bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-Friendly for Whom? An Aperture to the Lived Experiences of Older San Franciscans
Authors: Yeh Jarmin 
Published: August 2021

Abstract

Background and Objectives
Spatial practices and changing urban environments affecting identity, experiences, and everyday life were examined among a diverse sample of older adults as they negotiated and navigated an age-friendly city.

Research Design and Methods
Ethnographic interviews, observations, and visual methods were used to understand spatial practices and lived experiences of 4 older adults, who chronicled their lives using disposable cameras.

Results
Informant identities emerged in their everyday practices, reflecting varied positionalities that fundamentally shaped their notions of “age-friendly.” Informants sought to sustain or improve their lives while attempting to negotiate socioenvironmental forms and forces that often threatened their identity and increased their precarity.

Discussion and Implications
Contrast exists between “invariant” macro/meso issues all older adults face as they age and “multivariant” ways in which age is accomplished based on place, biography, and intersectionality. Age-friendly environments may simultaneously maintain the status quo and exacerbate inequalities. Gerontology must take seriously how stratified life chances can undermine seemingly universal potential benefits of age-friendly environments.
Reflection on modern methods: visualizing the effects of collinearity in distributed lag models
Authors: Basagaña Xavier , Barrera-Gómez Jose 
Published: August 2021

Abstract
Collinearity can be a problem in regression models. When examining the effects of an exposure at different time points, constrained distributed lag models can alleviate some of the problems caused by collinearity. Still, some consequences of collinearity may remain and they are often unexplored. We aimed to illustrate the effects of collinearity in the context of distributed lag models, and to provide a tool to assess whether the results of a study could be influenced by collinearity. We used simulations under different scenarios of hypothesized effects of an exposure to visualize the resulting curves of lagged effects. We analysed three real datasets: a cohort study looking for windows of vulnerability to air pollution, a time series study examining the linear association of air pollution with hospital admissions, and a time series study examining the non-linear association between temperature and mortality. We showed that collinearity could be the explanation for some unexpected results, e.g. for statistically significant associations in the opposite direction from that expected, or for wrongly suggesting that some periods are more important than others. We implemented the collin R package to explore the potential consequences of collinearity in the context of distributed lag models. Our visual tool can be a useful way to assess if the results of an analysis may be influenced by collinearity.
Identifying critical failure information of thermal damaged sandstone through acoustic emission signal
Authors: Zhang Weiqiang , Shi Zhoujian , Wang Zuoquan , Zhang Shaoteng 
Published: August 2021

Abstract
The changes in the acoustic emission signals of sandstone after treatment at different high temperatures are examined in this study. The results show that there is a critical point on the cumulative energy curve of the acoustic emission signals (almost between 60 and 90% of the ratio of the loading time and the total loading time), which can be used to identify the failure of sandstone that has been damaged by exposure to a temperature of 900°C. As the temperature increases, the position of the critical point gradually changes, which indicates that high temperatures increase the plasticity of rock, and this gradually reduces the brittleness. The changes in b-value of acoustic emission shows that the transition behavior of rock from brittleness to plasticity is more obvious at temperatures higher than 600°C, and the large-scale micro cracking takes place at that temperature range, which is the main reason for the weakening and brittleness and the strengthening of plasticity of the sandstone.
Genomic Assessment of Global Population Structure in a Highly Migratory and Habitat Versatile Apex Predator, the Tiger Shark (Galeocerdo cuvier)
Authors: Bernard Andrea M , Finnegan Kimberly A , Pavinski Bitar Paulina , Stanhope Michael J , Shivji Mahmood S 
Published: August 2021

