bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-Channel Whole-Head OPM-MEG: Helmet Design and a Comparison with a Conventional System
Authors: Hill Ryan M. , Boto Elena , Rea Molly , Holmes Niall , Leggett James , Coles Laurence A. , Papastavrou Manolis , Everton Sarah , Hunt Benjamin A.E. , Sims Dominic , Osborne James , Shah Vishal , Bowtell Richard , Brookes Matthew J. 
Published: March 2020

ABSTRACTMagnetoencephalography (MEG) is a powerful technique for functional neuroimaging, offering a non-invasive window on brain electrophysiology. MEG systems have traditionally been based on cryogenic sensors which detect the small extracranial magnetic fields generated by synchronised current in neuronal assemblies, however such systems have fundamental limitations. In recent years quantum-enabled devices, called optically-pumped magnetometers (OPMs), have promised to lift those restrictions, offering an adaptable, motion-robust MEG device, with improved data quality, at reduced cost. However, OPM-MEG remains a nascent technology, and whilst viable systems exist, most employ small numbers of sensors sited above targeted brain regions. Here, building on previous work, we construct a wearable OPM-MEG system with ‘whole-head’ coverage based upon commercially available OPMs, and test its capabilities to measure alpha, beta and gamma oscillations. We design two methods for OPM mounting; a flexible (EEG-like) cap and rigid (additively-manufactured) helmet. Whilst both designs allow for high quality data to be collected, we argue that the rigid helmet offers a more robust option with significant advantages for reconstruction of field data into 3D images of changes in neuronal current. Using repeat measurements in two participants, we show signal detection for our device to be highly robust. Moreover, via application of source-space modelling, we show that, despite having 5 times fewer sensors, our system exhibits comparable performance to an established cryogenic MEG device. While significant challenges still remain, these developments provide further evidence that OPM-MEG is likely to facilitate a step change for functional neuroimaging.HIGHLIGHTSA 49-channel whole-head OPM-MEG system is constructedSystem evaluated via repeat measurements of alpha, beta and gamma oscillationsTwo OPM-helmet designs are contrasted, a flexible (EEG-like) cap and a rigid helmetThe rigid helmet offers significant advantages for a viable OPM-MEG device49-channel OPM-MEG offers performance comparable to established cryogenic devices
Maternal cannabis vapor exposure causes long-term alterations in emotional reactivity, social behavior, and behavioral flexibility in offspring
Authors: Weimar Halle V. , Wright Hayden R. , Warrick Collin R. , Brown Amanda M. , Lugo Janelle M. , Freels Timothy G. , McLaughlin Ryan J. 
Published: March 2020

AbstractThe use of cannabis during pregnancy is a growing public health concern. As more states implement legislation permitting recreational cannabis use, there is an urgent need to better understand its impact on fetal neurodevelopment and its long-term effects in exposed offspring. Studies examining effects of prenatal cannabis exposure typically employ injections of synthetic cannabinoids or isolated cannabis constituents that may not accurately model cannabis use in human populations. To address this limitation, we have developed a novel e-cigarette technology-based system to deliver vaporized cannabis extracts to pregnant Long Evans rats. We used this model to determine effects of prenatal cannabis exposure on emotional, social, and cognitive endpoints of male and female offspring during early development and into adulthood. Dams were exposed to cannabis vapor (CANTHC: 400 mg/ml), vehicle vapor (VEH), or no vapor (AIR) twice daily during mating and gestation. Offspring exposed to CANTHCand VEH showed reduced weight gain relative to AIR offspring prior to weaning. CANTHCoffspring made more isolation-induced ultrasonic vocalizations (USVs) on postnatal day 6 (P6) relative to VEH-exposed offspring, which is indicative of increased emotional reactivity. Male CANTHCoffspring engaged in fewer social investigation behaviors than VEH-exposed male offspring during a social play test on P26. In adulthood, CANTHC-exposed offspring spent less time exploring the open arms of the elevated plus maze and exhibited dose-dependent deficits in behavioral flexibility in an attentional set-shifting task relative to AIR controls. These data collectively indicate that prenatal cannabis exposure causes enduring effects on the behavioral profile of offspring.
A ‘one-two punch’ therapy strategy to target chemoresistance in estrogen receptor positive breast cancer
Authors: Chi Feng , Liu Jiayi , Brady Samuel W. , Cosgrove Patrick A. , Nath Aritro , McQuerry Jasmine A. , Majumdar Sumana , Moos Philip J. , Chang Jeffrey T. , Kahn Michael , Bild Andrea H. 
Published: March 2020

