Paleogene time scale miscalibration: Evidence from the dating of the North Atlantic igneous province

Jolley et al. (2002) have proposed that the date of the Paleocene - Eocene thermal maximum is ca. 60 Ma, at least 5 m.y. older than currently estimated and, as a result, argue that the Paleogene time scale of Berggren et al. (1995) is grossly miscalibrated. The implications of this proposal are implausible, and we attribute the discrepancy in age noted by Jolley et al. (2002) to miscorrelation of the Staffa-type palynofloras and ambiguous isotopic dates from the North Atlantic igneous province

State estimation in quantum homodyne tomography with noisy data

In the framework of noisy quantum homodyne tomography with efficiency parameter $0 < \eta \leq 1$, we propose two estimators of a quantum state whose density matrix elements $\rho_{m,n}$ decrease like $e^{-B(m+n)^{r/ 2}}$, for fixed known $B>0$ and $0<r\leq 2$. The first procedure estimates the matrix coefficients by a projection method on the pattern functions (that we introduce here for $0<\eta \leq 1/2$), the second procedure is a kernel estimator of the associated Wigner function. We compute the convergence rates of these estimators, in $\mathbb{L}_2$ risk

Integrated Paleocene calcareous plankton magnetobiochronology and stable isotope stratigraphy: DSDP Site 384 (NW Atlantic Ocean)

At Deep Sea Drilling Site 384 (J-Anomaly Ridge, Grand Banks Continental Rise, NW Atlantic Ocean) Paleocene nannofossil chalks and oozes (∼70 m thick) are unconformably/disconformably underlain (∼168 m; upper Maastrichtian) and overlain (∼98.7 m; upper lower Eocene) by sediments of comparable lithologies. The chalks are more indurated in stratigraphically higher levels of the Paleocene reflecting increasing amounts of biosiliceous (radiolarians and diatoms) components. This site serves as an excellent location for an integrated calcareous and siliceous microfossil zonal stratigraphy and stable isotope stratigraphy. We report the results of a magnetostratigraphic study which, when incorporated with published magnetostratigraphic results, reveals an essentially complete magnetostratigraphic record spanning the interval from Magnetochron C31n (late Maastrichtian) to C25n (partim) (late Paleocene, Thanetian). Integrated magnetobiochronology and stable isotope stratigraphy support the interpretation of, and constrain the estimated duration of, a short hiatus (∼0.9 my) within the younger part of Chron C29r (including the K/P boundary) and an ∼6 my hiatus separating upper Paleocene (Magnetozone C25n) and upper lower Eocene (Magnetozone C22r) sediments. Some 30 planktonic foraminiferal datum levels [including the criteria used to denote the Paleocene planktonic foraminiferal (sub)tropical zonal scheme of Berggren and Miller, Micropaleontology 34 (4) (1988) 362–380 and Berggren et al., SEPM Spec. Publ. 54 (1995) 129–212, Geol. Soc. Am. Bull. 107 (11) (1995) 1272–1287], and nearly two dozen calcareous nannoplankton datum levels have been recognized and calibrated to the magnetochronology. Planktonic foraminiferal Subzones P4a and P4b of (upper Paleocene) Zone P4 are emended/redefined based on the discovery of a longer stratigraphic extension of Acarinina subsphaerica (into at last Magnetozone C25n). Stable isotope stratigraphies from benthic foraminifera and fine fraction (<38 μm) carbonate have been calibrated to the biochronology and magnetostratigraphy. A minimum in benthic foraminifer δ13C was reached near the Danian/Selandian boundary (within Chron C26r, planktonic foraminiferal Zone P3a and calcareous nannoplankton Zone NP4) and is followed by the rise to maximum δ13C values in the late Thanetian (near the base of C25n, in Zone P4c and NP9a, respectively) that can be used for global correlation in the Paleocene

