Biostratigraphy of Middle and Late Pennsylvanian (Desmoinesian-Virgilian) ammonoids

New stratigraphic ranges for genera of Desmoinesian-Virgilian ammonoids are presented, based on analysis of 40,000 specimens collected from over 70 ammonoid-bearing horizons that represent at least 40 successive stratigraphic levels in the North American midcontinent. These range revisions indicate that current generic-level ammonoid zonations are inadequate, especially for correlation of Pennsylvanian series and stage boundaries. Six high-confidence, largely generic-level first-occurrence zones are proposed for the Desmoinesian through Virgilian stages: Wellerites Zone, Eothalassoceras Zone, Pennoceras Zone, Preshumardites Zone, Pseudaktubites Zone, and Shumardites Zone. Fifteen zones of lesser confidence for correlation are also suggested. The Shumarditidae Plummer & Scott, 1937, is emended to include Preshumardites Plummer & Scott, 1937, Pseudaktubites gen. nov. (type species, Preshumardites stainbrooki Plummer & Scott, 1937), and Shumardites Smith, 1903. Early Permian (Sakmarian) species previously assigned to Preshumardites are reassigned to Andrianovia gen. nov. (type species ?Preshumardites sakmarae Ruzhencev, 1938). Aktubites Ruzhencev, 1955, Eoshumardites Popov, 1960, and Parashumardites Ruzhencev, 1939, previously included in the Shumarditidae, are assigned to the new family Parashumarditidae. Eovidrioceras inexpectans gen. nov., sp. nov. is included and is interpreted as the ancestor of the cyclobacean family Vidrioceratidae Plummer & Scott, 1937. The base of the revised Wellerites Zone, defined by the first occurrence of the nominate genus, approximates but does not coincide with the Atokan-Desmoinesian boundary. Recorrelation of the stratigraphic level of the Collinsville, Oklahoma, ammonoid locality from the "Seminole Formation" (basal Missourian) to the Holdenville Formation (upper Desmoinesian), based on lithostratigraphic evidence, effectively places the first occurrence of Eothalassoceras in the upper Desmoinesian. Because Wellerites apparently became extinct before the end of the Desmoinesian, the revised Eothalassoceras Zone is used to represent the upper Desmoinesian. The Middle-Upper Pennsylvanian boundary (Desmoinesian-Missourian boundary) can be recognized by the appearance of Pennoceras, which defines the base of the new Pennoceras Zone. The Pennoceras Zone is an excellent indicator of lower Missourian strata in the northern midcontinent, north-central Texas, the Marathon Uplift, and the Appalachian Basin. The new Preshumardites Zone occupies most of the upper part of the Missourian Stage. The appearance of the ancestral shumarditid Pseudaktubites, which defines the base of the new Pseudaktubites Zone, occurs one cycle below the Missourian-Virgilian boundary, which is currently recognized at the top of the South Bend Limestone Member in eastern Kansas. No recognizable biostratigraphic event coincides with the South Bend Member, thereby resulting in an uncorrelatable chronostratigraphic boundary. The largest changeover in ammonoid faunas takes place at the base of strata containing the upper part of the Pseudaktubites Zone (Pseudaktubites stainbrooki Subzone). The base of the Pseudaktubites stainbrooki Subzone is stratigraphically near the original Missourian-Virgilian boundary. It is recommended that the stratigraphic level containing the base of the Pseudaktubites stainbrooki Subzone be adopted as the official base of the Virgilian Stage. Recognition of the upper subzone of the Pseudaktubites Zone (Pseudaktubites stainbrooki Subzone) within the Colony Creek Shale Member in north-central Texas places the base of the Virgilian within the upper part of the Canyon Group and substantially below the current position at the Canyon-Cisco group boundary. Shumardites, a taxon previously used to mark the base of the Virgilian Stage, appears in early middle Virgilian strata; consequently, the revised Shumardites Zone represents the middle-upper Virgilian interval

Biostratigraphy of Middle and Late Pennsylvanian (Desmoinesian-Virgilian) ammonoids

