bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attribution of Land‐Use/Land‐Cover Change Induced Surface Temperature Anomaly: How Accurate Is the First‐Order Taylor Series Expansion?
Authors: Chen Chi , Wang Liang , Myneni Ranga B. , Li Dan 
Published: September 2020

AbstractLand surface temperature (LST) responds to land‐use/land‐cover change (LULCC), which modifies surface properties that control the surface energy balance (SEB). Quantifying changes in LST due to individual perturbations caused by LULCC is an attribution problem. Most attribution methods are based on the first‐order Taylor series expansion (FOTSE) of a linearized SEB equation. The accuracy of these methods is affected by the use of FOTSE at two places. The first is to linearize the SEB equation and to obtain an analytical solution for LST (the LST model), and the second is to obtain LST changes as the linear sum of concurrent changes in multiple factors (the attribution model). In this study, we systematically assess the importance of non‐linear effects lost in these linearization processes using the second‐order Taylor series expansion (SOTSE). Results show that while the SOTSE LST model outperforms the FOTSE LST model, the order of Taylor series expansion in the LST model does not significantly influence the attribution of LST changes. However, the SOTSE attribution model is considerably more accurate than the FOTSE attribution model, especially when the magnitude of perturbations is large. Results suggest that contributions from higher‐order and cross‐order terms in the attribution model can be as large as 50%. Sensitivity analysis further shows that non‐linear effects associated with changing surface resistance for LULCC scenarios with large perturbations (e.g., deforestation and urbanization) are particularly strong. In conclusion, we recommend using the FOTSE LST model and the SOTSE attribution model.
Tumor-derived HMGB1 induces CD62Ldim neutrophil polarization and promotes lung metastasis in triple-negative breast cancer
Authors: Wang Zhen , Yang Chenghui , Li Lili , Jin Xiaoyan , Zhang Zhigang , Zheng Haiyan , Pan Jun , Shi Liyun , Jiang Zhou , Su Ke , Li Baizhou , Shao Xuan , Qiu Fuming , Yan Jun , Huang Jian 
Published: September 2020

AbstractTriple-negative breast cancer (TNBC) is highly aggressive, difficult to treat and commonly develops visceral metastasis, including lung metastasis. We observed that High mobility group box 1 protein (HMGB1) was highly expressed in human TNBC and positively correlated with cancer metastasis. The hypoxic tumor environment is known to regulate HMGB1 secretion, but an understanding of the underlying mechanism by which tumor-derived HMGB1 regulates interstitial components and promotes breast cancer lung metastasis has remained elusive. The results of the present study showed that the number of CD62Ldim neutrophils, which have a strong ability to produce neutrophil extracellular traps (NETs), increased significantly in both peripheral blood and lung tissues in a mouse TNBC model and were regulated by tumor-derived HMGB1 through the TLR2 pathway. Furthermore, serum HMGB1 levels were positively correlated with CD62Ldim neutrophils in 86 breast cancer patients. We demonstrated that CD62Ldim neutrophils accelerated lung metastasis and that interventions targeting the “HMGB1-CD62Ldim neutrophil-NETs” axis could inhibit lung metastasis. Our results suggest that the combination of HMGB1 and CD62Ldim neutrophils is a potential marker for breast cancer lung metastasis and is novel target for future prevention and therapy.
Breast cancer survival in Nordic BRCA2 mutation carriers—unconventional association with oestrogen receptor status
Authors: Olafsdottir Elinborg J. , Borg Ake , Jensen Maj-Britt , Gerdes Anne-Marie , Johansson Anna L. V. , Barkardottir Rosa B. , Johannsson Oskar T. , Ejlertsen Bent , Sønderstrup Ida Marie Heeholm , Hovig Eivind , Lænkholm Anne-Vibeke , Hansen Thomas van Overeem , Olafsdottir Gudridur H. , Rossing Maria , Jonasson Jon G. , Sigurdsson Stefan , Loman Niklas , Nilsson Martin P. , Narod Steven A. , Tryggvadottir Laufey 
Published: September 2020

Abstract
Background
The natural history of breast cancer among BRCA2 carriers has not been clearly established. In a previous study from Iceland, positive ER status was a negative prognostic factor. We sought to identify factors that predicted survival after invasive breast cancer in an expanded cohort of BRCA2 carriers.

