Structural Geology of the Northeast Quarter of the Dutchman Butte Quadrangle, Southwest Oregon

The northeast quarter of the Dutchman Butte quadrangle straddles the boundary of the Mesozoic Klamath Mountains province and the Tertiary Coast Range province. The boundary in this area is controlled by a major easttrending fault zone, herein named the Canyonville fault zone. Jurassic Rogue, Dothan, and Otter Point Formations have been offset right-laterally at least 40 kilometers. In latest Jurassic and early Cretaceous time, the fault zone formed the shoreline along which sediments of the Myrtle Group were deposited. Movement on the Canyonville fault zone becale down-to-the-north in Eocene time forming the southern margin of the Eocene Coast Range basin. Rocks of the lower to middle Eocene Roseburg and Lookingglass Formations thin and pinch-out, and become shallow marine to nonmarine in character southward across the fault zone. Fault movement decreased in Lookingglass time, and essentially ceased by Tyee (middle Eocene) time. Eocene structures in the thesis area formed contemporaneously with sedimentation; individual structures controlled and were controlled by the stratigraphy of the Eocene units

Production of High Amounts of Hepatotoxin Nodularin and New Protease Inhibitors Pseudospumigins by the Brazilian Benthic Nostoc sp CENA543

Nostoc is a cyanobacterial genus, common in soils and a prolific producer of natural products. This research project aimed to explore and characterize Brazilian cyanobacteria for new bioactive compounds. Here we report the production of hepatotoxins and new protease inhibitors from benthic Nostoc sp. CENA543 isolated from a small, shallow, saline-alkaline lake in the Nhecolandia, Pantanal wetland area in Brazil. Nostoc sp. CENA543 produces exceptionally high amounts of nodularin-R. This is the first free-living Nostoc that produces nodularin at comparable levels as the toxic, bloom-forming, Nodularia spumigena. We also characterized pseudospumigins A-F, which are a novel family of linear tetrapeptides. Pseudospumigins are structurally related to linear tetrapeptide spumigins and aeruginosins both present in N. spumigena but differ in respect to their diagnostic amino acid, which is Ile/Leu/Val in pseudospumigins, Pro/mPro in spumigins, and Choi in aeruginosins. The pseudospumigin gene cluster is more similar to the spumigin biosynthetic gene cluster than the aeruginosin gene cluster. Pseudospumigin A inhibited trypsin (IC50 4.5 mu M after 1 h) in a similar manner as spumigin E from N. spumigena but was almost two orders of magnitude less potent. This study identifies another location and environment where the hepatotoxic nodularin has the potential to cause the death of eukaryotic organisms.Peer reviewe

Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease

Maternally skewed transmission of traits has been associated with genomic imprinting and oocytederived mRNA. We report canine congenital eye malformations, caused by an amino acid deletion (K12deI) near the N terminus of retinol-binding protein (RBP4). The disease is only expressed when both dam and offspring are deletion homozygotes. RBP carries vitamin A (retinol) from hepatic stores to peripheral tissues, including the placenta and developing eye, where it is required to synthesize retinoic acid. Gestational vitamin A deficiency is a known risk factor for ocular birth defects. The K12del mutation disrupts RBP folding in vivo, decreasing its secretion from hepatocytes to serum. The maternal penetrance effect arises from an impairment in the sequential transfer of retinol across the placenta, via RBP encoded by maternal and fetal genomes. Our results demonstrate a mode of recessive maternal inheritance, with a physiological basis, and they extend previous observations on dominant-negative RBP4 alleles in humans.Peer reviewe

Public Views of Dairy Calf Welfare and Dairy Consumption Habits of American Youth and Adults