AbstractBackgroundCancer cell phenotypes evolve over the course of a tumor’s treatment. The phenotypes that emerge and disappear over time will be specific to each drug regimen and type of cancer. Chemotherapy remains one of the most common and effective treatments for metastatic breast cancer patients; however, resistance to chemotherapy inevitably emerges. Cancer chemotherapy treatment regimens are not designed to target emerging chemo-resistance, despite its clear importance in progressive cancer. This study focuses on finding sequential treatment strategies that target acquired chemo-resistant states and optimize response to chemotherapy.MethodsIn this study, we used heterogeneous tumor samples from patients to identify subclones resistant to chemotherapy. Using flow cytometry for stem cell markers and DNA sequencing to define subclonal population changes, we measured the enrichment of cancer stem cell-like (CSL) phenotypes in subclones that survive chemotherapy. We then analyzed breast cancer patient tumor organoids and cell line acquisition of CSL traits following chemotherapy, as well as the ability of different drugs to reverse acquired resistance, using flow cytometry, mammosphere assays, and single cell RNA-sequencing analysis.ResultsWe show that in progressive estrogen receptor positive (ER+) metastatic breast cancer patients, resistant tumor subclones that emerge following chemotherapy have increased CSL abundance. Further, in vitro organoid growth of ER+ patient cancer cells also shows that chemotherapy treatment leads to increased abundance of ALDH+/CD44+ CSL cells. Chemotherapy induced CSL abundance is blocked by treatment with a pan-HDAC inhibitor, belinostat. Further, belinostat treatment diminished both mammosphere formation and size following chemotherapy, also indicating a decrease in progenitor CSL traits. HDAC inhibitors specific to class IIa (HDAC4, HDAC5) and IIb (HDAC6) were shown to primarily reverse the chemo-resistant CSL state. Single-cell RNA sequencing analysis with patient samples showed that HDAC targets and MYC signaling were promoted by chemotherapy and inhibited upon HDAC inhibitor treatment.ConclusionThese findings indicate that HDAC inhibition can block chemotherapy-induced drug resistant phenotypes with ‘one-two punch’ strategy in refractory breast cancer cells.
Mutant p53 suppresses innate immune signaling to promote tumorigenesis
Authors: Ghosh Monisankar , Saha Suchandrima , Bettke Julie , Nagar Rachana , Parrales Alejandro , Iwakuma Tomoo , van der Velden Adrianus W. M. , Martinez Luis A. 
Published: March 2020

ABSTRACTMutations in the p53 tumor suppressor occur very frequently in human cancer. Often, such mutations lead to the constitutive overproduction of mutant p53 (mtp53) proteins, which can exert a cancer-promoting gain-of-function (GOF). We have identified a novel mechanism by which mtp53 controls both cell-autonomous and non-cell autonomous signaling to promote cancer cell survival and suppress tumor immune surveillance. Mtp53 interferes with the function of the cytoplasmic DNA sensing machinery, cGAS-STING-TBK1-IRF3, that controls the activation of the innate immune response. We find that mtp53, but not wildtype p53, binds to TANK binding protein kinase (TBK1) and inhibits both its basal and agonist-induced activity. The association of mtp53 with TBK1 prevents the formation of a trimeric complex between TBK1-STING-IRF3, which is required for activation, nuclear translocation and transcriptional activity of IRF3. Mtp53 knockdown restores TBK1 activity, resulting in the transcriptional induction of IRF3 target genes and IRF3-dependent apoptosis. Furthermore, inactivation of innate immune signaling by mtp53 alters cytokine production resulting in immune evasion. Restored TBK1 signaling was sufficient to bypass mtp53 and reactivate cell-autonomous and non-cell autonomous tumor control. Thus, overriding mtp53’s inhibition of this cytosolic DNA sensing pathway may ultimately lead to restored immune cell function and cancer cell eradication.
IRF8 Governs Tumor-Associated Macrophage Control of T Cell Exhaustion
Authors: Nixon Briana G. , Kuo Fengshen , Liu Ming , Capistrano Kristelle , Do Mytrang , Franklin Ruth A. , Wu Xiaodi , Kansler Emily R. , Srivastava Raghvendra M. , Purohit Tanaya A. , Sanchez Alejandro , Vuong Lynda , Krishna Chirag , Morse Herbert C. , Hsieh James J. , Chan Timothy A. , Murphy Kenneth M. , Moon James J. , Hakimi A. Ari , Li Ming O. 
Published: March 2020

