There has been long debate on the asthenospheric versus lithospheric source for numerous intraplate basalts with ocean island basalt (OIB) and high time‐integrated U/Pb (HIMU)‐like source signatures ...that have erupted through the Zealandia continental crust. Analysis of 157 spinel facies peridotitic mantle xenoliths from 25 localities across Zealandia permits the first comprehensive regional description of the subcontinental lithospheric mantle (SCLM) and insights into whether it could be a source to the intraplate basalts. Contrary to previous assumptions, the Oligocene‐Miocene Zealandia SCLM is highly heterogeneous. It is composed of a refractory craton‐like domain (West Otago) adjacent to several moderately fertile domains (East Otago, North Otago, Auckland Islands). Each domain has an early history decoupled from the overlying Carboniferous and younger continental crust, and each domain has undergone varying degrees of depletion followed by enrichment. Clinopyroxene grains reveal trace element characteristics (low Ti/Eu, high Th/U) consistent with enrichment through reaction with carbonatite. This metasomatic overprint has a composition that closely matches HIMU in Sr, Pb ± Nd isotopes. However, clinopyroxene Hf isotopes are in part highly radiogenic and decoupled from the other isotope systems, and also mostly more radiogenic than the intraplate basalts. If the studied spinel facies xenoliths are representative of the thin Zealandia SCLM, the melting of garnet facies lithosphere could only be the intraplate basalt source if it had a less radiogenic Hf‐Nd isotope composition than the investigated spinel facies, or was mixed with asthenosphere‐derived melts containing less radiogenic Hf.
Key Points
SCLM beneath young Zealandia continent is ancient and regionally heterogeneous
Carbonatite metasomatism has imparted a HIMU‐like composition
Inspected SCLM has not directly contributed to the intraplate basalts
The genetic code-the binding specificity of all transfer-RNAs--defines how protein primary structure is determined by DNA sequence. DNA also dictates when and where proteins are expressed, and this ...information is encoded in a pattern of specific sequence motifs that are recognized by transcription factors. However, the DNA-binding specificity is only known for a small fraction of the approximately 1400 human transcription factors (TFs). We describe here a high-throughput method for analyzing transcription factor binding specificity that is based on systematic evolution of ligands by exponential enrichment (SELEX) and massively parallel sequencing. The method is optimized for analysis of large numbers of TFs in parallel through the use of affinity-tagged proteins, barcoded selection oligonucleotides, and multiplexed sequencing. Data are analyzed by a new bioinformatic platform that uses the hundreds of thousands of sequencing reads obtained to control the quality of the experiments and to generate binding motifs for the TFs. The described technology allows higher throughput and identification of much longer binding profiles than current microarray-based methods. In addition, as our method is based on proteins expressed in mammalian cells, it can also be used to characterize DNA-binding preferences of full-length proteins or proteins requiring post-translational modifications. We validate the method by determining binding specificities of 14 different classes of TFs and by confirming the specificities for NFATC1 and RFX3 using ChIP-seq. Our results reveal unexpected dimeric modes of binding for several factors that were thought to preferentially bind DNA as monomers.
Light irradiation activates a range of cellular processes in a variety of cell types, including stem cells, and can promote tissue repair. This study investigated the effects of light-emitting diode ...(LED) exposure on dental pulp cells (DPCs). Dose response analysis at 20-second intervals up to 120 seconds demonstrated that a LED array emitting 653-nm red light stimulated significantly increased cell growth at 3 and 7 days post-irradiation with 40 (149 mJ/cm2) and 60 (224 mJ/cm2) seconds of radiant exposure. Double-dosing cells at days 1 and 4 of a 7-day culture period with 60-second (224 mJ/cm2) LED exposure significantly increased cell growth compared with a single dosing regime. BrdU analysis demonstrated significantly increased proliferation rates associated with significantly increased ATP, nitric oxide (NO), and mitochondrial metabolic activity. LED-stimulated NO levels were not reduced by inhibition of NO-synthase activity. Light exposure also rescued the inhibition of mitochondrial dysfunction and increased levels of in vitro mineralization compared with control. Media exchange experiments indicated that autocrine signaling was not likely responsible for red-light-induced DPC activity. In conclusion, data analysis indicated that 653-nm LED irradiation promoted DPC responses relevant to tissue repair, and this is likely mediated by increased mitochondrial activity.
