bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual system assessment for predicting a transition to psychosis
Authors: Diamond Alexander , Silverstein Steven M. , Keane Brian P. 
Published: August 2022

AbstractThe field of psychiatry is far from perfect in predicting which individuals will transition to a psychotic disorder. Here, we argue that visual system assessment can help in this regard. Such assessments have generated medium-to-large group differences with individuals prior to or near the first psychotic episode or have shown little influence of illness duration in larger samples of more chronic patients. For example, self-reported visual perceptual distortions—so-called visual basic symptoms—occur in up to 2/3rds of those with non-affective psychosis and have already longitudinally predicted an impending onset of schizophrenia. Possibly predictive psychophysical markers include enhanced contrast sensitivity, prolonged backward masking, muted collinear facilitation, reduced stereoscopic depth perception, impaired contour and shape integration, and spatially restricted exploratory eye movements. Promising brain-based markers include visual thalamo-cortical hyperconnectivity, decreased occipital gamma band power during visual detection (MEG), and reduced visually evoked occipital P1 amplitudes (EEG). Potentially predictive retinal markers include diminished cone a- and b-wave amplitudes and an attenuated photopic flicker response during electroretinography. The foregoing assessments are often well-described mechanistically, implying that their findings could readily shed light on the underlying pathophysiological changes that precede or accompany a transition to psychosis. The retinal and psychophysical assessments in particular are inexpensive, well-tolerated, easy to administer, and brief, with few inclusion/exclusion criteria. Therefore, across all major levels of analysis—from phenomenology to behavior to brain and retinal functioning—visual system assessment could complement and improve upon existing methods for predicting which individuals go on to develop a psychotic disorder.
Regulation of CCL2 by EZH2 affects tumor-associated macrophages polarization and infiltration in breast cancer
Authors: Wang Ya-fang , Yu Lei , Hu Zong-long , Fang Yan-fen , Shen Yan-yan , Song Min-fang , Chen Yi 
Published: August 2022

AbstractTumor associated macrophages (TAMs) play an important role in tumorigenesis, development and anti-cancer drug therapy. However, very few epigenetic compounds have been elucidated to affect tumor growth by educating TAMs in the tumor microenvironment (TME). Herein, we identified that EZH2 performs a crucial role in the regulation of TAMs infiltration and protumoral polarization by interacting with human breast cancer (BC) cells. We showed that EZH2 inhibitors-treated BC cells induced M2 macrophage polarization in vitro and in vivo, while EZH2 knockdown exhibited the opposite effect. Mechanistically, inhibition of EZH2 histone methyltransferase alone by EZH2 inhibitors in breast cancer cells could reduce the enrichment of H3K27me3 on CCL2 gene promoter, elevate CCL2 transcription and secretion, contributing to the induction of M2 macrophage polarization and recruitment in TME, which reveal a potential explanation behind the frustrating results of EZH2 inhibitors against breast cancer. On the contrary, EZH2 depletion led to DNA demethylation and subsequent upregulation of miR-124-3p level, which inhibited its target CCL2 expression in the tumor cells, causing arrest of TAMs M2 polarization. Taken together, these data suggested that EZH2 can exert opposite regulatory effects on TAMs polarization through its enzymatic or non-enzymatic activities. Our results also imply that the effect of antitumor drugs on TAMs may affect its therapeutic efficacy, and the combined application with TAMs modifiers should be warranted to achieve great clinical success.
Activation of pancreatic stellate cells attenuates intracellular Ca2+ signals due to downregulation of TRPA1 and protects against cell death induced by alcohol metabolites
Authors: Kusiak Agnieszka A. , Jakubowska Monika A. , Stopa Kinga B. , Zhang Xiaoying , Huang Wei , Gerasimenko Julia V. , Gerasimenko Oleg V. , Sutton Robert , Petersen Ole H. , Ferdek Pawel E. 
Published: August 2022