AbstractUnderstanding the population dynamics of highly mobile, widely distributed, oceanic sharks, many of which are overexploited, is necessary to aid their conservation management. We investigated the global population genomics of tiger sharks (Galeocerdo cuvier), a circumglobally distributed, apex predator displaying remarkable behavioral versatility in its diet, habitat use (near coastal, coral reef, pelagic), and individual movement patterns (spatially resident to long-distance migrations). We genotyped 242 tiger sharks from 10 globally distributed locations at more than 2000 single nucleotide polymorphisms. Although this species often conducts massive distance migrations, the data show strong genetic differentiation at both neutral (FST = 0.125–0.144) and candidate outlier loci (FST = 0.570–0.761) between western Atlantic and Indo-Pacific sharks, suggesting the potential for adaptation to the environments specific to these oceanic regions. Within these regions, there was mixed support for population differentiation between northern and southern hemispheres in the western Atlantic, and none for structure within the Indian Ocean. Notably, the results demonstrate a low level of population differentiation of tiger sharks from the remote Hawaiian archipelago compared with sharks from the Indian Ocean (FST = 0.003–0.005, P &lt; 0.01). Given concerns about biodiversity loss and marine ecosystem impacts caused by overfishing of oceanic sharks in the midst of rapid environmental change, our results suggest it imperative that international fishery management prioritize conservation of the evolutionary potential of the highly genetically differentiated Atlantic and Indo-Pacific populations of this unique apex predator. Furthermore, we suggest targeted management attention to tiger sharks in the Hawaiian archipelago based on a precautionary biodiversity conservation perspective.
Biosynthesis and biological function of secondary metabolites of the rice blast fungus Pyricularia oryzae
Authors: Motoyama Takayuki , Yun Choong-Soo , Osada Hiroyuki 
Published: August 2021

Abstract
Filamentous fungi have many secondary metabolism genes and produce a wide variety of secondary metabolites with complex and unique structures. However, the role of most secondary metabolites remains unclear. Moreover, most fungal secondary metabolism genes are silent or poorly expressed under laboratory conditions and are difficult to utilize. Pyricularia oryzae, the causal pathogen of rice blast disease, is a well-characterized plant pathogenic fungus. P. oryzae also has a large number of secondary metabolism genes and appears to be a suitable organism for analyzing secondary metabolites. However, in case of this fungus, biosynthetic genes for only four groups of secondary metabolites have been well characterized. Among two of the four groups of secondary metabolites, biosynthetic genes were identified by activating secondary metabolism. These secondary metabolites include melanin, a polyketide compound required for rice infection; tenuazonic acid, a well-known mycotoxin produced by various plant pathogenic fungi and biosynthesized by a unique nonribosomal peptide synthetase–polyketide synthase hybrid enzyme; nectriapyrones, antibacterial polyketide compounds produced mainly by symbiotic fungi, including plant pathogens and endophytes, and pyriculols, phytotoxic polyketide compounds. This review mainly focuses on the biosynthesis and biological functions of the four groups of P. oryzae secondary metabolites.
Root infection by the nematode Meloidogyne incognita modulates leaf antiherbivore defenses and plant resistance to Spodoptera exigua
Authors: Mbaluto Crispus M , Vergara Fredd , van Dam Nicole M , Martínez-Medina Ainhoa 
Published: August 2021

Abstract
Studies on plant-mediated interactions between root parasitic nematodes and aboveground herbivores are rapidly increasing. However, outcomes for the interacting organisms vary, and the mechanisms involved remain ambiguous. We hypothesized that the impact of root infection by the root-knot nematode Meloidogyne incognita on the performance of the aboveground caterpillar Spodoptera exigua is modulated by the nematode’s infection cycle. We challenged root-knot nematode-infected tomato plants with caterpillars when the nematode’s infection cycle was at the invasion, galling, and reproduction stages. We found that M. incognita root infection enhanced S. exigua performance during the galling stage, while it did not affect the caterpillar’s performance at the invasion and reproduction stages. Molecular and chemical analyses performed at the different stages of the nematode infection cycle revealed that M. incognita root infection systemically affected the jasmonic acid-, salicylic acid-, and abscisic acid-related responses, as well as the changes in the leaf metabolome triggered during S. exigua feeding. The M. incognita-induced leaf responses varied over the nematode’s root infection cycle. These findings suggest that specific leaf responses triggered systemically by the nematode at its different life-cycle stages underlie the differential impact of M. incognita on plant resistance against the caterpillar S. exigua.
Inference of the optical depth to reionization from low multipole temperature and polarization Planck data
Authors: de Belsunce Roger , Gratton Steven , Coulton William , Efstathiou George 
Published: August 2021

ABSTRACT
This paper explores methods for constructing low multipole temperature and polarization likelihoods from maps of the cosmic microwave background anisotropies that have complex noise properties and partial sky coverage. We use Planck 2018 High Frequency Instrument (HFI) and updated SRoll2 temperature and polarization maps to test our methods. We present three likelihood approximations based on quadratic cross spectrum estimators: (i) a variant of the simulation-based likelihood (SimBaL) techniques used in the Planck legacy papers to produce a low multipole EE likelihood; (ii) a semi-analytical likelihood approximation (momento) based on the principle of maximum entropy; (iii) a density-estimation ‘likelihood-free’ scheme (delfi). Approaches (ii) and (iii) can be generalized to produce low multipole joint temperature-polarization (TTTEEE) likelihoods. We present extensive tests of these methods on simulations with realistic correlated noise. We then analyse the Planck data and confirm the robustness of our method and likelihoods on multiple inter- and intra-frequency detector set combinations of SRoll2 maps. The three likelihood techniques give consistent results and support a low value of the optical depth to reoinization, τ, from the HFI. Our best estimate of τ comes from combining the low multipole SRoll2momento (TTTEEE) likelihood with the CamSpec high multipole likelihood and is $\tau = 0.0627^{+0.0050}_{-0.0058}$. This is consistent with the SRoll2 team’s determination of τ, though slightly higher by ∼0.5σ, mainly because of our joint treatment of temperature and polarization.
The survival of globular clusters in a cuspy Fornax
Authors: Shao Shi , Cautun Marius , Frenk Carlos S , Reina-Campos Marta , Deason Alis J , Crain Robert A , Kruijssen J M Diederik , Pfeffer Joel 
Published: August 2021

ABSTRACT
It has long been argued that the globular clusters (GCs) in the Fornax dwarf galaxy indicate that its dark matter halo is likely to have a shallow density profile with a core of size ∼1 kpc. We revisit this argument by investigating analogues of Fornax formed in MOdelling Star cluster population Assembly In Cosmological Simulations within eagle (E-MOSAICS), a cosmological hydrodynamical simulation that follows the formation and evolution of GCs in the Evolution and Assembly of GaLaxies and their Environments (EAGLE) galaxy formation model. In eagle, Fornax-mass haloes are cuspy and well described by the Navarro–Frenk–White profile. We post-process the E-MOSAICS to account for GC orbital decay by dynamical friction, which is not included in the original model. Dynamical friction causes 33 per cent of GCs with masses $M_{\rm GC}\ge 4\times 10^4{~\rm M_\odot }$ to sink to the centre of their host with the majority being tidally disrupted before forming a nuclear star cluster. Fornax has a total of five GCs, an exceptionally large number compared to other galaxies of similar stellar mass. In the simulations, we find that only 3 per cent of the Fornax analogues have five or more GCs, while 30 per cent have only one and 35 per cent have none. We find that GC systems in satellites are more centrally concentrated than in field dwarfs, and that those formed in situ (45 per cent) are more concentrated than those that were accreted. The present-day radial distribution of GCs in E-MOSAICS Fornax analogues is indistinguishable from that in Fornax, demonstrating that the presence of five GCs in the central kiloparsec of Fornax is consistent with a cuspy dark matter halo.
Cooperative DNA binding mediated by KicGAS/ORF52 oligomerization allows inhibition of DNA-induced phase separation and activation of cGAS
Authors: Bhowmik Debipreeta , Du Mingjian , Tian Yuan , Ma Siming , Wu Jianjun , Chen Zhijian , Yin Qian , Zhu Fanxiu 
Published: August 2021

AbstractCyclic GMP-AMP synthase (cGAS) is a key DNA sensor that detects aberrant cytosolic DNA arising from pathogen invasions or genotoxic stresses. Upon binding to DNA, cGAS is activated and catalyzes the synthesis of cyclic GMP-AMP (cGAMP), which induces potent antimicrobial and antitumor responses. Kaposi sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that causes Kaposi sarcoma and several other malignancies. We previously reported that KSHV inhibitor of cGAS (KicGAS) encoded by ORF52, inhibits cGAS enzymatic activity, but the underlying mechanisms remained unclear. To define the inhibitory mechanisms, here we performed in-depth biochemical and functional characterizations of KicGAS, and mapped its functional domains. We found KicGAS self-oligomerizes and binds to double stranded DNA cooperatively. This self-oligomerization is essential for its DNA binding and cGAS inhibition. Interestingly, KicGAS forms liquid droplets upon binding to DNA, which requires collective multivalent interactions with DNA mediated by both structured and disordered domains coordinated through the self-oligomerization of KicGAS. We also observed that KicGAS inhibits the DNA-induced phase separation and activation of cGAS. Our findings reveal a novel mechanism by which DNA viruses target the host protein phase separation for suppression of the host sensing of viral nucleic acids.
BSCI-02. METPlatform identifies brain metastasis vulnerabilities and predicts patient response to therapy
Authors: Zhu Lucía , Blanco-Aparicio Carmen , Bertero Luca , Soffietti Riccardo , Weiss Tobias , Muñoz Javier , Sepúlveda Juan Manuel , Weller Michael , Pastor Joaquín , Valiente Manuel 
Published: August 2021

Abstract
The diagnosis of brain metastasis involves high morbidity and mortality and remains an unmet clinical need in spite of being the most common tumor in the brain. Exclusion of these cancer patients from clinical trials is a major cause of their limited therapeutic options. We report a novel drug-screening platform (METPlatform) based on organotypic cultures which allows identifying effective anti-metastasis agents in the presence of the organ microenvironment. By applying this approach to brain metastasis, we identified heat shock protein 90 (HSP90) as a promising therapeutic target for CNS dissemination. DEBIO-0932, a blood-brain barrier permeable HSP90 inhibitor, shows high potency against mouse and human brain metastases from different primary origin and oncogenomic profile at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis of brain metastases treated with the chaperone inhibitor revealed non-canonical clients of HSP90 as potential novel mediators of brain metastasis and actionable mechanisms of resistance driven by autophagy. Combined therapy using HSP90 and autophagy inhibitors showed synergistic effects compared to sublethal concentrations of each monotherapy, demonstrating the potential of METPlatform to design and test rationale combination therapies to target metastasis more effectively. Finally, we have exploited METPlatform as “avatars” to show that brain tumor PDOCs predict response of the corresponding patient to standard of care, thus proving the potential of METPlatform for improving personalized care in cancer. In conclusion, our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is fully compatible with human samples and questions the rationale of excluding patients with brain metastasis from clinical trials. We envision that METPlatform will be established as a clinically relevant strategy to personalize the management of metastatic disease in the brain and elsewhere.
BSCI-08. In vivo two-photon characterization of tumor-associated macrophages and microglia (TAM/M) and CX3CR1 during different steps of brain metastasis formation from lung cancer
Authors: Zhang Wenlong , Karschnia Philipp , von Mücke-Heim Iven-Alex , Mulazzani Matthias , Zhou Xiolan , Xu Tao , Blobner Jens , Teske Nico , Langer Sigrid , Thon Niklas , Ishikawa-Ankerhold Hellen , Straube Andreas , Tonn Joerg-Christian , von Baumgarten Louisa 
Published: August 2021

Abstract

Background
Brain metastases represent a common complication of lung cancer and dramatically limit prognosis in affected patients. The influence of tumor-associated macrophages and microglia (TAM/M) and their receptor CX3CR1 on different steps of brain metastasis formation from lung cancer is poorly characterized, but might be of therapeutic relevance.