Spinel facies dunite, harzburgite, lherzolite and wehrlite mantle xenoliths from a cluster of Miocene volcanoes in southern New Zealand preserve evidence of the complex evolution of the underlying ...continental mantle lithosphere. Spinel Cr# records melt extraction with some values indicative of near complete removal of clinopyroxene. LREE-enriched, low Ti/Eu and low Al
2
O
3
clinopyroxene and rare F-, LREE-rich apatite indicates subsequent interaction between peridotite and a metasomatising carbonatitic melt. The clearest metasomatic signature occurs in the formerly highly depleted samples because there was little or no pre-existing clinopyroxene to dilute the carbonatite signature. For the same reason, the isotopic character of the metasomatising agent is best observed in the formerly highly depleted peridotites (
87
Sr/
86
Sr = 0.7028–0.7031;
143
Nd/
144
Nd = 0.5129;
206
Pb/
204
Pb = 20.2–20.3). These isotope ratios are very close to, but slightly less radiogenic than, the HIMU end-member mantle reservoir. Nd isotope data imply carbonatite metasomatism occurred within the last several hundred million years, with ubiquitous pyroxene core-to-rim Al diffusion zoning indicating that it must pre-date cooling of the lithospheric mantle following Late Cretaceous–Eocene rifting of Zealandia from Gondwana. Metasomatism was significantly younger than ancient Re-depletion ages of ~2 Ga and shows that decoupling of peridotite isotope systems has occurred.
The orogenic Anita Peridotite in Fiordland, SW New Zealand, provides an opportunity to examine the composition of a large block of upper mantle exhumed from beneath a Cretaceous arc. This ...little-studied 1km20km massif is dominated by spinel-facies harzburgite and dunite. Olivine Mg# of 92-93, spinel Cr# of 70, orthopyroxene with low Al sub(2)O sub(3), and extremely depleted whole-rock geochemical characteristics indicate that the peridotite body experienced >30% melt extraction, probably within the spinel facies. Mineral compositions show some similarity to those of cratonic peridotitic mantle. Rare Cr-rich amphibole suggests that the peridotite has been subsequently re-enriched. Distinctive, coupled Eu and Sr anomalies in the amphiboles, which can be subdivided into three groups, are interpreted to show that they formed by hydration of metasomatic clinopyroxene-plagioclase aggregates. Measured amphibole super(87)Sr/ super(86)Sr (0.705-0.706), Nd ( +6.3 to+11.1), super(208)Pb/ super(204)Pb (37.8-38.9) and Hf ( +5.6 to 36.9) indicate that the metasomatic agent, which caused crystallization of clinopyroxene and plagioclase, had an isotopic composition similar to ocean island basalt. On the basis of isotopic data and mineral chemistry, the enriched nature of the peridotite is interpreted to have been caused by percolation of small volumes of a mafic silicate melt. Additional evidence for the passage of such melts is the rare occurrence of hornblendite veins and orthopyroxene hornblendite dykes. This peridotite body therefore preserves evidence of extreme melt depletion and the passage of silicate melts and hydrous fluids within the sub-arc mantle.
This study aimed to evaluate the irradiance and the quality of LED light curing units (LCUs) in primary and secondary clinics in the UK and to assess the effect of damage, contamination, use of ...protective sleeves, and distance of light tips to target on the irradiance and performance of LCUs.
The irradiance levels (mW/cm2) of 26 LED LCUs from general dental practices and 207 LED LCUs from two dental hospitals were measured using a digital radiometer (Blue Phase II, Ivoclar, Vivadent, Amherst, NY). Ten LED light guide tips (Satelec Mini, Acteon, Merignac, France) were selected to evaluate the effect of chipping, contamination (tip debris), and use of protective sleeves and tips to sensor distance on irradiance (mW/cm2) using a MARC Resin Calibrator (Blue Light Analytics, Halifax, Canada). Homogeneity of the light output was evaluated using a laser beam profiler (SP620; Ophir-Spiricon, North Longan, UT, USA). Statistical analysis was conducted using a one-way analysis of variance (ANOVA) with post hoc Tukey test (α=0.05) and linear regression with stepwise correlation tests.
Thirty-three percent of the LCUs delivered irradiance output less than 500 mW/cm2. The condition of the light curing tips was poor, with 16% contaminated with resin debris, 26% damaged, and 10% both contaminated and damaged. The irradiance output was significantly reduced in contaminated (62%) and chipped (50%) light curing tips and when using protective sleeves (24%) (p<0.05). Irradiance was also reduced when increasing the distance with 25% and 34% reduction at 7 mm and 10 mm, respectively (p<0.05).
There remains a lack of awareness of the need for regular monitoring and maintenance of dental LCUs. Damaged and contaminated light curing tips, use of protective sleeves, and increasing the distance from the restoration significantly reduced the irradiance output and the performance of the LCUs.
Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at very high frequency (∼70%) in uterine leiomyomas. However, the influence of these mutations on ...Mediator function and the molecular basis for their tumorigenic potential remain unknown. To clarify the impact of these mutations, we used affinity-purification mass spectrometry to establish the global protein-protein interaction profiles for both wild-type and mutant MED12. We found that uterine leiomyoma-linked mutations in MED12 led to a highly specific decrease in its association with Cyclin C-CDK8/CDK19 and loss of Mediator-associated CDK activity. Mechanistically, this occurs through disruption of a MED12-Cyclin C binding interface that we also show is required for MED12-mediated stimulation of Cyclin C-dependent CDK8 kinase activity. These findings indicate that uterine leiomyoma-linked mutations in MED12 uncouple Cyclin C-CDK8/19 from core Mediator and further identify the MED12/Cyclin C interface as a prospective therapeutic target in CDK8-driven cancers.
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•MED12 indirectly activates CDK8 by binding to a conserved surface groove on Cyclin C•Uterine leiomyoma-linked MED12 mutations disrupt the MED12-Cyclin C interface•Uterine leiomyoma-linked MED12 mutations uncouple Cyclin C-CDK8/19 from core Mediator
Uterine leiomyomas (fibroids) are the most common tumor in humans. Previously, somatic mutations in exon 2 of the RNA polymerase II Mediator subunit MED12 were discovered at high frequency (∼70%) in this tumor type. However, the impact of these mutations on Mediator function and the molecular basis for their tumorigenic potential remain unknown. In this study, Turunen et al. show that uterine leiomyoma-linked MED12 mutations disrupt a MED12-Cyclin C interface in Mediator, triggering loss of Mediator-associated CDK activity.
We report new U‐Pb zircon ages, geochemical and isotopic data for Mesozoic igneous rocks, and new seismic interpretations of mostly submerged South Zealandia (1.5 Mkm2). We use these data, along with ...existing geological and geophysical data sets, to refine the extent and nature of geological units. Our new 1:25 M geological map of South Zealandia provides a regional framework to investigate the rifting and breakup that formed Zealandia, Earth's most submerged continent. Samples of prerift (pre‐100 Ma) plutonic rocks can be matched with on‐land New Zealand igneous suites and indicate an east‐west strike for the subduction‐related 260 to 105‐Ma Median Batholith across the Campbell Plateau. The plutonic chronology of formerly contiguous plutonic rocks in West Antarctica reveals similar pulses and lulls to the Median Batholith. Contrary to previous interpretations, the Median Batholith does not coincide with the 1,600‐km‐long Campbell Magnetic Anomaly System. Instead we interpret the continental magnetic anomalies to represent a mainly mafic igneous unit, whose shape and extent is controlled by synrift structures related to Gondwana breakup. Correlatives of some of these unsampled igneous rocks may be exposed as circa 85 Ma alkalic volcanic rocks on the Chatham Islands. Extension directions varied by up to 65° from 100 to 80 Ma, and we suggest this allowed this large area to thin considerably before final rupture to form new oceanic crust. Synrift (90–80 Ma) structures cut the oroclinal bend in southern South Island and support a pre‐early Late Cretaceous age of orocline formation.
Key Points
The first geological map of 1.5‐Mkm2 submerged South Zealandia reveals an E‐W striking batholith with similar age pattern to Marie Byrd Land
The 1,600‐km‐long Campbell Magnetic Anomaly System is interpreted as due to failed rift mafic magmatism that preceded 80 Ma Zealandia breakup
Variation of extension direction over 20 Ma allowed this large area to thin considerably before breakup and formation of new ocean crust
Although the proteins that read the gene regulatory code, transcription factors (TFs), have been largely identified, it is not well known which sequences TFs can recognize. We have analyzed the ...sequence-specific binding of human TFs using high-throughput SELEX and ChIP sequencing. A total of 830 binding profiles were obtained, describing 239 distinctly different binding specificities. The models represent the majority of human TFs, approximately doubling the coverage compared to existing systematic studies. Our results reveal additional specificity determinants for a large number of factors for which a partial specificity was known, including a commonly observed A- or T-rich stretch that flanks the core motifs. Global analysis of the data revealed that homodimer orientation and spacing preferences, and base-stacking interactions, have a larger role in TF-DNA binding than previously appreciated. We further describe a binding model incorporating these features that is required to understand binding of TFs to DNA.
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► High-resolution binding profiles representing most human transcription factors ► High-throughput SELEX can identify long and dimeric sites ► Full-length protein and DNA-binding domain specificities are similar ► Adjacent bases affect TF-DNA binding more than previously thought
High-throughput SELEX is used to determine high-resolution binding profiles representing most human transcription factors. Base-stacking interactions, and dimer orientation and spacing preferences, have a larger role in TF-DNA binding than previously appreciated.
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