The primary objective of this study was to explore views of dairy calf welfare and dairy product consumption habits among youth and adults. The secondary objective was to explore views of dairy calf welfare and dairy product consumption habits among a subset of parent-child pairs. Participants 5–17 years of age (n = 463) and 18 years old or greater (n = 1,310) completed an in-person survey at the Minnesota State Fair (St. Paul, MN, USA) in summer 2018. A subset of these data was comprised of parent-child pairs (n = 188). The survey was administered via Qualtrics using iPads and included multiple-choice questions about demographics and calf welfare, an open-ended question on “what dairy calves need to have a good life,” and multiple-choice questions about participants' consumption of dairy products and nondairy alternative products. Content analysis was used for responses to the open-ended question, and concepts to describe dairy calf welfare views were identified. Fisher's exact test and Cohen's Kappa were used to investigate the relationships between parent-child pair responses about dairy calf welfare. In addition to these methods, prevalence-adjusted and bias-adjusted kappa (PABAK) were used to investigate the relationships between parent-child pair responses about consumption habits. The median age of all youth participants was 11 years and 61% were female, 82% were urban residents, and 63% did not have prior experience handling agricultural animals but 83% had visited a farm in the past. Most youth participants (94.4%) indicated that they consumed dairy products, while 47.1% consumed nondairy alternatives products. Median age range of all adult participants was 45–54 years, 65% were female, 82% urban residents, and 81% did not have prior experience handling agricultural animals but 63% had visited a farm in the past. Most adult participants (94%) indicated that they consumed dairy products and 47% indicated that they consumed nondairy alternative products. In response to “what dairy calves need to have a good life,” youth and adults most commonly focused on issues related to biological functioning (82 and 70% of youth and adults mentioning this concept, respectively), followed by natural living (44 and 50%, respectively), humane care (30 and 20%, respectively), and affective states (5% of both youth and adults). For the natural living concept of animal welfare, parent and child responses were slightly associated (Kappa = 0.19; P = 0.01; overall agreement = 61%). Almost all participants reported consuming dairy products, therefore, the agreement is high between parents and children because in most households (90%), both parents and children consume dairy products. However, child consumption was observed to be lower (75%, 9/12) when parents do not consume dairy than when parents do consume dairy (95%, 167/176), leading to a Kappa of 0.20 (P = 0.006, PABAK = 0.81) and a slight association between parents and children. The results suggest that biological functioning is highly valued by the public and views of parents and their children related to natural living in dairy calves are slightly associated

Evaluation of O2PLS in Omics data integration

Background: Rapid computational and technological developments made large amounts of omics data available in different biological levels. It is becoming clear that simultaneous data analysis methods are needed for better interpretation and understanding of the underlying systems biology. Different methods have been proposed for this task, among them Partial Least Squares (PLS) related methods. To also deal with orthogonal variation, systematic variation in the data unrelated to one another, we consider the Two-way Orthogonal PLS (O2PLS): an integrative data analysis method which is capable of modeling systematic variation, while providing more parsimonious models aiding interpretation. Results: A simulation study to assess the performance of O2PLS showed positive results in both low and higher dimensions. More noise (50 % of the data) only affected the systematic part estimates. A data analysis was conducted using data on metabolomics and transcriptomics from a large Finnish cohort (DILGOM). A previous sequential study, using the same data, showed significant correlations between the Lipo-Leukocyte (LL) module and lipoprotein metabolites. The O2PLS results were in agreement with these findings, identifying almost the same set of co-varying variables. Moreover, our integrative approach identified other associative genes and metabolites, while taking into account systematic variation in the data. Including orthogonal components enhanced overall fit, but the orthogonal variation was difficult to interpret. Conclusions: Simulations showed that the O2PLS estimates were close to the true parameters in both low and higher dimensions. In the presence of more noise (50 %), the orthogonal part estimates could not distinguish well between joint and unique variation. The joint estimates were not systematically affected. Simultaneous analysis with O2PLS on metabolome and transcriptome data showed that the LL module, together with VLDL and HDL metabolites, were important for the metabolomic and transcriptomic relation. This is in agreement with an earlier study. In addition more gene expression and metabolites are identified being important for the joint covariation

Risk of advanced fibrosis in first-degree relatives of with nonalcoholic liver disease

Peer reviewe

Groundwater resources assessment using integrated geophysical techniques in the southwestern region of Peninsular Malaysia.

