Cenomanian (early Late Cretaceous) ammonoid faunas of Western Europe - Part II: Diversity patterns and the end-Cenomanian anoxic event

Diversity patterns of ammonoids are analyzed and compared with the timing of anoxic deposits around the Cenomanian/Turonian (C/T) boundary in the Vocontian, Anglo-Paris, and Monster basins of Western Europe. Differing from most previous studies, which concentrate on a narrow time span bracketing the C/T boundary, the present analysis covers the latest Albian to Early Turonian interval for which a high resolution, ammonoid-based biochronology, including 34 Unitary Associations zones, is now available. During the latest Albian-Middle Cenomanian interval, species richness of ammonoids reveals a dynamical equilibrium oscillating around an average of 20 species, whereas the Late Cenomanian-Early Turonian interval displays an equilibrium centered on an average value of 6 species. The abrupt transition between these two successive equilibria lasted no longer than two Unitary Associations. The onset of the decline of species richness thus largely predates the spread of oxygen-poor water masses onto the shelves, while minimal values of species richness coincide with the Cenomanian-Turonian boundary only. The decline of species richness during the entire Late Cenomanian seems to result from lower origination percentages rather than from higher extinction percentages. This result is also supported by the absence of statistically significant changes in the extinction probabilities of the poly-cohorts. Separate analyses of species richness for acanthoceratids and heteromorphs, the two essential components of the Cenomanian ammonoid community, reveal that heteromorphs declined sooner than acanthoceratids. Moreover, acanthoceratids showed a later decline at the genus level than at the species level. Such a decoupling is accompanied by a significant increase in morphological disparity of acanthoceratids, which is expressed by the appearance of new genera. Last, during the Late Cenomanian, paedomorphic processes, juvenile innovations and reductions of adult size dominated the evolutionary radiation of acanthoceratids. Hence, the decrease in ammonoid species richness and their major evolutionary changes significantly predates the spread of anoxic deposits. Other environmental constraints such as global flooding of platforms, warmer and more equable climate, as well as productivity changes better correlate with the timing of diversity changes and evolutionary patterns of ammonoids and therefore, provide more likely causative mechanisms than anoxia alone.

Generation and function of mouse central memory and effector memory T cells

1. SUMMARY Based on functional and homing properties, two subsets of memory T lymphocytes have been defined both in humans and in mice. Central memory T cells (TCM cells) express the lymph node homing receptors CD62L and CCR7, have poor effector function and proliferate efficiently upon antigenic stimulation. Effector memory T cells (TEM cells) do not express CCR7, are mostly CD62L negative and therefore are excluded from lymph nodes, but are able to migrate to sites of inflammation where they exert immediate effector function by producing inflammatory cytokines and cytotoxic mediators. In the present work we have addressed two questions that emerged since the definition of TCM and TEM cells. Firstly, what are the priming conditions for generation of TCM and TEM and, secondly, what is the migratory capacity of TCM and TEM cells in inflammatory conditions. By using naive TCR-transgenic OT-I CD8+ T cells and OT-II CD4+ T cells and ovalbumin pulsed-mature dendritic cells (DCs) we set up an in vitro system in which the strength of T cell stimulation is controlled by varying the ratio of T cells and DCs and the duration of DC-T cell interaction. Using this system we found that precursors of TCM and TEM cells are generated at different strength of stimulation and that T cells capable of persisting in vivo in the absence of antigen and of mounting recall responses is optimally induced by intermediate stimulatory strength. In addition, we found that lymph nodes draining sites of mature DC or adjuvant inoculation recruit CD8+ CD62L- CCR7- effector and TEM cells. CD8+ T cell recruitment in reactive lymph nodes requires CXCR3 expression on T cells and occurs through high endothelial venules (HEVs) in concert with HEV lurninal expression of the CXCR3 ligand CXCL9. In reactive lymph nodes, recruited T cells establish stable interactions with and kill antigen-bearing DCs, limiting the ability of these DCs to activate CD4+ and CD8+ T cells. Taken togther these data define conditions for the generation of TCM and TEM cells and define an inflammatory pathway of effector T cell migration in lymph nodes. The inducible recruitment of blood-borne effector and TEM CD8+ cells to lymph nodes may represent a mechanism for terminating primary and limiting secondary immune responses.