AbstractAlcohol abuse, an increasing problem in developed societies, is one of the leading causes of acute and chronic pancreatitis. Alcoholic pancreatitis is often associated with fibrosis mediated by activated pancreatic stellate cells (PSCs). Alcohol toxicity predominantly depends on its non-oxidative metabolites, fatty acid ethyl esters, generated from ethanol and fatty acids. Although the role of non-oxidative alcohol metabolites and dysregulated Ca2+ signalling in enzyme-storing pancreatic acinar cells is well established as the core mechanism of pancreatitis, signals in PSCs that trigger fibrogenesis are less clear. Here, we investigate real-time Ca2+ signalling, changes in mitochondrial potential and cell death induced by ethanol metabolites in quiescent vs TGF-β-activated PSCs, compare the expression of Ca2+ channels and pumps between the two phenotypes and the consequences these differences have on the pathogenesis of alcoholic pancreatitis. The extent of PSC activation in the pancreatitis of different aetiologies has been investigated in three animal models. Unlike biliary pancreatitis, alcohol-induced pancreatitis results in the activation of PSCs throughout the entire tissue. Ethanol and palmitoleic acid (POA) or palmitoleic acid ethyl ester (POAEE) act directly on quiescent PSCs, inducing cytosolic Ca2+ overload, disrupting mitochondrial functions, and inducing cell death. However, activated PSCs acquire remarkable resistance against ethanol metabolites via enhanced Ca2+-handling capacity, predominantly due to the downregulation of the TRPA1 channel. Inhibition or knockdown of TRPA1 reduces EtOH/POA-induced cytosolic Ca2+ overload and protects quiescent PSCs from cell death, similarly to the activated phenotype. Our results lead us to review current dogmas on alcoholic pancreatitis. While acinar cells and quiescent PSCs are prone to cell death caused by ethanol metabolites, activated PSCs can withstand noxious signals and, despite ongoing inflammation, deposit extracellular matrix components. Modulation of Ca2+ signals in PSCs by TRPA1 agonists/antagonists could become a strategy to shift the balance of tissue PSCs towards quiescent cells, thus limiting pancreatic fibrosis.
Corosolic acid sensitizes ferroptosis by upregulating HERPUD1 in liver cancer cells
Authors: Peng Yingxiu , Li Ning , Tang Feifeng , Qian Chunmei , Jia Tingting , Liu Jingjin , Xu Yanfeng 
Published: August 2022

AbstractPrimary liver cancer is the third leading cause of cancer death in the world, and the lack of effective treatments is the main reason for the high mortality. Corosolic acid (CA) has been proved to have antitumor activity. In this study, we found that CA can sensitize liver cancer cells to ferroptosis, which is a regulated form of cell death characterized by iron-dependent lipid peroxides reaching lethal levels. Here, we revealed that CA can inhibit glutathione (GSH) synthesis via HERPUD1, decreasing the cellular GSH level and causing liver cancer cells to become more sensitive to ferroptosis. Mechanistically, further studies found that HERPUD1 reduced the ubiquitination of the GSS-associated E3 ubiquitin ligase MDM2, which promoted ubiquitination of GSS, thereby inhibiting GSH synthesis to increase ferroptosis susceptibility. Importantly, a mouse xenograft model also demonstrated that CA inhibits tumor growth via HERPUD1. Collectively, our findings suggesting that CA is a candidate component for the development of treatments against liver cancer.
Subcortical-cortical dynamical states of the human brain and their breakdown in stroke
Authors: Favaretto Chiara , Allegra Michele , Deco Gustavo , Metcalf Nicholas V. , Griffis Joseph C. , Shulman Gordon L. , Brovelli Andrea , Corbetta Maurizio 
Published: August 2022

AbstractThe mechanisms controlling dynamical patterns in spontaneous brain activity are poorly understood. Here, we provide evidence that cortical dynamics in the ultra-slow frequency range (<0.01–0.1 Hz) requires intact cortical-subcortical communication. Using functional magnetic resonance imaging (fMRI) at rest, we identify Dynamic Functional States (DFSs), transient but recurrent clusters of cortical and subcortical regions synchronizing at ultra-slow frequencies. We observe that shifts in cortical clusters are temporally coincident with shifts in subcortical clusters, with cortical regions flexibly synchronizing with either limbic regions (hippocampus/amygdala), or subcortical nuclei (thalamus/basal ganglia). Focal lesions induced by stroke, especially those damaging white matter connections between basal ganglia/thalamus and cortex, provoke anomalies in the fraction times, dwell times, and transitions between DFSs, causing a bias toward abnormal network integration. Dynamical anomalies observed 2 weeks after stroke recover in time and contribute to explaining neurological impairment and long-term outcome.
PIF7 is a master regulator of thermomorphogenesis in shade
Authors: Burko Yogev , Willige Björn Christopher , Seluzicki Adam , Novák Ondřej , Ljung Karin , Chory Joanne 
Published: August 2022

