bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decision Outcomes in Sport: Influence of Type and Level of Stress
Authors: Hepler Teri J. , Andre Matt 
Published: December 2020

In two experiments, the authors investigated the influence of stress type (i.e., low/no stress, mental, and physical), level (i.e., low, moderate, and high), and Type × Level interaction on intuitive decision frequency, decision quality, and decision speed. Participants were exposed to mental (i.e., color word task, mental arithmetic) and/or physical stress (i.e., running) and then required to make decisions regarding videotaped offensive situations in basketball. Intuitive decision frequency, decision quality, and decision speed were measured for each trial. Study 1 used a between-subjects design whereby 20 participants were randomly assigned to each of the five stress conditions. Results revealed that moderate stress was associated with faster decisions. Study 2 replicated the design and aim of Study 1 using a within-subject methodology (n = 42). Results suggested that moderate stress levels produced better, faster decisions. In conclusion, moderate levels of stress were associated with the most desirable decision outcomes.
Hotspot signatures at the North American passive margin
Authors: Tao Zhongmin , Li Aibing , Fischer Karen M. 
Published: December 2020

AbstractThe presence of localized low-velocity anomalies in the upper mantle beneath the passive Atlantic margin in North America is a puzzling geophysical observation. Whether the anomalies are caused by the remnant heat from past hotspots or ongoing asthenospheric upwelling is still debated. We addressed the formation of the anomalies based on a recent velocity model for eastern North America, which reveals new information on their shapes and anisotropic signatures. The low-velocity anomaly in New England appears as a narrow column above 90 km depth and broadens westward at depths of 120–200 km. Two slow anomalies are imaged under the central Appalachian Mountains between 140 km and 240 km. These low velocities correspond to pronounced positive radial anisotropy (Vsh &gt; Vsv), indicating a dominantly horizontal asthenospheric flow. They also coincide with the tracks of the Great Meteor hotspot (140–115 Ma) and an inferred hidden hotspot (60–50 Ma). The anomalies in the central Appalachians could be due to lithospheric interaction with the second hotspot and subsequent lithospheric instabilities. The complex shape of the New England anomaly is consistent with interaction with both hotspots. The first hotspot could have eroded the base of the lithosphere, forming a channel, and the second hotspot could have further thinned the lithosphere and produced a localized cavity at shallow depths. Consequently, the indented lithosphere base would have filled with channelized asthenospheric flow or produced small-scale convection, helping to sustain the slow anomaly. Low-velocity anomalies at the North America passive margin are likely the consequences of prior hotspot interactions.
Mechanical contrast and asymmetric distribution of crustal deformation across plate boundaries: Insights from the northern Dead Sea fault system
Authors: Dembo Neta , Granot Roi , Hamiel Yariv 
Published: December 2020

Abstract
The distribution of permanent deformation near strike-slip plate boundaries and the underlying controlling variables are commonly poorly understood. Here we examine the crustal deformation across the northern Dead Sea fault system based on paleomagnetic observations and mechanical modeling. We focus our investigation on the region of the Lebanese restraining bend where the fault system strikes obliquely to the general Sinai-Arabia plate motion. We construct a series of crustal elasto-plastic models in which kinematics is based on geodetic measurements, and the geometry of the plate boundary is constrained by gravity data. Both the observed regional vertical axis rotations and the model results display significant counterclockwise rotations (as much as ∼50°) confined to the northern Sinai microplate located west of the bend. On the other hand, relatively minor rotations (&lt;∼10°) are displayed for the adjacent Arabian plate. Our results, validated by structural evidence, suggest that the northern Sinai microplate is mechanically weaker than the adjacent crust of the Arabian plate. This mechanical contrast, along with the oblique convergence and change of slip rate along the Dead Sea fault system, is required to simulate the observed rotations. We propose that the crustal mechanical contrast across plate boundaries is a key parameter responsible for the distribution pattern of permanent vertical axis rotations.
Inconsistent effects of nitrogen canopy enrichment and soil warming on black spruce epiphytic phyllosphere bacterial communities, taxa, and functions
Authors: Khlifa Rim , Houle Daniel , Morin Hubert , Kembel Steven W. 
Published: December 2020

