bluuebunny/crossref_metadata_2025_split huggingface dataset:
Every single conidium in Aspergillus fumigatus caspofungin tolerant strains are intrinsically caspofungin tolerant
Authors: Valero Clara , Colabardini Ana Cristina , de Castro Patrícia Alves , Amich Jorge , Bromley Michael J. , Goldman Gustavo H. 
Published: February 2022

AbstractAspergillus fumigatus is a human fungal pathogen that causes a disease named aspergillosis. Echinocandins, such as the fungistatic drug caspofungin (CAS) are used as second-line therapy. Some A. fumigatus clinical isolates can survive and grow in higher CAS concentrations, a phenomenon known as “caspofungin paradoxical effect” (CPE). Here we investigate if CPE is due to a subpopulation of conidia produced by a CAS tolerant strain, indicative of a persistence phenotype or is caused by all the conidia which would be consistent with a tolerance phenotype. We evaluated 67 A. fumigatus clinical isolates for CPE growth and used a novel CPE Index (CPEI) classified them as CPE+ (CPEI ≥ 0.40) or CPE− (CPEI ≤ 0.20). Conidia produced by three CPE+ clinical isolates, CEA17 (CPEI=0.52), Af293 (CPEI=0.64), CM7555 (CPEI=0.58) all showed the ability to grow in high levels of CAS while all conidia produced by the CPE− isolate IFM61407 (CPEI=0.12) strain showed no evidence of tolerance. Given the importance of calcium/calcineurin/transcription factor CrzA pathway in CPE regulation, we also evaluated ΔcrzAAf293 (CPE−) and ΔcrzACEA17 (CPE+) conidia tolerance to CAS. All ΔcrzACEA17 conidia showed CPE+ while 100 % of ΔcrzAAf293 spores are CPE−. As all spores derived from an individual strain are phenotypically indistinct with respect to CPE it is likely that CPE is a genetically encoded adaptive trait that should be considered an antifungal tolerant phenotype. As the CPEI shows that the strength of the CPE is not uniform between strains we propose that the mechanisms that govern this phenomenon are multi-factorial.
Real-time monitoring of the effectiveness of six COVID-19 vaccines in Hungary in 2021 using the screening method
Authors: Krisztina Horváth J. , Ferenci Tamás , Ferenczi Annamária , Túri Gergő , Röst Gergely , Oroszi Beatrix 
Published: February 2022

AbstractSeveral studies have reported a waning of the effectiveness of COVID-19 vaccines. We report real-life vaccine effectiveness in Hungary, estimated with the screening method, in 2021, i.e., covering the dominance of both the Alpha and the Delta variant, and including the booster roll-out. Hungary is in the unique position to use six different vaccines (including the Sputnik V and Sinopharm vaccines, for which limited evidence was available prior to the present study) in the same, relatively homogeneous population. All vaccines provided high level of protection initially which declined over time. While the picture is different in each age group, the waning of immunity is apparent for all vaccines and especially in the younger age groups and the Sinopharm, Sputnik-V and AstraZeneca vaccines, which performed similarly. This is clearly reversed by booster doses, more prominent for those vaccines, where recipients were more likely to take the booster dose (which were the aforementioned three vaccines). Booster doses were almost exclusively mRNA vaccines. Overall, two vaccines, Pfizer/BioNTech and Moderna tend to produce the best results in all age groups, and even with waning taken into account.
The effect of cytoskeleton inhibitors on coccolith morphology inCoccolithus braarudiiandScyphosphaera apsteinii
Authors: Langer Gerald , Probert Ian , Taylor Alison , Harper Glenn M. , Brownlee Colin , Wheeler Glen 
Published: February 2022

