Distal Exposures of the Miocene Peach Spring Tuff in the Marble and Ship Mountains, CA

The Peach Springs Tuff (PST) is a uniquely identifiable ignimbrite deposit formed by a large caldera-forming volcanic eruption during the early Miocene era. Previous investigations (e.g., Miller et al., 1986; Neilson et al., 1990) have suggested that distal ignimbrite deposits located within the Mojave region of southern California belong to the PST eruptive event. To address this hypothesis, this study investigates ignimbrite samples collected from outcrops within the Marble Mountains (n = 6) and Ship Mountains (n = 8) of southern California. Petrographic analysis reveals the abundance of quartz, sanidine, titanite, hornblende, and biotite in most ignimbrite samples. These mineral phases agree well with previous heavy mineral studies of the PST (Gusa, 1986). Electron Probe Micro-Analysis (EPMA) reveals average biotite, hornblende, and sanidine compositions that closely match PST values. Our data suggests that the ignimbrite deposits in the Marble and Ship mountains are distal exposures of the PST

Megacrystic Potassium Feldspar Magmatism In The Southern Mojave Desert, California

Investigating the textural, chemical, and chronological records preserved within crystal populations can provide insight into the processes which operate during magma ascent, emplacement, and crystallization. K-feldspar megacrysts offer an excellent opportunity to explore these records, particularly in chemically-evolved systems. Understanding megacryst formation bears on a fundamental issue in granite petrogenesis, namely whether the textural and chemical features preserved within granitoid intrusions reflect primary magmatic processes or late-stage crystallization and subsolidus reorganization. To expand our understanding of megacryst formation, we investigated a suite of K-feldspar megacrysts from the Sheep Hole Pluton (SHP) in Southern California. SHP megacrysts are euhedral, ranging from 1-8cm in length. Petrographic analysis and SEM/EDS mapping reveals abundant plagioclase (~40%), quartz (~35%), biotite (~10%), titanite (~10%), and hornblende (~5%) inclusions. Other accessory phases include Fe-Ti oxides, apatite, allanite, and zircon. Many of these inclusions, especially euhedral plagioclase, biotite, and titanite, are preferentially orientated along diffuse oscillatory zoning boundaries in the host megacryst. EPMA analyses collected along megacryst core-to-rim traverses reveal Or78-93 compositions with dramatic fluctuations in Ba concentrations (0.89 - 2.73 wt%). Core and rim analyses of plagioclase inclusions were also collected via EPMA. These analyses reveal that plagioclase inclusions contain oligoclase to andesine cores (An19 - An34) and albite-rich rims (An3 - An10). Although SHP megacrysts are much older than megacrysts described in previous studies, the textural and chemical observations are strikingly similar. We favor a magmatic origin for these megacrysts and interpret these similarities to suggest that a common magmatic process is responsible for K-feldspar megacryst formation

The role of the axial melt lens in crustal accretion at fast-spreading mid-ocean ridges

Fast-spreading mid-ocean ridges (MOR) are underlain by a thin, quasi-steady-state melt or crystal mush body at the base of the sheeted dykes, referred to as the axial melt lens (AML). Although the AML is thought to play a key role in the development of MOR basalts (MORB), debate persists regarding the composition of the AML and the role it plays in the accretion of the lower crust. I address this question by studying a suite of varitextured gabbronorites from the Hess Deep rift valley in the equatorial Pacific Ocean which are interpreted to have formed in the AML of the East Pacific Rise. This unique sample set provides an unparalleled opportunity to conduct the first comprehensive investigation of the AML at a fast-spreading MOR. To facilitate this study, I here develop a method for the quantitative assessment of compositional distribution (QACD) in whole-thin-section element maps. QACD facilitates rapid data collection and processing to generate mineral modes, element and molar-ratio maps, and quantifying full-sample compositional distributions. My application of QACD to the Hess Deep AML suite reveals that mineral phases within the AML here are too evolved to be in equilibrium with MORB. I test the broader applicability of this conclusion by conducting detailed mapping and sampling of an analogous AML horizon in the Oman Ophiolite (Wadi Saq, Ibra Valley). This section is characterised by an evolved sheeted dyke complex rooting into a quartz diorite-hosted AML, supporting the supposition that the AML accommodates the fractionation of highly-evolved melts. I propose a model wherein the AML is predominantly fed by small volumes of evolved interstitial melts expelled from the underlying crystal mush. In the months preceding decadal eruption events, short-lived, focused injections of primitive melts into the AML mix with the extant highly-fractionated melt and trigger eruptions. This model reconciles the apparent mismatch between the volcanic and plutonic records and inferences made on geophysical and petrological grounds. I suggest that the AML is an active player in the development of MORB, permitting the fractionation and storage of evolved melts expelled from the underlying crystal mush and recording the mixing of that material with primitive melt, hence fulfilling more of a passive role with respect to lower crustal accretion than previously proposed