Methods
We studied 608 women with invasive breast cancer and a pathogenic BRCA2 mutation (variant) from four Nordic countries. Information on prognostic factors and treatment was retrieved from health records and by analysis of archived tissue specimens. Hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression.

Results
About 77% of cancers were ER-positive, with the highest proportion (83%) in patients under 40 years. ER-positive breast cancers were more likely to be node-positive (59%) than ER-negative cancers (34%) (P < 0.001). The survival analysis included 584 patients. Positive ER status was protective in the first 5 years from diagnosis (multivariate HR = 0.49; 95% CI 0.26–0.93, P = 0.03); thereafter, the effect was adverse (HR = 1.91; 95% CI 1.07–3.39, P = 0.03). The adverse effect of positive ER status was limited to women who did not undergo endocrine treatment (HR = 2.36; 95% CI 1.26–4.44, P = 0.01) and patients with intact ovaries (HR = 1.99; 95% CI 1.11–3.59, P = 0.02).

Conclusions
The adverse effect of a positive ER status in BRCA2 carriers with breast cancer may be contingent on exposure to ovarian hormones.
BDA-366, a putative Bcl-2 BH4 domain antagonist, induces apoptosis independently of Bcl-2 in a variety of cancer cell models
Authors: Vervloessem Tamara , Sasi Binu K. , Xerxa Elena , Karamanou Spyridoula , Kale Justin , La Rovere Rita M. , Chakraborty Supriya , Sneyers Flore , Vogler Meike , Economou Anastassios , Laurenti Luca , Andrews David W. , Efremov Dimitar G. , Bultynck Geert 
Published: September 2020

AbstractSeveral cancer cell types, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL) upregulate antiapoptotic Bcl-2 to cope with oncogenic stress. BH3 mimetics targeting Bcl-2’s hydrophobic cleft have been developed, including venetoclax as a promising anticancer precision medicine for treating CLL patients. Recently, BDA-366 was identified as a small molecule BH4-domain antagonist that could kill lung cancer and multiple myeloma cells. BDA-366 was proposed to switch Bcl-2 from an antiapoptotic into a proapoptotic protein, thereby activating Bax and inducing apoptosis. Here, we scrutinized the therapeutic potential and mechanism of action of BDA-366 in CLL and DLBCL. Although BDA-366 displayed selective toxicity against both cell types, the BDA-366-induced cell death did not correlate with Bcl-2-protein levels and also occurred in the absence of Bcl-2. Moreover, although BDA-366 provoked Bax activation, it did neither directly activate Bax nor switch Bcl-2 into a Bax-activating protein in in vitro Bax/liposome assays. Instead, in primary CLL cells and DLBCL cell lines, BDA-366 inhibited the activity of the PI3K/AKT pathway, resulted in Bcl-2 dephosphorylation and reduced Mcl-1-protein levels without affecting the levels of Bcl-2 or Bcl-xL. Hence, our work challenges the current view that BDA-366 is a BH4-domain antagonist of Bcl-2 that turns Bcl-2 into a pro-apoptotic protein. Rather, our results indicate that other mechanisms beyond switching Bcl-2 conformation underlie BDA-366’s cell-death properties that may implicate Mcl-1 downregulation and/or Bcl-2 dephosphorylation.
Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis
Authors: O’Neill John S. , Hoyle Nathaniel P. , Robertson J. Brian , Edgar Rachel S. , Beale Andrew D. , Peak-Chew Sew Y. , Day Jason , Costa Ana S. H. , Frezza Christian , Causton Helen C. 
Published: September 2020

AbstractYeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs). YROs share features with circadian rhythms and interact with, but are independent of, the cell division cycle. Here, we show that YROs minimise energy expenditure by restricting protein synthesis until sufficient resources are stored, while maintaining osmotic homeostasis and protein quality control. Although nutrient supply is constant, cells sequester and store metabolic resources via increased transport, autophagy and biomolecular condensation. Replete stores trigger increased H+ export which stimulates TORC1 and liberates proteasomes, ribosomes, chaperones and metabolic enzymes from non-membrane bound compartments. This facilitates translational bursting, liquidation of storage carbohydrates, increased ATP turnover, and the export of osmolytes. We propose that dynamic regulation of ion transport and metabolic plasticity are required to maintain osmotic and protein homeostasis during remodelling of eukaryotic proteomes, and that bioenergetic constraints selected for temporal organisation that promotes oscillatory behaviour.
Multiple capsid protein binding sites mediate selective packaging of the alphavirus genomic RNA
Authors: Brown Rebecca S. , Anastasakis Dimitrios G. , Hafner Markus , Kielian Margaret 
Published: September 2020

AbstractThe alphavirus capsid protein (Cp) selectively packages genomic RNA (gRNA) into the viral nucleocapsid to produce infectious virus. Using photoactivatable ribonucleoside crosslinking and an innovative biotinylated Cp retrieval method, here we comprehensively define binding sites for Semliki Forest virus (SFV) Cp on the gRNA. While data in infected cells demonstrate Cp binding to the proposed genome packaging signal (PS), mutagenesis experiments show that PS is not required for production of infectious SFV or Chikungunya virus. Instead, we identify multiple Cp binding sites that are enriched on gRNA-specific regions and promote infectious SFV production and gRNA packaging. Comparisons of binding sites in cytoplasmic vs. viral nucleocapsids demonstrate that budding causes discrete changes in Cp-gRNA interactions. Notably, Cp’s top binding site is maintained throughout virus assembly, and specifically binds and assembles with Cp into core-like particles in vitro. Together our data suggest a model for selective alphavirus genome recognition and assembly.
SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood
Authors: Ng Dianna L. , Goldgof Gregory M. , Shy Brian R. , Levine Andrew G. , Balcerek Joanna , Bapat Sagar P. , Prostko John , Rodgers Mary , Coller Kelly , Pearce Sandra , Franz Sergej , Du Li , Stone Mars , Pillai Satish K. , Sotomayor-Gonzalez Alicia , Servellita Venice , Martin Claudia Sanchez San , Granados Andrea , Glasner Dustin R. , Han Lucy M. , Truong Kent , Akagi Naomi , Nguyen David N. , Neumann Neil M. , Qazi Daniel , Hsu Elaine , Gu Wei , Santos Yale A. , Custer Brian , Green Valerie , Williamson Phillip , Hills Nancy K. , Lu Chuanyi M. , Whitman Jeffrey D. , Stramer Susan L. , Wang Candace , Reyes Kevin , Hakim Jill M. C. , Sujishi Kirk , Alazzeh Fariba , Pham Lori , Thornborrow Edward , Oon Ching-Ying , Miller Steve , Kurtz Theodore , Simmons Graham , Hackett John , Busch Michael P. , Chiu Charles Y. 
Published: September 2020

AbstractGiven the limited availability of serological testing to date, the seroprevalence of SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seroreactivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors in early April 2020. We additionally describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3–11.0 days for these 3 assays. Neutralizing antibodies rose in tandem with immunoglobulin titers following symptom onset, and positive percent agreement between detection of IgG and neutralizing titers was >93%. These findings emphasize the importance of using highly accurate tests for surveillance studies in low-prevalence populations, and provide evidence that seroreactivity using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity.
mTOR-mediated cancer drug resistance suppresses autophagy and generates a druggable metabolic vulnerability
Authors: Gremke Niklas , Polo Pierfrancesco , Dort Aaron , Schneikert Jean , Elmshäuser Sabrina , Brehm Corinna , Klingmüller Ursula , Schmitt Anna , Reinhardt Hans Christian , Timofeev Oleg , Wanzel Michael , Stiewe Thorsten 
Published: September 2020

AbstractCancer cells have a characteristic metabolism, mostly caused by alterations in signal transduction networks rather than mutations in metabolic enzymes. For metabolic drugs to be cancer-selective, signaling alterations need to be identified that confer a druggable vulnerability. Here, we demonstrate that many tumor cells with an acquired cancer drug resistance exhibit increased sensitivity to mechanistically distinct inhibitors of cancer metabolism. We demonstrate that this metabolic vulnerability is driven by mTORC1, which promotes resistance to chemotherapy and targeted cancer drugs, but simultaneously suppresses autophagy. We show that autophagy is essential for tumor cells to cope with therapeutic perturbation of metabolism and that mTORC1-mediated suppression of autophagy is required and sufficient for generating a metabolic vulnerability leading to energy crisis and apoptosis. Our study links mTOR-induced cancer drug resistance to autophagy defects as a cause of a metabolic liability and opens a therapeutic window for the treatment of otherwise therapy-refractory tumor patients.
A rationally designed bicyclic peptide remodels Aβ42 aggregation in vitro and reduces its toxicity in a worm model of Alzheimer’s disease
Authors: Ikenoue Tatsuya , Aprile Francesco A. , Sormanni Pietro , Ruggeri Francesco S. , Perni Michele , Heller Gabriella T. , Haas Christian P. , Middel Christoph , Limbocker Ryan , Mannini Benedetta , Michaels Thomas C. T. , Knowles Tuomas P. J. , Dobson Christopher M. , Vendruscolo Michele 
Published: September 2020

