BORIS (CTCFL) Is Not Expressed in Most Human Breast Cell Lines and High Grade Breast Carcinomas

BORIS (CTCFL) is the only known paralog of the versatile regulatory protein CTCF, a multifunctional DNA binding protein that mediates distinct gene regulatory functions involved in cell growth, differentiation, and apoptosis. Unlike CTCF, the expression of BORIS is normally restricted to specific cells in testes (the only cells where CTCF is not expressed), where it may play a role in reprogramming the methylation pattern of male germ line DNA. Frequent amplification of the 20q13.2 region, which contains the BORIS gene, and expression of BORIS transcripts in diverse human tumors and cell lines have led to the hypothesis that aberrant expression of BORIS may play a role in tumorigenesis by interfering with CTCF functions. However, recent studies using more quantitative methods indicate low frequency of BORIS expression in melanoma, ovarian, prostate, and bladder carcinomas. To investigate the relationship between chromosome 20q13 amplification and BORIS mRNA levels within breast cancer cell lines and tissues, we developed a quantitative RT-PCR assay to measure the levels of BORIS mRNA. Endpoint RT-PCR assays were also used to investigate the possible expression of alternatively spliced variants. Using multiple primer sets and controls, we found that neither mature BORIS transcripts nor spliced variants are commonly expressed at detectable levels in malignant breast cells or tissues, although endogenous BORIS transcripts can be induced in MCF-7 cells following 5-aza-2′-deoxycytidine treatment. In conclusion, in most breast cancer cells, endogenous BORIS is unlikely to be expressed at sufficient levels to interfere with CTCF functions. Thus it is improbable that aberrant BORIS expression plays a role in most human breast cancers

Can we relate diffusion timescales to magmatic flux and crustal permeability? The case of Villarrica and Osorno volcanoes (Chile)

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What modulates eruptive styles at Villarrica and Osorno volcanoes (Chile)?

Villarrica and Osorno are two active stratovolcanoes in the Central Southern Volcanic Zone (CSVZ) of the Chilean Andes that share several geochemical characteristics: near-primary, tholeiitic parent magmas (50-53 wt. % SiO2), overlapping major/trace element differentiation trends, and comparable storage conditions [1-4]. Yet, their eruptive styles contrast each other significantly. Villarrica is a steady-state, open-vent stratovolcano with a lava lake since 1985, which produced ~100 low to moderate intensity Strombolian eruptions and lava flows since 1579 CE. Osorno is a closed-vent stratovolcano with 10x less eruptions for the same period. We initially proposed that differences in eruptive style and frequency could be due to a relatively higher degree of crustal permeability under Villarrica than Osorno due to the Liquiñe-Ofqui Fault Zone [5]. Preliminary analyses show that both volcanoes have broadly similar olivine chemistry ranges and multimodal distributions, with minor differences in olivine and melt chemistry/textures between Villarrica (Fo72-87) and Osorno (Fo66-82) [4,5]. Diffusion timescales for both volcanoes are mostly 250 days. This suggests the degree of crustal permeability underneath the volcanoes are likely comparable, prompting consideration of other factors. In this contribution, we evaluate the role of magma supply rate, storage conditions, and slab input in modulating eruptive styles at Osorno and Villarrica based on an updated dataset of magma storage conditions, diffusion timescales, geochemical data compilations, and inferences drawn from published literature. We find that magma storage conditions of both volcanoes are similar to each other at T~1100°C, P~200 MPa, along with comparable input of fluids released from the down-going slab. The multimodality in olivine chemistry, diversity in types of olivine growth zones and textures, timescale ranges, coupled with the relatively high magma supply rate estimates for Villarrica from the literature suggest magma supply rate could modulate eruptive style at Villarrica and Osorno. With this contribution, we aim to further current understanding of subduction zone magmatism and geodynamics, with implications on volcanic hazard reduction. 1. Vergara et al. (2004). J. S. Am. Earth Sci. 17: 227-238. 2. Morgado et al. (2015). JVGR, 306: 1-16. 3. Pizarro et al. (2019). JVGR. 384: 48-63. 4. Bechon et al. (2022). Lithos. 106777. 5. Romero et al. (2022). Bull. Volc. 85 (2)

