Showing papers by "Collège de France published in 2003"

Search for neutrino oscillations on a long base-line at the CHOOZ nuclear power station

Abstract: This final article about the CHOOZ experiment presents a complete description of the $\bar{ u}_e$ source and detector, the calibration methods and stability checks, the event reconstruction procedures and the Monte Carlo simulation. The data analysis, systematic effects and the methods used to reach our conclusions are fully discussed. Some new remarks are presented on the deduction of the confidence limits and on the correct treatment of systematic errors.

Modulation of oestrogen receptor signalling by association with the activated dioxin receptor.

Abstract: Environmental contaminants affect a wide variety of biological events in many species. Dioxins are typical environmental contaminants that exert adverse oestrogen-related effects. Although their anti-oestrogenic actions are well described, dioxins can also induce endometriosis and oestrogen-dependent tumours, implying possible oestrogenic effects. However, the molecular mechanism underlying oestrogen-related actions of dioxins remains largely unknown. A heterodimer of the dioxin receptor (AhR) and Arnt, which are basic helix-loop-helix/PAS-family transcription factors, mediates most of the toxic effects of dioxins. Here we show that the agonist-activated AhR/Arnt heterodimer directly associates with oestrogen receptors ER-alpha and ER-beta. This association results in the recruitment of unliganded ER and the co-activator p300 to oestrogen-responsive gene promoters, leading to activation of transcription and oestrogenic effects. The function of liganded ER is attenuated. Oestrogenic actions of AhR agonists were detected in wild-type ovariectomized mouse uteri, but were absent in AhR-/- or ER-alpha-/- ovariectomized mice. Our findings suggest a novel mechanism by which ER-mediated oestrogen signalling is modulated by a co-regulatory-like function of activated AhR/Arnt, giving rise to adverse oestrogen-related actions of dioxin-type environmental contaminants.

Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse

Abstract: The DNA damage-dependent poly(ADP-ribose) polymerases, PARP-1 and PARP-2, homo- and heterodimerize and are both involved in the base excision repair (BER) pathway. Here, we report that mice carrying a targeted disruption of the PARP-2 gene are sensitive to ionizing radiation. Following alkylating agent treatment, parp-2(-/-)-derived mouse embryonic fibroblasts exhibit increased post-replicative genomic instability, G(2)/M accumulation and chromosome mis-segregation accompanying kinetochore defects. Moreover, parp-1(-/-)parp-2(-/-) double mutant mice are not viable and die at the onset of gastrulation, demonstrating that the expression of both PARP-1 and PARP-2 and/or DNA-dependent poly(ADP-ribosyl) ation is essential during early embryogenesis. Interestingly, specific female embryonic lethality is observed in parp-1(+/-)parp-2(-/-) mutants at E9.5. Meta phase analyses of E8.5 embryonic fibroblasts highlight a specific instability of the X chromosome in those females, but not in males. Together, these results support the notion that PARP-1 and PARP-2 possess both overlapping and non-redundant functions in the maintenance of genomic stability.

A directional strategy for monitoring Cre-mediated recombination at the cellular level in the mouse

Abstract: Functional redundancies, compensatory mechanisms, and lethal phenotypes often prevent the full analysis of gene functions through generation of germline null mutations in the mouse The use of site-specific recombinases, such as Cre, which catalyzes recombination between loxP sites, has allowed the engineering of mice harboring targeted somatic mutations, which are both temporally controlled and cell-type restricted Many Cre-expressing mouse lines exist, but only a few transgenic lines are available that harbor a reporter gene whose expression is dependent on a Cre-mediated event Moreover, their use to monitor gene ablation at the level of individual cells is often limited, as in some tissues the reporter gene may be silenced, be affected by position-effect variegation, or reside in a chromatin configuration inaccessible for recombination Thus, one cannot validly extrapolate from the expression of a reporter transgene to an identical ablation pattern for the conditional allele of a given gene By combining the ability of Cre recombinase to invert or excise a DNA fragment, depending on the orientation of the flanking loxP sites, and the availability of both wild-type (WT) and mutant loxP sites, we designed a Cre-dependent genetic switch (FLEx switch) through which the expression of a given gene is turned off, while the expression of another one is concomitantly turned on We demonstrate the efficiency and reliability of this switch to readily detect, in the mouse, at the single cell level, Cre-mediated gene ablation We discuss how this strategy can be used to generate genetic modifications in a conditional manner

NSD1 is essential for early post-implantation development and has a catalytically active SET domain