New stratigraphic ranges for genera of Desmoinesian-Virgilian ammonoids are presented, based on analysis of 40,000 specimens collected from over 70 ammonoid-bearing horizons that represent at least 40 successive stratigraphic levels in the North American midcontinent. These range revisions indicate that current generic-level ammonoid zonations are inadequate, especially for correlation of Pennsylvanian series and stage boundaries. Six high-confidence, largely generic-level first-occurrence zones are proposed for the Desmoinesian through Virgilian stages: Wellerites Zone, Eothalassoceras Zone, Pennoceras Zone, Preshumardites Zone, Pseudaktubites Zone, and Shumardites Zone. Fifteen zones of lesser confidence for correlation are also suggested. The Shumarditidae Plummer & Scott, 1937, is emended to include Preshumardites Plummer & Scott, 1937, Pseudaktubites gen. nov. (type species, Preshumardites stainbrooki Plummer & Scott, 1937), and Shumardites Smith, 1903. Early Permian (Sakmarian) species previously assigned to Preshumardites are reassigned to Andrianovia gen. nov. (type species ?Preshumardites sakmarae Ruzhencev, 1938). Aktubites Ruzhencev, 1955, Eoshumardites Popov, 1960, and Parashumardites Ruzhencev, 1939, previously included in the Shumarditidae, are assigned to the new family Parashumarditidae. Eovidrioceras inexpectans gen. nov., sp. nov. is included and is interpreted as the ancestor of the cyclobacean family Vidrioceratidae Plummer & Scott, 1937. The base of the revised Wellerites Zone, defined by the first occurrence of the nominate genus, approximates but does not coincide with the Atokan-Desmoinesian boundary. Recorrelation of the stratigraphic level of the Collinsville, Oklahoma, ammonoid locality from the "Seminole Formation" (basal Missourian) to the Holdenville Formation (upper Desmoinesian), based on lithostratigraphic evidence, effectively places the first occurrence of Eothalassoceras in the upper Desmoinesian. Because Wellerites apparently became extinct before the end of the Desmoinesian, the revised Eothalassoceras Zone is used to represent the upper Desmoinesian. The Middle-Upper Pennsylvanian boundary (Desmoinesian-Missourian boundary) can be recognized by the appearance of Pennoceras, which defines the base of the new Pennoceras Zone. The Pennoceras Zone is an excellent indicator of lower Missourian strata in the northern midcontinent, north-central Texas, the Marathon Uplift, and the Appalachian Basin. The new Preshumardites Zone occupies most of the upper part of the Missourian Stage. The appearance of the ancestral shumarditid Pseudaktubites, which defines the base of the new Pseudaktubites Zone, occurs one cycle below the Missourian-Virgilian boundary, which is currently recognized at the top of the South Bend Limestone Member in eastern Kansas. No recognizable biostratigraphic event coincides with the South Bend Member, thereby resulting in an uncorrelatable chronostratigraphic boundary. The largest changeover in ammonoid faunas takes place at the base of strata containing the upper part of the Pseudaktubites Zone (Pseudaktubites stainbrooki Subzone). The base of the Pseudaktubites stainbrooki Subzone is stratigraphically near the original Missourian-Virgilian boundary. It is recommended that the stratigraphic level containing the base of the Pseudaktubites stainbrooki Subzone be adopted as the official base of the Virgilian Stage. Recognition of the upper subzone of the Pseudaktubites Zone (Pseudaktubites stainbrooki Subzone) within the Colony Creek Shale Member in north-central Texas places the base of the Virgilian within the upper part of the Canyon Group and substantially below the current position at the Canyon-Cisco group boundary. Shumardites, a taxon previously used to mark the base of the Virgilian Stage, appears in early middle Virgilian strata; consequently, the revised Shumardites Zone represents the middle-upper Virgilian interval

Validation of a Blood-Based Laboratory Test to Aid in the Confirmation of a Diagnosis of Schizophrenia

We describe the validation of a serum-based test developed by Rules-Based Medicine which can be used to help confirm the diagnosis of schizophrenia. In preliminary studies using multiplex immunoassay profiling technology, we identified a disease signature comprised of 51 analytes which could distinguish schizophrenia (n = 250) from control (n = 230) subjects. In the next stage, these analytes were developed as a refined 51-plex immunoassay panel for validation using a large independent cohort of schizophrenia (n = 577) and control (n = 229) subjects. The resulting test yielded an overall sensitivity of 83% and specificity of 83% with a receiver operating characteristic area under the curve (ROC-AUC) of 89%. These 51 immunoassays and the associated decision rule delivered a sensitive and specific prediction for the presence of schizophrenia in patients compared to matched healthy controls

Caenorhabditis elegans Myotubularin MTM-1 Negatively Regulates the Engulfment of Apoptotic Cells