Does gender really matter in cathlab

Purpose: Results of some PCI clinical trials indicated more procedure related complications and worse clinical outcomes in women than men, but due to a lower representation of female patients this question still remains open. We aimed toinvestigate characteristics and early and late clinical outcomes in female patients as compared to male when treated in a real life setting with a new generation DES.Methods: Among 3069 consecutive patients treated with Nobori DES, and enrolled in NOBORI 2 study, 675 were female. The primary endpoint of the study is target lesion failure (TLF), a composite of cardiac death, MI and target lesion revascularization (TLR) at 12 months. Data are entered in an electronic database; all adverse events are adjudicated by an independent clinical event committee and independent corelabs analyse all angiograms.Results: Compared to male patients, female patients were significantly older (68±10 vs ± 63±11 years; p<0.001), had higher incidence of diabetes (37% vs 27%; p<0.001) and hypertension (75% vs 66%; p<0.001), but lower frequency of previous MI, PCI/CABG and smoking history. Lesion characteristics were similar in two genders, except for lesions located at bifurcation which were more frequent inmale patients (22% vs 15% inmale and female patients respectively; p<0.001). Majority of QCA assessed parameters were similar with the exception for RVD, post-procedure MLD in-segment and %DS in-stent which were significantly lower in female patients (p<0.05 for all). In table 1 results at 6 months follow-up are presented and at the time of presentation 1 year results will be available. Table 1. Clinical results at 6 months follow-up Male (n=2394) Female (n=675) P value Cardiac Death 12 (0.5%) 5 (0.7%) 0.5550 MI 5 (2.1%) 4 (1.3%) 0.5089 TLR rate 17 (0.7%) 13 (1.9%) 0.0124 TLF rate 44 (1.8%) 17 (2.5%) 0.2745 Stent Thrombosis 12 (0.5%) 6 (0.9%) 0.2548Conclusions: Results indicate that there are differences in the demographics and risk factors in female and male patient's population. The frequency of adverse events at 6 months is low in both populations, showing trend toward slightly higher rate in female patients, particularly for target lesion revascularization.

Performance evaluation of a new fourth-generation HIV combination antigen-antibody assay.

Education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (HIV). The importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. The Elecsys(®) HIV combi PT assay is a fourth-generation antigen-antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and improved specificity. We aimed to determine how early the assay could detect infection compared with existing assays; whether all HIV variants could be detected; and the assay's specificity using samples from blood donors, routine specimens, and patients with potential cross-reacting factors. Samples were identified as positive by the Elecsys(®) assay 4.9 days after a positive polymerase chain reaction result (as determined by the panel supplier), which was earlier than the 5.3-7.1 days observed with comparators. The analytical sensitivity of the Elecsys(®) HIV combi PT assay for the HIV-1 p24 antigen was 1.05 IU/mL, which compares favorably with the comparator assays. In addition, the Elecsys(®) assay identified all screened HIV subtypes and displayed greater sensitivity to HIV-2 homologous antigen and antibodies to HIV-1 E and O and HIV-2 than the other assays. Overall, the specificity of the Elecsys(®) assay was 99.88 % using samples from blood donors and 99.81 % when analyzing unselected samples. Potential cross-reacting factors did not interfere with assay performance. The Elecsys(®) HIV combi PT assay is a sensitive and specific assay that has been granted the CE mark according to Directive 2009/886/EC.

Triathlon event distance specialization: training and injury effects.

We conducted a preliminary, questionnaire-based, retrospective analysis of training and injury in British National Squad Olympic distance (OD) and Ironman distance (IR) triathletes. The main outcome measures were training duration and training frequency and injury frequency and severity. The number of overuse injuries sustained over a 5-year period did not differ between OD and IR. However, the proportions of OD and IR athletes who were affected by injury to particular anatomical sites differed (p < 0.05). Also, fewer OD athletes (16.7 vs. 36.8%, p < 0.05) reported that their injury recurred. Although OD sustained fewer running injuries than IR (1.6 +/- 0.5 vs. 1.9 +/- 0.3, p < 0.05), more subsequently stopped running (41.7 vs. 15.8%) and for longer (33.5 +/- 43.0 vs. 16.7 +/- 16.6 days, p < 0.01). In OD, the number of overuse injuries sustained inversely correlated with percentage training time, and number of sessions, doing bike hill repetitions (r = -0.44 and -0.39, respectively, both p < 0.05). The IR overuse injury number correlated with the amount of intensive sessions done (r = 0.67, p < 0.01 and r = 0.56, p < 0.05 for duration of "speed run" and "speed bike" sessions). Coaches should note that training differences between triathletes who specialize in OD or IR competition may lead to their exhibiting differential risk for injury to specific anatomical sites. It is also important to note that cycle and run training may have a "cumulative stress" influence on injury risk. Therefore, the tendency of some triathletes to modify rather than stop training when injured-usually by increasing load in another discipline from that in which the injury first occurred-may increase both their risk of injury recurrence and time to full rehabilitation.

First-generation linkage map for the European tree frog (Hyla arborea) with utility in congeneric species.

BACKGROUND: Western Palearctic tree frogs (Hyla arborea group) represent a strong potential for evolutionary and conservation genetic research, so far underexploited due to limited molecular resources. New microsatellite markers have recently been developed for Hyla arborea, with high cross-species utility across the entire circum-Mediterranean radiation. Here we conduct sibship analyses to map available markers for use in future population genetic applications. FINDINGS: We characterized eight linkage groups, including one sex-linked, all showing drastically reduced recombination in males compared to females, as previously documented in this species. Mapping of the new 15 markers to the ~200 My diverged Xenopus tropicalis genome suggests a generally conserved synteny with only one confirmed major chromosome rearrangement. CONCLUSIONS: The new microsatellites are representative of several chromosomes of H. arborea that are likely to be conserved across closely-related species. Our linkage map provides an important resource for genetic research in European Hylids, notably for studies of speciation, genome evolution and conservation.

Generation and validation of a normative, age-specific reference curve for lumbar spine trabecular bone score (TBS) in French women.

Age-related changes in lumbar vertebral microarchitecture are evaluated, as assessed by trabecular bone score (TBS), in a cohort of 5,942 French women. The magnitude of TBS decline between 45 and 85 years of age is piecewise linear in the spine and averaged 14.5 %. TBS decline rate increases after 65 years by 50 %. INTRODUCTION: This study aimed to evaluate age-related changes in lumbar vertebral microarchitecture, as assessed by TBS, in a cohort of French women aged 45-85 years. METHODS: An all-comers cohort of French Caucasian women was selected from two clinical centers. Data obtained from these centers were cross-calibrated for TBS and bone mineral density (BMD). BMD and TBS were evaluated at L1-L4 and for all lumbar vertebrae combined using GE-Lunar Prodigy densitometer images. Weight, height, and body mass index (BMI) also were determined. To validate our all-comers cohort, the BMD normative data of our cohort and French Prodigy data were compared. RESULTS: A cohort of 5,942 French women aged 45 to 85 years was created. Dual-energy X-ray absorptiometry normative data obtained for BMD from this cohort were not significantly different from French prodigy normative data (p = 0.15). TBS values at L1-L4 were poorly correlated with BMI (r = -0.17) and weight (r = -0.14) and not correlated with height. TBS values obtained for all lumbar vertebra combined (L1, L2, L3, L4) decreased with age. The magnitude of TBS decline at L1-L4 between 45 and 85 years of age was piecewise linear in the spine and averaged 14.5 %, but this rate increased after 65 years by 50 %. Similar results were obtained for other region of interest in the lumbar spine. As opposed to BMD, TBS was not affected by spinal osteoarthrosis. CONCLUSION: The age-specific reference curve for TBS generated here could therefore be used to help clinicians to improve osteoporosis patient management and to monitor microarchitectural changes related to treatment or other diseases in routine clinical practice.

Modulation of proteasomal activity required for the generation of a cytotoxic T lymphocyte-defined peptide derived from the tumor antigen MAGE-3.