Methods
We established an orthotopic cerebral metastasis model using CX3CR1-proficient (CX3CR1GFP/wt) and -deficient (CX3CR1GFP/GFP) mice with green-fluorescent TAM/M. A cranial window was prepared, and intracarotid injection of red-fluorescent Lewis Lung Carcinoma-cells (tdtLLC) was performed two weeks later. Formation of brain metastases was followed by repetitive two-photon laser scanning microscopy.

Results
After intracarotid injection, intravascular tumor cells extravasated into the cerebral parenchyma and eventually formed micrometastases (≤50 cells) and mature macrometastases (&gt;50 cells). We observed phagocytosis of extravasated tumor cells by TAM/M during early steps of metastatic growth. Notably, these anti-tumor effects of TAM/M diminished during later steps of metastasis formation and were accompanied by TAM/M accumulation and activation. CX3CR1-deficiency resulted in a lower number of extravasated tumor cells, and only a small number of TAM/M were visualized during early steps of metastasis formation (extravasation, formation of micrometastases) in such mice. In contrast, progression of extravasated tumor cells into micrometastases was more frequently found in CX3CR1-deficient mice. Overall, these mechanisms resulted in a comparable number of mature macrometastases between CX3CR1-deficient and -proficient mice.

Conclusion
Our findings indicate that unspecific inhibition of CX3CR1 might not be a suitable therapeutic approach to prevent cerebral dissemination of lung cancer cells. Given the close interaction between TAM/M and tumour cells during metastasis formation, other therapeutic approaches targeting TAM/M function warrant evaluation. Such concepts might be evaluated in vivo using the herein established orthotopic mouse model.
BSCI-10. Invasive growth of brain metastases is driven by cancer cell-pSTAT3+ reactive astrocyte crosstalk
Authors: Dankner Matthew , Maritan Sarah , Zhuang Rebecca , Caron Maxime , Priego Neibla , Valiente Manuel , Petrecca Kevin , Siegel Peter 
Published: August 2021

Abstract

Background
Brain metastases (BrM) with a highly invasive (HI) histological growth pattern are associated with poor prognosis compared to minimally invasive (MI) masses. Compared to MI lesions, HI BrM form greater contacts with cells in the peritumoral brain, particularly reactive astrocytes (RAs). RAs expressing phosphorylated STAT3 (pSTAT3+RAs) have been shown to promote BrM colonization. Here, we investigate the role of pSTAT3+RAs in promoting invasive growth of HI BrM.

Methods
We performed immunohistochemistry to identify pSTAT3+RAs in HI and MI human and patient-derived xenograft BrM. We assessed how pharmacological STAT3 inhibition or RA-specific STAT3 genetic ablation affected HI and MI BrM growth in vivo. scRNA-seq data generated from HI BrM astrocytes were integrated with published RA secretome data to identify STAT3 targets expressed by RAs that may drive invasion. Cancer cell invasion was modeled in vitro using a brain slice-tumor co-culture assay.

Results
HI BrM display increased pSTAT3-positivity within RAs when compared to MI lesions. Pharmacological STAT3 inhibition with Legasil (Silibinin) or genetic ablation decreased in vivo growth of HI, but not MI, BrM. Brain slice cultures treated with STAT3-activating cytokines induced cancer cell invasion, a response that was ablated following STAT3 inhibition. Chi3L1 was identified as a STAT3 target expressed by RAs. Cancer cells treated with recombinant Chi3L1 showed greater invasion into brain slice cultures compared to untreated cells.

Conclusions
pSTAT3+RAs are over-represented in HI BrM, rendering HI BrM preferentially sensitive to STAT3 inhibition. pSTAT3+RAs functionally contribute to BrM invasion within the brain, in part through Chi3L1-mediated activity. This work identifies STAT3 and Chi3L1 as clinically relevant therapeutic targets in management of HI BrM.