SummaryTumor progression is associated with overstimulation of cytotoxic T lymphocytes (CTLs), resulting in a dysfunctional state of exhaustion. How T cell exhaustion is elicited in the tumor remains poorly understood. Here we show that tumor-associated macrophages (TAMs) present cancer cell antigen and induce CTL exhaustion through a gene expression program dependent on the transcription factor interferon regulatory factor-8 (IRF8). In a transgenic model of murine breast cancer, CTL priming was supported by IRF8-dependent dendritic cells; yet, CTL exhaustion required TAM expression of IRF8, and its ablation suppressed tumor growth. An analysis of the highly immune-infiltrated human renal cell carcinoma tumors revealed abundant TAMs that expressed IRF8 and were enriched for an IRF8 gene expression signature. The IRF8 signature co-segregated with T cell exhaustion markers and was negatively associated with long-term patient survival. Thus, CTL exhaustion is promoted by TAMs via IRF8, and this crosstalk may be disrupted in TAM-targeted therapies.
Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs
Authors: Todkar Kiran , Chikhi Lilia , Desjardins Véronique , El-Mortada Firas , Pépin Geneviève , Germain Marc 
Published: March 2020

AbstractMost cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles (EVs), small vesicles that allow the transfer of material between cells. While under pro-inflammatory conditions, this mitochondrial content can further enhance inflammation, its role in the absence of inflammation remains elusive. Here, we demonstrate that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins into EVs. Importantly, the distinction between material to be included into EVs and damaged mitochondrial content to be excluded was dependent on their selective targeting to one of two distinct Mitochondria-Derived Vesicles (MDVs) pathways, MDVs being small vesicles carrying material between mitochondria and other organelles. Sorting nexin 9 (Snx9)-dependent MDVs were required to target mitochondrial proteins into EVs, while the Parkinson’s disease related protein Parkin blocked this process by targeting damaged mitochondrial content to lysosomes. Our results thus provide important insight into the interplay between mitochondrial quality control mechanisms and mitochondria driven immune responses.
A mechanism to prevent transformation of the Whi3 mnemon into a prion
Authors: Lau Yasmin , Parfenova Iuliia , Saarikangas Juha , Nichols Richard A. , Barral Yves , Caudron Fabrice 
Published: March 2020

AbstractIn response to deceptive courtship, budding yeast cells escape pheromone induced cell cycle arrest through coalescence of the G1/S inhibitor Whi3 into a dominant inactive super-assembly. Strikingly, Whi3 super-assemblies remain stable over many cell cycles in the mother cells and are not passed on to the daughter cells. Thereby, Whi3 coalescence encodes memory, conferring to it the property of a mnemon (Whi3mnem), a protein which conformational change maintain a trait that is permanent in the mother cell but is not inherited by daughter cells. Mnemons share structural features with prions, which are self-templating protein conformations that are inherited by daughter cells. Yet, how the maintenance and asymmetric inheritance of Whi3mnemare achieved is unknown. Here, we report that Whi3mnemis closely associated with endoplasmic reticulum (ER) membranes and retained in the mother cell by the presence of lateral membrane diffusion barriers at the bud neck. Strikingly, barrier defects made Whi3mnempropagate in a mitotically stable manner, like a prion. Alike Whi3mnem, transformation of Whi3 into a prion required its poly-glutamine prion-like domain. Thus, we propose that Whi3mnemis in a self-templating state, lending temporal stability to the memory that it encodes, while its anchorage into the compartmentalized membranes of the ER ensures its confinement in the mother cell and prevents its infectious propagation. These results suggest that confined self-templating super-assembly is a powerful mechanism for the long-term encoding of information.
Optimization of mouse embryonic stem cell culture for organoid and chimeric mice production
Authors: Martin-Lemaitre Cécilie , Alcheikh Yara , Naumann Ronald , Honigmann Alf 
Published: March 2020

