contain a genetic system called the integron that is located in the chromosome and that can integrate and excise DNA elements called mobile gene cassettes (MGCs) by site-specific recombination. Large arrays of MGCs are found in V. cholerae strains. For instance, the O1 El Tor strain N16961 contains 179 MGCs. Since integron arrays are dynamic through recombination and excision of MGCs, it was hypothesized that the MGC composition in a given V. cholerae pandemic strain would be useful as a phylogenetic typing system. To address this, a PCR-based method was used to rapidly characterize the MGC composition of V. cholerae arrays. The results showed that the MGC composition of pandemic V. cholerae cassette arrays is relatively conserved, providing further evidence that these strains have evolved from a common progenitor. Comparison of MGC composition between the V. cholerae pandemic strains was also able to resolve the evolution of O139 from a subgroup of O1 El Tor. This level of differentiation of closely related V. cholerae isolates was more sensitive than conventional single-gene phylogeny or multi-locus sequence analysis. Using this method, novel MGCs from an O1 classical strain and an Argentinian O139 isolate were also identified, and a major deletion in the MGC array in all pandemic O139 strains and a subset of O1 El Tor strains was identified. Analysis of sequenced V. cholerae integron arrays showed that their evolution can proceed by rearrangements and deletions/insertions of large portions of MGCs in addition to the insertion or excision of single MGCs.

How big is the iceberg of which organellar genes in nuclear genomes are but the tip?

As more and more complete bacterial and archaeal genome sequences become available, the role of lateral gene transfer (LGT) in shaping them becomes more and more clear. Over the long term, it may be the dominant force, affecting most genes in most prokaryotes. We review the history of LGT, suggesting reasons why its prevalence and impact were so long dismissed. We discuss various methods purporting to measure the extent of LGT, and evidence for and against the notion that there is a core of never-exchanged genes shared by all genomes, from which we can deduce the "true" organismal tree. We also consider evidence for, and implications of, LGT between prokaryotes and phagocytic eukaryotes.

Activation of brain stem neurons by irritant chemical stimulation of the throat assessed by c-fos immunohistochemistry.

The method of c-fos immunohistochemistry was used to identify the brain stem distribution of neurons activated following irritant chemical stimulation of the laryngopharyngeal mucosa. In pentobarbital-anesthetized rats, either water (control), nicotine (600 mM, 1 ml) or capsaicin (330 microM, 1 ml) was applied to the pharynx via a cannula placed posterior to the soft palate. Following nicotine and capsaicin, there was a significant increase in fos-like immunoreactivity (FLI) compared with controls in the following areas: nucleus of the solitary tract from the level of the pyramidal decussation caudally to the level of the area postrema rostrally; dorsomedial aspect of trigeminal subnucleus caudalis (Vc); and paratrigeminal islands interspersed in the spinal trigeminal tract. There was significantly more FLI in Vc and paratrigeminal nuclei following capsaicin than following nicotine, while the reverse was true for NTS. In addition, there was a significant increase in FLI in area postrema and the ventrolateral medullary region dorsal to the lateral reticular nucleus following nicotine but not capsaicin. The distributions of FLI in NTS, area postrema, Vc, and paratrigeminal nuclei are consistent with prior anatomical tract-tracing studies and suggest roles for these brain stem regions in mediating sensory and reflex responses to irritant chemical stimulation of the upper respiratory mucosa.

Effects of excitatory amino acid receptor antagonists on pulpal blood flow of the rat mandibular incisor.

Pulpal blood flow (PBF) changes have been monitored by laser Doppler flowmetry on rat mandibular incisors. Electrical stimulation (10 sec, 50 microA, 2 ms, 20 Hz) of one incisor induced a blood flow decrease followed by a blood flow increase. The effect of intravenous administration of antagonists of ionotropic glutamate receptors (iGluRs) and antagonists of metabotropic glutamate receptors (mGluRs) was compared with that of those obtained from animals treated with the vehicle alone. No long-term effect on basal PBF was observed, except a remaining increase of 34.5% (p < 0.05, n = 5) for ketamine (10 mg/kg), an iGluR antagonist, and of 37% (p < 0.05, n = 5) for MCPG (7.5 mg/kg), an mGluR antagonist. In animals treated with iGluR antagonists, acute changes in PBF after stimulation were not significantly different from those observed with vehicle. In animals treated with mGluR antagonists, the blood flow decrease was significantly enhanced in amplitude and duration for MCPG (7.5 mg/kg), respectively, +73% and +92% (p < 0.05, n = 5). These results suggest that Group I mGluRs participate in the regulation of the immediate pulpal blood flow decrease induced by electrical stimulation of the lower incisor in the rat.

