Contrasting carbonate depositional systems for Pliocene cool-water limestones cropping out in central Hawke's Bay, New Zealand

Pliocene limestone formations in central Hawke's Bay (eastern North Island, New Zealand) accumulated on and near the margins of a narrow forearc basin seaway within the convergent Australia/Pacific plate boundary zone. The active tectonic setting and varied paleogeographic features of the limestone units investigated, in association with probable glacioeustatic sea-level fluctuations, resulted in complex stratigraphic architectures and contrasting types of carbonate accumulation on either side of the seaway. Here, we recognise recurring patterns of sedimentary facies, and sequences and systems tracts bounded by key physical surfaces within the limestone sheets. The facies types range from Bioclastic (B) to Siliciclastic (S) end-members via Mixed (M) carbonate-siliciclastic deposits. Skeletal components are typical cool-water associations dominated by epifaunal calcitic bivalves, bryozoans, and especially barnacles. Siliciclastic contents vary from one formation to another, and highlight siliciclastic-rich limestone units in the western ranges versus siliciclastic-poor limestone units in the eastern coastal hills. Heterogeneities in facies types, stratal patterns, and also in diagenetic pathways between eastern and western limestone units are considered to originate in the coeval occurrence in different parts of the forearc basin of two main morphodynamic carbonate systems over time

Pliocene-Pleistocene marine cyclothems, Wanganui Basin, New Zealand: a lithostratigraphic framework

The Rangitikei River valley between Mangaweka and Vinegar Hill and the surrounding Ohingaiti region in eastern Wanganui Basin contains a late Pliocene to early Pleistocene (c. 2.6-1.7 Ma), c. 1100 m thick, southward-dipping (4-9deg.), marine cyclothemic succession. Twenty sedimentary cycles occur within the succession, each of which contains coarse-grained (siliciclastic sandstone and coquina) and fine-grained (siliciclastic siltstone) units. Nineteen of the cycles are assigned to the Rangitikei Group (new). Six new formations are defined within the Rangitikei Group, and their distribution in the Ohingaiti region is represented in a new geologic map. The new formations are named: Mangarere, Tikapu, Makohine, Orangipongo, Mangaonoho, and Vinegar Hill. Each formation comprises one or more cyclothems and includes a previously described and named distinctive basal horizon. Discrete sandstones, siltstones, and coquinas within formations are assigned member status and correspond to systems tracts in sequence stratigraphic nomenclature. The members provide the link between the new formational lithostratigraphy and the sequence stratigraphy of the Rangitikei Group. Base of cycle coquina members accumulated during episodes of sediment starvation associated with stratigraphic condensation on an open marine shelf during sea-level transgressions. Siltstone members accumulated in mid-shelf environments (50-100 m water depth) during sea-level highstands, whereas the overlying sandstone members are ascribed to inner shelf and shoreface environments (0-50 m water depth) and accumulated during falling eustatic sea-level conditions. Repetitive changes in water depth of 50-100 m magnitude are consistent with a glacio-eustatic origin for the cyclothems, which correspond to an interval of Earth history when successive glaciations in the Northern Hemisphere are known to have occurred. Moreover, the chronology of the Rangitikei River section indicates that Rangitikei Group cyclothems accumulated during short duration, 41 ka cycles in continental ice volume attributed to the dominance of the Milankovitch obliquity orbital parameter. The Ohingaiti region has simple postdepositional structure. The late Pliocene formations dip generally to the SSW between 4deg. and 9deg.. Discernible discordances of c. 1deg. between successively younger formations are attributed to synsedimentary tilting of the shelf concomitant with migration of the tectonic hingeline southward into the basin. The outcrop distribution of the Rangitikei Group is strongly influenced by this regional tilt and also by three major northeast-southwest oriented, high-angle reverse faults (Rauoterangi, Pakihikura, and Rangitikei Faults)

Anatomy and origin of authochthonous late Pleistocene forced regression deposits, east Coromandel inner shelf, New Zealand: implications for the development and definition of the regressive systems tract