AbstractThe calcite platelets of coccolithophores (Haptophyta), the coccoliths, are among the most elaborate biomineral structures. How these unicellular algae accomplish the complex morphogenesis of coccoliths is still largely unknown. It has long been proposed that the cytoskeleton plays a central role in shaping the growing coccoliths. Previous studies have indicated that disruption of the microtubule network led to defects in coccolith morphogenesis inEmiliania huxleyiandCoccolithus braarudii. Disruption of the actin network also led to defects in coccolith morphology inE. huxleyi, but its impact on coccolith morphology inC. braarudiiwas less clear, as coccolith secretion was largely inhibited under the conditions used. A more detailed examination of the role of actin and microtubule networks is therefore required to address the wider role of the cytoskeleton in coccolith morphogenesis. In this study, we have examined coccolith morphology inC. braarudiiandScyphosphaera apsteiniifollowing treatment with the microtubule inhibitors vinblastine and colchicine (S. apsteiniionly) and the actin inhibitor cytochalasin B. We found that all cytoskeleton inhibitors induced coccolith malformations, strongly suggesting that both microtubules and actin filaments are instrumental in morphogenesis. By demonstrating the requirement for the microtubule and actin networks in coccolith morphogenesis in diverse species, our results suggest that both of these cytoskeletal elements are likely to play conserved roles in defining coccolith morphology.
Aquatic long-term persistence ofFrancisella tularensisssp.holarcticais driven by water temperature and transition to a viable but non-culturable state
Authors: Brunet Camille D. , Peyroux Julien , Pondérand Léa , Bouillot Stéphanie , Girard Thomas , Faudry Éric , Maurin Max , Caspar Yvan 
Published: February 2022

AbstractFrancisella tularensisis a highly virulent bacterium causing tularemia zoonosis. An increasing proportion of infections occur through contaminated hydro-telluric sources, especially for the subspeciesholarctica(Fth). Although this bacterium has been detected in several aquatic environments, the mechanisms of its long-term persistence in water are not yet elucidated. We evaluated the culturability and the viability of a virulentFthstrain in independent microcosms filled with nutrient-poor water. At 37°C, the bacteria remained culturable for only one week, while culturability was extended to 6 weeks at 18°C and up to 11 weeks at 4°C. However, while the viability of the bacteria declined similarly to culturability at 37°C, the viability of the bacteria remained stable overtime at 18°C and 4°C for more than 24 months, long after loss of culturability. We identified water temperature as one of the major factors driving the aquatic survival ofFththrough a transition of the wholeFthpopulation in a viable but non-culturable (VBNC) state. Low temperature of water (≤18°C) favors the persistence of the bacteria in a VBNC state, while a temperature above 30°C kills culturable and VBNCFthbacteria. These findings provide new insights into the environmental cycle ofFrancisella tularensisthat suggest that the yet unidentified primary reservoir of the subspeciesholarcticamay be the aquatic environment itself in which the bacteria could persist for months or years without the need for a host.
SARS-CoV-2 has not emerged in roe, red or fallow deer in Germany or Austria during the COVID 19 pandemic
Authors: Moreira-Soto Andres , Walzer Christian , Czirják Gábor Á. , Richter Martin , Marino Stephen F. , Posautz Annika , de Yebra Pau Rodo , McEwen Gayle K. , Drexler Jan Felix , Greenwood Alex D. 
Published: February 2022

AbstractSpillover of SARS-CoV-2 to North American white tailed deer (Odocoileus virginianus) has been documented. We evaluated pre and pandemic exposure of German and Austrian deer species using a SARS-CoV-2 pseudoneutralization assay. In stark contrast to North American white tailed deer, we found no evidence of SARS-CoV-2 exposure.Article Summary LineUsing a sensitive serological assay, 433 pre and pandemic deer samples from Germany and Austria tested negative for SARS-CoV-2-specific antibodies highlighting a major difference between central European and North American deer exposure and in their epidemiologic roles.
Unsupervised physiological noise correction of fMRI data using phase and magnitude information (PREPAIR)
Authors: Bancelin David , Bachrata Beata , Bollmann Saskia , de Lima Cardoso Pedro , Szomolanyi Pavol , Trattnig Siegfried , Robinson Simon Daniel 
Published: February 2022

AbstractOf the sources of noise which affect BOLD fMRI, respiration and cardiac fluctuations are responsible for the largest part of the variance, particularly at high and ultra-high field. Existing approaches to removing physiological noise either use external recordings, which can be unwieldy and unreliable, or attempt to identify physiological noise from the magnitude fMRI data. Data-driven approaches are limited by sensitivity, temporal aliasing and the need for user interaction. In the light of the sensitivity of the phase of the MR signal to local changes in the field stemming from physiological processes, we have developed an unsupervised physiological noise correction method which uses the information carried in both the phase and the magnitude of EPI data. Our technique, Physiological Regressor Estimation from Phase and mAgnItude, sub-tR (PREPAIR) derives time series signals which are sampled at the slice TR from both phase and magnitude images. It allows physiological noise to be captured without aliasing, and efficiently removes other sources of signal fluctuations which are not related to physiology, prior to regressor estimation. We demonstrate that the physiological signal time courses identified with PREPAIR not only agree well with those from external devices, but also retrieve challenging cardiac dynamics. The removal of physiological noise was as effective as that achieved with the most commonly used approach based on external recordings, RETROICOR. In comparison with widely used physiological noise correction tools which do not use external signals, PESTICA and FIX, PREPAIR removed more respiratory and cardiac noise and achieved a larger increase in tSNR at both 3 T and 7 T.
Alternative c-MYC mRNA transcripts as an additional tool for c-Myc2 and c-MycS production in BL60 tumors
Authors: Ibrahim Dina , Faumont Nathalie , Troutaud Danielle , Feuillard Jean , Diab-Assaf Mona , Oulmouden Ahmad 
Published: February 2022

