The foraminiferids of the Cannonball Formation (Paleocene, Danian) and their paleoenvironmental significance : Grant, Morton and Oliver counties, North Dakota

Two hundred-forty samples (of which fifty-five contained micro fossils) were collected from six measured sections in the Cannonball Formation (Paleocene, Danian) in Grant, Morton and Oliver Counties, North Dakota. Twenty-six species of benthonic foraminiferids were identified from these samples: 6 textulariines, 2 miliolines and 18 rotaliines. No planktonic foraminiferids were found. The fauna is characterized by a predominance of individuals of textulariines, especially the lituolids. Although the Cannonball Formation is characterized by an alternating sequence of sandstones and mudstones\u3e the foraminiferid fauna was restricted to the mudstone facies in the upper and upper-middle part of the formation. Two characteristic assemblages based on dominant families and genera are recognized, the lituolid (dominantly arenaceous) and nodosari.id (dominantly calcareous) assemblage. R-mode cluster analysis shows three distinct clusters of species: one corresponds to the lituolid assemblages, another corresponds to the nodosariid assemblage, and the third is composed of species that are represented only rarely in the fora miniferid fauna. The. Q-mode cluster analysis shows a high level of correlation between two lithologic units in two widely separated stratigraphic sections; other foraminiferid correlations were not possible because of the sparse occurrence of foraminiferids in other stratigraphic sections. The two assemblage, the dominance of arenaceous forms, the absence of planktonic forms and the occurrence of the mic:rofauna in the mudstone facies suggests nearshora, shallow (less than 100 m), possibly cooler, protected environments such as shallow bays behind barrier islands. The dominance of textulariines in the sediments is indicative of lower than normal marine salinity

Foraminiferids of the Cannonball Formation (Paleocene, Danian) in western North Dakota

In 1974 and 1975 about 2800 samples (of which 265 contained foram iniferids) of the Cannonball Formation were collected from 60 water test wells and two oil wells in Adams, Bowman, Burleigh, Divide, Dunn, Grant, Mercer, Morton, Oliver, Sioux, and Ward Counties in western North Dakota. Fifty species of benthonic foraminiferids and four species of planktonic foraminiferids were identified including eight textulariines, two milio lines and 44 rotaliines. Taxa reported for the first time from the Can nonball include: Reophax sp. (2 species), Am:mobaculites expansus Plummer, Spiroplectammina wilcoxensis Cushman and Ponton, Quinqueloculina plummerae Cushman and Todd, Dentalina eocenica Cushman, Lenticulina alabamensis (Cushman), L. ark.ansasana (Cushman and Todd), L. turbinata (Plummer), Lingulina sp., Spirobolivina emmendorferi (Jennings), Rosalina sp., Pararotalia perclara.(Loeblich and Tappan), Fursenkoina sp., Caucasina marylandica (Nogan), Nonion graniferum (Terquem), Pullenia quinqueloba (Reuss), and Anomalinoides umboniferus Schwager. A total of 93 species, including those I collected, has been reported from the Cannonball. The foraminiferid fauna occurs commonly in the mudstone lithofacies and rarely in the sandstone lithofacies in the lower to lower upper Cannon ball. Two foraminiferid assemblages are recognized from R-mode cluster analysis, the Caucasina-Bulimina and Cibicidoides-Ceratobulimina assem blages. Little lateral and vertical continuity in the assemblages suggests strong environmental control and mixing during well drilling. The presence of Globorotalia pseudobulloides and Globoconusa duabjergensis in my samples suggests that the Cannonball is Danian (earliest Paleocene). The shallow-water affinities of the foraminiferid assemblages and small size and scarcity of planktonic foraminiferids suggest deposition in water depths of 100 m or less. The dominance of textulariines, including Ammobaculites, in western Adams and eastern Bowman Counties, indicates brackish-water environments in that area. A large, shallow, protected lagoon west of a north-trending barrier island chain is envisioned as a possible complex of depositional environments for the Cannonball. Brackish-water environments are thought to have occurred on the landward side of the lagoon with normal marine environments near the seaward side of the lagoon