Histopathologic Overlap between Fibrosing Mediastinitis and IgG4-Related Disease

Fibrosing mediastinitis (FM) and IgG4-related disease (IgG4-RD) are two fibroinflammatory disorders with potentially overlapping clinical and radiological features. In this paper, we looked for histopathologic features of IgG4-RD and enumerated infiltrating IgG4-positive plasma cells within mediastinal tissue biopsies from FM patients. We identified 15 consecutive FM surgical mediastinal tissue biopsies between 1985 and 2006. All patients satisfied the clinical and radiological diagnostic criteria for FM. All patients had either serological or radiological evidence of prior histoplasmosis or granulomatous disease, respectively. Formalin-fixed paraffin-embedded tissue sections of all patients were stained for H&E, IgG, and IgG4. Three samples met the predefined diagnostic criteria for IgG4-RD. In addition, characteristic histopathologic changes of IgG4-RD in the absence of diagnostic numbers of tissue infiltrating IgG4-positive plasma cells were seen in a number of additional cases (storiform cell-rich fibrosis in 11 cases, lymphoplasmacytic infiltrate in 7 cases, and obliterative phlebitis/arteritis in 2 cases). We conclude that up to one-third of histoplasmosis or granulomatous-disease-associated FM cases demonstrate histopathological features of IgG4-RD spectrum. Whether these changes occur as the host immune response against Histoplasma or represent a manifestation of IgG4-RD remains to be determined. Studies to prospectively identify these cases and evaluate their therapeutic responses to glucocorticoids and/or other immunosuppressive agents such as rituximab are warranted

Impact of sample acquisition and linear amplification on gene expression profiling of lung adenocarcinoma: laser capture micro-dissection cell-sampling versus bulk tissue-sampling

<p>Abstract</p> <p>Background</p> <p>The methods used for sample selection and processing can have a strong influence on the expression values obtained through microarray profiling. Laser capture microdissection (LCM) provides higher specificity in the selection of target cells compared to traditional bulk tissue selection methods, but at an increased processing cost. The benefit gained from the higher tissue specificity realized through LCM sampling is evaluated in this study through a comparison of microarray expression profiles obtained from same-samples using bulk and LCM processing.</p> <p>Methods</p> <p>Expression data from ten lung adenocarcinoma samples and six adjacent normal samples were acquired using LCM and bulk sampling methods. Expression values were evaluated for correlation between sample processing methods, as well as for bias introduced by the additional linear amplification required for LCM sample profiling.</p> <p>Results</p> <p>The direct comparison of expression values obtained from the bulk and LCM sampled datasets reveals a large number of probesets with significantly varied expression. Many of these variations were shown to be related to bias arising from the process of linear amplification, which is required for LCM sample preparation. A comparison of differentially expressed genes (cancer vs. normal) selected in the bulk and LCM datasets also showed substantial differences. There were more than twice as many down-regulated probesets identified in the LCM data than identified in the bulk data. Controlling for the previously identified amplification bias did not have a substantial impact on the differences identified in the differentially expressed probesets found in the bulk and LCM samples.</p> <p>Conclusion</p> <p>LCM-coupled microarray expression profiling was shown to uniquely identify a large number of differentially expressed probesets not otherwise found using bulk tissue sampling. The information gain realized from the LCM sampling was limited to differential analysis, as the absolute expression values obtained for some probesets using this study's protocol were biased during the second round of amplification. Consequently, LCM may enable investigators to obtain additional information in microarray studies not easily found using bulk tissue samples, but it is of critical importance that potential amplification biases are controlled for.</p

Does the availability of positron emission tomography modify diagnostic strategies for solitary pulmonary nodules? An observational study in France

International audienceBACKGROUND: Previous studies showed that at the individual level, positron emission tomography (PET) has some benefits for patients and physicians in terms of cancer management and staging. We aimed to describe the benefits of (PET) in the management of solitary pulmonary nodules (SPNs) in a population level, in terms of the number of diagnostic and invasive tests performed, time to diagnosis and factors determining PET utilization. METHODS: In an observational study, we examined reports of computed tomography (CT) performed and mentioning "spherical lesion", "nodule" or synonymous terms. We found 11,515 reports in a before-PET period, 2002-2003, and 20,075 in an after-PET period, 2004-2005. Patients were followed through their physician, who was responsible for diagnostic management. RESULTS: We had complete data for 112 patients (73.7%) with new cases of SPN in the before-PET period and 250 (81.4%) in the after-PET period. Patients did not differ in mean age (64.9 vs. 64.8 years). The before-PET patients underwent a mean of 4 tests as compared with 3 tests for the after-PET patients (p = 0.08). Patients in the before-PET period had to wait 41.4 days, on average, before receiving a diagnosis as compared with 24.0 days, on average, for patients in the after-PET period who did not undergo PET (p < 0.001). In the after-PET period, 11% of patients underwent PET during the diagnostic process. A spiculated nodule was more likely to determine prescription for PET (p < 0.001). Multivariate analysis revealed that patients in both periods underwent fewer tests when PET was prescribed by general practitioners (p < 0.001) and if the nodule was not spiculated (p < 0.001). The proportion of unnecessary invasive approaches prescribed (47% vs. 49%) did not differ between the groups. CONCLUSION: In our study, 1 year after the availability of PET, the technology was not the first choice for diagnostic management of SPN. Even though we observed a tendency for reduced number of tests and mean time to diagnosis with PET, these phenomena did not fully relate to PET availability in health communities. In addition, the availability of PET in the management of SPN diagnosis did not reduce the overall rate of unnecessary invasive approaches

