Stratigraphy and depositional environments of the Three Forks Formation (Upper Devonian), Williston Basin, North Dakota

The Three Forks Formation (Upper Devonian) is present in the subsurface in the western two-thirds of North Dakota and is generally conformable with the underlying Birdbear Formation and the overlying Bakken Formation. The Three Forks attains a maximum thickness of 265 feet (81 meters) in the central basin, east and south of the Nesson Anticline, and thins to an erosional edge in eastern North Dakota. The Three Forks is composed of micrite and dolomicrite, which may be fcssiliferous and argillaceous. From the study of core samples and detailed petrographic analysis of thin sections, five lithofacies were recognized and their extent determined. These lithofacies are: micrite, argillaceous micrite, dolomicrite, argillaceous dolomicrite, and argillaceous biomicrite. Major criteria used in categorization of each lithofacies were fossil biota, sedimentary structures, and other lithologic features. Sedimentation of the Three Forks Formation occurred in an epeiric sea setting. The five lithofacies represent deposition in supralittoral, littoral, and low-energy sublittoral environmen~s. These environments were formed approximately parallel to the periphery of the basin. Of the three energy zones depicted for an epeiric sea depositional setting, the Three Forks is interpreted to have been deposited solely within the most landward, lowest energy zone. Extreme sea level fluctuations and resultant progradations are responsible for the widespread distribution of argillaceous material. Allochthonous material was distributed by wind-generated waves and currents. Repeated transgressions and regressions caused the lateral migration of environments and produced the complex mosaic of lithe, facies. Major diagenetic features within the Three Forks include dolorritization, anhydritization, and calcite recrystallization (neorrorphism). Dolomitization is best accounted for by the evaporative pumping model, which may also have been responsible for anhydrite formation in the supralittoral environment. Eight structural types of anhydrite are present in those rocks interpreted as being deposited in an arid, supralittoral environment. These structural types are: nodular, distorted nodular, bedded nodular, distorted bedded nodular, distorted nodular mosaic, bedded nodular mosaic, distorted mosaic, and bedded massive. Calcite recrystallization involves microspar and pseudospar formation

RIPK3-mediated cell death is involved in DUX4-mediated toxicity in facioscapulohumeral dystrophy

BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is caused by mutations leading to the aberrant expression of the DUX4 transcription factor in muscles. DUX4 was proposed to induce cell death, but the involvement of different death pathways is still discussed. A possible pro-apoptotic role of DUX4 was proposed, but as FSHD muscles are characterized by necrosis and inflammatory infiltrates, non-apoptotic pathways may be also involved. METHODS: We explored DUX4-mediated cell death by focusing on the role of one regulated necrosis pathway called necroptosis, which is regulated by RIPK3. We investigated the effect of necroptosis on cell death in vitro and in vivo experiments using RIPK3 inhibitors and a RIPK3-deficient transgenic mouse model. RESULTS: We showed in vitro that DUX4 expression causes a caspase-independent and RIPK3-mediated cell death in both myoblasts and myotubes. In vivo, RIPK3-deficient animals present improved body and muscle weights, a reduction of the aberrant activation of the DUX4 network genes, and an improvement of muscle histology. CONCLUSIONS: These results provide evidence for a role of RIPK3 in DUX4-mediated cell death and open new avenues of research

Publisher Correction: Necroptosis Mediates Myofibre Death in Dystrophin-deficient Mice

The original version of this article contained an error in Fig. 3. In panel c, the labels 'mdx' and 'mdx Ripk3-/-' were inadvertently inverted. This has now been corrected in the PDF and HTML versions of the Article

A Novel Hepatitis C Virus Genotyping Method Based on Liquid Microarray

The strategy used to treat HCV infection depends on the genotype involved. An accurate and reliable genotyping method is therefore of paramount importance. We describe here, for the first time, the use of a liquid microarray for HCV genotyping. This liquid microarray is based on the 5′UTR — the most highly conserved region of HCV — and the variable region NS5B sequence. The simultaneous genotyping of two regions can be used to confirm findings and should detect inter-genotypic recombination. Plasma samples from 78 patients infected with viruses with genotypes and subtypes determined in the Versant™ HCV Genotype Assay LiPA (version I; Siemens Medical Solutions, Diagnostics Division, Fernwald, Germany) were tested with our new liquid microarray method. This method successfully determined the genotypes of 74 of the 78 samples previously genotyped in the Versant™ HCV Genotype Assay LiPA (74/78, 95%). The concordance between the two methods was 100% for genotype determination (74/74). At the subtype level, all 3a and 2b samples gave identical results with both methods (17/17 and 7/7, respectively). Two 2c samples were correctly identified by microarray, but could only be determined to the genotype level with the Versant™ HCV assay. Genotype “1” subtypes (1a and 1b) were correctly identified by the Versant™ HCV assay and the microarray in 68% and 40% of cases, respectively. No genotype discordance was found for any sample. HCV was successfully genotyped with both methods, and this is of prime importance for treatment planning. Liquid microarray assays may therefore be added to the list of methods suitable for HCV genotyping. It provides comparable results and may readily be adapted for the detection of other viruses frequently co-infecting HCV patients. Liquid array technology is thus a reliable and promising platform for HCV genotyping