AbstractBicyclic peptides have great therapeutic potential since they can bridge the gap between small molecules and antibodies by combining a low molecular weight of about 2 kDa with an antibody-like binding specificity. Here we apply a recently developed in silico rational design strategy to produce a bicyclic peptide to target the C-terminal region (residues 31–42) of the 42-residue form of the amyloid β peptide (Aβ42), a protein fragment whose aggregation into amyloid plaques is linked with Alzheimer’s disease. We show that this bicyclic peptide is able to remodel the aggregation process of Aβ42 in vitro and to reduce its associated toxicity in vivo in a C. elegans worm model expressing Aβ42. These results provide an initial example of a computational approach to design bicyclic peptides to target specific epitopes on disordered proteins.
Scavenging by threatened turtles regulates freshwater ecosystem health during fish kills
Authors: Santori Claudia , Spencer Ricky-John , Thompson Michael B. , Whittington Camilla M. , Burd Thomas H. , Currie Samantha B. , Finter Timothy J. , Van Dyke James U. 
Published: September 2020

AbstractHumans are increasing the frequency of fish kills by degrading freshwater ecosystems. Simultaneously, scavengers like freshwater turtles are declining globally, including in the Australian Murray–Darling Basin. Reduced scavenging may cause water quality problems impacting both ecosystems and humans. We used field and mesocosm experiments to test whether scavenging by turtles regulates water quality during simulated fish kills. In the field, we found that turtles were important scavengers of fish carrion. In mesocosms, turtles rapidly consumed carrion, and water quality in mesocosms with turtles returned to pre-fish kill levels faster than in turtle-free controls. Our experiments have important ecological implications, as they suggest that turtles are critical scavengers that regulate water quality in freshwater ecosystems. Recovery of turtle populations may be necessary to avoid the worsening of ecosystem health, particularly after fish kills, which would have devastating consequences for many freshwater species.
Efficacy of microbicides for inactivation of Ebola–Makona virus on a non-porous surface: a targeted hygiene intervention for reducing virus spread
Authors: Cutts Todd A. , Robertson Catherine , Theriault Steven S. , Nims Raymond W. , Kasloff Samantha B. , Rubino Joseph R. , Ijaz M. Khalid 
Published: September 2020

AbstractMicrobicides play critical roles in infection prevention and control of Ebola virus by decontaminating high-touch environmental surfaces (HITES), interrupting the virus-HITES-hands nexus. We evaluated the efficacy of formulations containing different microbicidal actives for inactivating Ebola virus–Makona strain (EBOV/Mak) on stainless-steel carriers per ASTM E2197-11. Formulations of sodium hypochlorite (NaOCl) (0.05–1%), ethanol (70%), chloroxylenol (PCMX) (0.12–0.48% by weight) in hard water, and a ready-to-use disinfectant spray with 58% ethanol (EDS), were tested at contact times of 0, or 0.5 to 10 min at ambient temperature. EBOV/Mak was inactivated (> 6 log10) by 70% ethanol after contact times ≥ 2.5 min, by 0.5% and 1% NaOCl or EDS (> 4 log10) at contact times ≥ 5 min, and by 0.12–0.48% PCMX (> 4.2 log10) at contact times ≥ 5 min. Residual infectious virus in neutralized samples was assessed by passage on cells and evaluation for viral cytopathic effect. No infectious virus was detected in cells inoculated with EBOV/Mak exposed to NaOCl (0.5% or 1%), PCMX (0.12% to 0.48%), or EDS for ≥ 5 min. These results demonstrate ≥ 6 log10 inactivation of EBOV/Mak dried on prototypic surfaces by EDS or formulations of NaOCl (≥ 0.5%), PCMX (≥ 0.12%), or 70% ethanol at contact times ≥ 5 min.
Whole transcriptome approach to evaluate the effect of aluminium hydroxide in ovine encephalon
Authors: Varela-Martínez Endika , Bilbao-Arribas Martin , Abendaño Naiara , Asín Javier , Pérez Marta , de Andrés Damián , Luján Lluís , Jugo Begoña M. 
Published: September 2020