Phyllosphere microbial communities have received considerable attention given their important influence on their plant hosts and on ecosystem functioning. In a context where climate change threatens the sustainability of ecosystems, it is important to understand how phyllosphere microbes will respond to changes in their environment. We used 16S rRNA gene amplicon sequencing to quantify phyllosphere bacterial communities of black spruce (Picea mariana (Mill.) B.S.P.) exposed to nitrogen canopy enrichment and soil warming in the boreal forest of Quebec, Canada. The treatments were applied from April to September 2015 and the sampling was done in September. Neither treatment influenced the overall community structure and diversity of black spruce phyllosphere bacterial communities. However, some bacterial taxa and inferred microbial functions did differ among treatments, revealing in particular a stronger response of some bacteria to soil warming rather than nitrogen enrichment. Our results suggest that soil warming could potentially induce more changes in phyllosphere bacterial taxa abundances and functions than could nitrogen addition, with potential consequences for microbial diversity and boreal forest ecosystem function under likely climate change scenarios. Our study suggests avenues for further research to integrate a more mechanistic understanding of the importance of phyllosphere microbes for black spruce and boreal forest ecosystems.
Marine dinocysts, acritarchs and less well-known NPP: tintinnids, ostracod and foraminiferal linings, copepod and worm remains
Authors: Mudie P. J. , Marret F. , Gurdebeke P. R. , Hartman J. D. , Reid P. C. 
Published: December 2020

Abstract

Nine non-pollen palynomorph (NPP) groups occur in Quaternary marine and brackish-water sediments; these groups represent various planktonic or micro- to macrobenthic organisms. Some extant NPP were previously classified as fossil Acritarcha, Chitinozoa or scolecodonts. We refer to reviews of these fossils and their applications for Paleozoic–Mesozoic biostratigraphy and palaeoecology but focus on extant marine NPP that can be studied by laboratory culture, genetics or micro-geochemical methods. Marine NPP include resting cysts of planktonic dinoflagellates and prasinophytes, tintinnids and other cilates, copepod eggs and skeletal remains, and various microzoobenthos: microforaminiferal organic linings, ostracod mandibles and carapace linings, various worm egg capsules and mouthparts. New micro-Fourier Transform Infrared spectroscopy spectra suggest the probable affinities of the tintinnid cyst type P and
Beringiella
. Our applications in marine biodiversity and provincialism studies emphasize under-studied polar regions and neglected ice-algae nano-plankton and compare climate-based NPP distributions to Ocean Biogeographic Information System realms. Trophic relationships are outlined using sediment-trap studies. Seasonal to annual-scale investigations of palaeoproduction provide new perspectives on ocean carbon budgets during times of rapid climate change and atmospheric carbon increase. More taxonomic and source-linkage studies of non-dinocyst marine NPP are needed but we outline potentials for studies of hemispheric or global-scale shifts in marine food webs as driven by ocean warming.
Abstract A08: PI3Kbeta regulates beta-1 integrin signaling in invadopodia through formation of PI(3,4)P2
Authors: Erami Zahra , Bresnick Anne R. , Backer Jonathan M. 
Published: December 2020

