bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial and metabolic remodeling in human skin fibroblasts in response to glucose availability
Authors: Costa Cláudio F. , Pinho Sónia A. , Pinho Sonia L.C. , Miranda-Santos Inês , Bagshaw Olivia , Stuart Jeffrey , Oliveira Paulo J. , Cunha-Oliveira Teresa 
Published: February 2021

AbstractCell culture conditions highly influence cell metabolismin vitro. This is relevant for preclinical assays, for which fibroblasts are an interesting cell model, with applications in regenerative medicine, diagnostics and therapeutic development for personalized medicine as well as in the validation of ingredients for cosmetics. Given these cells’ short lifespan in culture, we aimed to identify the best cell culture conditions and promising markers to study mitochondrial health and stress in Normal Human Dermal Fibroblasts (NHDF). We tested the effect of reducing glucose concentration in the cell medium from high glucose (HGm) to a more physiological level (LGm), or its complete removal and replacement by galactose (OXPHOSm), always in the presence of glutamine and pyruvate. We have demonstrated that only with OXPHOSm it was possible to observe the selective inhibition of mitochondrial ATP production. This reliance on mitochondrial ATP was accompanied by changes in oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), oxidation of citric acid cycle substrates, fatty acids, lactate and other substrates, mitochondrial network extension and polarization and changes in several key transcripts related to energy metabolism. We also evaluated the relevance of galactose, glutamine and pyruvate for OXPHOS stimulation, by comparing OCR and ECAR in the presence or absence of these substrates. Galactose and pyruvate seem to be important, but redundant, to promote OXPHOS, whereas glutamine was essential. We concluded that LGm does not promote significant metabolic changes but the short-term adaptation to OXPHOSm is ideal for studying mitochondrial health and stress in NHDF.Author ContributionsCC, SAP, SLCP and IMS performed experiments. TCO and PJO designed research and acquired funding. JS, and OB analyzed data. CC and TCO analyzed data and wrote the paper. All authors contributed to the final version of the manuscript.
Activation of Cytochrome C Peroxidase Function Through Coordinated Foldon Loop Dynamics upon Interaction with Anionic Lipids
Authors: Li Mingyue , Sun Wanyang , Tyurin Vladimir A. , DeLucia Maria , Ahn Jinwoo , Kagan Valerian E. , van der Wel Patrick C.A. 
Published: February 2021

ABSTRACTCardiolipin (CL) is a mitochondrial anionic lipid that plays important roles in the regulation and signaling of mitochondrial apoptosis. CL peroxidation catalyzed by the assembly of CL-cytochrome c (cyt c) complexes at the inner mitochondrial membrane is a critical checkpoint. The structural changes in the protein, associated with peroxidase activation by CL and different anionic lipids, are not known at a molecular level. To better understand these peripheral protein-lipid interactions, we compare how phosphatidylglycerol (PG) and CL lipids trigger cyt c peroxidase activation, and correlate functional differences to structural and motional changes in membrane-associated cyt c. Structural and motional studies of the bound protein are enabled by magic angle spinning solid state NMR spectroscopy, while lipid peroxidase activity is assayed by mass spectrometry. PG binding results in a surface-bound state that preserves a nativelike fold, which nonetheless allows for significant peroxidase activity, though at a lower level than binding its native substrate CL. Lipid-specific differences in peroxidase activation are found to correlate to corresponding differences in lipid-induced protein mobility, affecting specific protein segments. The dynamics of omega loops C and D are upregulated by CL binding, in a way that is remarkably controlled by the protein:lipid stoichiometry. In contrast to complete chemical denaturation, membrane-induced protein destabilization reflects a destabilization of select cyt c foldons, while the energetically most stable helices are preserved. Our studies illuminate the interplay of protein and lipid dynamics in the creation of lipid peroxidase-active proteolipid complexes implicated in early stages of mitochondrial apoptosis.
Nuclear Hormone Receptor NHR-49 controls a HIF-1-independent hypoxia adaptation pathway inCaenorhabditis elegans
Authors: Doering Kelsie R. S. , Cheng Xuanjin , Milburn Luke , Ratnappan Ramesh , Ghazi Arjumand , Miller Dana L. , Taubert Stefan 
Published: February 2021

AbstractThe response to insufficient oxygen (hypoxia) is orchestrated by the conserved Hypoxia-Inducible Factor (HIF). However, HIF-independent hypoxia response pathways exist that act in parallel to HIF to mediate the physiological hypoxia response. Here, we describe a HIF-independent hypoxia response pathway controlled byCaenorhabditis elegansNuclear Hormone Receptor NHR-49, an orthologue of mammalian Peroxisome Proliferator-Activated Receptor alpha (PPARα). We show thatnhr-49is required for worm survival in hypoxia and is synthetic lethal withhif-1in this context, demonstrating that these factors act independently. RNA-seq analysis shows that in hypoxianhr-49regulates a set of genes that arehif-1-independent, including autophagy genes that promote hypoxia survival. We further show that Nuclear Hormone Receptornhr-67is a negative regulator and Homeodomain-interacting Protein Kinasehpk-1is a positive regulator of the NHR-49 pathway. Together, our experiments define a new, essential hypoxia response pathway that acts in parallel to the well-known HIF-mediated hypoxia response.
qc3C: reference-free quality control for Hi-C sequencing data
Authors: DeMaere Matthew Z. , Darling Aaron E. 
Published: February 2021

AbstractHi-C is a sample preparation method that enables high-throughput sequencing to capture genome-wide spatial interactions between DNA molecules. The technique has been successfully applied to solve challenging problems such as 3D structural analysis of chromatin, scaffolding of large genome assemblies and more recently the accurate resolution of metagenome-assembled genomes (MAGs). Despite continued refinements, however, Hi-C library preparation remains a complex laboratory protocol and diligent quality management is recommended to avoid costly failure. Current wet-lab protocols for Hi-C library QC provide only a crude assay, while commonly used sequence-based QC methods demand a reference genome; the quality of which can skew results. We propose a new, reference-free approach for Hi-C library quality assessment that requires only a modest amount of sequencing data. The algorithm builds upon the observation that proximity ligation events are likely to createk-mers that would not naturally occur in the sample. Our software tool (qc3C) is to our knowledge the first to implement a reference-free Hi-C QC tool, and also provides reference-based QC, enabling Hi-C to be more easily applied to non-model organisms and environmental samples. We characterise the accuracy of the new algorithm on simulated and real datasets and compare it to reference-based methods.
A synaptic novelty signal to switch hippocampal attractor networks from generalization to discrimination
Authors: Gómez-Ocádiz Ruy , Trippa Massimiliano , Posani Lorenzo , Cocco Simona , Monasson Rémi , Schmidt-Hieber Christoph 
Published: February 2021

AbstractEpisodic memory formation and recall are complementary processes that put conflicting requirements on neuronal computations in the hippocampus. How this challenge is resolved in hippocampal circuits is unclear. To address this question, we obtainedin vivowhole-cell patch-clamp recordings from dentate gyrus granule cells in head-fixed mice trained to explore and distinguish between familiar and novel virtual environments. We find that granule cells consistently show a small transient depolarization of their membrane potential upon transition to a novel environment. This synaptic novelty signal is sensitive to local application of atropine, indicating that it depends on metabotropic acetylcholine receptors. A computational model suggests that the observed transient synaptic response to novel environments may lead to a bias in the granule cell population activity, which can in turn drive the downstream attractor networks to a new state, thereby favoring the switch from generalization to discrimination when faced with novelty. Such a novelty-driven cholinergic switch may enable flexible encoding of new memories while preserving stable retrieval of familiar ones.
Characterization of late structural maturation with a neuroanatomical marker that considers both cortical thickness and intracortical myelination
Authors: Maingault Sophie , Pepe Antonietta , Mazoyer Bernard , Tzourio-Mazoyer Nathalie , Crivello Fabrice 
Published: February 2021