AbstractThe size of plant organs is highly responsive to environmental conditions. The plant’s embryonic stem, or hypocotyl, displays phenotypic plasticity, in response to light and temperature. The hypocotyl of shade avoiding species elongates to outcompete neighboring plants and secure access to sunlight. Similar elongation occurs in high temperature. However, it is poorly understood how environmental light and temperature cues interact to effect plant growth. We found that shade combined with warm temperature produces a synergistic hypocotyl growth response that dependent on PHYTOCHROME-INTERACTING FACTOR 7 (PIF7) and auxin. This unique but agriculturally relevant scenario was almost totally independent on PIF4 activity. We show that warm temperature is sufficient to promote PIF7 DNA binding but not transcriptional activation and we demonstrate that additional, unknown factor/s must be working downstream of the phyB-PIF-auxin module. Our findings will improve the predictions of how plants will respond to increased ambient temperatures when grown at high density.
Highly hydrated paramagnetic amorphous calcium carbonate nanoclusters as an MRI contrast agent
Authors: Dong Liang , Xu Yun-Jun , Sui Cong , Zhao Yang , Mao Li-Bo , Gebauer Denis , Rosenberg Rose , Avaro Jonathan , Wu Ya-Dong , Gao Huai-Ling , Pan Zhao , Wen Hui-Qin , Yan Xu , Li Fei , Lu Yang , Cölfen Helmut , Yu Shu-Hong 
Published: August 2022

AbstractAmorphous calcium carbonate plays a key role as transient precursor in the early stages of biogenic calcium carbonate formation in nature. However, due to its instability in aqueous solution, there is still rare success to utilize amorphous calcium carbonate in biomedicine. Here, we report the mutual effect between paramagnetic gadolinium ions and amorphous calcium carbonate, resulting in ultrafine paramagnetic amorphous carbonate nanoclusters in the presence of both gadolinium occluded highly hydrated carbonate-like environment and poly(acrylic acid). Gadolinium is confirmed to enhance the water content in amorphous calcium carbonate, and the high water content of amorphous carbonate nanoclusters contributes to the much enhanced magnetic resonance imaging contrast efficiency compared with commercially available gadolinium-based contrast agents. Furthermore, the enhanced T1 weighted magnetic resonance imaging performance and biocompatibility of amorphous carbonate nanoclusters are further evaluated in various animals including rat, rabbit and beagle dog, in combination with promising safety in vivo. Overall, exceptionally facile mass-productive amorphous carbonate nanoclusters exhibit superb imaging performance and impressive stability, which provides a promising strategy to design magnetic resonance contrast agent.
Cytoplasmic forces functionally reorganize nuclear condensates in oocytes
Authors: Al Jord Adel , Letort Gaëlle , Chanet Soline , Tsai Feng-Ching , Antoniewski Christophe , Eichmuller Adrien , Da Silva Christelle , Huynh Jean-René , Gov Nir S. , Voituriez Raphaël , Terret Marie-Émilie , Verlhac Marie-Hélène 
Published: August 2022

AbstractCells remodel their cytoplasm with force-generating cytoskeletal motors. Their activity generates random forces that stir the cytoplasm, agitating and displacing membrane-bound organelles like the nucleus in somatic and germ cells. These forces are transmitted inside the nucleus, yet their consequences on liquid-like biomolecular condensates residing in the nucleus remain unexplored. Here, we probe experimentally and computationally diverse nuclear condensates, that include nuclear speckles, Cajal bodies, and nucleoli, during cytoplasmic remodeling of female germ cells named oocytes. We discover that growing mammalian oocytes deploy cytoplasmic forces to timely impose multiscale reorganization of nuclear condensates for the success of meiotic divisions. These cytoplasmic forces accelerate nuclear condensate collision-coalescence and molecular kinetics within condensates. Disrupting the forces decelerates nuclear condensate reorganization on both scales, which correlates with compromised condensate-associated mRNA processing and hindered oocyte divisions that drive female fertility. We establish that cytoplasmic forces can reorganize nuclear condensates in an evolutionary conserved fashion in insects. Our work implies that cells evolved a mechanism, based on cytoplasmic force tuning, to functionally regulate a broad range of nuclear condensates across scales. This finding opens new perspectives when studying condensate-associated pathologies like cancer, neurodegeneration and viral infections.
Invariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor
Authors: Macleod Olivia J. S. , Cook Alexander D. , Webb Helena , Crow Mandy , Burns Roisin , Redpath Maria , Seisenberger Stefanie , Trevor Camilla E. , Peacock Lori , Schwede Angela , Kimblin Nicola , Francisco Amanda F. , Pepperl Julia , Rust Steve , Voorheis Paul , Gibson Wendy , Taylor Martin C. , Higgins Matthew K. , Carrington Mark 
Published: August 2022