Abstract
The PI3Kbeta isoform of PI 3-kinase, which is activated downstream from both RTKs and GPCRs, is an important regulator of invadopodia formation. We have previously reported that in MDA-MB-231 breast cancer cells, replacement of endogenous PI3Kbeta with kinase dead (KD) or GPCR-uncoupled (KK-DD) mutants leads to defects in invadopodia-mediated gelatin degradation. We have now studied the mechanism by which loss of PI3Kbeta signaling affects invadopodia. While the number of invadopodia precursors is unaffected by mutation of PI3Kbeta, formation of mature invadopodia is reduced in cells expressing KK-DD and KD PI3Kbeta mutants. Previous studies have demonstrated a role for beta-1 integrins in invadopodia maturation, and PI3Kbeta has been implicated in integrin signaling in platelets. We therefore tested whether mutation of PI3Kbeta would affect integrin signaling in breast cancer cells. In both haptotaxis and cell spreading assays on collagen I, cells expressing KD or KK-DD PI3Kbeta showed a significant impairment. Haptotaxis and cell spreading was also inhibited by TGX221 (PI3Kbeta inhibitor) and pertussis toxin (PTX), but not by specific inhibitors of other Class I PI3Ks. To distinguish whether PI3Kbeta was acting on integrins by inside-out versus outside-in mechanisms, we treated cells with the activating beta-1 integrin antibody TS2/16, which bypasses inside-out regulation of integrin binding. TS2/16 increased cell spreading on gelatin, but this was blocked by TGX221, suggesting that PI3Kbeta acts downstream of beta-1 integrins. Importantly, haptotaxis and cell spreading were not affected by an Akt inhibitor, but were blocked by an inhibitor of SHIP2, which hydrolyzes PIP3 to produce PI[3,4]P2. These data suggest that integrin signaling requires the coupling of Gbeta/gamma-mediated activation of PI3Kbeta to the production of PI[3,4]P2. Finally, to determine whether PI3Kbeta was involved in beta-1 integrin signaling in invadopodia, we plated starved cells on high-density fibrillar collagen (HDFC), which drives invadopodia formation through beta-1 integrin activation. Collagen degradation on HDFC was blocked by inhibition of PI3Kbeta or SHIP2, but not PI3Kalpha. Moreover, recruitment of the PI(3,4)P2 binding protein lamellipodin to invadopodia was reduced by inhibition of PI3Kbeta. In summary, beta-1 integrin signaling in the context of invadopodia maturation requires signaling through PI3Kbeta. We propose that heterotrimeric G-protein activation of PI3Kbeta is necessary for formation of PI(3,4)P2 in invadopodia, which is required for invadopodial maturation.
Citation Format: Zahra Erami, Anne R. Bresnick, Jonathan M. Backer. PI3Kbeta regulates beta-1 integrin signaling in invadopodia through formation of PI(3,4)P2 [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A08.
Abstract A18: Selectively targeting PI3K isoforms to treat glioblastoma
Authors: Pridham Kevin J. , Le Lamvy , Guo Sujuan , Varghese Robin T. , Liang Yanping , Rodgers Cara M. , Simonds Gary R. , Kelly Deborah F. , Sheng Zhi 
Published: December 2020

Abstract
The phosphatidylinositide 3-kinase (PI3K) family consists of four catalytic isoforms (PIK3CA, B, D, and G that encode p110alpha, beta, delta, and gamma, respectively), which play deviating roles in the formation and progression of different types of cancer such as breast and colon cancers. However, whether these PI3K isoforms function differently or equivalently in glioblastoma has not yet been explored. Glioblastoma is the most common and aggressive malignant glioma and patients often succumb to tumor recurrence, a progressive disease state that significantly contributes to the poor prognosis of glioblastoma. PI3K signaling is hyperactivated and mutated in glioblastoma; however, targeting PI3K to treat this cancer has not yet been successful. Given that PI3K isoforms are functionally divergent, it is very likely that selectively targeting PI3K catalytic isoforms is a more effective and discriminating approach to treating GBM. This possibility is supported by the following lines of evidence. Firstly, among four PI3K catalytic isoforms, PIK3CB is highly expressed in glioblastoma and high levels of PIK3CB exhibit the strongest correlation with the incidence, risk (time to develop recurrence), and survival of glioblastoma recurrence based upon expression data of PI3K isoforms and patient data from The Cancer Genome Atlas. Secondly, PI3K is often hyperactivated in glioblastoma cells with high levels of p110beta, but not other p110s, and depletion of p110beta inactivates, whereas knockdown of other p110s has no effect on, PI3K activity as well as glioblastoma cell survival. Thirdly, the selective activation of p110beta may be due primarily to a gap junction protein connexin 43 because this cell surface protein activates p110beta in p110beta-high glioblastoma cells through a selective interaction between connexin 43 and p110beta. Lastly, glioblastoma cells display differential responses to p110 isoform-selective inhibitors. Only p110beta selective inhibitors effectively activate apoptosis in, suppress the viability of, and impede the xenograft growth of p110beta hyperactivated glioblastoma cells. More importantly, p110beta inhibitors are much less toxic to normal astrocytes than other p110 inhibitors. These findings have revealed molecular details underlying the divergent roles of PI3K catalytic isoforms in glioblastoma, which will foster a rational design of more effective PI3K-based therapies for this deadly disease.
Citation Format: Kevin J. Pridham, Lamvy Le, Sujuan Guo, Robin T. Varghese, Yanping Liang, Cara M. Rodgers, Gary R. Simonds, Deborah F. Kelly, Zhi Sheng. Selectively targeting PI3K isoforms to treat glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A18.
Abstract A26: mTOR inhibition promotes differentiation of human regulatory T cells via privileged mRNA translation
Authors: Volta Viviana , Ernlund Amanda , Gadi Abhilash , Valeta-Magara Amanda , de la Parra Columba , Patel Preeyam , Schneider Robert J. 
Published: December 2020