ABSTRACTThe cortical ribbon changes throughout a person’s lifespan, with the most significant changes occurring during crucial development and aging periods. Changes during adulthood are rarely investigated due to the scarcity of neuroimaging data during this period. After childhood, the brain loses gray matter, which is evidenced by an apparent reduction in cortical thickness (CT); one factor of this thinning process is intense ongoing intracortical myelination (MYEL). Here, we report age-related changes in CT, MYEL, and their ratio in 447 participants aged 18 to 57 years (BIL&GIN cohort). We propose the CT/MYEL ratio to be a multimodal cortical maturation index (MATUR) capable of reflecting 1) stages during which CT and MYEL patterns diverge and 2) the regional differences in cortical maturation that occur in adulthood. Age mainly decreased CT in all cortical regions, with larger reductions occurring in the bilateral insular lobes, temporal and frontal poles, and cingulate cortices. Age led to a linear increase in MYEL in the entire cortex and larger increases in the primary motor, auditory, and visual cortices. The effects of age on the MATUR index were characterized by both linear and quadratic components. The linear component mimicked the pattern found in CT, with 1) a robust amplification of the global and regional effects of age on CT and 2) evidence of new bilateral linear decreases in the frontal and cortical cortices. Most importantly, age exhibited additional large quadratic effects on the MATUR index in the bilateral frontal (more prominent in the right hemisphere), parietal, temporal, and cingulate regions that were not highlighted by the CT metric. Thus, the MATUR index was more sensitive to age-related cortical structural changes during adulthood than was either CT or MYEL alone. As evidenced by the large quadratic component of the effect of age, the newly proposed maturation index dramatically improved the characterization of the regional cortical territories, uncovering the latest brain maturation steps that occur before stabilization and deterioration occur in mid- and late adulthood.
Catching a liar through facial expression of fear
Authors: Shen Xunbing , Fan Gaojie , Niu Caoyuan , Chen Zhencai 
Published: February 2021

AbstractThe leakage theory in the field of deception detection predicted that liars could not repress the leaked felt emotions (e.g., the fear or delight); and people who were lying would feel fear (to be discovered), especially under the high-stake situations. Therefore, we assumed that the aim of revealing deceits could be reached via analyzing the facial expression of fear. Detecting and analyzing the subtle leaked fear facial expressions is a challenging task for laypeople. It is, however, a relatively easy job for computer vision and machine learning. To test the hypothesis, we analyzed video clips from a game show “The moment of truth” by using OpenFace (for outputting the Action Units of fear and face landmarks) and WEKA (for classifying the video clips in which the players was lying or telling the truth). The results showed that some algorithms could achieve an accuracy of greater than 80% merely using AUs of fear. Besides, the total durations of AU 20 of fear were found to be shorter under the lying condition than under the truth-telling condition. Further analysis found the cause why durations of fear were shorter was that the duration from peak to offset of AU20 under the lying condition was less than that under the truth-telling condition. The results also showed that the facial movements around the eyes were more asymmetrical while people telling lies. All the results suggested that there do exist facial clues to deception, and fear could be a cue for distinguishing liars from truth-tellers.
Influenza virus ribonucleoprotein complex formation occurs in the nucleolus
Authors: Miyamoto Sho , Nakano Masahiro , Morikawa Takeshi , Hirabayashi Ai , Tamura Ryoma , Fujita Yoko , Hirose Nanami , Muramoto Yukiko , Noda Takeshi 
Published: February 2021

AbstractInfluenza A virus double-helical ribonucleoprotein complex (vRNP) performs transcription and replication of viral genomic RNA (vRNA). Unlike most RNA viruses, vRNP formation accompanied by vRNA replication is carried out in the nucleus of virus-infected cell. However, the precise subnuclear site remains unknown. Here, we report the subnuclear site of vRNP formation in influenza virus. We found that all vRNP components were colocalized in the nucleolus of virus-infected cells at early stage of infection. Mutational analysis showed that nucleolar localization of viral nucleoprotein, a major vRNP component, is critical for functional double-helical vRNP formation. Furthermore, nucleolar disruption of virus-infected cells inhibited vRNP component assembly into double-helical vRNPs, resulting in decreased vRNA transcription and replication. Collectively, our findings demonstrate that the vRNA replication-coupled vRNP formation occurs in the nucleolus, demonstrating the importance of the nucleolus for influenza virus life cycle.
Could Italy host the new coronavirus before China?
Authors: Tichopád Aleš , Pecen Ladislav 
Published: February 2021

