104 research outputs found
Canine Infectious Papillomatosis
On September 22,1941, an eighteen-month old, male Cocker Spaniel was admitted to the Charles Henry Stange Memorial Clinic showing papillomata between the toes of both fore-feet. No history was obtained as to the rate of growth or the length of time the warts had existed
Textural variations in Neogene pelagic carbonate ooze at DSDP Site 593, southern Tasman Sea, and their paleoceanographic implications
Changes in Neogene sediment texture in pelagic carbonate-rich oozes on the Challenger Plateau, southern Tasman Sea, are used to infer changes in depositional paleocurrent velocities. The most obvious record of textural change is in the mud:sand ratio. Increases in the sand content are inferred to indicate a general up-core trend towards increasing winnowing of sediments resulting from increasing flow velocity of Southern Component Intermediate Water (SCIW), the forerunner of Antarctic Intermediate Water. In particular, the intervals c. 19-14.5 Ma, c. 9.5-8 Ma, and after 5 Ma are suggested to be times of increased SCIW velocity and strong sediment winnowing. Within the mud fraction, the fine silt to coarse clay sizes from 15.6 to 2 µm make the greatest contribution to the sediments and are composed of nannofossil plates. During extreme winnowing events it is the fine silt to very coarse clay material (13-3 µm) within this range that is preferentially removed, suggesting the 10 µm cohesive silt boundary reported for siliciclastic sediments does not apply to calcitic skeletal grains. The winnowed sediment comprises coccolithophore placoliths and spheres, represented by a mode at 4-7 µm.
Further support for seafloor winnowing is gained from the presence in Hole 593 of a condensed sedimentary section from c. 18 to 14 Ma where the sand content increases to c. 20% of the bulk sample. Associated with the condensed section is a 6 m thick orange unit representing sediments subjected to particularly oxygen-rich, late early to early middle Miocene SCIW. Together these are inferred to indicate increased SCIW velocity resulting in winnowed sediment associated with faster arrival of oxygen-rich surface water subducted to form SCIW. Glacial development of Antarctica has been recorded from many deep-sea sites, with extreme glacials providing the mechanism to increase watermass flow. Miocene glacial zones Mi1b-Mi6 are identified in an associated oxygen isotope record from Hole 593, and correspond with times of particularly invigorated paleocirculation, bottom winnowing, and sediment textural changes
Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer
Prostate is the most frequent cancer in men. Prostate cancer progression is driven by androgen steroid hormones, and delayed by androgen deprivation therapy (ADT). Androgens control transcription by stimulating androgen receptor (AR) activity, yet also control pre-mRNA splicing through less clear mechanisms. Here we find androgens regulate splicing through AR-mediated transcriptional control of the epithelial-specific splicing regulator ESRP2. Both ESRP2 and its close paralog ESRP1 are highly expressed in primary prostate cancer. Androgen stimulation induces splicing switches in many endogenous ESRP2-controlled mRNA isoforms, including splicing switches correlating with disease progression. ESRP2 expression in clinical prostate cancer is repressed by ADT, which may thus inadvertently dampen epithelial splice programmes. Supporting this, treatment with the AR antagonist bicalutamide (Casodex) induced mesenchymal splicing patterns of genes including FLNB and CTNND1. Our data reveals a new mechanism of splicing control in prostate cancer with important implications for disease progression.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site
Global and local controlson continental margin stratigraphy
Integrated Ocean Drilling Program (IODP) Expedition 317 was devoted to understanding
the relative importance of global sea level (eustasy) versus local tectonic and sedimentary processes in controlling continental margin sedimentary cycles. The expedition
recovered sediments from the Eocene to recent period, with a particular focus
on the sequence stratigraphy of the late Miocene to recent, when global sea level change was dominated by glacioeustasy. Drilling in the Canterbury Basin, on the eastern
margin of the South Island of New Zealand, takes advantage of high rates of Neogene
sediment supply, which preserves a high-frequency (0.1–0.5 m.y.) record of depositional cyclicity. The Canterbury Basin provides an opportunity to study the complex interactions between processes responsible for the preserved stratigraphic record
of sequences because of the proximity of an uplifting mountain chain, the Southern Alps, and strong ocean currents. Currents have locally built large, elongate sediment drifts within the prograding Neogene section. Expedition 317 did not drill into one of these elongate drifts, but currents are inferred to have strongly influenced deposition across the basin, including in locations lacking prominent mounded drifts.