AbstractWhile studying c-Myc protein expression in several Burkitt lymphoma cell lines and in lymph nodes from a mouse model bearing a translocated c-MYC gene from the human BL line IARC-BL60, we surprisingly discovered a complex electrophoretic profile. Indeed, the BL60 cell line carrying the t(8;22) c-MYC translocation exhibits a simple pattern, with a single c-Myc2 isoform. Analysis of the c-MYC transcripts expressed by tumor lymph nodes in the mouse λc-MYC (Avy/a) showed for the first time five transcripts associated with t(8;22) c-MYC translocation. The five transcripts were correlated with the production of c-Myc2 and c-MycS, and loss of c-Myc1. The contribution of these transcripts to the oncogenic activation of the t(8;22) c-MYC is discussed.
Cardiac and gastric interoception have distinct neural substrates
Authors: Haruki Yusuke , Ogawa Kenji 
Published: February 2022

AbstractInteroception, or an awareness of the internal body state, guides agents in adaptive behavior by informing them of ongoing bodily signals, such as heart rate or energy status. However, it is still unclear whether the human brain represents the differences in the subjective experience of interoception differently. Hence, we directly compared the neural activation for cardiac (awareness related to heartbeats) and gastric (awareness related to the stomach) interoception in the same population (healthy human, N = 31). Participants were asked to focus on their heart and stomach sensations to be aware of interoception in a magnetic resonance imaging scanner. The results indicated that neural activation underlying gastric interoception encompassed larger brain regions, including the occipitotemporal visual cortices, bilateral primary motor cortex, primary somatosensory cortex, left orbitofrontal cortex, and bilateral hippocampal regions. Cardiac interoception, however, selectively activated the right anterior insula extending to the frontal operculum more compared to gastric interoception. Moreover, our detailed analyses focusing on the insula, the most relevant region for interoception, revealed that the left dorsal middle insula encoded cardiac and gastric interoception in different activation patterns but not the posterior insula. Our results demonstrate that cardiac and gastric interoception have distinct neural substrates; in particular, the selective brain activation may reflect differences in the functional roles of cardiac and gastric interoception.Significance statementInteroception, subjective senses that arise from within the body, plays a critical role in maintaining adaptive behavior by informing of the ongoing bodily states, such as heart rate and energy status. Although interoception has various characteristics depending on its source signals, previous neuroimaging studies have extensively used cardiac interoception (senses related to heartbeats), making it unclear whether the brain differently encodes diverse experiences of interoception. Here, we demonstrate that cardiac interoception and gastric interoception (senses related to the stomach) have distinct neural substrates by combining mass-univariate analysis with multivoxel pattern analysis for fMRI data. Our findings suggest that the selective brain activation may reflect differences in the functional roles of cardiac and gastric interoception.
MicroRNA-155 regulates osteogenesis and bone mass phenotype via targeting S1PR1 gene
Authors: Zheng Zhichao , Wu Lihong , Li Zhicong , Tang Ruoshu , Li Hongtao , Huang Yinyin , Ye Zhitong , Xiao Dong , Lin Xiaolin , Wu Gang , Jaspers Richard T , Pathak Janak L. 
Published: February 2022

