A Detailed Study of Giants and Horizontal Branch Stars in M68: Atmospheric Parameters and Chemical Abundances

In this paper, we present a detailed high-resolution spectroscopic study of post main sequence stars in the Globular Cluster M68. Our sample, which covers a range of 4000 K in $T_{eff}$, and 3.5 dex in $log(g)$, is comprised of members from the red giant, red horizontal, and blue horizontal branch, making this the first high-resolution globular cluster study covering such a large evolutionary and parameter space. Initially, atmospheric parameters were determined using photometric as well as spectroscopic methods, both of which resulted in unphysical and unexpected $T_{eff}$, $log(g)$, $\xi_{t}$, and [Fe/H] combinations. We therefore developed a hybrid approach that addresses most of these problems, and yields atmospheric parameters that agree well with other measurements in the literature. Furthermore, our derived stellar metallicities are consistent across all evolutionary stages, with $\langle$[Fe/H]$\rangle$ = $-$2.42 ($\sigma$ = 0.14) from 25 stars. Chemical abundances obtained using our methodology also agree with previous studies and bear all the hallmarks of globular clusters, such as a Na-O anti-correlation, constant Ca abundances, and mild $r$-process enrichment.Comment: Accepted to the Astronomical Journa

Imagination Enviro-Station: Students Connecting Students to Ecological Sustainability

The development of an environmental identity is viewed by many as essential if we are to reorganize our societies toward ecological sustainability (Bell 2009; Clayton and Opotow 2003; Thomashow 2002). That, along with an eye toward environmental justice, was the major impetus for our graduate seminar in applied environmental sociology to partner with an elementary school in our small city of Hammond, LA, during the spring semester of 2010. After conducting focus groups with a group of fourth to sixth grade students and holding decision-making discussions with them for this community-based research (CBR) project, we went about two projects – planting native, “water loving” trees and installing rain barrels to mitigate flooding on their playground. A major goal of the project and purpose of CBR is to democratize the knowledge-making process (Strand et al. 2003). Thus, we sought to assist the students in gaining valuable skills. Specifically, students learned how to sustainably remedy their school’s drainage problem, enhance their outdoor space, encourage more communal interaction, and develop more of an ecological identity (Thomashow 2002). We also hoped to plant the seeds of future career possibilities that would benefit their communities. This paper traces the development and learning outcomes of this CBR project focused on environmental identity

Elucidation of focal adhesion kinase as a modulator of migration and invasion and as a potential therapeutic target in chronic lymphocytic leukemia

The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance, leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier, and the lymph node interaction between CLL cells and activated T cells. Initially, CLL cells were co-cultured with CD40L-expressing fibroblasts and exhibited an activated B-cell phenotype, and their transcriptional signatures demonstrated the upregulation of pro-survival and anti-apoptotic genes and overrepresentation of the NF-κB signaling pathway. Using our dynamic circulating model, we were able to study the transcriptomics and miRNomics associated with CLL migration. More than 3000 genes were altered when CLL cells underwent transendothelial migration, with an overrepresentation of adhesion and cell migration gene sets. From this analysis, an upregulation of the FAK signaling pathway was observed. Importantly, PTK2 (FAK) gene expression was significantly upregulated in migrating CLL cells (PTK2 Fold-change = 4.9). Here we demonstrate that TLR9 agonism increased levels of p-FAK (p ≤ 0.05), which could be prevented by pharmacological inhibition of FAK with defactinib (p ≤ 0.01). Furthermore, a reduction in CLL cell migration and invasion was observed when FAK was inhibited (p ≤ 0.0001), supporting a role for FAK in both CLL migration and tissue invasion. When taken together, our data highlights the potential for combining FAK inhibition with current targeted therapies as a more effective treatment regime for CLL

Targeting the non-canonical NF-κB pathway in chronic lymphocytic leukemia and multiple myeloma

In this study, we evaluated an NF-κB inducing kinase (NIK) inhibitor, CW15337, in primary chronic lymphocytic leukemia (CLL) cells, CLL and multiple myeloma (MM) cell lines and normal B-and T-lymphocytes. Basal NF-κB subunit activity was characterized using an enzyme linked immunosorbent assay (ELISA), and the effects of NIK inhibition were then assessed in terms of cytotoxicity and the expression of nuclear NF-κB subunits following monoculture and co-culture with CD40L-expressing fibroblasts, as a model of the lymphoid niche. CW15337 induced a dose-dependent increase in apoptosis, and nuclear expression of the non-canonical NF-κB subunit, p52, was correlated with sensitivity to CW15337 (p = 0.01; r2 = 0.39). Co-culture on CD40L-expressing cells induced both canonical and non-canonical subunit expression in nuclear extracts, which promoted in vitro resistance against fludarabine and ABT-199 (venetoclax) but not CW15337. Furthermore, the combination of CW15337 with fludarabine or ABT-199 showed cytotoxic synergy. Mechanistically, CW15337 caused the selective inhibition of non-canonical NF-κB subunits and the transcriptional repression of BCL2L1, BCL2A1 and MCL1 gene transcription. Taken together, these data suggest that the NIK inhibitor, CW15337, exerts its effects via suppression of the non-canonical NF-κB signaling pathway, which reverses BCL2 family-mediated resistance in the context of CD40L stimulation