Abstract
Regulatory T cells (Tregs) maintain immune system homeostasis in the organism. In the tumor microenvironment, however, Tregs can hinder the antitumor immune response. Treg maturation in peripheral sites (pTregs) requires inhibition of protein kinase mTORC1, which paradoxically blocks mRNA translation. mTORC1 phosphorylates (inactivates) 4E-BP1, a negative regulator of the translation initiation factor eIF4E. When mTORC1 is active, 4E-BP1 is hyperphosphorylated and releases eIF4E, which can then bind the mRNA cap structure and promote eIF4F complex assembly and ribosome recruitment. Inhibition of mTORC1 results in hypo-phosphorylation (activation) of 4E-BP1, which then binds and sequesters eIF4E, preventing its interaction with the cap and ribosome association to the mRNA. Using human CD4+ T cells differentiated in vitro, we show that mTORC1 inhibition strongly impairs protein synthesis, yet with exposure to TGFbeta is essential to mediate iTreg differentiation and immune suppression activity. We found that TGFbeta reprograms the T-cell transcriptome, while mTORC1 inhibition reprograms the translatome (genome-wide translation signature), mediating Treg differentiation. Genome-wide transcription and translation profiling identified TGFbeta-upregulated mRNAs resistant to mTORC1 inhibition, in part due to their 5'-untranslated regions, that induce Treg differentiation and immune-suppression activity. These include canonical pTreg fate-determining mRNAs FOXP3, CTLA-4, CD101 and CD103, among others. Inhibition of mTORC1 alone, or TGFbeta alone, induces iTregs with poor immune-suppression activity. Treg differentiation is therefore mediated by an mTORC1-independent privileged mRNA translation mechanism that converts activated CD4+ T cells to Tregs. These findings are quite relevant in the tumor microenvironment, where mTORC1-inhibiting conditions such as hypoxia and deprivation of nutrients and energy are present. Investigation of molecular targets acting in this mTORC1/eIF4E-independent translation of Treg mRNAs is ongoing. These targets could be drugged to selectively inhibit Treg differentiation in the tumor microenvironment, thus allowing effector cells to mount the response against cancer cells.
Citation Format: Viviana Volta, Amanda Ernlund, Abhilash Gadi, Amanda Valeta-Magara, Columba de la Parra, Preeyam Patel, Robert J. Schneider. mTOR inhibition promotes differentiation of human regulatory T cells via privileged mRNA translation [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A26.
Abstract A29: Targeted disruption of PI3K/Akt/mTOR signaling pathway induces cell cycle arrest, apoptosis, autophagy, and inhibits inflammation, invasion, and angiogenesis of OSCC cells
Authors: Aggarwal Sadhna , John Sarah , Das Satya N. , Sharma Suresh C. 
Published: December 2020

