bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproducible abnormalities of functional gradient reliably predict clinical and cognitive symptoms in schizophrenia
Authors: Wang Meng , Li Ang , Liu Yong , Yan Hao , Sun Yuqing , Song Ming , Chen Jun , Chen Yunchun , Wang Huaning , Guo Hua , Wan Ping , Lv Luxian , Yang Yongfeng , Li Peng , Lu Lin , Yan Jun , Wang Huiling , Zhang Hongxing , Zhang Dai , Jiang Tianzi , Liu Bing 
Published: November 2020

AbstractBackgroundSchizophrenia (SZ) typically manifests heterogeneous phenotypes involving positive, negative and cognitive symptoms. However, the underlying neural mechanisms of these symptoms keep unclear. Functional gradient is a fascinating measure to characterize continuous, hierarchical organization of brain.MethodsWe aimed to investigate whether reproducible disruptions of functional gradient existed in SZ compared to normal controls (NC), and these abnormalities were associated with severity of clinical and cognitive symptoms in SZ. All analyses were implemented in two independent large-sample multi-site datasets (discovery dataset, 400 SZ and 336 NC; replication dataset, 279 SZ and 262 NC). First, functional gradient across cerebral cortex was calculated in each subject. Second, vertex-wise comparisons of cortical gradient between SZ and NC groups were performed to identify abnormalities in SZ. Meanwhile, reproducible and robustness analyses were implemented to validate these abnormalities. Finally, regression analyses were performed using generalized additive models to link these abnormalities to severity of clinical and cognitive symptoms in SZ.ResultsWe found an abnormal gradient map in SZ in the discovery dataset, which was reproducible in the replication dataset. The abnormal gradient pattern was also robust when performing methodological alternatives and control analyses. Further, these reproducible abnormalities can reliably predict symptoms of clinical and cognitive domains across the two independent datasets.ConclusionThese findings demonstrated that alterations in functional gradient can provide a reliable signature of SZ, characterizing the heterogenous symptoms of clinical or cognitive domains, and may be further investigated to understand the neurobiological mechanisms of these symptoms.Impact StatementIn our study, using functional gradient measure and statistical learning technology and two independent multi-site case-control resting-state fMRI datasets (discovery dataset: 736 subjects; replication dataset: 541 subjects), we comprehensively investigated functional hierarchical organization in the cerebral cortex of SZ and its association with interindividual severity of symptoms. We found reproducible and robust abnormalities of functional gradient existed in SZ, which provided a reliable signature to characterize negative and general psychopathology symptoms, as well as cognitive deficits. Our findings can provide new insights to understand the neurobiological mechanisms of clinical and cognitive symptoms in SZ.
Memory Transfer of Random Time Patterns Across Modalities
Authors: HiJee Kang , Ryszard Auksztulewicz , Chi Hong Chan , Drew Cappotto , Vani Gurusamy Rajendran , Jan Wilbert Hendrik Schnupp 
Published: November 2020

AbstractPerception is sensitive to statistical regularities in the environment, including temporal characteristics of sensory inputs. Interestingly, temporal patterns implicitly learned within one modality can also be recognised in another modality. However, it is unclear how cross-modal learning transfer affects neural responses to sensory stimuli. Here, we recorded neural activity of human volunteers (N=24, 12 females, 12 males) using electroencephalography (EEG), while participants were exposed to brief sequences of randomly-timed auditory or visual pulses. Some trials consisted of a repetition of the temporal pattern within the sequence, and subjects were tasked with detecting these trials. Unknown to the participants, some trials reappeared throughout the experiment, enabling implicit learning. Replicating previous behavioural findings, we showed that participants benefit from temporal information learned in audition, and that they can apply this information to stimuli presented in vision. Such memory transfer was not observed from vision to audition. However, using an analysis of EEG response learning curves, we showed that learning temporal structures both within and across modalities modulates single-trial EEG response amplitudes in both conditions (audition to vision and vision to audition). Interestingly, the neural correlates of temporal learning within modalities relied on modality-specific brain regions, while learning transfer affected activity in frontal regions, suggesting distinct mechanisms. The cross-modal effect could be linked to frontal beta-band activity. The neural effects of learning transfer were similar both when temporal information learned in audition was transferred to visual stimuli and vice versa. Thus, both modality-specific mechanisms for learning of temporal information, and general mechanisms which mediate learning transfer across modalities, have distinct physiological signatures that are observable in the EEG.
Competition-based screening secures the evolutionary stability of a defensive microbiome
Authors: Worsley Sarah F. , Innocent Tabitha M. , Holmes Neil A. , Al-Bassam Mahmoud M. , Wilkinson Barrie , Murrell J. Colin , Boomsma Jacobus J. , Yu Douglas W. , Hutchings Matthew I. 
Published: November 2020