Ancient Adaptive Evolution of the Primate Antiviral DNA-Editing Enzyme APOBEC3G

Host genomes have adopted several strategies to curb the proliferation of transposable elements and viruses. A recently discovered novel primate defense against retroviral infection involves a single-stranded DNA-editing enzyme, APOBEC3G, that causes hypermutation of HIV. The HIV-encoded virion infectivity factor (Vif) protein targets APOBEC3G for destruction, setting up a genetic conflict between the APOBEC3G and Vif genes. This kind of conflict leads to rapid fixation of mutations that alter amino acids at the protein–protein interface, referred to as positive selection. We show that the APOBEC3G gene has been subject to strong positive selection throughout the history of primate evolution. Unexpectedly, this selection appears more ancient than, and is likely only partially caused by, modern lentiviruses. Furthermore, five additional APOBEC genes in the human genome appear to be engaged in similar genetic conflicts, displaying some of the highest signals for positive selection in the human genome. Despite being only recently discovered, editing of RNA and DNA may thus represent an ancient form of host defense in primate genomes

Chlamydia trachomatis Co-opts GBF1 and CERT to Acquire Host Sphingomyelin for Distinct Roles during Intracellular Development

The obligate intracellular pathogen Chlamydia trachomatis replicates within a membrane-bound inclusion that acquires host sphingomyelin (SM), a process that is essential for replication as well as inclusion biogenesis. Previous studies demonstrate that SM is acquired by a Brefeldin A (BFA)-sensitive vesicular trafficking pathway, although paradoxically, this pathway is dispensable for bacterial replication. This finding suggests that other lipid transport mechanisms are involved in the acquisition of host SM. In this work, we interrogated the role of specific components of BFA-sensitive and BFA-insensitive lipid trafficking pathways to define their contribution in SM acquisition during infection. We found that C. trachomatis hijacks components of both vesicular and non-vesicular lipid trafficking pathways for SM acquisition but that the SM obtained from these separate pathways is being utilized by the pathogen in different ways. We show that C. trachomatis selectively co-opts only one of the three known BFA targets, GBF1, a regulator of Arf1-dependent vesicular trafficking within the early secretory pathway for vesicle-mediated SM acquisition. The Arf1/GBF1-dependent pathway of SM acquisition is essential for inclusion membrane growth and stability but is not required for bacterial replication. In contrast, we show that C. trachomatis co-opts CERT, a lipid transfer protein that is a key component in non-vesicular ER to trans-Golgi trafficking of ceramide (the precursor for SM), for C. trachomatis replication. We demonstrate that C. trachomatis recruits CERT, its ER binding partner, VAP-A, and SM synthases, SMS1 and SMS2, to the inclusion and propose that these proteins establish an on-site SM biosynthetic factory at or near the inclusion. We hypothesize that SM acquired by CERT-dependent transport of ceramide and subsequent conversion to SM is necessary for C. trachomatis replication whereas SM acquired by the GBF1-dependent pathway is essential for inclusion growth and stability. Our results reveal a novel mechanism by which an intracellular pathogen redirects SM biosynthesis to its replicative niche

Constraining the conditions of magmatic differentiation under Villarrica stratovolcano (Central Southern Volcanic Zone, Chile)

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Insights on mantle melting below Osorno Volcano (Southern Volcanic Zone, Chile)

Knowing the extent of mantle wedge melting below volcanic arcs is critical to improve magma genesis models. During the last decades, experimental petrology provided significant data and ready to be used models to retrieve the melting conditions producing primary magmas (Mg# >0.7, Ni > 150ppm, Cr > 1000 ppm after Baker et al. (1994) and Grove et al. (2012)). The Central Southern Volcanic zone (CSVZ, southern Chile) of the Andean arc lies on a thin continental crust (50-30 km : Tassara and Echaurren, 2012) and is crosscut by a major transcrustal fault (LOFZ : Cembrano and Lara, 2009) which speed up magma ascent. As a consequence, (near-) primary magmas have been sampled in the area avoiding the blurring of its original characteristics by deep (MASH) (Hildreth and Moorbath, 1988) to shallower (differentiation) magmatic processes. Osorno is one of the CSVZ volcano that possess the most primitive recorded rocks (Mg# =0.72, MgO: 10.23-10.53 wt%, Cr: 584-745 ppm, Ni: 171-179 ppm, Fo# of olivines up to Fo89) in the area. Using lherzolite melting experiments (Hirose and Kushiro, 1993) as well as numerical (Lee et al., 2009), empirical (Wood, 2004) and chemical models (Kelley et al., 2006) together with modal batch melting equations (Hickey-Vargas et al., 2016a, 2016b), we retrieved temperature, pressure, mantle water content and mantle melting rate (F) below Osorno. Temperatures range from 1303 to 1327 °C, pressures from 10.5 to 13.6 kbar (around MOHO depth, ca. 35-44 km), mantle water content from 0.08 to 0.33 wt% and F from 0.12 to 0.22. The uncertainty on F values reflects the difficulty to precisely estimate this parameter. However, this range allows better constraining geophysical models. Values estimated using a global arc numerical model (Turner et al., 2016; F ≈ 0.11 at ca. 60 km and T≈1100°C, mantle H2O =0.6 wt%) or using Arc basalt simulator, isotopes and trace elements (Jacques et al., 2014; F = 1.6-5.5, P=19 kbar, T = 1240°C) vary significantly from our data emphasizing the remaining gap of knowledge of the mantle melting conditions. Our results nonetheless agree with those calculated at La Picada (Vander Auwera et al., 2019) or southwards (Watt et al., 2013; Weller and Stern, 2018) in the southern SVZ