Abstract
Purpose: The phosphoinositide-3-kinase (PI3K) pathway is frequently altered in human cancer. This has led to the development and study of novel PI3K inhibitors for targeted therapy and also to overcome resistance to radiotherapy.
Method: The antitumor effects of PI3K inhibitors (PI-828, PI-103 and PX-866) in terms of cell proliferation, colony formation, induction of apoptosis, cell cycle arrest, invasion, autophagy, and pNF- κB/p65 translocation in SCC-4, SCC-9 and SCC-25 cells were studied by performing MTT, clonogenic, DAPI staining, propidium iodide staining, annexin–V binding, Matrigel invasion, acridine orange staining and immunofluorescence assay. Western blot assay was performed to assess the alteration in the expression of various proteins.
Result: PI-828 and PI-103 treatment exhibited dose-dependent inhibition of growth and proliferation of OSCC cells with a concomitant induction of apoptosis, altered cell cycle regulation and decreased invasiveness (p &lt;0.01). PX-866 induced apoptosis, cell cycle arrest, autophagy and a significant decrease in the invasiveness of oral cancer cells as compared to untreated cells (p &lt;0.01). These compounds significantly reduced expression of COX-2, Cyclin-D and VEGF in the treated cells besides cytoplasmic accumulation of pNF-κB/p65 protein. In addition to PI3Kα, inactivation of downstream components, i.e., Akt and mTOR was seen.
Conclusion: PI3K inhibitors such as PI-103, PI-828 and PX-866 may be developed as potential chemotherapeutic agents for effective treatment of OSCC and other malignancies associated with activated PI3K/Akt pathway.
Note: This abstract was not presented at the conference.
Citation Format: Sadhna Aggarwal, Sarah John, Satya N. Das, Suresh C. Sharma. Targeted disruption of PI3K/Akt/mTOR signaling pathway induces cell cycle arrest, apoptosis, autophagy, and inhibits inflammation, invasion, and angiogenesis of OSCC cells [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A29.
Abstract B07: TAK228 enhances antitumor activity of eribulin in triple-negative breast cancer
Authors: Owusu-Brackett Nicci , Evans Kurt W. , Akcakanat Argun , Yuca Erkan , Dumbrava Ecaterina Ileana , Janku Filip , Meric-Bernstam Funda 
Published: December 2020

Abstract
Background: Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) negatively regulates the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway. Triple-negative breast cancers (TNBC) are often PTEN-deficient, making mTOR a compelling target. We evaluated the efficacy of catalytic mTOR inhibitor TAK228 alone and in combination with eribulin in TNBC.
Methods: We tested TAK228 in combination with eribulin in a panel of TNBC cell lines with cell proliferation assays. Western blot analysis was performed to assess PTEN status and PI3K pathway inhibition. In vivo, antitumor efficacy of TAK228 as a single agent as well as in combination with eribulin was evaluated.
Results: Five of eight triple-negative breast cell lines were sensitive to TAK228, independent of PIK3CA/PTEN status. Western blotting demonstrated inhibition of mTORC1/2 signaling as demonstrated by decreased phospho-AKT, phospho-S6 and phospho-4EBP1. In vitro, TAK228 was synergistic with eribulin in all eight TNBC cell lines. The combination of TAK228 and eribulin did not enhance apoptosis but increased G2/M growth arrest (p&lt;0.001). In vivo, TAK228 led to modest growth inhibition in TNBC derived xenografts with no tumor regression observed. In two TNBC PDXs with PTEN loss, one with intrinsic eribulin sensitivity, another eribulin resistance, TAK228 in combination with eribulin did not enhance in vivo efficacy. In a third PTEN-negative TNBC model, eribulin alone achieved disease stabilization, but the combination of TAK228 and eribulin led to significantly smaller tumor volumes compared to eribulin alone (p&lt;0.0001).
Conclusion: TAK228 enhanced the antitumor efficacy of eribulin in TNBC models in vitro and enhanced in vivo activity in selected models. Further study is needed to determine the potential of this combination and optimal patient selection strategies.
Citation Format: Nicci Owusu-Brackett, Kurt W. Evans, Argun Akcakanat, Erkan Yuca, Ecaterina Ileana Dumbrava, Filip Janku, Funda Meric-Bernstam. TAK228 enhances antitumor activity of eribulin in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr B07.