Management of trichobezoar: case report and literature review

Trichobezoars (hair ball) are usually located in the stomach, but may extend through the pylorus into the duodenum and small bowel (Rapunzel syndrome). They are almost always associated with trichotillomania and trichophagia or other psychiatric disorders. In the literature several treatment options are proposed, including removal by conventional laparotomy, laparoscopy and endoscopy. We present our experience with four patients and provide a review of the recent literature. According to our experience and in line with the published results, conventional laparotomy is still the treatment of choice. In addition, psychiatric consultation is necessary to prevent relapses

CD4-Independent Human Immunodeficiency Virus Infection Involves Participation of Endocytosis and Cathepsin B

During a comparison of the infectivity of mNDK, a CD4-independent human immunodeficiency virus type 1 (HIV-1) strain, to various cell lines, we found that HeLa cells were much less susceptible than 293T and TE671 cells. Hybridoma cells between HeLa and 293T cells were as susceptible as 293T cells, suggesting that cellular factors enhance the mNDK infection in 293T cells. By screening a cDNA expression library in HeLa cells, cystatin C was isolated as an enhancer of the mNDK infection. Because cathepsin B protease, a natural ligand of cystatin C, was upregulated in HeLa cells, we speculated that the high levels of cathepsin B activities were inhibitory to the CD4-independent infection and that cystatin C enhanced the infection by impairing the excessive cathepsin B activity. Consistent with this idea, pretreatment of HeLa cells with 125 µM of CA-074Me, a cathepsin B inhibitor, resulted in an 8-fold enhancement of the mNDK infectivity. Because cathepsin B is activated by low pH in acidic endosomes, we further examined the potential roles of endosomes in the CD4-independent infection. Suppression of endosome acidification or endocytosis by inhibitors or by an Eps15 dominant negative mutant reduced the infectivity of mNDK in which CD4-dependent infections were not significantly impaired. Taken together, these results suggest that endocytosis, endosomal acidification, and cathepsin B activity are involved in the CD4-independent entry of HIV-1

Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity

Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing cells that lack CD4 have been generated in the laboratory. These CD4-independent HIV-1 variants are sensitive to neutralization by multiple antibodies that recognize different envelope glycoprotein epitopes. The mechanisms underlying CD4 independence, global sensitivity to neutralization and the association between them are still unclear. By studying HIV-1 variants that differ in requirements for CD4, we investigated the contribution of CD4 binding to virus entry. CD4 engagement exposes the coreceptor-binding site and increases the “intrinsic reactivity” of the envelope glycoproteins; intrinsic reactivity describes the propensity of the envelope glycoproteins to negotiate transitions to lower-energy states upon stimulation. Coreceptor-binding site exposure and increased intrinsic reactivity promote formation/exposure of the HR1 coiled coil on the gp41 transmembrane glycoprotein and allow virus entry upon coreceptor binding. Intrinsic reactivity also dictates the global sensitivity of HIV-1 to perturbations such as exposure to cold and the binding of antibodies and small molecules. Accordingly, CD4 independence of HIV-1 was accompanied by increased susceptibility to inactivation by these factors. We investigated the role of intrinsic reactivity in determining the sensitivity of primary HIV-1 isolates to inhibition. Relative to the more common neutralization-resistant (“Tier 2-like”) viruses, globally sensitive (“Tier 1”) viruses exhibited increased intrinsic reactivity, i.e., were inactivated more efficiently by cold exposure or by a given level of antibody binding to the envelope glycoprotein trimer. Virus sensitivity to neutralization was dictated both by the efficiency of inhibitor/antibody binding to the envelope glycoprotein trimer and by envelope glycoprotein reactivity to the inhibitor/antibody binding event. Quantitative differences in intrinsic reactivity contribute to HIV-1 strain variability in global susceptibility to neutralization and explain the long-observed relationship between increased inhibitor sensitivity and decreased entry requirements for target cell CD4