Radiographic evaluation of the prevalence and technical quality of root canal treatment in a French subpopulation.

AIM: This study was undertaken to examine the prevalence and technical quality of root fillings and the periapical status of endodontically treated teeth in a French subpopulation. METHODOLOGY: Full-mouth periapical radiographs were obtained from 208 consecutive adult patients seeking care within the dental service provided by the Hôtel-Dieu in Paris. The occurrence and technical quality of root fillings were assessed for each root according to the position and the density of the obturation. The periapical status was evaluated using the Periapical Index Scoring System. The type of coronal restoration and the presence of posts were also noted. RESULTS: Of the 8743 roots included in the survey, 23% were root-filled. An acceptable standard of treatment was found in 21% of roots with 16% of these cases associated with signs of periapical disease. In roots with unacceptable root-fillings, 27% had periapical pathology. A post was seen in 26% of the root-filled canals, with 29% of these cases associated with periapical pathology. An intracoronal restoration existed in 30% of the filled roots, of which 22% exhibited a periapical lesion. An extra-coronal restoration was present in 60% of the filled roots, of which 24% had radiographic signs of periapical pathology. The remaining 10% of filled roots that had no coronal restoration were associated with periapical pathology in 33% of cases. At least one periapical lesion was seen in 63% of the patients. CONCLUSION: The results demonstrate a high prevalence of root-filled teeth and poor technical quality of treatment. Roots presenting with acceptable root fillings were associated with a lower prevalence of periapical pathology (P < 0.001). Posts in roots were associated with periapical pathology significantly more than in roots without posts (P < 0.001).

Solid stress facilitates spheroid formation: potential involvement of hyaluronan.

When neoplastic cells grow in confined spaces in vivo, they exert a finite force on the surrounding tissue resulting in the generation of solid stress. By growing multicellular spheroids in agarose gels of defined mechanical properties, we have recently shown that solid stress inhibits the growth of spheroids and that this growth-inhibiting stress ranges from 45 to 120 mmHg. Here we show that solid stress facilitates the formation of spheroids in the highly metastatic Dunning R3327 rat prostate carcinoma AT3.1 cells, which predominantly do not grow as spheroids in free suspension. The maximum size and the growth rate of the resulting spheroids decreased with increasing stress. Relieving solid stress by enzymatic digestion of gels resulted in gradual loss of spheroidal morphology in 8 days. In contrast, the low metastatic variant AT2.1 cells, which grow as spheroids in free suspension as well as in the gels, maintained their spheroidal morphology even after stress removal. Histological examination revealed that most cells in AT2.1 spheroids are in close apposition whereas a regular matrix separates the cells in the AT3.1 gel spheroids. Staining with the hyaluronan binding protein revealed that the matrix between AT3.1 cells in agarose contained hyaluronan, while AT3.1 cells had negligible or no hyaluronan when grown in free suspension. Hyaluronan was found to be present in both free suspensions and agarose gel spheroids of AT2.1. We suggest that cell-cell adhesion may be adequate for spheroid formation, whereas solid stress may be required to form spheroids when cell-matrix adhesion is predominant. These findings have significant implications for tumour growth, invasion and metastasis.

LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis.

Lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 is thought to be restricted to lymph vessels and has been used as such to show that tumor lymphangiogenesis occurs on overexpression of lymphangiogenic factors in mouse tumor models. However, these studies have not yet been corroborated in human tumors. Here we show, first, that LYVE-1 is not exclusive to the lymph vessels. Indeed, LYVE-1 is also present in normal hepatic blood sinusoidal endothelial cells in mice and humans. Surprisingly, LYVE-1 is absent from the angiogenic blood vessels of human liver tumors and only weakly present in the microcirculation of regenerative hepatic nodules in cirrhosis, though both vessels are largely derived from the liver sinusoids. Second, we propose a novel approach to identify lymphatics in human and murine liver. By combining LYVE-1 and Prox 1 (a transcription factor) immunohistochemistry, we demonstrate that lymphatics are abundant in cirrhosis. In contrast, in human hepatocellular carcinoma and liver metastases, they are restricted to the tumor margin and surrounding liver. The absence of intratumor lymphatics in hepatocellular carcinomas and liver metastases may impair molecular and cellular transport in these tumors. Finally, the presence of LYVE-1 in liver sinusoidal endothelia suggests that LYVE-1 has functions beyond the lymph vascular system.

Defining the core of nontransferable prokaryotic genes: the euryarchaeal core.