We have analyzed the presentation of human histocompatability leukocyte antigen-A*0201-associated tumor peptide antigen MAGE-3271-279 by melanoma cells. We show that specific cytotoxic T lymphocyte (CTL)-recognizing cells transfected with a minigene encoding the preprocessed fragment MAGE-3271-279 failed to recognize cells expressing the full length MAGE-3 protein. Digestion of synthetic peptides extended at the NH2 or COOH terminus of MAGE-3271-279 with purified human proteasome revealed that the generation of the COOH terminus of the antigenic peptide was impaired. Surprisingly, addition of lactacystin to purified proteasome, though partially inhibitory, resulted in the generation of the antigenic peptide. Furthermore, treatment of melanoma cells expressing the MAGE-3 protein with lactacystin resulted in efficient lysis by MAGE-3271-279-specific CTL. We therefore postulate that the generation of antigenic peptides by the proteasome in cells can be modulated by the selective inhibition of certain of its enzymaticactivities.

Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis.

Background: Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance. Methods: We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-backworking memory tasks as well as oddball detection and passive fixation tasks. Results: We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory-related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls. Limitations: Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out. Conclusion: The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.

Follicular lymphoma at relapse after rituximab containing regimens: comparison of time to event intervals prior to and after (90) Y-ibritumomab-tiuxetan.

Radioimmunotherapies with Zevalin® (RIT-Z) showed encouraging results in patients with relapsed/refractory follicular lymphoma (FL), leading frequently to failure-free intervals longer than those achieved by the last previous therapy. We compared time-to-event variables obtained before and after RIT-Z in patients with relapsed FL, previously exposed to rituximab. All patients with relapsed non-transformed, non-refractory, non-rituximab-naïve FL who have been treated with RIT-Z in two different centres in Europe were included. Staging and response were assessed by contrast-enhanced CT in all patients; PET/CT was performed according to local availability. Event-free survival (EFS) and time to next treatment (TTNT) following the last previous therapy and after RIT-Z were compared. Pre-therapy characteristics were tested in univariate analyses for prediction of outcomes. A description of the patterns of relapse was also provided. Among 70 patients treated, only 16 fulfilled the inclusion criteria. They were treated with a median of 3 prior lines of chemo-immunotherapies, including a median of 2 rituximab-containing regimens; 6 patients had undergone myeloablative chemotherapy with autologous stem cell rescue (ASCT). Overall response rates were 10 (62%) CR/CRu, 3 (19%) PR and 3 (19%) PD; response rates were similar in patients with prior ASCT. After RIT-Z only few patients obtained EFS and TTNT longer than after the last previous therapy. All four patients receiving rituximab maintenance were without progression 12 months after RIT-Z. Relapses occurred in both previously and newly involved sites; a significant association was found between the number of pathologic sites involved prior to RIT-Z and subsequent TTNT. Despite the excellent response rate, the duration of response was shorter than the previous one confirming the known trend of relapses to occur earlier after subsequent treatments. Rituximab maintenance after RIT-Z showed encouraging results in terms of prolonging EFS, warranting further studies. Copyright © 2010 John Wiley &amp; Sons, Ltd.

Generation and characterization of a Notch1 signaling-specific reporter mouse line.

Signaling through the Notch1 receptor is essential for the control of numerous developmental processes during embryonic life as well as in adult tissue homeostasis and disease. Since the outcome of Notch1 signaling is highly context-dependent, and its precise physiological and pathological role in many organs is unclear, it is of great interest to localize and identify the cells that receive active Notch1 signals in vivo. Here, we report the generation and characterization of a BAC-transgenic mouse line, N1-Gal4VP16, that when crossed to a Gal4-responsive reporter mouse line allowed the identification of cells undergoing active Notch1 signaling in vivo. Analysis of embryonic and adult N1-Gal4VP16 mice demonstrated that the activation pattern of the transgene coincides with previously observed activation patterns of the endogenous Notch1 receptor. Thus, this novel reporter mouse line provides a unique tool to specifically investigate the spatial and temporal aspects of Notch1 signaling in vivo. genesis 50:700-710, 2012. © 2012 Wiley Periodicals, Inc.