AbstractAfrican trypanosomes are extracellular pathogens of mammals and are exposed to the adaptive and innate immune systems. Trypanosomes evade the adaptive immune response through antigenic variation, but little is known about how they interact with components of the innate immune response, including complement. Here we demonstrate that an invariant surface glycoprotein, ISG65, is a receptor for complement component 3 (C3). We show how ISG65 binds to the thioester domain of C3b. We also show that C3 contributes to control of trypanosomes during early infection in a mouse model and provide evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance. Deposition of C3b on pathogen surfaces, such as trypanosomes, is a central point in activation of the complement system. In ISG65, trypanosomes have evolved a C3 receptor which diminishes the downstream effects of C3 deposition on the control of infection.
Natural and anthropogenic contributions to the hurricane drought of the 1970s–1980s
Authors: Rousseau-Rizzi Raphaël , Emanuel Kerry 
Published: August 2022

AbstractAtlantic hurricane activity experienced a pronounced lull during the 1970s and 1980s. The current explanation that anthropogenic aerosol radiative forcing cooled the sea surface locally fails to capture the magnitude of this large decrease in activity. To explain this hurricane drought, we propose that the radiative effects of sulfate aerosols from Europe and North-America decreased precipitation in the Sahara-Sahel region, leading to an enhancement of dust regional emissions and transport over the Atlantic. This dust in turn enhanced the local decrease of sea-surface temperature and of hurricane activity. Here, we show that dust emissions from the Sahara peaked in phase with regional sulfate aerosol optical thickness and Sahel drought conditions, and that dust optical depth variations alone can explain nearly half of the sea-surface temperature depression in the 1970s and 1980s.
Heterostrain-enabled ultrahigh electrostrain in lead-free piezoelectric
Authors: Feng Wei , Luo Bingcheng , Bian Shuaishuai , Tian Enke , Zhang Zili , Kursumovic Ahmed , MacManus-Driscoll Judith L. , Wang Xiaohui , Li Longtu 
Published: August 2022

AbstractPiezoelectric materials provide high strain and large driving forces in actuators and can transform electrical energy into mechanical energy. Although they were discovered over 100 years ago, scientists are still searching for alternative lead-free piezoelectrics to reduce their environmental impact. Developing high-strain piezoelectric materials has been a long-term challenge, particularly challenging for the design of high-strain polycrystalline piezoelectrics containing no toxic lead element. In this work, we report one strategy to enhance the electrostrain via designing “heterostrain” through atomic-scale defect engineering and mesoscale domain engineering. We achieve an ultrahigh electrostrain of 2.3% at high temperature (220 °C) in lead-free polycrystalline ceramics, higher than all state-of-the-art piezoelectric materials, including lead-free and lead-based ceramics and single crystals. We demonstrate practical solutions for achieving high electrostrain in low-cost environmentally piezoelectric for various applications.
Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer
Authors: Rugo Hope S. , Tolaney Sara M. , Loirat Delphine , Punie Kevin , Bardia Aditya , Hurvitz Sara A. , O’Shaughnessy Joyce , Cortés Javier , Diéras Véronique , Carey Lisa A. , Gianni Luca , Piccart Martine J. , Loibl Sibylle , Goldenberg David M. , Hong Quan , Olivo Martin , Itri Loretta M. , Kalinsky Kevin 
Published: August 2022