Combined geophysical techniques such as multi-electrode resistivity, induced polarization, and borehole geophysical techniques were carried out on volcano-sedimentary rocks in the north of Gemas as part of the groundwater resource’s investigations. The result identifies four resistivity units: the tuffaceous mudstone, tuffaceous sandstone, the tuff bed, and the shale layer. Two types of aquifer systems in terms of storage were identified within the area: one within a fracture system (tuff), which is the leaky area through which vertical flow of groundwater occurs, and an intergranular property of the sandy material of the aquifer which includes sandstone and tuffaceous sandstone. The result also reveals that the aquifer occupies a surface area of about 3,250,555 m2 with a mean depth of 43.71 m and a net volume of 9.798 × 107 m3. From the approximate volume of the porous zone (28 %) and the total aquifer volume, a usable capacity of (274.339 ± 30.177) × 107 m3 of water in the study area can be deduced. This study provides useful information that can be used to develop a much broader understanding of the nature of groundwater potential in the area and their relationship with the local geology

Antifungal Compounds from Cyanobacteria

Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such as peptides, polyketides and alkaloids. Here, we tested cyanobacteria from a wide variety of environments for antifungal activity. The potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1, Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To our knowledge, this is the first description of Anabaena strains that produce scytophycins. We detected antifungal glycolipopeptide hassallidin production in Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These strains were isolated from brackish and freshwater samples collected in Brazil, the Czech Republic and Finland. In addition, three cyanobacterial strains, Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3, produced unidentified antifungal compounds that warrant further characterization. Interestingly, all of the strains shown to produce antifungal compounds in this study belong to Nostocales or Stigonematales cyanobacterial orders.Peer reviewe

Gene expression differences between stroke-associated and asymptomatic carotid plaques

Atherosclerotic carotid stenosis is an important risk factor for stroke. Carotid plaques (CPs) causing stroke may present a distinct type of molecular pathology compared with transient ischemic attack (TIA)-associated or asymptomatic plaques. We compared the gene expression profiles of CPs from stroke patients (n = 12) and asymptomatic patients (n = 9), both with similar risk factors and severity of carotid stenosis (>70%). Sixty probes showed over 1.5-fold expression difference at 5% false discovery rate. Functional clustering showed enrichment of genes in 51 GO categories and seven pathways, the most significant of which relate to extracellular-matrix interaction, PPAR gamma signaling, scavanger receptor activity, and lysosomal activity. Differential expression of ten genes was confirmed in an extended replication group (n = 43), where the most significant expression differences were found in CD36 (2.1-fold change, p = 0.005), CD163 (1.7-fold change, p = 0.007) and FABP4 (2.2-fold change, p = 0.015). These include four genes not previously linked to plaque destabilization: GLUL (2.2-fold change, p = 0.016), FUCA1 (2.2-fold change, p = 0.025), IL1RN (1.6-fold change, p = 0.034), and S100A8 (2.5-fold change, p = 0.047). Strong correlations were found to plaque ulceration, plaque hemorrhage, and markers of apoptosis and proliferation (activated caspase 3, TUNEL, and Ki67). Protein expression of these genes was confirmed by immunohistochemistry and was found in the atheromatous areas of CPs critical for plaque destabilization. This study presents a comprehensive transcriptional analysis of stroke-associated CPs and demonstrates a significant transcriptome difference between stroke-associated and asymptomatic CPs. Follow-up studies on the identified genes are needed to define whether they could be used as biomarkers of symptomatic CPs or have a role in plaque destabilization

Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system philadelphia chromosome positive leukemia

Although imatinib, a BCR-ABL tyrosine kinase inhibitor, is used to treat acute Philadelphia chromosome-positive (Ph+) leukemia, it does not prevent central nervous system (CNS) relapses resulting from poor drug penetration through the blood-brain barrier. Imatinib and dasatinib (a dual-specific SRC/BCR-ABL kinase inhibitor) were compared in a pre-clinical mouse model of intracranial Ph+ leukemia. Clinical dasatinib treatment in patients with CNS Ph+ leukemia was assessed. In preclinical studies, dasatinib increased survival, whereas imatinib failed to inhibit intracranial tumor growth. Stabilization and regression of CNS disease were achieved with continued dasatinib administration. The drug also demonstrated substantial activity in 11 adult and pediatric patients with CNS Ph+ leukemia. Eleven evaluable patients had clinically significant, long-lasting responses, which were complete in 7 patients. In 3 additional patients, isolated CNS relapse occurred during dasatinib therapy; and in 2 of them, it was caused by expansion of a BCR-ABL-mutated dasatinib-resistant clone, implying selection pressure exerted by the compound in the CNS. Dasatinib has promising therapeutic potential in managing intracranial leukemic disease and substantial clinical activity in patients who experience CNS relapse while on imatinib therapy. This study is registered at ClinicalTrials. gov as CA180006 (#NCT00108719) and CA180015 (#NCT00110097)