Abstract: The nuclear receptor-binding SET domain-containing protein (NSD1) belongs to an emerging family of proteins, which have all been implicated in human malignancy To gain insight into the biological functions of NSD1, we have generated NSD1-deficient mice by gene disruption Homozygous mutant NSD1 embryos, which initiate mesoderm formation, display a high incidence of apoptosis and fail to complete gastrulation, indicating that NSD1 is a developmental regulatory protein that exerts function(s) essential for early post-implantation development We have also examined the enzymatic potential of NSD1 and found that its SET domain possesses intrinsic histone methyltransferase activity with specificity for Lys36 of histone H3 (H3-K36) and Lys20 of histone H4 (H4-K20)

Cohomological Invariants in Galois Cohomology

Abstract: Cohomological invariants, Witt invariants, and trace forms: Contents by J.-P. Serre and S. Garibaldi Introduction by J.-P. Serre and S. Garibaldi The notion of "invariant" by J.-P. Serre and S. Garibaldi Cohomological preliminaries: The local case by J.-P. Serre and S. Garibaldi Cohomological preliminaries: The function field case by J.-P. Serre and S. Garibaldi Specialization properties of cohomological invariants by J.-P. Serre and S. Garibaldi Restriction and corestriction of invariants by J.-P. Serre and S. Garibaldi Cohomological invariants of $O_n,SO_n,\ldots$ by J.-P. Serre and S. Garibaldi Cohomological invariants of etale algebras by J.-P. Serre and S. Garibaldi Witt invariants by J.-P. Serre and S. Garibaldi The trace form in dimension $\le 7$ by J.-P. Serre and S. Garibaldi A letter from M. Rost to J-P. Serre by M. Rost A letter from J-P. Serre to R. S. Garibaldi by J.-P. Serre A letter from B. Totaro to J-P. Serre by B. Totaro Rost invariants of simply connected algebraic groups: Contents by A. Merkurjev and S. Garibaldi Rost invariants of simply connected algebraic groups by A. Merkurjev and S. Garibaldi The groups $H^{d+1}(F,\mathbb{Q}^mathbb{Z}(d))$ by A. Merkurjev and S. Garibaldi Tables of Dynkin indices by A. Merkurjev and S. Garibaldi Bibliography Index of notation Index of terms.

Angiopoietin-Like 4 Is a Proangiogenic Factor Produced during Ischemia and in Conventional Renal Cell Carcinoma

Abstract: Ischemic and solid tumor tissues are less well perfused than normal tissue, leading to metabolic changes and chronic hypoxia, which in turn promotes angiogenesis. We identified human angiopoietin-like 4 (angptl4) as a gene with hypoxia-induced expression in endothelial cells. We showed that the levels of both mRNA and protein for ANGPTL4 increased in response to hypoxia. When tested in the chicken chorioallantoic membrane assay, ANGPTL4 induced a strong proangiogenic response, independently of vascular endothelial growth factor. In human pathology, ANGPTL4 mRNA is produced in ischemic tissues, in conditions such as critical leg ischemia. In tumors, ANGPTL4 is produced in the hypoxic areas surrounding necrotic regions. We observed particularly high levels of ANGPTL4 mRNA in tumor cells of conventional renal cell carcinoma. Other benign and malignant renal tumor cells do not produce ANGPTL4 mRNA. This molecule therefore seems to be a marker of conventional renal cell carcinoma. ANGPTL4, originally identified as a peroxisome proliferator-activated receptor α and γ target gene, has potential for use as a new diagnostic tool and a potential therapeutic target, modulating angiogenesis both in tumors and in ischemic tissues. This study also suggests that ANGPTL4 may provide a link between metabolic disorders and hypoxia-induced angiogenesis.

Slippy and sticky microtextured solids

Abstract: The aim of this paper is to describe the possibility of achieving super-hydrophobic materials by tailoring their surface topography. Water droplets easily slip or roll down on such surfaces. However, it is found that microtextures on a solid can generate sticky surfaces as well, and the conditions for avoiding such an effect are discussed.

Delta-Notch signaling controls the generation of neurons/glia from neural stem cells in a stepwise process.