AbstractMicroRNA-155 (miR155) is overexpressed in various inflammatory diseases and cancer, in which bone resorption and osteolysis are frequently observed. However, the role of miR155 on osteogenesis and bone mass phenotype is still unknown. Here, we report a low bone mass phenotype in the long bone of miR155-Tg mice compared with control mice. In contrast, miR155-KO mice showed a high bone mass phenotype. miR155-KO mice showed robust bone regeneration in the ectopic and orthotopic model, but miR155-Tg mice showed compromised bone regeneration compared with the control mice. Similarly, the osteogenic differentiation potential of bone marrow stromal stem cells (BMSCs) from miR155-KO mice was robust and miR155-Tg was compromised compared with that of control mice. Moreover, miR155 knockdown in BMSCs from control mice showed higher osteogenic differentiation potential, supporting the results from miR155-KO mice. TargetScan analysis predicted S1PR1 as a target gene of miR155, which was further confirmed by luciferase assay and miR155 knockdown. S1PR1 overexpression in BMSCs robustly promoted osteogenic differentiation without affecting cell viability and proliferation. Thus, miR155 showed a catabolic effect on osteogenesis and bone mass phenotype via interaction with the S1PR1 gene, suggesting inhibition of miR155 as a potential strategy for bone regeneration and bone defect healing.
Hinokitiol alters Gene Expression in Aspergillus fumigatus, protects against fungal keratitis by Reducing Fungal Load, LOX-1, Proinflammatory cytokines and Neutrophil Infiltration
Authors: Ma Shuqin , Lin Hao , Peng Xudong , Li Cui , Wang Qian , Xu Qiang , He Mengting , Shao Dan , Liu Xing , Zhao Guiqiu , Lin Jing 
Published: February 2022

AbstractHinokitiol (HK), a tropolone-related compound found in cupressaceous plants, has antifungal and anti-inflammatory properties. But its roles in Aspergillus fumigatus ( A.F. ) keratitis remains unknown. This study examined the antifungal activity of HK against A.F. and investigated its possible mechanisms at the ultrastructural and transcriptional levels. We tested the minimum inhibitory concentration (MIC) of HK against A.F.. Our data showed that the MIC50 was 2 μg/ml and MIC90 was 8 μg/ml, and HK could significantly inhibit the spore germination and mycelial growth of A.F.. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations showed that HK induced significant changes in hyphal morphology and microstructure, including cell membrane rupture and intracellular structural disorder. Adhesion assay and biofilm assay experiments showed that HK reduced the adhesion of spores to human corneal epithelial cells (HCECs) and inhibited the formation of biofilms. The genetic changes of A.F. after HK treatment were analyzed by RNA sequencing, and a total of 2487 differentially expressed genes (DEGs) were identified, including the down-regulated DEGs related to carbohydrate and various amino acid metabolism, ribosome biogenesis, asexual reproduction, and up-regulated DEGs related to steroid biosynthesis through GO and KEGG enrichment analysis. RNA-seq results suggested that HK may play an antifungal effect by destroying the structural integrity of its wall and membrane, inhibiting protein biosynthesis and the growth and reproduction of A.F..10 μg/ml HK, which had no effect on proliferation and migration of HCECs, was used in the treatment of murine fungal keratitis (FK). We found that HK eyedrop treatment could reduce the severity of FK by reducing corneal fungal burden, neutrophil infiltration, and the expression of LOX-1 and pro-inflammatory factors. HK is expected to be a safe and effective new drug for FK treatment.Author summaryFK is a serious common blind-causing eye disease. The current clinical antifungal drugs have the disadvantages of low bioavailability and high corneal toxicity, which greatly limit the clinical effectiveness. Therefore, there is an urgent need for a new, safe and effective treatment for FK. HK had shown great antifungal capacity against A.F., amazingly well anti-inflammatory effect and real improvement in murine FK in our research. These findings provide a theoretical basis for the application of HK as an antifungal drug and reveal the potential of HK to be applied in the clinical treatment of FK.
Systematic Evaluation of Different R-loop Mapping Methods: Achieving Consensus, Resolving Discrepancies and Uncovering Distinct Types of RNA:DNA Hybrids
Authors: Chen Jia-Yu , Lim Do-Hwan , Chen Liang , Zhou Yongli , Zhang Fangliang , Shao Changwei , Zhang Xuan , Li Hairi , Wang Dong , Zhang Dong-Er , Fu Xiang-Dong 
Published: February 2022