AbstractCuticular microbiomes ofAcromyrmexleaf-cutting ants are exceptional because they are freely colonizable, and yet the prevalence ofPseudonocardia, a native vertically transmitted symbiont that controlsEscovopsisfungus-garden disease, is never compromised. Game theory suggests thatcompetition-based screeningcan allow the selective recruitment of antibiotic-producing bacteria from the environment, by fomenting and biasing competition for abundant host resources. Mutual symbiont aggression benefits the host and also maintains native symbiont viability. Here we use RNA-stable isotope probing (RNA-SIP) to confirm predictions thatAcromyrmexcuticles can maintain a range of microbial symbionts. We then used dual-RNA-sequencing and bioassays to show that vertically transmittedPseudonocardiastrains produce antibacterials that differentially reduce the growth rates of other microbes, ultimately eliminating non-antibiotic-producing strains that might parasitize the symbiosis while still allowing antibiotic-producingStreptomycesstrains to survive. Open cuticular microbiomes can thus maintain a specific co-evolved mutualism by restricting access for other bacterial strains.
Insights into kinetics, release, and behavioral effects of brain-targeted hybrid nanoparticles for cholesterol delivery in Huntington’s disease
Authors: Birolini Giulia , Valenza Marta , Ottonelli Ilaria , Passoni Alice , Favagrossa Monica , Duskey Jason T. , Bombaci Mauro , Vandelli Maria Angela , Colombo Laura , Bagnati Renzo , Caccia Claudio , Leoni Valerio , Taroni Franco , Forni Flavio , Ruozi Barbara , Salmona Mario , Tosi Giovanni , Cattaneo Elena 
Published: November 2020

AbstractSupplementing brain cholesterol is emerging as a potential treatment for Huntington’s disease (HD), a genetic neurodegenerative disorder characterized, among other abnormalities, by inefficient brain cholesterol biosynthesis. However, delivering cholesterol to the brain is challenging due to the bloodbrain barrier (BBB), which prevents it from reaching the striatum, especially, with therapeutically relevant doses.Here we describe the distribution, kinetics, release, and safety of novel hybrid polymeric nanoparticles made of PLGA and cholesterol which were modified with an heptapeptide (g7) for BBB transit (hybrid-g7-NPs-chol). We show that these NPs rapidly reach the brain and target neural cells. Moreover, deuterium-labeled cholesterol from hybrid-g7-NPs-chol is released in a controlled manner within the brain and accumulates over time, while being rapidly removed from peripheral tissues and plasma. We confirm that systemic and repeated injections of the new hybrid-g7-NPs-chol enhanced endogenous cholesterol biosynthesis, prevented cognitive decline, and ameliorated motor defects in HD animals, without any inflammatory reaction.In summary, this study provides insights about the benefits and safety of cholesterol delivery through advanced brain-permeable nanoparticles for HD treatment.
Polymerization of misfolded protein lowers CX3CR1 expression in human PBMCs
Authors: Tumpara Srinu , Ballmaier Matthias , Wrenger Sabine , König Mandy , Lehmann Matthias , Lichtinghagen Ralf , Martinez-Delgado Beatriz , DeLuca David , Jedicke Nils , Welte Tobias , Fromme Malin , Strnad Pavel , Stolk Jan , Janciauskiene Sabina 
Published: November 2020