Abstract: We examined the role of Notch signaling on the generation of neurons and glia from neural stem cells by using neurospheres that are clonally derived from neural stem cells. Neurospheres prepared from Dll1 lacZ/lacZ mutant embryos segregate more neurons at the expense of both oligodendrocytes and astrocytes. This mutant phenotype could be rescued when Dll1 lacZ/lacZ spheres were grown and/or differentiated in the presence of conditioned medium from wild-type neurospheres. Temporal modulation of Notch by soluble forms of ligands indicates that Notch signaling acts in two steps. Initially, it inhibits the neuronal fate while promoting the glial cell fate. In a second step, Notch promotes the differentiation of astrocytes, while inhibiting the differentiation of both neurons and oligodendrocytes.

Estradiol enhances primary antigen‐specific CD4 T cell responses and Th1 development in vivo. Essential role of estrogen receptor α expression in hematopoietic cells

Abstract: It is widely accepted that females have superior immune responses than males, but the ways by which sex hormones may enhance T cell responses are still poorly understood. In the present study, we analyzed the effect of estrogens on CD4 T cell activation and differentiation after immunization with exogenous antigens. We show that administration of low doses of 17beta-estradiol (E2) to castrated female mice results in a striking increase of antigen-specific CD4 T cell responses and in the selective development of IFN-gamma-producing cells. Quantitative assessment of the frequency of T cells bearing a public TCR beta chain CDR3 motif demonstrated that the clonal size of primary antigen-specific CD4 T cells was dramatically increased in immune lymph nodes from E2-treated mice. By using mice with disrupted estrogen receptor (ER) alpha or beta genes, we show that ERalpha, but not ERbeta, was necessary for the enhanced E2-driven Th1 cell responsiveness. Furthermore, ERalpha expression in hematopoietic cells was essential, since E2 effects on Th1 responses were only observed in mice reconstituted with bone marrow cells from ERalpha+/+, but not ERalpha-deficient mice. These results demonstrate that estrogen administration promotes strong antigen-specific Th1 cell responses in a mechanism that requires functional expression of ERalpha in hematopoietic cells.

Water spring: A model for bouncing drops

Abstract: It has been shown that a water drop can bounce persistently, when thrown on a super-hydrophobic substrate. We present here scaling arguments which allow us to predict the maximal deformation and the contact time of the drop. This approach is completed by a model describing the flow inside the drop, and by original experimental data.

Reappraisal of the human vestibular cortex by cortical electrical stimulation study.

Abstract: The cortical areas with vestibular input in humans were assessed by electrical stimulation in 260 patients with partial epilepsy who had undergone stereotactic intracerebral electroencephalogram recordings before surgery. Vestibular symptoms were electrically induced on 44 anatomical sites in 28 patients. The patients experienced illusions of rotation (yaw plane: 18, pitch plane: 6, roll plane: 6), translations (n = 6), or indefinable feelings of body motion (n = 8). Almost all vestibular sites were located in the cortex (41/44): in the temporal (n = 19), parietal (n = 14), frontal (n = 5), occipital (n = 2), and insular (n = 1) lobes. Among these sites, we identified a lateral cortical temporoparietal area we called the temporo-peri-Sylvian vestibular cortex (TPSVC), from which vestibular symptoms, and above all rotatory sensations, were particularly easily elicited (24/41 cortical sites, 58.5%). This area extended above and below the Sylvian fissure, mainly inside Brodmann areas 40, 21, and 22. It included the parietal operculum (9/24 TPSVC sites) which was particularly sensitive for eliciting pitch plane illusions, and the mid and posterior part of the first and second temporal gyri (15/24 TPSVC sites) which preferentially caused yaw plane illusions. We suggest that the TPSVC could be homologous with the monkey's parietoinsular vestibular cortex.

The regional pattern of retinoic acid synthesis by RALDH2 is essential for the development of posterior pharyngeal arches and the enteric nervous system.