SPLUS J142445.34-254247.1: An R-Process Enhanced, Actinide-Boost, Extremely Metal-Poor star observed with GHOST

We report on the chemo-dynamical analysis of SPLUS J142445.34-254247.1, an extremely metal-poor halo star enhanced in elements formed by the rapid neutron-capture process. This star was first selected as a metal-poor candidate from its narrow-band S-PLUS photometry and followed up spectroscopically in medium-resolution with Gemini South/GMOS, which confirmed its low-metallicity status. High-resolution spectroscopy was gathered with GHOST at Gemini South, allowing for the determination of chemical abundances for 36 elements, from carbon to thorium. At [Fe/H]=-3.39, SPLUS J1424-2542 is one of the lowest metallicity stars with measured Th and has the highest logeps(Th/Eu) observed to date, making it part of the "actinide-boost" category of r-process enhanced stars. The analysis presented here suggests that the gas cloud from which SPLUS J1424-2542 was formed must have been enriched by at least two progenitor populations. The light-element (Z<=30) abundance pattern is consistent with the yields from a supernova explosion of metal-free stars with 11.3-13.4 Msun, and the heavy-element (Z>=38) abundance pattern can be reproduced by the yields from a neutron star merger (1.66Msun and 1.27Msun) event. A kinematical analysis also reveals that SPLUS J1424-2542 is a low-mass, old halo star with a likely in-situ origin, not associated with any known early merger events in the Milky Way.Comment: 26 pages, 11 figures, accepted for publication on Ap

Modern meat: the next generation of meat from cells

Modern Meat is the first textbook on cultivated meat, with contributions from over 100 experts within the cultivated meat community. The Sections of Modern Meat comprise 5 broad categories of cultivated meat: Context, Impact, Science, Society, and World. The 19 chapters of Modern Meat, spread across these 5 sections, provide detailed entries on cultivated meat. They extensively tour a range of topics including the impact of cultivated meat on humans and animals, the bioprocess of cultivated meat production, how cultivated meat may become a food option in Space and on Mars, and how cultivated meat may impact the economy, culture, and tradition of Asia

TLR9 expression in chronic lymphocytic leukemia identifies a promigratory subpopulation and novel therapeutic target

Chronic lymphocytic leukemia (CLL) remains incurable despite B-cell receptor–targeted inhibitors revolutionizing treatment. This suggests that other signaling molecules are involved in disease escape mechanisms and resistance. Toll-like receptor 9 (TLR9) is a promising candidate that is activated by unmethylated cytosine guanine dinucleotide–DNA. Here, we show that plasma from patients with CLL contains significantly more unmethylated DNA than plasma from healthy control subjects (P < .0001) and that cell-free DNA levels correlate with the prognostic markers CD38, β(2)-microglobulin, and lymphocyte doubling time. Furthermore, elevated cell-free DNA was associated with shorter time to first treatment (hazard ratio, 4.0; P = .003). We also show that TLR9 expression was associated with in vitro CLL cell migration (P < .001), and intracellular endosomal TLR9 strongly correlated with aberrant surface expression (sTLR9; r = 0.9). In addition, lymph node–derived CLL cells exhibited increased sTLR9 (P = .016), and RNA-sequencing of paired sTLR9(hi) and sTLR9(lo) CLL cells revealed differential transcription of genes involved in TLR signaling, adhesion, motility, and inflammation in sTLR9(hi) cells. Mechanistically, a TLR9 agonist, ODN2006, promoted CLL cell migration (P < .001) that was mediated by p65 NF-κB and STAT3 transcription factor activation. Importantly, autologous plasma induced the same effects, which were reversed by a TLR9 antagonist. Furthermore, high TLR9 expression promoted engraftment and rapid disease progression in a NOD/Shi-scid/IL-2Rγ(null) mouse xenograft model. Finally, we showed that dual targeting of TLR9 and Bruton’s tyrosine kinase (BTK) was strongly synergistic (median combination index, 0.2 at half maximal effective dose), which highlights the distinct role for TLR9 signaling in CLL and the potential for combined targeting of TLR9 and BTK as a more effective treatment strategy in this incurable disease