High-resolution seismic reflection data from the east Coromandel coast, New Zealand, provide details of the sequence stratigraphy beneath an autochthonous, wave dominated inner shelf margin during the late Quaternary (0-140 ka). Since c. 1 Ma, the shelf has experienced limited subsidence and fluvial sediment input, producing a depositional regime characterised by extensive reworking of coastal and shelf sediments during glacio-eustatic sea-level fluctuations. It appears that only one complete fifth-order (c. 100 000 yr) depositional sequence is preserved beneath the inner shelf, the late Pleistocene Waihi Sequence, suggesting any earlier Quaternary sequences were mainly cannibalised into successively younger sequences. The predominantly Holocene-age Whangamata Sequence is also evident in seismic data and modern coastal deposits, and represents an incomplete depositional sequence in its early stages of formation. A prominent aspect of the sequence stratigraphy off parts of the east Coromandel coast is the presence of forced regressive deposits (FRDs) within the regressive systems tract (RST) of the late Pleistocene Waihi Sequence. The FRDs are interpreted to represent regressive barrier-shoreface sands that were sourced from erosion and onshore reworking of underlying Pleistocene sediments during the period of slow falling sea level from isotope stages 5 to 2 (c. 112-18 ka). The RST is volumetrically the most significant depositional component of the Waihi Sequence; the regressive deposits form a 15-20 m thick, sharp-based, tabular seismic unit that downsteps and progrades continuously across the inner shelf. The sequence boundary for the Waihi Sequence is placed at the most prominent, regionally correlative, and chronostratigraphically significant surface, namely an erosional unconformity characterised in many areas by large incised valleys that was generated above the RST. This unconformity is interpreted as a surface of maximum subaerial erosion generated during the last glacial lowstand (c. 18 ka). Although the base of the RST is associated with a prominent regressive surface of erosion, this is not used as the sequence boundary as it is highly diachronous and difficult to identify and correlate where FRDs are not developed. The previous highstand deposits are limited to subaerial barrier deposits preserved behind several modern Holocene barriers along the coast, while the transgressive systems tract is preserved locally as incised-valley fill deposits beneath the regressive surface of erosion at the base of the RST. Many documented late Pleistocene RSTs have been actively sourced from fluvial systems feeding the shelf and building basinward-thickening, often stacked wedges of FRDs, for which the name allochthonous FRDs is suggested. The Waihi Sequence RST is unusual in that it appears to have been sourced predominantly from reworking of underlying shelf sediments, and thus represents an autochthonous FRD. Autochthonous FRDs are also present on the Forster-Tuncurry shelf in southeast Australia, and may be a common feature in other shelf settings with low subsidence and low sediment supply rates, provided shelf gradients are not too steep, and an underlying source of unconsolidated shelf sediments is available to source FRDs. The preservation potential of such autochthonous FRDs in ancient deposits is probably low given that they are likely to be cannibalised during subsequent sea-level falls

From cylindrical to non‐cylindrical foreland basin: Pliocene–Pleistocene evolution of the Po Plain–Northern Adriatic basin (Italy)

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Abrupt global events in the Earth's history: a physics perspective

The timeline of the Earth's history reveals quasi-periodicity of the geological record over the last 542 Myr, on timescales close, in the order of magnitude, to 1 Myr. What is the origin of this quasi-periodicity? What is the nature of the global events that define the boundaries of the geological time scale? I propose that a single mechanism is responsible for all three types of such events: mass extinctions, geomagnetic polarity reversals, and sea-level fluctuations. The mechanism is fast, and involves a significant energy release. The mechanism is unlikely to have astronomical causes, both because of the energies involved, and because it acts quasi-periodically. It must then be sought within the Earth itself. And it must be capable of reversing the Earth's magnetic field. The last requirement makes it incompatible with the consensus model of the origin of the geomagnetic field - the hydromagnetic dynamo operating in the Earth's fluid core. In the second part of the paper, I show that a vast amount of seemingly unconnected geophysical and geological data can be understood in a unified way if the source of the Earth's main magnetic field is a ~200-km-thick lithosphere, repeatedly magnetized as a result of methane-driven oceanic eruptions, which produce ocean flow capable of dynamo action. The eruptions are driven by the interplay of buoyancy forces and exsolution of dissolved gas, which accumulates in the oceanic water masses prone to stagnation and anoxia. Polarity reversals, mass extinctions, and sequence boundaries are consequences of these eruptions. Unlike the consensus model of geomagnetism, this scenario is consistent with the paleomagnetic data showing that "directional changes during a [geomagnetic polarity] reversal can be astonishingly fast, possibly occurring as a nearly instantaneous jump from one inclined dipolar state to another in the opposite hemisphere".Comment: Final journal version. New title, significant changes. Supersedes v.