The Nlrp3 inflammasome regulates acute graft-versus-host disease

The success of allogeneic hematopoietic cell transplantation is limited by acute graft-versus-host disease (GvHD), a severe complication accompanied by high mortality rates. Yet, the molecular mechanisms initiating this disease remain poorly defined. In this study, we show that, after conditioning therapy, intestinal commensal bacteria and the damage-associated molecular pattern uric acid contribute to Nlrp3 inflammasome-mediated IL-1β production and that gastrointestinal decontamination and uric acid depletion reduced GvHD severity. Early blockade of IL-1β or genetic deficiency of the IL-1 receptor in dendritic cells (DCs) and T cells improved survival. The Nlrp3 inflammasome components Nlrp3 and Asc, which are required for pro-IL-1β cleavage, were critical for the full manifestation of GvHD. In transplanted mice, IL-1β originated from multiple intestinal cell compartments and exerted its effects on DCs and T cells, the latter being preferentially skewed toward Th17. Compatible with these mouse data, increased levels of active caspase-1 and IL-1β were found in circulating leukocytes and intestinal GvHD lesions of patients. Thus, the identification of a crucial role for the Nlrp3 inflammasome sheds new light on the pathogenesis of GvHD and opens a potential new avenue for the targeted therapy of this severe complication

Formation of the Isthmus of Panama

The formation of the Isthmus of Panama stands as one of the greatest natural events of the Cenozoic, driving profound biotic transformations on land and in the oceans. Some recent studies suggest that the Isthmus formed manymillions of years earlier than the widely recognized age of approximately 3 million years ago (Ma), a result that if true would revolutionize our understanding of environmental, ecological, and evolutionary change across the Americas. To bring clarity to the question of when the Isthmus of Panama formed, we provide an exhaustive review and reanalysis of geological, paleontological, and molecular records. These independent lines of evidence converge upon a cohesive narrative of gradually emerging land and constricting seaways,withformationof theIsthmus of Panama sensustricto around 2.8 Ma. The evidence used to support an older isthmus is inconclusive, and we caution against the uncritical acceptance of an isthmus before the Pliocene.Facultad de Ciencias Naturales y Muse

Recruitment of the Major Vault Protein by InlK: A Listeria monocytogenes Strategy to Avoid Autophagy

L. monocytogenes is a facultative intracellular bacterium responsible for listeriosis. It is able to invade, survive and replicate in phagocytic and non-phagocytic cells. The infectious process at the cellular level has been extensively studied and many virulence factors have been identified. Yet, the role of InlK, a member of the internalin family specific to L. monocytogenes, remains unknown. Here, we first show using deletion analysis and in vivo infection, that InlK is a bona fide virulence factor, poorly expressed in vitro and well expressed in vivo, and that it is anchored to the bacterial surface by sortase A. We then demonstrate by a yeast two hybrid screen using InlK as a bait, validated by pulldown experiments and immunofluorescence analysis that intracytosolic bacteria via an interaction with the protein InlK interact with the Major Vault Protein (MVP), the main component of cytoplasmic ribonucleoproteic particules named vaults. Although vaults have been implicated in several cellular processes, their role has remained elusive. Our analysis demonstrates that MVP recruitment disguises intracytosolic bacteria from autophagic recognition, leading to an increased survival rate of InlK over-expressing bacteria compared to InlK− bacteria. Together these results reveal that MVP is hijacked by L. monocytogenes in order to counteract the autophagy process, a finding that could have major implications in deciphering the cellular role of vault particles