Abstract: Targeted inactivation of the mouse retinaldehyde dehydrogenase 2 (RALDH2/ALDH1a2), the enzyme responsible for early embryonic retinoic acid synthesis, is embryonic lethal because of defects in early heart morphogenesis. Transient maternal RA supplementation from E7.5 to (at least) E8.5 rescues most of these defects, but the supplemented Raldh2(-/-) mutants die prenatally, from a lack of septation of the heart outflow tract (Niederreither, K., Vermot, J., Messaddeq, N., Schuhbaur, B., Chambon, P. and Dolle, P. (2001). Development 128, 1019-1031). We have investigated the developmental basis for this defect, and found that the RA-supplemented Raldh2(-/-) embryos exhibit impaired development of their posterior (3rd-6th) branchial arch region. While the development of the first and second arches and their derivatives, as well as the formation of the first branchial pouch, appear to proceed normally, more posterior pharyngeal pouches fail to form and the pharyngeal endoderm develops a rudimentary, pouch-like structure. All derivatives of the posterior branchial arches are affected. These include the aortic arches, pouch-derived organs (thymus, parathyroid gland) and post-otic neural crest cells, which fail to establish segmental migratory pathways and are misrouted caudally. Patterning and axonal outgrowth of the posterior (9th-12th) cranial nerves is also altered. Vagal crest deficiency in Raldh2(-/-) mutants leads to agenesis of the enteric ganglia, a condition reminiscent of human Hirschprung's disease. In addition, we provide evidence that: (i) wildtype Raldh2 expression is restricted to the posteriormost pharyngeal mesoderm; (ii) endogenous RA response occurs in both the pharyngeal endoderm and mesoderm, and extends more rostrally than Raldh2 expression up to the 2nd arch; (iii) RA target genes (Hoxa1, Hoxb1) are downregulated in both the pharyngeal endoderm and mesoderm of mutant embryos. Thus, RALDH2 plays a crucial role in producing RA required for pharyngeal development, and RA is one of the diffusible mesodermal signals that pattern the pharyngeal endoderm.

Mouse placenta is a major hematopoietic organ.

Abstract: Placenta and yolk sac from 8- to 17-day-old (E8-E17) mouse embryos/fetuses were investigated for the presence of in vitro clonogenic progenitors. At E8-E9, the embryonic body from the umbilicus caudalwards was also analysed. Fetal liver was analysed beginning on E10. At E8, between five and nine somite pairs (sp), placenta, yolk sac and embryonic body yielded no progenitors. The first progenitors appeared at E8.5 at the stage of 15 sp in the yolk sac, 18 sp in the embryonic body, 20 sp in the placenta and only at E12 in the fetal liver (absent at E10, at E11 not determined). Progenitors with a high proliferation potential that could be replated for two months, as well as the whole range of myeloid progenitors, were found at all stages in all organs. However, the earliest of these progenitors (these yielding large, multilineage colonies) were 2-4 times more frequent in the placenta than in the yolk sac or fetal liver. In the fetal liver, late progenitors were more frequent and the cellularity increased steeply with developmental age. Thus, the fetal liver, which is a recognized site for amplification and commitment, has a very different hematopoietic developmental profile from placenta or yolk sac. Placentas were obtained from GFP transgenic embryos in which only the embryonic contribution expressed the transgene. 80% of the colonies derived from these placental cells were GFP+, and so originated from the fetal component of the placenta. These data point to the placenta as a major hematopoietic organ that is active during most of pregnancy.

Multidetector multicomponent spectral matching and applications for cosmic microwave background data analysis

Abstract: We present a new method for analysing multidetector maps containing several astrophysical components. Our method, based on matching the data to a model in the spectral domain, permits us to estimate jointly the spatial power spectra of the components and of the noise, as well as their mixing coefficients. It is of particular relevance for analysis of millimetre-wave maps of cosmic microwave background (CMB) anisotropies.

Antihelium-3 production in lead-lead collisions at 158 A GeV/c

Abstract: The NA52 experiment measured particle and antiparticle yields at 0° production angle over a wide range in rapidity in lead-lead (Pb-Pb) collisions at 158 A GeV/c with a minimum bias trigger. Besides (106) antiprotons () and (103) antideuterons () a total of five antihelium-3 () were found. The resulting invariant differential production cross sections at pt0 GeV/c turn out to be E (d3σ)/(dp3) = (2.5 ± 1.8) × 10-7 bc3 GeV-2 at a rapidity of y = 3.4 in the laboratory system and (5.9 ± 3.4) × 10-8 bc3 GeV-2 at y = 4.0. The results are discussed in the framework of a simple coalescence model.

PARP-3 localizes preferentially to the daughter centriole and interferes with the G1/S cell cycle progression.

Abstract: A novel member of the poly(ADP-ribose) polymerase (PARP) family, hPARP-3, is identified here as a core component of the centrosome. hPARP-3 is preferentially localized to the daughter centriole throughout the cell cycle. The N-terminal domain (54 amino acids) of hPARP-3 is responsible for its centrosomal localization. Full-length hPAPR-3 (540 amino acids, with an apparent mass of 67 kDa) synthesizes ADP-ribose polymers during its automodification. Overexpression of hPARP-3 or its N-terminal domain does not influence centrosomal duplication or amplification but interferes with the G1/S cell cycle progression. PARP-1 also resides for part of the cell cycle in the centrosome and interacts with hPARP-3. The presence of both PARP-1 and PARP-3 at the centrosome may link the DNA damage surveillance network to the mitotic fidelity checkpoint.

