Stable oxygen isotope record of the Eocene-Oligocene transition in the southern North Sea Basin: positioning the Oi-1 event

Preliminary stable oxygen isotope data are presented from the southern North Sea Basin successions, ranging from the Lutetian to Rupelian. Analyses were performed on fish otoliths, nuculid bivalves and benthic foraminifera and are presented as bulk delta(18)O values relative to a well established regional sequence stratigraphic framework. The most significant positive shift in delta(18)O values clearly falls at the top of the regionally recognised Bassevelde 3 sequence, which base corresponds to the Eocene-Oligocene GSSP boundary. The here documented delta(18)O shift is closely associated with the base of the traditional Rupelian unit-stratotype and is tentatively correlated to the globally recognised Oi-1 event

CX3CR1+ Cell–Mediated Salmonella Exclusion Protects the Intestinal Mucosa during the Initial Stage of Infection

During Salmonella Typhimurium infection, intestinal CX3CR1(+) cells can either extend transepithelial cellular processes to sample luminal bacteria or, very early after infection, migrate into the intestinal lumen to capture bacteria. However, until now, the biological relevance of the intraluminal migration of CX3CR1(+) cells remained to be determined. We addressed this by using a combination of mouse strains differing in their ability to carry out CX3CR1-mediated sampling and intraluminal migration. We observed that the number of S. Typhimurium traversing the epithelium did not differ between sampling-competent/migration-competent C57BL/6 and sampling-deficient/migration-competent BALB/c mice. In contrast, in sampling-deficient/migration-deficient CX3CR1(-/-) mice the numbers of S. Typhimurium penetrating the epithelium were significantly higher. However, in these mice the number of invading S. Typhimurium was significantly reduced after the adoptive transfer of CX3CR1(+) cells directly into the intestinal lumen, consistent with intraluminal CX3CR1(+) cells preventing S. Typhimurium from infecting the host. This interpretation was also supported by a higher bacterial fecal load in CX3CR1(+/gfp) compared with CX3CR1(gfp/gfp) mice following oral infection. Furthermore, by using real-time in vivo imaging we observed that CX3CR1(+) cells migrated into the lumen moving through paracellular channels within the epithelium. Also, we reported that the absence of CX3CR1-mediated sampling did not affect Ab responses to a noninvasive S. Typhimurium strain that specifically targeted the CX3CR1-mediated entry route. These data showed that the rapidly deployed CX3CR1(+) cell-based mechanism of immune exclusion is a defense mechanism against pathogens that complements the mucous and secretory IgA Ab-mediated system in the protection of intestinal mucosal surface

The pandemic of online research in times of COVID-19

The COVID-19 pandemic has led to an explosion of online research using rating scales. While this approach can be useful, two of the major challenges affecting the quality of this type of research include selection bias and the use of non-validated scales. Online research is prone to various forms of selection bias, including self-selection bias, non-response bias or only reaching specific subgroups. The use of rating scales requires contextually validated scales that meet psychometrical properties such as validity, reliability and - for cross-country comparisons - invariance across settings. We discuss options to prevent or tackle these challenges. Researchers, readers, editors and reviewers need to take a critical stance towards research using this type of methodology

Individualization of Irinotecan Treatment: A Review of Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics

Since its clinical introduction in 1998, the topoisomerase I inhibitor irinotecan has been widely used in the treatment of solid tumors, including colorectal, pancreatic, and lung cancer. Irinotecan therapy is characterized by several dose-limiting toxicities and large interindividual pharmacokinetic variability. Irinotecan has a highly complex metabolism, including hydrolyzation by carboxylesterases to its active metabolite SN-38, which is 100- to 1000-fold more active compared with irinotecan itself. Several phase I and II enzymes, including cytochrome P450 (CYP) 3A4 and uridine diphosphate glucuronosyltransferase (UGT) 1A, are involved in the formation of inactive metabolites, making its metabolism prone to environmental and genetic influences. Genetic variants in the DNA of these enzymes and transporters coul