AbstractThe CX3CR1 (chemokine (C-X3-C motif) receptor 1) expression levels on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. The factors implicated in the regulation of CX3CR1 and its specific ligand CX3CL1 (fractalkine) expression remain largely unknown. Recent studies provide evidence that host‘s misfolded proteins occurring in the forms of polymers or amyloid fibrils can regulate CX3CR1 expression. Herein, we present a novel example that polymers of human ZZ alpha1-antitrypsin (Z-AAT) protein, resulting from its conformational misfolding due to the Z (Glu342Lys) mutation inSERPINA1gene, strongly lower CX3CR1 expression in human PBMCs. We also show that extracellular polymers of Z-AAT are internalized by PBMCs, which parallels with increased intracellular levels of CX3CR1 protein. Our findings support the role of extracellular misfolded proteins in CX3CR1 regulation and encourage conducting further studies on this issue.
Deuterium-depletion has no significant impact on the mutation rate ofEscherichia coli, invalidating the Double D-Bridge Hypothesis
Authors: Ajibola Walliyulahi , Karcagi Ildikó , Somlyai Gábor , Somlyai Ildikó , Fehér Tamás 
Published: November 2020

AbstractDeuterium (D), the second most abundant isotope of hydrogen is present in natural waters at an approximate concentration of 145-155 ppm (cca. 1.5E-4 atom/atom). D is known to influence various biological processes due to its physical and chemical properties, which significantly differ from those of hydrogen. For example, increasing D-concentration to >1000-fold above its natural abundance has been shown to increase the frequency of genetic mutations in several species. The Double D-Bridge Hypothesis, formulated with the intent of explaining the mechanism of D-mutagenicity is based on the calculation that the theoretical frequency of A:T base pairs that comprise two D-bridges instead of H-bridges is 2E-8, which is equal to the mutation rate of certain species. To experimentally challenge this hypothesis, and to infer the mutagenicity of D present at natural concentrations, we investigated the effect of a nearly 100-fold reduction of D concentration on the bacterial mutation rate. Using fluctuation tests, we measured the mutation rate of threeEscherichia coligenes (cycA, ackAandgalK) in media containing D at either <2 ppm or 150 ppm concentrations. Out of 15 pair-wise fluctuation analyses, nine indicated a significant decrease, while three marked the significant increase of the mutation/culture value upon D-depletion. Overall, growth in D-depleted minimal medium led to a geometric mean of 0.663-fold (95% confidence interval: 0.483-0.911) change in the mutation rate. This falls nowhere near the expected 10,000-fold reduction, indicating that the Double D-Bridge Hypothesis does not hold. In addition, the combined results did not display a statistically significant change in the mutation/culture value, the mutation rate or the mutant frequency upon D-depletion. The potential mutagenic effect of D present at natural concentrations onE. coliis therefore below the limit of detection using the indicated methods.
Genetic dissection of the mitochondrial lipoylation pathway in yeast
Authors: Pietikäinen Laura P. , Rahman M. Tanvir , Hiltunen J. Kalervo , Dieckmann Carol L. , Kastaniotis Alexander J. 
Published: November 2020

ABSTRACTBackgroundLipoylation of 2-ketoacid dehydrogenases is essential for mitochondrial function in eukaryotes. While the basic principles of the lipoylation processes have been worked out, we still lack a thorough understanding of the details of this important post-translational modification pathway. Here we used yeast as a model organism to characterize substrate usage by the highly conserved eukaryotic octanoyl/lipoyl transferasesin vivoand queried how amenable the lipoylation system is to supplementation with exogenous substrate.ResultsWe show that the requirement for mitochondrial fatty acid synthesis to provide substrates for lipoylation of the 2-ketoacid dehydrogenases can be bypassed by supplying the cells with free lipoic acid (LA) or octanoic acid (C8) and a mitochondrially targeted fatty acyl/lipoyl activating enzyme. We also provide evidence that theS. cerevisiaelipoyl transferase Lip3, in addition to transferring LA from the glycine cleavage system H protein to the pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGD) E2 subunits, can transfer this cofactor from the PDH complex to the KGD complex. In support of yeast as a model system for human metabolism, we demonstrate that the human octanoyl/lipoyl transferases can substitute for their counterparts in yeast to support respiratory growth and protein lipoylation. Like the wild-type yeast enzyme, the human lipoyl transferase LIPT1 responds to LA supplementation in the presence of the activating enzyme LplA.ConclusionsIn the yeast model system, the eukaryotic lipoylation pathway can use free LA and C8 as substrates when fatty/lipoic acid activating enzymes are targeted to mitochondria. Lip3 LA transferase has a wider substrate specificity than previously recognized. We show that these features of the lipoylation mechanism in yeast are conserved in mammalian mitochondria. Our findings have important implications for the development of effective therapies for the treatment of LA or mtFAS deficiency-related disorders.
ThePhyscomitrium (Physcomitrella) patensPpKAI2L receptors for strigolactones and related compounds highlight MAX2 dependent and independent pathways
Authors: Lopez-Obando Mauricio , Guillory Ambre , Boyer François-Didier , Cornu David , Hoffmann Beate , Le Bris Philippe , Pouvreau Jean-Bernard , Delavault Philippe , Rameau Catherine , de Saint Germain Alexandre , Bonhomme Sandrine 
Published: November 2020