AbstractR-loop, a three-stranded nucleic acid structure, has been recognized to play pivotal roles in critical physiological and pathological processes. Multiple technologies have been developed to profile R-loops genome-wide, but the existing data suffer from major discrepancies on determining genuine R-loop localization and its biological functions. Here, we experimentally and computationally evaluate eight representative R-loop mapping technologies, and reveal inherent biases and artifacts of individual technologies as key sources of discrepancies. Analyzing signals detected with different R-loop mapping strategies, we note that genuine R-loops predominately form at gene promoter regions, whereas most signals in gene body likely result from structured RNAs as part of repeat-containing transcripts. Interestingly, our analysis also uncovers two classes of R-loops: The first class consists of typical R-loops where the single-stranded DNA binding protein RPA binds both the template and non-template strands. By contrast, the second class appears independent of Pol II-mediated transcription and is characterized by RPA binding only in the template strand. These two different classes of RNA:DNA hybrids in the genome suggest distinct biochemical activities involved in their formation and regulation. In sum, our findings will guide future use of suitable technology for specific experimental purposes and the interpretation of R-loop functions.
ABPP-HT* - Deep meets fast for activity-based profiling of deubiquitylating enzymes using advanced DIA mass spectrometry methods
Authors: Jones Hannah B. L. , Heilig Raphael , Davis Simon , Fischer Roman , Kessler Benedikt M. , Pinto-Fernández Adán 
Published: February 2022

AbstractActivity-based protein profiling (ABPP) uses a combination of activity-based chemical probes with mass spectrometry (MS) to selectively characterise a particular enzyme or enzyme class. ABPP has proven invaluable for profiling enzymatic inhibitors in drug discovery. When applied to cell extracts and cells, challenging the ABP-enzyme complex formation with a small molecule can simultaneously inform on potency, selectivity, reversibility/binding affinity, permeability, and stability. ABPP can also be applied to pharmacodynamic studies to inform on cellular target engagement within specific organs when applied to in vivo models. Recently, we established separate high depth and high throughput ABPP (ABPP-HT) protocols for the profiling of deubiquitylating enzymes (DUBs). However, the combination of the two, deep and fast, in one method has been elusive. To further increase the sensitivity of the current ABPP-HT workflow we implemented state-of-the-art data-independent acquisition (DIA) and data-dependent acquisition (DDA) MS analysis tools. Hereby, we describe an improved methodology, ABPP-HT* (enhanced high-throughput-compatible activity-based protein profiling), that in combination with DIA MS methods allowed for the consistent profiling of 35-40 DUBs and provided a reduced number of missing values, whilst maintaining a throughput of 100 samples per day.
Accurate staging of chick embryonic tissues via deep learning
Authors: Groves Ian , Holmshaw Jacob , Furley David , Towers Matthew , Evans Benjamin D. , Placzek Marysia , Fletcher Alexander G. 
Published: February 2022

ABSTRACTRecent work has indicated a need for increased temporal resolution for studies of the early chick brain. Over a 10-hour period, the developmental potential of progenitor cells in the HH10 brain changes, and concomitantly, the brain undergoes subtle changes in morphology. We asked if we could train a deep convolutional neural network to sub-stage HH10 brains from a small dataset (<200 images). By augmenting our images with a combination of biologically informed transformations and data-driven preprocessing steps, we successfully trained a classifier to sub-stage HH10 brains to 87.1% test accuracy. To determine whether our classifier could be generally applied, we re-trained it using images (<250) of randomised control and experimental chick wings, and obtained similarly high test accuracy (86.1%). Saliency analyses revealed that biologically relevant features are used for classification. Our strategy enables training of image classifiers for various applications in developmental biology with limited microscopy data.SUMMARY STATEMENTWe train a deep convolutional network that can be generally applied to accurately classify chick embryos from images. Saliency analyses show that classification is based on biologically relevant features.
Representational dynamics of memories for real-life events
Authors: Jeunehomme Olivier , Heinen Rebekka , Stawarczyk David , Axmacher Nikolai , D’Argembeau Arnaud 
Published: February 2022

SummaryThe continuous flow of experience that characterizes real-life events is not recorded as such in episodic memory but is condensed as a succession of event segments separated by temporal discontinuities. To unravel the neural basis of this representational structure, we recorded real-life events using wearable camera technology and used fMRI to investigate brain activity during their temporal unfolding in memory. We found that, compared to the representation of static scenes in memory, dynamically unfolding memory representations were associated with greater activation of the posterior medial episodic network. Strikingly, by analyzing the autocorrelation of brain activity patterns at successive time points throughout the retrieval period, we found that this network showed higher temporal dynamics when recalling events that included a higher density of event segments. These results reveal the key role of the posterior medial network in representing the dynamic unfolding of the event segments that constitute real-world memories.