A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Since 1999, patients presenting with brain metastases (BM) from breast cancer (BC) are treated in our institution with a carmustine (BCNU) - methotrexate (MTX) combination. We report here our clinical experience regarding this combination.</p> <p>Patients and Methods</p> <p>Patients were treated by a combination of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 day cycle. Treatment was continued until progression or unacceptable toxicity.</p> <p>Results</p> <p>50 patients were treated between 1999 and 2007. 94% of the patients presented with concomitant extra-cerebral disease. Median number of previous metastatic setting chemotherapy regimens was 2 (0-5). Median number of cycles was 3 (1-20). There were 11 objective responses (23% [95%CI 12-37]) among 48 evaluable patients. Median progression-free survival and overall survival (OS) were 4.2 (95%CI: 2.8-5.3) and 6.9 (4.2-10.7) months respectively, with a one-year OS rate of 32% (20-46). Median Relative Dose Intensity for BCNU and MTX were 0.98 (0.31-1.1) and 0.96 (0.57-1.66) respectively. There were 2 presumed treatment-related deaths. One patient developed febrile neutropenia. Performance status, BS-BM score and presence of liver metastases were associated with OS in univariate analysis.</p> <p>Conclusions</p> <p>This combination appears to be effective and well tolerated in good performance status BC patients presenting with BM.</p

Tuberculosis in Pediatric Antiretroviral Therapy Programs in Low- and Middle-Income Countries: Diagnosis and Screening Practices

Background The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. Methods We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study. Results Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children. Conclusions Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected childre

A Selectable and Excisable Marker System for the Rapid Creation of Recombinant Poxviruses

Genetic manipulation of poxvirus genomes through attenuation, or insertion of therapeutic genes has led to a number of vector candidates for the treatment of a variety of human diseases. The development of recombinant poxviruses often involves the genomic insertion of a selectable marker for purification and selection purposes. The use of marker genes however inevitably results in a vector that contains unwanted genetic information of no therapeutic value.Here we describe an improved strategy that allows for the creation of marker-free recombinant poxviruses of any species. The Selectable and Excisable Marker (SEM) system incorporates a unique fusion marker gene for the efficient selection of poxvirus recombinants and the Cre/loxP system to facilitate the subsequent removal of the marker. We have defined and characterized this new methodological tool by insertion of a foreign gene into vaccinia virus, with the subsequent removal of the selectable marker. We then analyzed the importance of loxP orientation during Cre recombination, and show that the SEM system can be used to introduce site-specific deletions or inversions into the viral genome. Finally, we demonstrate that the SEM strategy is amenable to other poxviruses, as demonstrated here with the creation of an ectromelia virus recombinant lacking the EVM002 gene.The system described here thus provides a faster, simpler and more efficient means to create clinic-ready recombinant poxviruses for therapeutic gene therapy applications

Multiple Phosphatidylinositol 3-Kinases Regulate Vaccinia Virus Morphogenesis

Poxvirus morphogenesis is a complex process that involves the successive wrapping of the virus in host cell membranes. We screened by plaque assay a focused library of kinase inhibitors for those that caused a reduction in viral growth and identified several compounds that selectively inhibit phosphatidylinositol 3-kinase (PI3K). Previous studies demonstrated that PI3Ks mediate poxviral entry. Using growth curves and electron microscopy in conjunction with inhibitors, we show that that PI3Ks additionally regulate morphogenesis at two distinct steps: immature to mature virion (IMV) transition, and IMV envelopment to form intracellular enveloped virions (IEV). Cells derived from animals lacking the p85 regulatory subunit of Type I PI3Ks (p85α−/−β−/−) presented phenotypes similar to those observed with PI3K inhibitors. In addition, VV appear to redundantly use PI3Ks, as PI3K inhibitors further reduce plaque size and number in p85α−/−β−/− cells. Together, these data provide evidence for a novel regulatory mechanism for virion morphogenesis involving phosphatidylinositol dynamics and may represent a new therapeutic target to contain poxviruses

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity