Efficiency in Collecting Fossils

Two hundred seventy-two kilograms of sediments and fossils were collected from 1 meter square plots on lake beach and river gravel bars to compare the efficiency of surface collecting with that of intensive laboratory processing. Collecting fossils by visual inspection of the outcrop required an average of 14 minutes 56 seconds per square meter and resulted in 319 vertebrate and 1320 invertebrate fossils. The ratio of time spent collecting and processing sediments to time spent in surface collecting fossils was 4.66:1. The ratio of invertebrates produced by the intensive laboratory process to invertebrates produced by surface collecting was 4.80:1. Vertebrate fossils produced by the intensive process amounted to only 0.91 of the amount collected on the surface. Surface collecting is, therefore, the more efficient collecting method, particularly for vertebrate fossils

Pleistocene Mammals from the South Sulphur River, Hunt County, Texas

Preliminary collecting and excavating along the South Sulphur River has produced a diverse list of fossil mammals. The pampathere, Holmesina septentrionalis, and the large armadillo, Dasypus bellus, with their southern affinities from the extinct megafauna, were found in association with Microtus pennsylvanicus, which has a northern distribution at present. This combination of species argues for climatic conditions and biotic communities during the Pleistocene that have no modern counterparts

Novel cell adhesion/migration pathways are predictive markers of HDAC inhibitor resistance in cutaneous T cell lymphoma

BACKGROUND: Treatment for Cutaneous T Cell Lymphoma (CTCL) is generally not curative. Therefore, selecting therapy that is effective and tolerable is critical to clinical decision-making. Histone deacetylase inhibitors (HDACi), epigenetic modifier drugs, are commonly used but effective in only ~30% of patients. There are no predictive markers of HDACi response and the CTCL histone acetylation landscape remains unmapped. We sought to identify pre-treatment molecular markers of resistance in CTCL that progressed on HDACi therapy. METHODS: Purified T cells from 39 pre/post-treatment peripheral blood samples and skin biopsies from 20 patients were subjected to RNA-seq and ChIP-seq for histone acetylation marks (H3K14/9 ac, H3K27ac). We correlated significant differences in histone acetylation with gene expression in HDACi-resistant/sensitive CTCL. We extended these findings in additional CTCL patient cohorts (RNA-seq, microarray) and using ELISA in matched CTCL patient plasma. FINDINGS: Resistant CTCL exhibited high levels of histone acetylation, which correlated with increased expression of 338 genes (FDR \u3c 0·05), including some novel to CTCL: BIRC5 (anti-apoptotic); RRM2 (cell cycle); TXNDC5, GSTM1 (redox); and CXCR4, LAIR2 (cell adhesion/migration). Several of these, including LAIR2, were elevated pre-treatment in HDACi-resistant CTCL. In CTCL patient plasma (n = 6), LAIR2 protein was also elevated (p \u3c 0·01) compared to controls. INTERPRETATION: This study is the first to connect genome-wide differences in chromatin acetylation and gene expression to HDACi-resistance in primary CTCL. Our results identify novel markers with high pre-treatment expression, such as LAIR2, as potential prognostic and/or predictors of HDACi-resistance in CTCL. FUNDING: NIH:CA156690, CA188286; NCATS: WU-ICTS UL1 TR000448; Siteman Cancer Center: CA091842

Study and characterization of a novel small heat shock protein from Babesia

Many proteins can easily attain a non-native fold and be of no use or even a detriment to the host. The host cell has a myriad of molecules dedicated to assisting nascent and existing proteins in folding properly and maintaining the native fold. Of these molecular chaperones, the small Heat Shock Proteins (sHSP’s) are an important group and worthy of study. The sHSP’s are a diverse group of proteins that have in common an a-crystallin domain and generally display a chaperone activity. A sHSP (HSP20) isolated from the cattle parasite Babesia bovis has similar activities, and limited sequence homology to other a-crystallins. The gene encoding HSP20 was cloned into an expression system where the gene product was induced and purified for study. It was shown that HSP20 inhibits thermally induced aggregation of alcohol dehydrogenase at equimolar ratios. HSP20 was also used to significantly reduce amyloid formation of the b-Amyloid (1-40) Peptide in vitro at the sub-stoichiometric ratio of 1:10. A study of the oligomeric forms of HSP20 using size exclusion chromatography and gel electrophoresis revealed a broad range of multimers present in solution. The distribution of oligomers was affected by altering the solution conditions and concentration of the protein. The domains responsible for multimerization of HSP20 were mapped via sequence homology with known a-crystallins. These regions correspond to 12 carboxy-terminal amino acids and 50 amino-terminal amino acids. Truncated versions of HSP20 lacking these proposed oligomerization domains were created using PCR of the original gene and cloning into an expression vector as before. Using size exclusion chromatography, gel electrophoresis and analytical centrifugation, we show that the deleted domains alter the multimeric population of the protein in solution. The carboxy-terminal domain has a slight effect on multimerization while the amino-terminal deletion results in a drastic reduction in any multimers above a dimer under the conditions tested. Despite this drastic change in the multimerization of HSP20, there were no changes in the activities observed when compared to the full-length form. From this we conclude that the regions responsible for multimerization play little role in the observed activities of HSP20

Influence of Actinomycin D on the Synthesis of Protocatechuate Oxygenase in Pseudomonas Fluorescens

Microbiolog

An evidence-based framework for priority clinical research questions for COVID-19

Background On 31 December, 2019, the World Health Organization China Country Office was informed of cases of pneumonia of unknown aetiology. Since then, there have been over 75000 cases globally of the 2019 novel coronavirus (COVID-19), 2000 deaths, and over 14000 cases recovered. Outbreaks of novel agents represent opportunities for clinical research to inform real-time public health action. In 2018, we conducted a systematic review to identify priority research questions for Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-related coronavirus (MERS-CoV). Here, we review information available on COVID-19 and provide an evidenced-based framework for priority clinical research in the current outbreak. Methods Three bibliographic databases were searched to identify clinical studies published on SARS-CoV and MERS-CoV in the outbreak setting. Studies were grouped thematically according to clinical research questions addressed. In February 2020, available information on COVID19 was reviewed and compared to the results of the SARS-CoV and MERS-CoV systematic review. Results From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. For COVID19, some information on clinical presentation, diagnostic testing, and aetiology is available but many clinical research gaps have yet to be filled. Conclusions Based on a systematic review of other severe coronaviruses, we summarise the state of clinical research for COVID-19, highlight the research gaps, and provide recommendations for the implementation of standardised protocols. Databased on internationally standardised protocols will inform clinical practice real-time