AbstractSacituzumab govitecan (SG) is an anti-Trop-2 antibody-drug conjugate with an SN-38 payload. In the ASCENT study, patients with metastatic triple-negative breast cancer (mTNBC) relapsed/refractory to ≥2 prior chemotherapy regimens (≥1 in the metastatic setting), received SG or single-agent treatment of physician’s choice (eribulin, vinorelbine, capecitabine, or gemcitabine). This ASCENT safety analysis includes the impact of age and UGT1A1 polymorphisms, which hinder SN-38 detoxification. SG demonstrated a manageable safety profile in patients with mTNBC, including those ≥65 years; neutropenia/diarrhea are key adverse events (AE). Patients with UGT1A1 *28/*28 genotype versus those with 1/*28 and *1/*1 genotypes had higher rates of grade ≥3 SG-related neutropenia (59% vs 47% and 53%), febrile neutropenia (18% vs 5% and 3%), anemia (15% vs 6% and 4%), and diarrhea (15% vs 9% and 10%), respectively. Individuals with UGT1A1 *28/*28 genotype should be monitored closely; active monitoring and routine AE management allow optimal therapeutic exposure of SG.
ZNF92, an unexplored transcription factor with remarkably distinct breast cancer over-expression associated with prognosis and cell-of-origin
Authors: Kamran Mohammad , Bhattacharya Udayan , Omar Mohamed , Marchionni Luigi , Ince Tan A. 
Published: August 2022

AbstractTumor phenotype is shaped both by transforming genomic alterations and the normal cell-of-origin. We identified a cell-of-origin associated prognostic gene expression signature, ET-9, that correlates with remarkably shorter overall and relapse free breast cancer survival, 8.7 and 6.2 years respectively. The genes associated with the ET-9 signature are regulated by histone deacetylase 7 (HDAC7) partly through ZNF92, a previously unexplored transcription factor with a single PubMed citation since its cloning in 1990s. Remarkably, ZNF92 is distinctively over-expressed in breast cancer compared to other tumor types, on a par with the breast cancer specificity of the estrogen receptor. Importantly, ET-9 signature appears to be independent of proliferation, and correlates with outcome in lymph-node positive, HER2+, post-chemotherapy and triple-negative breast cancers. These features distinguish ET-9 from existing breast cancer prognostic signatures that are generally related to proliferation and correlate with outcome in lymph-node negative, ER-positive, HER2-negative breast cancers. Our results suggest that ET-9 could be also utilized as a predictive signature to select patients for HDAC inhibitor treatment.
TLR agonists induce sustained IgG to hemagglutinin stem and modulate T cells following newborn vaccination
Authors: Clemens Elene A. , Holbrook Beth C. , McNeilly Brendan , Kanekiyo Masaru , Graham Barney S. , Alexander-Miller Martha A. 
Published: August 2022

AbstractThe newborn immune system is characterized by diminished immune responses that leave infants vulnerable to virus-mediated disease and make vaccination more challenging. Optimal vaccination strategies for influenza A virus (IAV) in newborns should result in robust levels of protective antibodies, including those with broad reactivity to combat the variability in IAV strains across seasons. The stem region of the hemagglutinin (HA) molecule is a target of such antibodies. Using a nonhuman primate model, we investigate the capacity of newborns to generate and maintain antibodies to the conserved stem region following vaccination. We find adjuvanting an inactivated vaccine with the TLR7/8 agonist R848 is effective in promoting sustained HA stem-specific IgG. Unexpectedly, HA stem-specific antibodies were generated with a distinct kinetic pattern compared to the overall response. Administration of R848 was associated with increased influenza-specific T follicular helper cells as well as Tregs with a less suppressive phenotype, suggesting adjuvant impacts multiple cell types that have the potential to contribute to the HA-stem response.
Greenland ice sheet climate disequilibrium and committed sea-level rise
Authors: Box Jason E. , Hubbard Alun , Bahr David B. , Colgan William T. , Fettweis Xavier , Mankoff Kenneth D. , Wehrlé Adrien , Noël Brice , van den Broeke Michiel R. , Wouters Bert , Bjørk Anders A. , Fausto Robert S. 
Published: August 2022

AbstractIce loss from the Greenland ice sheet is one of the largest sources of contemporary sea-level rise (SLR). While process-based models place timescales on Greenland’s deglaciation, their confidence is obscured by model shortcomings including imprecise atmospheric and oceanic couplings. Here, we present a complementary approach resolving ice sheet disequilibrium with climate constrained by satellite-derived bare-ice extent, tidewater sector ice flow discharge and surface mass balance data. We find that Greenland ice imbalance with the recent (2000–2019) climate commits at least 274 ± 68 mm SLR from 59 ± 15 × 103 km2 ice retreat, equivalent to 3.3 ± 0.9% volume loss, regardless of twenty-first-century climate pathways. This is a result of increasing mass turnover from precipitation, ice flow discharge and meltwater run-off. The high-melt year of 2012 applied in perpetuity yields an ice loss commitment of 782 ± 135 mm SLR, serving as an ominous prognosis for Greenland’s trajectory through a twenty-first century of warming.