What is the magma storage depth under Osorno volcano (41°S, CSVZ, Chile)

The depth at which magma chamber processes take place below magmatic arcs and the parameters controlling them are highly debated. These questions are fundamental for our understanding of the global magma differentiation as well as the formation of the continental crust at convergent margins, but also for evaluating the risks associated with volcanic eruptions. In the Central Southern Volcanic Zone (Central-SVZ) of the Chilean Andes, a thin continental crust (30-40 km) and the occurrence of a major fault zone (Linquiñe-Ofqui) likely favor rapid magma ascent. This segment of the arc is as a consequence one of the most active in Chile with several recent eruptions (e.g. Llaima 2009, Cordon Caulle 2011, Calbuco 2015, Villarrica 2015 & 2019). The Central-SVZ is characterized by dominant mafic lavas (basalts, basaltic andesites), few rhyodacitic lavas, a noticeable compositional (Daly) gap in the intermediate compositions (andesites). Noteworthy, amphibole is usually absent, except in a few volcanoes (e.g. Calbuco) or only occurs as microliths in enclaves, which suggests rather low water contents. These observations contrast sharply with the Northern-SVZ where andesitic lavas are dominant and hydrous phases common. We focused our research on the eruptive products of Osorno volcano (41°S, CSVZ) located between two volcanoes (Calbuco and Cordon Caulle) which recently showed very explosive eruptions and partly overlies an older Pleistocene eroded volcanic edifice (La Picada). A large series of samples were collected in four units spanning 200 kyr. They define a differentiation trend ranging from tholeiitic basalts to calk-alkaline dacites with a Daly Gap between 58 wt. % and 63 wt. % SiO2. Plagioclase and olivine are dominant before the gap while plagioclase and clino- and orthopyroxene dominate afterwards. The use of recent thermobarometric models revealed two main storage regions: (1) at the MOHO interface (1-1.2GPa) and (2), at the upper/lower crust interface with rather low pressures (likely ≤0.3 Gpa). While at (1) primary magmas differentiate, (2) is interpreted as the depth of major differentiation and volatile exsolution. Thermodynamic simulations (Gualda et al., 2012; Ghiorso & Gualda, 2015) support these (2) depth estimates and reproduce the main paragenesis by simple fractional crystallization at 0.1-0.2 GPa. Our results may explain the recent seismic unrest below Osorno (from 2015 to 2019) with earthquakes mostly taking place between 0.1-0.3 GPa (4-10km below the summit). We suggest that Osorno is an important target to perform a comprehensive petrological study aiming at characterizing the Central-SVZ magmatic arc and the magmatic storage depths. How to cite: Bechon, T., Vander Auwera, J., Namur, O., Fugmann, P., Bolle, O., and Lara, L.: What is the magma storage depth under Osorno Volcano (Southern Volcanic Zone, Chile)?, EGU General Assembly 2020, Online, 4–8 May 2020, EGU2020-4848, https://doi.org/10.5194/egusphere-egu2020-4848, 202

Profondeur de différenciation sous le volcan Osorno (Chili)

Brève présentation des profondeurs de différenciations sous le volcan Osorno (Chili) à travers l'étude de la géochimie de ses roches