Bilateral exostoses of the internal auditory canal

A 54-year-old female patient presented to her physician with a 3-year-old history of bilateral tinnitus and hearing loss. She also complained of paresthesia in the periauricular area. There were no episodes of imbalance or vertigo

The structures and total (minor + major) merger histories of massive galaxies up to z = 3 in the HST GOODS NICMOS Survey: A possible solution to the size evolution problem

We investigate the total major (> 1:4 by stellar mass) and minor (> 1:100 by stellar mass) merger history of a population of 80 massive (M_* > 10^11 M_sol) galaxies at high redshifts (z = 1.7 - 3). We utilize extremely deep and high resolution HST H-band imaging from the GOODS NICMOS Survey (GNS), which corresponds to rest-frame optical wavelengths at the redshifts probed. We find that massive galaxies at high redshifts are often morphologically disturbed, with a CAS deduced merger fraction f_m = 0.23 +/- 0.05 at z = 1.7 - 3. We find close accord between close pair methods (within 30 kpc apertures) and CAS methods for deducing major merger fractions at all redshifts. We deduce the total (minor + major) merger history of massive galaxies with M_* > 10^9 M_sol galaxies, and find that this scales roughly linearly with log-stellar-mass and magnitude range. We test our close pair methods by utilizing mock galaxy catalogs from the Millennium Simulation. We compute the total number of mergers to be (4.5 +/- 2.9) / from z = 3 to the present, to a stellar mass sensitivity threshold of ~ 1:100 (where \tau_m is the merger timescale in Gyr which varies as a function of mass). This corresponds to an average mass increase of (3.4 +/- 2.2) x 10^11 M_sol over the past 11.5 Gyrs due to merging. We show that the size evolution observed for these galaxies may be mostly explained by this merging.Comment: 19 pages, 10 figures, re-submitted to ApJ after a positive referee report, originally submitted on Sept 20 201

Casimir-like effect on a granular pile

We investigate experimentally a Casimir-like effect in a three-dimensional pile of rice, which has a power-law avalanche size distribution. We observe the change in distance between two Plexiglas sheets placed on the pile parallel to each other and parallel to the mean avalanche flow direction, while rice grains are continuously and uniformly falling on top of the pile. The resulting avalanches are fluctuations, confinement of which is found to drive the two plates together. During 25-h experimental runs, for initial intersheet distances ranging from 20.0 to 90.0 mm we observe changes in the range from 6.0 mm to less than 1.0 mm. A similar distance dependence is obtained from a simple analytical model. © 2010 The American Physical Society

Interferon-alpha treatment rapidly clears Hepatitis e virus infection in humanized mice

Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals. Rapid viral clearance by pegIFNα was confirmed in HEV gt1, but not in Hepatitis B Virus infected animals. No ISG induction was observed in untreated HEV gt3 and gt1 infected humanized livers compared to control chimeric mice, irrespective of the human hepatocyte donor, viral isolate or HEV infection duration. Human specific ISG transcript levels in mouse liver increased significantly after pegIFNα treatment and induced high circulating human CXCL10 in mouse serum. In conclusion, HEV gt1 and gt3 infections do not elicit innate intrahepatic immune responses and remain highly sensitive to pegIFNα in immunocompromised humanized mice

LLL 44-4 : Micronutrients in acute disease and critical illness.

Micronutrients (MN), i.e. trace elements and vitamins, are essential components of the diet in relatively small amounts in any form of nutrition, with special needs in critically ill patients. Critical illness is characterised by the presence of inflammation and oxidative stress. MNs are tightly involved in antioxidant and immune defences. In addition, some conditions, and treatments result in large losses of biological fluids containing MNs: therefore, acute renal injury requiring renal replacement therapy, acute intestinal failure, and major burns and trauma are at high risk of acute depletion of body stores, and of deficiency. MN requirements are increased above standard DRI. Blood level interpretation is complicated by inflammation: some biomarkers assist the status determination. Due to the acute challenges of critical illness, it of utmost importance to cover the needs to maintain the organism's endogenous immune and antioxidant defences, and capacity to repair tissues. Practical strategies are proposed