AbstractThe pandemic of the COVID-19 disease caused by the SARS-CoV-2 virus has been believed to originate in China and spread later to other parts of the world. It is well acknowledged that the first diseased individuals appeared in China as early as in December 2019, and possibly even earlier in November. It has also been well established that the virus stroke Italy later in January or in February 2020, distinctly after the outbreak in China. Paper by Apolone et al. published in a local Italian medical journal in November 2020 however exposed this chronology to doubt.By fitting early part of the epidemic curve with the exponential model and extrapolating it backwards in time, we could estimate the day-zero of the epidemic and calculated its confidence intervals in Italy and China. We also calculated how probable it is that Italy encountered the virus prior 1 January 2020.We determined an early portion of the epidemic curve representing unhindered exponential growth which fit the exponential model with high determination >0.97 in both countries. We suggest that the day-zero in China and Italy was 8 December (95% CI: 3 Dec., 20 Dec.) and 22 January (95% CI: 16 Jan., 29 Jan.), respectively. We could with high confidence reject that Italy encountered the virus earlier than China (p <0.01).Based on our analysis we oppose the findings published by Apolone at al. and view the proposed pre-pandemic presence of the virus in Italy as very unlikely.
Characterization of growth and development of sorghum genotypes with differential susceptibility toStriga hermonthica
Authors: Kawa Dorota , Taylor Tamera , Thiombiano Benjamin , Musa Zayan , Vahldick Hannah E. , Walmsley Aimee , Bucksch Alexander , Bouwmeester Harro , Brady Siobhan M. 
Published: February 2021

AbstractVariation in strigolactone composition in sorghum root exudates underlies its resistance to the parasitic weed,Striga hermonthica. Root exudates of the Striga susceptible variety Shanqui Red (SQR) contain primarily 5-deoxystrigol, which has a high efficiency of inducing Striga germination. SRN39 roots primarily exude orobanchol, leading to reduced Striga germination and making this variety resistant to Striga. This structural diversity in exuded strigolactones is determined by the polymorphism in theLGS1(LOW GERMINATION STIMULANT 1) locus. Yet, the effects of thelgs1mutation as well as the consequences of the vast genetic diversity between SQR and SRN39 have not been addressed in terms of growth and development. Here, we demonstrate additional consequences ofLGS1loss-of-function by phenotypic and molecular characterization. A suite of genes related to metabolism was differentially expressed between SQR and SRN39. Increased levels of gibberellin precursors in SRN39 were accompanied with its slower growth rate and developmental delay and we observed an overall increased SRN39 biomass. The slow-down in growth and differences in transcriptome profiles of SRN39 were strongly associated with plant age. Additionally, analyses of multipleLGS1loss-of-function genotypes indicated that strigolactone stereochemistry influences root system architecture. In summary, we demonstrate that the consequences of thelgs1mutation reach further than the changes in strigolactone profile in the root exudate and translate into alterations in growth and development.HighlightSRN39 and Shanqui Red are models for sorghum genotypes that are resistant and susceptible, respectively, toStriga hermonthica. Additional differences in plant growth, development, and hormone abundance should be considered when assessing Striga tolerance.
Differences in gait stability and acceleration characteristics between healthy young and older females
Authors: Zhang Yuge , Zhou Xinglong , Pijnappels Mirjam , Bruijn Sjoerd M. 
Published: February 2021