Multidisciplinary approach to the child with sex chromosomal mosaicism including a Y-containing cell line

Children born with sex chromosomal mosaicism including material derived from the Y chromosome may present with a broad phenotypical spectrum. Both boys and girls can present with Turner features and functional health problems typically associated with Turner syndrome, but the presence of Y-chromosomal material can modify some aspects of the condition. We retrospectively analyzed the results of our cohort of 21 individuals (14 boys, 7 girls) with sex chromosomal mosaicism including Y-derived material followed at Ghent University Hospital according to our local multidisciplinary Turner surveillance protocol. Results were compared with literature data, focusing on similarities and differences between girls and boys with this condition. Age at diagnosis was lower in boys compared to girls but the difference was not significant. Short stature is a key feature of the condition both in girls and boys, but skeletal maturation may be different between groups. The effects of growth-hormone therapy remain unclear. Cardiac (33%), ear-nose- throat (ENT) (77.8%) and renal (28.6%) problems were as prevalent in boys as in girls from our cohort, and did not differ from literature data. In line with literature reports, a significant difference in the presence of premalignant germ cell tumors between males (0%) and females (42.9%) was found (p = 0.026). Taken together, this study demonstrates the similarities between girls with Turner syndrome and children with sex chromosomal mosaicism including Y-derived material, regardless of the child's gender. Nowadays, girls with Turner syndrome are offered a dedicated multidisciplinary follow-up in many centers. We advocate a similar follow-up program for all children who have sex chromosomal mosaicism that includes Y-derived material, with special attention to growth, cardiac and ear-nose-throat problems, gonadal function and malignancies

Comprehensive miRNA expression profiling in human T-cell acute lymphoblastic leukemia by small RNA-sequencing

T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that can be classified into different molecular genetic subtypes according to their mRNA gene expression profile. In this study, we applied RNA sequencing to investigate the full spectrum of miRNA expression in primary T-ALL patient samples, T-ALL leukemia cell lines and healthy donor thymocytes. Notably, this analysis revealed that genetic subtypes of human T-ALL also display unique miRNA expression signatures, which are largely conserved in human T-ALL cell lines with corresponding genetic background. Furthermore, small RNA-sequencing also unraveled the variety of isoforms that are expressed for each miRNA in T-ALL and showed that a significant number of miRNAs are actually represented by an alternative isomiR. Finally, comparison of CD34(+) and CD4(+) CD8(+) healthy donor thymocytes and T-ALL miRNA profiles allowed identifying several novel miRNAs with putative oncogenic or tumor suppressor functions in T-ALL. Altogether, this study provides a comprehensive overview of miRNA expression in normal and malignant T-cells and sets the stage for functional evaluation of novel miRNAs in T-ALL disease biology

A Novel t(8;14)(q24;q11) Rearranged Human Cell Line as a Model for Mechanistic and Drug Discovery Studies of NOTCH1-Independent Human T-Cell Leukemia

MYC-translocated T-lineage acute lymphoblastic leukemia (T-ALL) is a rare subgroup of T-ALL associated with CDKN2A/B deletions, PTEN inactivation, and absence of NOTCH1 or FBXW7 mutations. This subtype of T-ALL has been associated with induction failure and aggressive disease. Identification of drug targets and mechanistic insights for this disease are still limited. Here, we established a human NOTCH1-independent MYC-translocated T-ALL cell line that maintains the genetic and phenotypic characteristics of the parental leukemic clone at diagnosis. The University of Padua T-cell acute lymphoblastic leukemia 13 (UP-ALL13) cell line has all the main features of the above described MYC-translocated T-ALL. Interestingly, UP-ALL13 was found to harbor a heterozygous R882H DNMT3A mutation typically found in myeloid leukemia. Chromatin immunoprecipitation coupled with high-throughput sequencing for histone H3 lysine 27 (H3K27) acetylation revealed numerous putative super-enhancers near key transcription factors, including MYC, MYB, and LEF1. Marked cytotoxicity was found following bromodomain-containing protein 4 (BRD4) inhibition with AZD5153, suggesting a strict dependency of this particular subtype of T-ALL on the activity of super-enhancers. Altogether, this cell line may be a useful model system for dissecting the signaling pathways implicated in NOTCH1-independent T-ALL and for the screening of targeted anti-leukemia agents specific for this T-ALL subgroup