Carbenoxolone blockade of neuronal network activity in culture is not mediated by an action on gap junctions.

Abstract: Spontaneous activity in the central nervous system is strongly suppressed by blockers of gap junctions (GJs), suggesting that GJs contribute to network activity. However, the lack of selective GJ blockers prohibits the determination of their site of action, i.e. neuronal versus glial. Astrocytes are strongly coupled through GJs and have recently been shown to modulate synaptic transmission, yet their role in neuronal network activity was not analysed. The present study investigated the effects and site of action of the GJ blocker, carbenoxolone (CBX), on neuronal network activity. To this end, we used cultures of hippocampal or cortical neurons, plated on astrocytes. In these cultures neurons display spontaneous synchronous activity and GJs are found only in astrocytes. CBX induced in these neurons a reversible suppression of spontaneous action potential discharges, synaptic currents and synchronised calcium oscillations. Moreover, CBX inhibited oscillatory activity induced by the GABAA antagonist, bicuculline. These effects were not due to blockade of astrocytic GJs, since they were not mimicked nor occluded by endothelin-1 (ET-1), a peptide known to block astrocytic GJs. Also, these effects were still present in co-cultures of wild-type neurons plated on astrocytes originating from connexin-43 (Cx43) knockout mice, and in neuronal cultures which contain few isolated astrocytes. CBX was not likely to exert its effect through neuronal GJs either, as immunostaining for major neuronal connexins (Cx) as well as dye or electrical coupling, were not detected in the different models of cultured neurons examined. Finally while CBX (at 100 μm) did not modify presynaptic transmitter release and postsynaptic responses to glutamate, it did cause an increase in the action potential threshold and strongly decreased the firing rate in response to a sustained depolarising current. These data demonstrate that CBX does not exert its action on network activity of cultured neurons through astrocytic GJs and suggest that it has direct effects on neurons, not involving GJs.

Multiple Promoters in the WNK1 Gene: One Controls Expression of a Kidney-Specific Kinase-Defective Isoform

Abstract: WNK1 is a serine-threonine kinase, the expression of which is affected in pseudohypoaldosteronism type II, a Mendelian form of arterial hypertension. We characterized human WNK1 transcripts to determine the molecular mechanisms governing WNK1 expression. We report the presence of two promoters generating two WNK1 isoforms with a complete kinase domain. Further variations are achieved by the use of two polyadenylation sites and tissue-specific splicing. We also determined the structure of a kidney-specific isoform regulated by a third promoter and starting at a novel exon. This transcript is kinase defective and has a predominant expression in the kidney compared to the other WNK1 isoforms, with, furthermore, a highly restricted expression profile in the distal convoluted tubule. We confirmed that the ubiquitous and kidney-specific promoters are functional in several cells lines and identified core promoters and regulatory elements. In particular, a strong enhancer element upstream from the kidney-specific exon seems specific to renal epithelial cells. Thus, control of human WNK1 gene expression of kinase-active or -deficient isoforms is mediated predominantly through the use of multiple transcription initiation sites and tissue-specific regulatory elements.

The North Anatolian fault in the Sea of Marmara

Abstract: [1] Using the detailed geometry and tectonics of the Main Marmara fault that connects the Gulf of Izmit fault with the Ganos fault established by Le Pichon et al. [2001] and the new GPS data set recently analyzed by Meade et al. [2002], we confirm the existence of a Marmara block delimited to the north by the northern branch of the North Anatolian fault (the Marmara branch) and to the south by the southern branch. The kinematics of this block indicate that the Marmara branch that crosses the Sea of Marmara is close to pure dextral strike slip at a rate of 23 mm/yr on its whole length. The short Cinarcik section is the only one where a significant extensional component is predicted. A simple kinematic model accounts for slip partitioning there, with 8–10 mm/yr of extension to the south of the basin and 23 mm/yr of dextral strike slip along the northern Cinarcik margin. The new GPS data demonstrate the existence of important asymmetric elastic loading along the Main Marmara fault that may have significant implications for the seismotectonics of the area. The expected future large earthquake may rupture the whole main Marmara fault. The partitioning in the Cinarcik basin may produce magnitude 7 normal faulting earthquakes if their repetition time is about 250 years. The 1896 earthquake may have been one of these normal fault earthquakes. The Marmara block is less than 1 Ma. Prior to its formation, it was part of the Anatolian block. At this time the Ganos fault was already a dextral strike-slip fault, but the fault system in the Sea of Marmara would have been affected by an extensional component increasing toward the east that accounts for the increasing size of the sedimentary basins eastward.