Launching a Novel Preclinical Infrastructure: Comparative Oncology Trials Consortium Directed Therapeutic Targeting of TNFα to Cancer Vasculature

Background: Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC). The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. Methodology/Principal Findings: Through this established infrastructure, the first trial of the COTC (COTC001) evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF) to αV integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24) determined an optimal safe dose (5 x 1012 transducing units intravenous) of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%), stable disease in six (43%), and disease progression in six (43%) via Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions/Significance: The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies

A comparative study between mixed-type tumours from human salivary and canine mammary glands

<p>Abstract</p> <p>Background</p> <p>In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours.</p> <p>Methods</p> <p>Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin.</p> <p>Results</p> <p>After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions.</p> <p>Conclusion</p> <p>There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations.</p

FLT3 mutations in canine acute lymphocytic leukemia

<p>Abstract</p> <p>Background</p> <p>FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, and a poorer prognosis. A better understanding of the molecular consequences of FLT3 activation would allow improved therapeutic strategies in these patients. Canine lymphoproliferative diseases, including lymphoma and acute leukemias, share evolutionarily conserved chromosomal aberrations and exhibit conserved mutations within key oncogenes when compared to their human counterparts. A small percentage of canine acute lymphocytic leukemias (ALL) also exhibit <it>FLT3 </it>ITD mutations.</p> <p>Methods</p> <p>We molecularly characterized <it>FLT3 </it>mutations in two dogs and one cell line, by DNA sequencing, gene expression analysis via quantitative real-time PCR, and sensitivity to the FLT3 inhibitor lestaurtinib via <it>in vitro </it>proliferation assays. FLT 3 and downstream mediators of FLT3 activation were assessed by Western blotting.</p> <p>Results</p> <p>The canine B-cell leukemia cell line, GL-1, and neoplastic cells from 2/7 dogs diagnosed cytologically with ALL were found to have <it>FLT3 </it>ITD mutations and <it>FLT3 </it>mRNA up-regulation. Lestaurtinib, a small molecule FLT3 inhibitor, significantly inhibited the growth of GL-1 cells, while not affecting the growth of two other canine lymphoid cell lines without the <it>FLT3 </it>mutation. Finally, western blots were used to confirm the conserved downstream mediators of <it>FLT3 </it>activating mutations.</p> <p>Conclusions</p> <p>These results show that ALL and FLT3 biology is conserved between canine and human patients, supporting the notion that canine ALL, in conjunction with the GL-1 cell line, will be useful in the development of a relevant large animal model to aid in the study of human FLT3 mutant leukemias.</p

Habitat properties are key drivers of Borrelia burgdorferi (s.l.) prevalence in Ixodes ricinus populations of deciduous forest fragments

Background: The tick Ixodes ricinus has considerable impact on the health of humans and other terrestrial animals because it transmits several tick-borne pathogens (TBPs) such as B. burgdorferi (sensu lato), which causes Lyme borreliosis (LB). Small forest patches of agricultural landscapes provide many ecosystem services and also the disservice of LB risk. Biotic interactions and environmental filtering shape tick host communities distinctively between specific regions of Europe, which makes evaluating the dilution effect hypothesis and its influence across various scales challenging. Latitude, macroclimate, landscape and habitat properties drive both hosts and ticks and are comparable metrics across Europe. Therefore, we instead assess these environmental drivers as indicators and determine their respective roles for the prevalence of B. burgdorferi in I. ricinus. Methods: We sampled I. ricinus and measured environmental properties of macroclimate, landscape and habitat quality of forest patches in agricultural landscapes along a European macroclimatic gradient. We used linear mixed models to determine significant drivers and their relative importance for nymphal and adult B. burgdorferi prevalence. We suggest a new prevalence index, which is pool-size independent. Results: During summer months, our prevalence index varied between 0 and 0.4 per forest patch, indicating a low to moderate disservice. Habitat properties exerted a fourfold larger influence on B. burgdorferi prevalence than macroclimate and landscape properties combined. Increasingly available ecotone habitat of focal forest patches diluted and edge density at landscape scale amplified B. burgdorferi prevalence. Indicators of habitat attractiveness for tick hosts (food resources and shelter) were the most important predictors within habitat patches. More diverse and abundant macro- and microhabitat had a diluting effect, as it presumably diversifies the niches for tick-hosts and decreases the probability of contact between ticks and their hosts and hence the transmission likelihood.[br/] Conclusions: Diluting effects of more diverse habitat patches would pose another reason to maintain or restore high biodiversity in forest patches of rural landscapes. We suggest classifying habitat patches by their regulating services as dilution and amplification habitat, which predominantly either decrease or increase B. burgdorferi prevalence at local and landscape scale and hence LB risk. Particular emphasis on promoting LB-diluting properties should be put on the management of those habitats that are frequently used by humans. In the light of these findings, climate change may be of little concern for LB risk at local scales, but this should be evaluated further