AbstractOur aim was to evaluate differences in gait acceleration intensity, variability and stability of feet and trunk between older females and young females using inertial sensors. Twenty older females (OF; mean age 68.4, SD 4.1 years) and eighteen young females (YF; mean age 22.3, SD 1.7 years) were asked to walk straight for 100 meters at their preferred speed, while wearing inertial sensors on heels and lower back. We calculated spatiotemporal measures, foot and trunk acceleration characteristics and their variability, as well as trunk stability using the local divergence exponent (LDE). Two-way analysis of variance (including the factors foot and age), Student’s t-test, and Mann–Whitney U test were used to compare statistical differences of measures between groups. Cohen’s d effects were calculated for each variable. Foot maximum vertical acceleration and amplitude, trunk-foot vertical acceleration attenuation, as well as their variability were significantly smaller in OF than in YF. In contrast, trunk mediolateral acceleration amplitude, maximum vertical acceleration, and amplitude, as well as their variability were significantly larger in OF than in YF. Moreover, OF showed lower stability (i.e., higher LDE values) in mediolateral acceleration, mediolateral and vertical angular velocity of the trunk. Even though we measured healthy older females, these participants showed lower vertical foot accelerations with higher vertical trunk acceleration, lower trunk-foot vertical acceleration attenuation, less gait stability, and more variability of the trunk, and hence, were more likely to fall. These findings suggest that instrumented gait measurements may help for early detection of changes or impairments in gait performance, even before this can be observed by clinical eye or gait speed.
Distinct Synaptic Transfer Functions in Same-Type Photoreceptors
Authors: Schröder Cornelius , Oesterle Jonathan , Berens Philipp , Yoshimatsu Takeshi , Baden Tom 
Published: February 2021

SUMMARYMany sensory systems use ribbon-type synapses to transmit their signals to downstream circuits. The properties of this synaptic transfer fundamentally dictate which aspects in the original stimulus will be accentuated or suppressed, thereby partially defining the detection limits of the circuit. Accordingly, sensory neurons have evolved a wide variety of ribbon geometries and vesicle pool properties to best support their diverse functional requirements. However, the need for diverse synaptic functions does not only arise across neuron types, but alsowithin. Here we show that UV-cones, a single type of photoreceptor of the larval zebrafish eye, exhibit striking differences in their synaptic ultrastructure and consequent calcium to glutamate transfer function depending on their location in the eye. We arrive at this conclusion by combining serial section electron microscopy and simultaneous “dual-colour” 2-photon imaging of calcium and glutamate signals from the same synapsein vivo. We further use the functional dataset to fit a cascade-like model of the ribbon synapse with different vesicle pool sizes, transfer rates and other synaptic properties. Exploiting recent developments in simulation-based inference, we obtain full posterior estimates for the parameters and compare these across different retinal regions. The model enables us to extrapolate to new stimuli and to systematically investigate different response behaviours of various ribbon configurations. We also provide an interactive, easy-to-use version of this model as an online tool. Overall, we show that already on the synaptic level of single neuron types there exist highly specialized mechanisms which are advantageous for the encoding of different visual features.
Projecting ancient ancestry in modern-day Arabians and Iranians: a key role of the past exposed Arabo-Persian Gulf on human migrations
Authors: Ferreira Joana C. , Alshamali Farida , Montinaro Francesco , Cavadas Bruno , Torroni Antonio , Pereira Luisa , Raveane Alessandro , Fernandes Veronica 
Published: February 2021

AbstractArabian Peninsula is strategic for investigations centred on the structuring of the modern human population in the three main groups, in the awake of the out-of-Africa migration. Despite the poor climatic conditions for recovery of ancient DNA human evidence in Arabia, the availability of genomic data from neighbouring ancient specimens and of informative statistical tools allow better modelling the ancestry of these populations. We applied this approach to a dataset of 741,000 variants screened in 291 Arabians and 78 Iranians, and obtained insightful evidence. The west-east axis was a strong forcer of population structure in the Peninsula, and, more importantly, there were clear continuums throughout time linking west Arabia with Levant, and east Arabia with Iran and Caucasus. East Arabians also displayed the highest levels of the basal Eurasian lineage of all tested modern-day populations, a signal that was maintained even after correcting for possible bias due to recent sub-Saharan African input in their genomes. Not surprisingly, east Arabians were also the ones with higher similarity with Iberomaurusians, who were so far the best proxy for the basal Eurasians amongst the known ancient specimens. The basal Eurasian lineage is the signature of ancient non-Africans that diverged from the common European-East Asian pool before 50 thousand years ago, and before the later interbred with Neanderthals. Our results are strong evidence to include the exposed basin of the Arabo-Persian Gulf as possible home of basal Eurasians, to be investigated further on namely by searching ancient Arabian human specimens.