During programmed cell death, apoptotic cells are recognized and rapidly engulfed by phagocytes. Although a number of genes have been identified that promote cell corpse engulfment, it is not well understood how phagocytosis of apoptotic cells is negatively regulated. Here we have identified Caenorhabditis elegans myotubularin MTM-1 as a negative regulator of cell corpse engulfment. Myotubularins (MTMs) constitute a large, highly conserved family of lipid phosphatases. MTM gene mutations are associated with various human diseases, but the cellular functions of MTM proteins are not clearly defined. We found that inactivation of MTM-1 caused significant reduction in cell corpses in strong loss-of-function mutants of ced-1, ced-6, ced-7, and ced-2, but not in animals deficient in the ced-5, ced-12, or ced-10 genes. In contrast, overexpression of MTM-1 resulted in accumulation of cell corpses. This effect is dependent on the lipid phosphatase activity of MTM-1. We show that loss of mtm-1 function accelerates the clearance of cell corpses by promoting their internalization. Importantly, the reduction of cell corpses caused by mtm-1 RNAi not only requires the activities of CED-5, CED-12, and CED-10, but also needs the functions of the phosphatidylinositol 3-kinases (PI3Ks) VPS-34 and PIKI-1. We found that MTM-1 localizes to the plasma membrane in several known engulfing cell types and may modulate the level of phosphatidylinositol 3-phosphate (PtdIns(3)P) in vivo. We propose that MTM-1 negatively regulates cell corpse engulfment through the CED-5/CED-12/CED-10 module by dephosphorylating PtdIns(3)P on the plasma membrane

Estimating error rates for single molecule protein sequencing experiments.

The practical application of new single molecule protein sequencing (SMPS) technologies requires accurate estimates of their associated sequencing error rates. Here, we describe the development and application of two distinct parameter estimation methods for analyzing SMPS reads produced by fluorosequencing. A Hidden Markov Model (HMM) based approach, extends whatprot, where we previously used HMMs for SMPS peptide-read matching. This extension offers a principled approach for estimating key parameters for fluorosequencing experiments, including missed amino acid cleavages, dye loss, and peptide detachment. Specifically, we adapted the Baum-Welch algorithm, a standard technique to estimate transition probabilities for an HMM using expectation maximization, but modified here to estimate a small number of parameter values directly rather than estimating every transition probability independently. We demonstrate a high degree of accuracy on simulated data, but on experimental datasets, we observed that the model needed to be augmented with an additional error type, N-terminal blocking. This, in combination with data pre-processing, results in reasonable parameterizations of experimental datasets that agree with controlled experimental perturbations. A second independent implementation using a hybrid of DIRECT and Powell's method to reduce the root mean squared error (RMSE) between simulations and the real dataset was also developed. We compare these methods on both simulated and real data, finding that our Baum-Welch based approach outperforms DIRECT and Powell's method by most, but not all, criteria. Although some discrepancies between the results exist, we also find that both approaches provide similar error rate estimates from experimental single molecule fluorosequencing datasets

Cryo-EM structure of OSCA1.2 from Oryza sativa elucidates the mechanical basis of potential membrane hyperosmolality gating

Sensing and responding to environmental water deficiency and osmotic stresses are essential for the growth, development, and survival of plants. Recently, an osmolality-sensing ion channel called OSCA1 was discovered that functions in sensing hyperosmolality in Arabidopsis Here, we report the cryo-electron microscopy (cryo-EM) structure and function of an OSCA1 homolog from rice (Oryza sativa; OsOSCA1.2), leading to a model of how it could mediate hyperosmolality sensing and transport pathway gating. The structure reveals a dimer; the molecular architecture of each subunit consists of 11 transmembrane (TM) helices and a cytosolic soluble domain that has homology to RNA recognition proteins. The TM domain is structurally related to the TMEM16 family of calcium-dependent ion channels and lipid scramblases. The cytosolic soluble domain possesses a distinct structural feature in the form of extended intracellular helical arms that are parallel to the plasma membrane. These helical arms are well positioned to potentially sense lateral tension on the inner leaflet of the lipid bilayer caused by changes in turgor pressure. Computational dynamic analysis suggests how this domain couples to the TM portion of the molecule to open a transport pathway. Hydrogen/deuterium exchange mass spectrometry (HDXMS) experimentally confirms the conformational dynamics of these coupled domains. These studies provide a framework to understand the structural basis of proposed hyperosmolality sensing in a staple crop plant, extend our knowledge of the anoctamin superfamily important for plants and fungi, and provide a structural mechanism for potentially translating membrane stress to transport regulation