SummaryIn vitrostem cell culture is demanding in terms of manpower and media supplements. In recent years, new protocols have been developed to expand pluripotent embryonic stem cells in suspension culture, which greatly simplifies cell handling and scalability. However, it is still unclear how suspension culture protocols with different supplements affect pluripotency, cell homogeneity and cell differentiation compared to established adherent culture methods. Here we tested four different culture conditions for mouse embryonic stem cells (mESC) and quantified chimerism and germ line transmission as well asin vitrodifferentiation into three-dimensional neuro-epithelia. We found that suspension culture supplemented with CHIR99021/LIF offers the best compromise between culturing effort, robust pluripotency and cell homogeneity. Our work provides a guideline for simplifying mESC culture and should encourage more cell biology labs to use stem cell-based organoids as model systems.
Carbon ion dosimetry on a fluorescent nuclear track detector using widefield microscopy
Authors: Walsh Dietrich W.M. , Liew Hans , Schlegel Julian , Mairani Andrea , Abdollahi Amir , Niklas Martin 
Published: March 2020

AbstractFluorescent nuclear track detectors (FNTD) are solid-state dosimeters used in a wide range of dosimetric and biomedical applications in research worldwide. FNTDs are a core but currently underutilized dosimetry tool in the field of radiation biology which are inherently capable of visualizing the tracks of ions used in hadron therapy. The ions that traverse the FNTD deposit their energy according to their linear energy transfer (LET) and transform colour centres to form trackspots around their trajectory. These trackspots have fluorescent properties which can be visualized by fluorescence microscopy enabling a well-defined dosimetric readout with a spatial component indicating the trajectory of individual ions. The current method used to analyse the FNTDs is laser scanning confocal microscopy (LSM). LSM enables a precise localization of track spots in x, y and z however due to the scanning of the laser spot across the sample, requires a long time for large samples. This body of work conclusively shows for the first time that the readout of the trackspots present after 0.5 Gy carbon ion irradiation in the FNTD can be captured with a widefield microscope (WF). The WF readout of the FNTD is a factor ∼10 faster, for an area 2.97 times the size making the method nearly a factor 19 faster in track acquisition than LSM. The dramatic decrease in image acquisition time in WF presents an alternative to LSM in FNTD workflows which are limited by time, such as biomedical sensors which combine FNTDs with live cell imaging.
Surgery and Radioactive Iodine Therapeutic Strategy for Patients Greater than 60 Years of Age with Differentiated Thyroid Cancer
Authors: Tang Tao , Zhang Wei , Zhi Jingtai , Ruan Xianhui , Hu Linfei , Chen Xiaoyu , Wang Zhaohui , Zheng Xiangqian , Gao Ming 
Published: March 2020

AbstractPurposeThe purpose of the current study was to determine whether older patients with differentiated thyroid cancer (DTC) who received surgical treatment had a better cause-specific survival (CSS) than patients who were recommended surgery, but declined, and whether patients who underwent post-operative RAI-131 therapy had an impact on CSS based on TNM staging and number of lymph node metastases for all total or near-total thyroidectomy patients.Patients and MethodsAll DTC patients information were obtained from the SEER*Stat 8.3.6 program, and only patients ≥ 60 years or older were considered. The patients were divided into two groups (underwent surgery and surgery recommend, but not performed). Furthermore, patients were grouped as follows: T4; N1b; M1; T1-3N0-1a; specific number of lymph node metastases; and total or near-total thyroidectomy.ResultsThe 120-month cause-specific survival (CSS) rate of females and males showed a gradual declining trend from 60-64 to ≥80 years of age in the group that underwent surgery. The CSS rate of females and males showed a marked downward and irregular trend with an increase in age in the recommended, but no surgery group. Univariate analysis indicated that the surgery group had a higher 120-month CSS in females in most stages and males, compared with the no surgery group. RAI-131 therapy was associated with an improved 80-month CSS in T4/N1b/M1 females (P<0.0183) and males (P<0.0011). There was no CSS difference in females or males between the T1-3N0 and T1-3N1a patients. There was no statistical difference between the two subgroups.ConclusionsSurgical treatment should be recommended for elderly DTC patients because surgery can lead to a better CSS. High-risk patients achieve a higher benefit-to-risk ratio with RAI-131 therapy. To avoid the adverse effects associated with RAI-131 therapy, a multidisciplinary discussion should be arranged for intermediate- and low-risk patients.
Consistency of superb microvascular imaging and contrast enhanced ultrasonography in detecting intraplaque neovascularization: a meta-analysis
Authors: Yang Fang , Wang Cong 
Published: March 2020