Upper Miocene to recent sedimentary sequences were cored in a transect of three sites on the continental shelf (landward to basinward, Sites U1353, U1354, and U1351) and one on the continental slope (Site U1352). The transect provides a stratigraphic record of depositional cycles across the shallow-water environment most directly affected
by relative sea level change. Lithologic boundaries, provisionally correlative with seismic sequence boundaries, have been identified in cores from each site and provide insights into the origins of seismically resolvable sequences. This record will be used to estimate the timing and amplitude of global sea level change and to document
the sedimentary processes that operate during sequence formation. Sites U1353 and U1354 provide significant, double-cored, high-recovery sections through the Holocene
and late Quaternary for high-resolution study of recent glacial cycles in a continental
shelf setting.
Continental slope Site U1352 represents a complete section from modern slope terrigenous
sediment to hard Eocene limestone, with all the associated lithologic, biostratigraphic,
physical, geochemical, and microbiological transitions. The site also provides a record of ocean circulation and fronts during the last ~35 m.y. The early Oligocene (~30 Ma) Marshall Paraconformity was the deepest drilling target of Expedition
317 and is hypothesized to represent intensified current erosion or nondeposition associated with the initiation of thermohaline circulation following the separation of Australian and Antarctica.
Expedition 317 set a number of scientific ocean drilling records: (1) deepest hole drilled in a single expedition and second deepest hole in the history of scientific ocean drilling (Hole U1352C, 1927 m); (2) deepest hole and second deepest hole drilled by the R/V JOIDES Resolution on a continental shelf (Hole U1351B, 1030 m; Hole U1353B, 614 m); (3) shallowest water depth for a site drilled by the JOIDES Resolution
for scientific purposes (Site U1353, 84.7 m water depth); and (4) deepest sample
taken by scientific ocean drilling for microbiological studies (1925 m, Site U1352).
Expedition 317 supplements previous drilling of sedimentary sequences for sequence stratigraphic and sea level objectives, particularly drilling on the New Jersey margin (Ocean Drilling Program [ODP] Legs 150, 150X, 174A, and 174AX and IODP Expedition
313) and in the Bahamas (ODP Leg 166), but includes an expanded Pliocene section.
Completion of at least one transect across a geographically and tectonically distinct siliciclastic margin was the necessary next step in deciphering continental margin stratigraphy. Expedition 317 also complements ODP Leg 181, which focused on drift development in more distal parts of the Eastern New Zealand Oceanic Sedimentary
System (ENZOSS).Integrated Ocean Drilling Program Management InternationalPublished2.2. Laboratorio di paleomagnetismorestricte
Slow slip source characterized by lithological and geometric heterogeneity
Slow slip events (SSEs) accommodate a significant proportion of tectonic plate motion at subduction zones, yet little is known about the faults that actually host them. The shallow depth (<2 km) of well-documented SSEs at the Hikurangi subduction zone offshore New Zealand offers a unique opportunity to link geophysical imaging of the subduction zone with direct access to incoming material that represents the megathrust fault rocks hosting slow slip. Two recent International Ocean Discovery Program Expeditions sampled this incoming material before it is entrained immediately down-dip along the shallow plate interface. Drilling results, tied to regional seismic reflection images, reveal heterogeneous lithologies with highly variable physical properties entering the SSE source region. These observations suggest that SSEs and associated slow earthquake phenomena are promoted by lithological, mechanical, and frictional heterogeneity within the fault zone, enhanced by geometric complexity associated with subduction of rough crust
ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression
Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3FAX-Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics
International ocean discovery program expedition 375 preliminary report: Hikurangi subduction margin coring and observatories unlocking the secrets of slow slip through drilling to sample and monitor the forearc and subducting plate, 8 March - 5 May 2018
Slow slip events (SSEs) at the northern Hikurangi subduction margin, New Zealand, are among the best-documented shallow SSEs on Earth. International Ocean Discovery Program Expedition 375 was undertaken to investigate the processes and in situ conditions that underlie subduction zone SSEs at the northern Hikurangi Trough by (1) coring at four sites, including an active fault near the deformation front, the upper plate above the high-slip SSE sourc e region, and the incoming sedimentary succession in the Hikurangi Trough and atop the Tūranganui Knoll Seamount, and (2) installing borehole observatories in an active thrust near the deformation front and in the upper plate overlying the slow slip source region. Logging-while-drilling (LWD) data for this project were acquired as part of Expedition 372 (26 November 