AbstractAluminium hydroxide adjuvants are crucial for livestock and human vaccines. Few studies have analysed their effect on the central nervous system in vivo. In this work, lambs received three different treatments of parallel subcutaneous inoculations during 16 months with aluminium-containing commercial vaccines, an equivalent dose of aluminium hydroxide or mock injections. Brain samples were sequenced by RNA-seq and miRNA-seq for the expression analysis of mRNAs, long non-coding RNAs and microRNAs and three expression comparisons were made. Although few differentially expressed genes were identified, some dysregulated genes by aluminium hydroxide alone were linked to neurological functions, the lncRNA TUNA among them, or were enriched in mitochondrial energy metabolism related functions. In the same way, the miRNA expression was mainly disrupted by the adjuvant alone treatment. Some differentially expressed miRNAs had been previously linked to neurological diseases, oxidative stress and apoptosis. In brief, in this study aluminium hydroxide alone altered the transcriptome of the encephalon to a higher degree than commercial vaccines that present a milder effect. The expression changes in the animals inoculated with aluminium hydroxide suggest mitochondrial disfunction. Further research is needed to elucidate to which extent these changes could have pathological consequences.
Harmonic motion imaging of human breast masses: an in vivo clinical feasibility
Authors: Saharkhiz Niloufar , Ha Richard , Taback Bret , Li Xiaoyue Judy , Weber Rachel , Nabavizadeh Alireza , Lee Stephen A. , Hibshoosh Hanina , Gatti Vittorio , Kamimura Hermes A. S. , Konofagou Elisa E. 
Published: September 2020

AbstractNon-invasive diagnosis of breast cancer is still challenging due to the low specificity of the imaging modalities that calls for unnecessary biopsies. The diagnostic accuracy can be improved by assessing the breast tissue mechanical properties associated with pathological changes. Harmonic motion imaging (HMI) is an elasticity imaging technique that uses acoustic radiation force to evaluate the localized mechanical properties of the underlying tissue. Herein, we studied the in vivo feasibility of a clinical HMI system to differentiate breast tumors based on their relative HMI displacements, in human subjects. We performed HMI scans in 10 female subjects with breast masses: five benign and five malignant masses. Results revealed that both benign and malignant masses were stiffer than the surrounding tissues. However, malignant tumors underwent lower mean HMI displacement (1.1 ± 0.5 µm) compared to benign tumors (3.6 ± 1.5 µm) and the adjacent non-cancerous tissue (6.4 ± 2.5 µm), which allowed to differentiate between tumor types. Additionally, the excised breast specimens of the same patients (n = 5) were imaged post-surgically, where there was an excellent agreement between the in vivo and ex vivo findings, confirmed with histology. Higher displacement contrast between cancerous and non-cancerous tissue was found ex vivo, potentially due to the lower nonlinearity in the elastic properties of ex vivo tissue. This preliminary study lays the foundation for the potential complementary application of HMI in clinical practice in conjunction with the B-mode to classify suspicious breast masses.
Monitoring PSA levels as chemical state-variables in metal-oxide memristors
Authors: Tzouvadaki Ioulia , Stathopoulos Spyros , Abbey Tom , Michalas Loukas , Prodromakis Themis 
Published: September 2020

AbstractMedical interventions increasingly rely on biosensors that can provide reliable quantitative information. A longstanding bottleneck in realizing this, is various non-idealities that generate offsets and variable responses across sensors. Current mitigation strategies involve the calibration of sensors, performed in software or via auxiliary compensation circuitry thus constraining real-time operation and integration efforts. Here, we show that bio-functionalized metal-oxide memristors can be utilized for directly transducing biomarker concentration levels to discrete memory states. The introduced chemical state-variable is found to be dependent on the devices’ initial resistance, with its response to chemical stimuli being more pronounced for higher resistive states. We leverage this attribute along with memristors’ inherent state programmability for calibrating a biosensing array to render a homogeneous response across all cells. Finally, we demonstrate the application of this technology in detecting Prostate Specific Antigen in clinically relevant levels (ng/ml), paving the way towards applications in large multi-panel assays.