AbstractThis meta-analysis aimed to identify the consistency of superb microvascular imaging(SMI) and contrast-enhanced ultrasonography(CEUS) in detecting intraplaque neovascularization(IPN). We searched PubMed, Web of Science, Cochrane Library, CISCOM, and CBM databases without language restrictions. Meta-analysis was conducted using STATA version 15.1 software. We calculated the pooled Kappa index. Ten studies that met all inclusion criteria were included in this meta-analysis. A total of 608 carotid plaques were assessed through both SMI and CEUS. The pooled summary Kappa index was 0.743(95 % CI=0.696-0.790) with statistical significance(z= 31.14, p<0.01). We found no evidence for publication bias (t=-1.21, p=0.261). Our meta-analysis indicates that SMI and CEUS display a good consistency in detecting IPN of carotid plaque, that is to say SMI ultrasound maybe a promising alternative to CEUS for detecting IPN of carotid plaque.
Experimental production of anti-membrane bound variable surface glycoglycoprotein (anti-VSGm) antibodies forin vitroandin situimmunostaining of pathogenic African trypanosomes
Authors: Okwong-Oketch Reymick , Nsubuga Julius , Ayebare Peter , Nsadha Zachary , Lubega George William , Nanteza Ann 
Published: March 2020

AbstractBackgroundThe variant surface glycoprotein (VSG) of the African trypanosomes is the major membrane protein of the plasma membrane of the bloodstream stage of the parasite. African trypanosomiasis (sleeping sickness in humans and nagana in animals) is caused by the systemic infection of the host by several sub-species of the extracellular haemoflagellate protozoa under genus Trypanosoma. As a defense barrier against the host immune response, the entire surface of the bloodstream form of trypanosome is covered with densely packed molecules of VSG that determines the antigenic phenotype of the parasite. Variant surface glycoprotein has a C-terminal domain that is highly conserved in various species of trypanosomes.MethodsThe membrane bound VSG (VSGm) protein was prepared without denaturing the homologous region and by including numerous variable antigen types fromTrypanosoma brucei bruceiparasites. The purified VSGm native trypanosome protein was used to produce anti-VSGm immune sera in rabbits. The indirect immunofluorescence assay (IFA) was used to detect trypanosomes from mice blood, artificial culture media and cattle histological sections.ResultsThe resultant immune sera were able to detect different strains and species of African trypanosomes fromin vivoandin situsources after immunostaining. Anti-VSGm antibodies also demonstrated a unique property to locate trypanosomes within the histological tissues even after the trypanosome’s morphology had been distorted.ConclusionThe produced immune sera can be utilized for immunohistochemistry to detectTrypanosoma speciesin various fluids and tissues.Author summary
Mitochondrial-Derived Compartments Facilitate Cellular Adaptation to Amino Acid Stress
Authors: Schuler Max-Hinderk , English Alyssa M. , Campbell Thane J. , Shaw Janet M. , Hughes Adam L. 
Published: March 2020

SUMMARYAmino acids are essential building blocks of life. However, increasing evidence suggests that elevated amino acids cause cellular toxicity associated with numerous metabolic disorders. How cells cope with elevated amino acids remains poorly understood. Here, we show that a previously identified cellular structure, themitochondrial-derivedcompartment (MDC), is a dynamic, lumen-containing organelle that functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and remove Tom70, a surface receptor required for import of nutrient carriers of the SLC25 family. MDC formation is regulated by levels of mitochondrial carriers, and its activation by amino acids occurs simultaneously with removal of plasma membrane-localized transporters via the multi-vesicular body (MVB) pathway. Combined loss of MDC and MVB formation renders cells sensitive to elevated amino acids, suggesting these pathways operate as a coordinated network to protect cells from amino acid toxicity.