2017-4 January 2018; see th e Expedition 372 Preliminary Report for further details on the LWD acquisition program). Northern Hikurangi subduction margin SSEs recur every 1-2 years and thus provide an ideal opportunity to monitor deformation and associated changes in chemical and physical properties throughout the slow slip cycle. Sampling of material from the sedimentary section and oceanic basement of the subducting plate reveals the rock properties, composition, lithology, and structural character of material that is transported downdip into the SSE source region. A recent seafloor geodetic experiment raises the possibility that SSEs at northern Hikurangi may propagate all the way to the trench, indicating that the shallow thrust fault zone targeted during Expedition 375 may also lie in the SSE rupture area. Hence, sampling at this location provides insights into the composition, physical properties, and architecture of a shallow fault that may host slow slip. Expedition 375 (together with the Hikurangi subduction LWD component of Expedition 372) was designed to address three fundamental scientific objectives: (1) characterize the state and composition of the incoming plate and shallow plate boundary fault near the trench, which comprise the protolith and initial conditions for fault zone rock at greater depth and which may itself host shallow slow slip; (2) characterize material properties, thermal regime, and stress conditions in the upper plate above the core of the SSE source region; and (3) install observatories at an active thrust near the deformation front and in the upper plate above the SSE source to measure temporal variations in deformation, temperature, and fluid flow. The observatories will monitor volumetric strain (via pore pressure as a proxy) and the evolution of physical, hydrological, and chemical properties throughout the SSE cycle. Together, the coring, logging, and observatory data will test a suite of hypotheses about the fundamental mechanics and behavior of SSEs and their relationship to great earthquakes along the subduction interface
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio
Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth
Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression
Expedition 372B/375 summary
Slow slip events (SSEs) at the northern Hikurangi subduction margin, New Zealand, are among the best-documented shallow SSEs on Earth. International Ocean Discovery Program Expeditions 372 and 375 were undertaken to investigate the processes and in situ conditions that underlie subduction zone SSEs at the northern Hikurangi Trough. We accomplished this goal by (1) coring and geophysical logging at four sites, including penetration of an active thrust fault (the Pāpaku fault) near the deformation front, the upper plate above the SSE source region, and the incoming sedimentary succession in the Hikurangi Trough and atop the Tūranganui Knoll seamount; and (2) installing borehole observatories in the Pāpaku fault and in the upper plate overlying the slow slip source region. Logging-while-drilling (LWD) data for this project were acquired as part of Expedition 372, and coring, wireline logging, and observatory installations were conducted during Expedition 375.
Northern Hikurangi subduction margin SSEs recur every 1–2 y and thus provide an ideal opportunity to monitor deformation and associated changes in chemical and physical properties throughout the slow slip cycle. In situ measurements and sampling of material from the sedimentary section and oceanic basement of the subducting plate reveal the rock properties, composition, lithology, and structural character of material that is transported downdip into the SSE source region. A recent seafloor geodetic experiment raises the possibility that SSEs at northern Hikurangi may propagate to the trench, indicating that the shallow thrust fault (the Pāpaku fault) targeted during Expeditions 372 and 375 may also lie in the SSE rupture area and host a portion of the slip in these events. Hence, sampling and logging at this location provides insights into the composition, physical properties, and architecture of a shallow fault that may host slow slip.
Expeditions 372 and 375 were designed to address three fundamental scientific objectives:
Characterize the state and composition of the incoming plate and shallow fault near the trench, which comprise the protolith and initial conditions for fault zone rock at greater depth and which may itself host shallow slow slip;
Characterize material properties, thermal regime, and stress conditions in the upper plate directly above the SSE source region; and
Install observatories in the Pāpaku fault near the deformation front and in the upper plate above the SSE source to measure temporal variations in deformation, temperature, and fluid flow. The observatories will monitor volumetric strain (via pore pressure as a proxy) and the evolution of physical, hydrological, and chemical properties throughout the SSE cycle.
Together, the coring, logging, and observatory data will test a suite of hypotheses about the fundamental mechanics and behavior of SSEs and their relationship to great earthquakes along the subduction interface
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