Retinoids Regulate Survival and Antigen Presentation by Immature Dendritic Cells

Abstract: Maturation of dendritic cells (DCs) is a critical step for the induction of an immune response. We have examined the role of retinoid nuclear receptor pathways in this process. Retinoids induce DC apoptosis, in the absence of inflammatory signals, through retinoic acid receptor (RAR)α/retinoic X receptor (RXR) heterodimers. In contrast, via a cross talk with inflammatory cytokines, retinoids increase DNA binding activity of nuclear factor κB in DCs, trigger membrane major histocompatibility complex class II and costimulatory molecule expression, induce the differentiation of immature DCs into mature DCs, and enhance antigen-specific T cell response. This maturation of DCs is mediated via a RXR-dependent/RAR-independent pathway and via an RARα/RXR pathway distinct from the one responsible for apoptosis. Apoptosis and activation, mediated through distinct nuclear retinoid receptor pathways, can be dissociated from each other with selective synthetic retinoids. We identify a novel cellular function for retinoids and suggest that selective retinoids might be of interest for controlling antigen presentation.

Entanglement of a mesoscopic field with an atom induced by photon graininess in a cavity.

Abstract: We observe that a mesoscopic field made of several tens of microwave photons exhibits quantum features when interacting with a single Rydberg atom in a high-Q cavity. The field is split into two components whose phases differ by an angle inversely proportional to the square root of the average photon number. The field and the atomic dipole are phase entangled. These manifestations of photon graininess vanish at the classical limit. This experiment opens the way to studies of large quantum state superpositions at the quantum-classical boundary.

Limits on Galactic dark matter with 5 years of EROS SMC data

Abstract: Five years of EROS data towards the Small Magellanic Cloud have been searched for gravitational microlensing events, using a new, more accurate method to assess the impact of stellar blending on the efficiency. Four long-duration candidates have been found which, if they are microlensing events, hint at a non-halo population of lenses. Combined with results from other EROS observation programs, this analysis yields strong limits on the amount of Galactic dark matter made of compact objects. Less than 25% of a standard halo can be composed of objects with a mass between 2 10^-7 Msol and 1 Msol at the 95% C.L.

Local stress relaxation and shear banding in a dry foam under shear.

Abstract: We have developed a realistic simulation of 2D dry foams under quasistatic shear. After a short transient, a shear-banding instability is observed. These results are compared with measurements obtained on real 2D (confined) foams. The numerical model allows us to exhibit the mechanical response of the material to a single plastication event. From the analysis of this elastic propagator, we propose a scenario for the onset and stability of the flow localization process in foams, which should remain valid for most athermal amorphous systems under creep flow.

On the bone histology of some Triassic pseudosuchian archosaurs and related taxa

Abstract: The long bone histology of some major groups of extinct Triassic crocodile relatives (phytosaurs, aetosaurs, poposaurs) is generally similar to that of living and fossil crocodylomorphs. Early deposition of more or less fibro-lamellar, fast-growing tissue gives way to cycles of deposition of a layer of less well-vascularized, predominantly parallel-fibered bone, followed by an annulus of nearly avascular bone and a line of arrested growth (LAG). These cycles, forming the so-called lamellar-zonal pattern of bone tissue suggesting slow growth, differ from the situation in most ornithosuchians (pterosaurs and dinosaurs), in which the pattern is generally that of fast-growing fibro-lamellar tissue throughout, that may become less vascular and eventually avascular only as full size is reached. LAGs are common, but annuli are not. Although the pseudosuchian pattern is presumed primitive for archosaurs, erythrosuchians (non-archosaurian Archosauriformes) apparently grew much like dinosaurs did, so the pseudosuchian pattern may not necessarily be primitive for Archosauriformes. Moreover, the histological patterns of the basal crocodylomorph Terrestrisuchus suggest elevated growth rates compared to typical crocodiles, though not as high as those of dinosaurs and pterosaurs. In general, there is a clear difference in histological tissue types, and hence in growth regimes and rates, between pseudosuchians and ornithosuchians, which extends back to the separation of these two archosaurian lineages at least by the Middle Triassic.