If lateral gene transfer (LGT) has affected all genes over the course of prokaryotic evolution, reconstruction of organismal phylogeny is compromised. However, if a core of genes is immune to transfer, then the evolutionary history of that core might be our most reliable guide to the evolution of organisms. Such a core should be preferentially included in the subset of genes shared by all organisms, but where universally conserved genes have been analyzed, there is too little phylogenetic signal to allow determination of whether or not they indeed have the same history (Hansmann and Martin 2000; Teichmann and Mitchison 1999). Here we look at a more restricted set, 521 homologous genes (COGs) simultaneously present in four sequenced euryarchaeal genomes. Although there is overall little robust phylogenetic signal in this data set, there is, among well-supported trees, strong representation of all three possible four-taxon topologies. "Informational" genes seem no less subject to LGT than are "operational genes," within the euryarchaeotes. We conclude that (i) even in this collection of conserved genes there has been extensive LGT (orthologous gene replacement) and (ii) the notion that there is a core of nontransferable genes (the "core hypothesis") has not been proven and may be unprovable.

Bacterial origin for the isoprenoid biosynthesis enzyme HMG-CoA reductase of the archaeal orders Thermoplasmatales and Archaeoglobales.

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase or HMGR) fulfills an essential role in archaea, as it is required for the synthesis of isoprenoid ethers, the main component of archaeal cell membranes. There are two clearly homologous but structurally different classes of the enzyme, one found mainly in eukaryotes and archaea (class 1), and the other found in bacteria (class 2). This feature facilitated the identification of several cases of interdomain lateral gene transfer (LGT), in particular, the bacterial origin for the HMGR gene from the archaeon Archaeoglobus fulgidus. In order to investigate if this LGT event was recent and limited in its scope or had a broad and long-term impact on the recipient and its related lineages, the HMGR gene was amplified and sequenced from a variety of archaea. The survey covered close relatives of A. fulgidus, the only archaeon known prior to this study to possess a bacterial-like HMGR; representatives of each main euryarchaeal group were also inspected. All culturable members of the archaeal group Archaeoglobales were found to display an HMGR very similar to the enzyme of the bacterium Pseudomonas mevalonii. Surprisingly, two species of the genus Thermoplasma also harbor an HMGR of bacterial origin highly similar to the enzymes found in the Archaeoglobales. Phylogenetic analyses of the HMGR gene and comparisons to reference phylogenies from other genes confirm a common bacterial origin for the HMGRs of Thermoplasmatales and Archaeoglobales. The most likely explanation of these results includes an initial bacteria-to-archaea transfer, followed by a another event between archaea. Their presence in two divergent archaeal lineages suggests an important adaptive role for these laterally transferred genes.

Decorin inhibits endothelial migration and tube-like structure formation: role of thrombospondin-1.

Interactions between endothelial cell receptors and the extracellular matrix (ECM) play a critical, yet poorly understood role in angiogenesis. Based on the anti-adhesive role of decorin, we hypothesized that decorin binding to ECM molecules such as thrombospondin-1 (TSP-1) plays a regulatory role in endothelial tube-like structure (TLS) formation. To test this hypothesis, endothelial cells were plated on TSP-1, decorin, or mixed substrates of TSP-1 plus decorin. TLS formation was induced by applying type I collagen on the confluent endothelial monolayer. Cartilage decorin inhibited the formation of TLSs in a concentration-dependent manner. On substrates of high decorin concentrations (2.5 and 5.0 microg/cm(2)) the reduction in TLSs was due either to a reduction in the number of adhering cells or to decreased cell migration. At low decorin concentrations (0.05 and 0.25 microg/cm(2)) the reduction in TLSs was independent of the number of attached cells. Time-lapse video microscopy revealed that decorin substrates facilitated homotypic aggregation and isolated cord formation at the expense of endothelial migration and TLS formation. Consistent with the reduced migration, endothelial cells formed fewer vinculin-positive focal adhesions and actin-stress fibers on decorin substrates. Endothelial migration and TLS formation were also significantly inhibited by skin decorin and the protein core of cartilage decorin. The inhibition of TLS formation by the protein core of cartilage decorin was potentiated by TSP-1. These findings suggest that decorin alone or in combination with TSP-1 interferes with the activation of endothelial cell receptors by ECM molecules, thus blocking intracellular signals that induce cytoskeletal reorganization, migration, and TLS formation.

Microbial genomes: dealing with diversity.

We have now complete genome sequences of several pairs of closely related prokaryotes (conspecific strains or congeneric species). Surprisingly, even strains of the same species can differ by as much as 20% in gene content. Conceptual and methodological approaches for dealing with such diversity are now being developed, and should transform microbial genomics.