ABSTRACTIn flowering plants, the α/β hydrolase DWARF14 (D14) perceives strigolactone (SL) hormones and interacts with the F-box protein MORE AXILLARY GROWTH2 (MAX2) to regulate developmental processes. The key SL biosynthetic enzyme, CAROTENOID CLEAVAGE DEOXYGENASE8 (CCD8), is present in the mossPhyscomitrium (Physcomitrella) patens,and PpCCD8-derived compounds regulate plant extension. Based on germination assays using seeds of the parasitic plantPhelipanche ramosa,we propose that these compounds are non-canonical SLs. Perception of PpCCD8-derived compounds does not require the PpMAX2 homolog. Candidate receptors are among the 13PpKAI2LIKE-A to -Lgenes, homologous to the ancestralD14paralogKARRIKIN INSENSITIVE2 (KAI2).In Arabidopsis, AtKAI2 is the receptor for a still elusive endogenous KAI2-Ligand (KL). We show that inP. patens,among SL analogs, the (+)-GR24 enantiomer is a good mimic for PpCCD8-derived compounds, while the effects of the (-)-GR24 enantiomer, a KL mimic in flowering plants, are opposite. Interaction and binding assays of seven PpKAI2L proteins using pure enantiomers pinpoint at stereoselectivity towards (-)-GR24 for the (A-E) clade. Enzyme assays highlight strong hydrolytic activity of the PpKAI2L-H protein. Moss mutants for allPpKAI2Lgene subclades were obtained and tested for their response to both enantiomers. We show thatPpKAI2L-Ato-Egenes are not involved in PpCCD8-derived compound perception, but act in a PpMAX2-dependant pathway. In contrast, mutations inPpKAI2L-G, and-Jgenes abolish the response to (+)-GR24, suggesting that encoded proteins are receptors for PpCCD8-derived SLs.
Protective face mask filter capable of inactivating SARS-CoV-2, and methicillin-resistantStaphylococcus aureusandStaphylococcus epidermidis
Authors: Martí Miguel , Tuñón-Molina Alberto , Aachmann Finn Lillelund , Muramoto Yukiko , Noda Takeshi , Takayama Kazuo , Serrano-Aroca Ángel 
Published: November 2020

AbstractFace masks have globally been accepted to be an effective protective tool to prevent bacterial and viral transmission, especially against indoor aerosol transmission. However, commercial face masks contain filters that are made of materials that are not capable of inactivating neither SARS-CoV-2 nor multidrug-resistant bacteria. Therefore, symptomatic and asymptomatic individuals can infect other people even if they wear them because some viable viral or bacterial loads can escape from the masks. Furthermore, viral or bacterial contact transmission can occur after touching the mask, which constitutes an increasing source of contaminated biological waste. Additionally, bacterial pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex and their resistance to antibiotics in pneumonia treatment is increasing at an alarming rate. In this regard, herein, we report the development of a novel protective non-woven face mask filter fabricated with a biofunctional coating of benzalkonium chloride that is capable of inactivating SARS-CoV-2 in one minute of contact, and the life-threatening methicillin-resistantStaphylococcus aureusandStaphylococcus epidermidis.Nonetheless, despite the results obtained, further studies are needed to ensure the safety and correct use of this technology for the mass production and commercialization of this broad-spectrum antimicrobial face mask filter. Our novel protective non-woven face mask filter would be useful for many health care workers and researchers working in this urgent and challenging field.
Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats
Authors: Drake RAR , Steel KAJ , Apps R , Lumb BM , Pickering AE 
Published: November 2020

AbstractThe loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the periaqueductal grey (PrL-P) to the development of neuropathic pain in rats using combined opto- and chemo-genetic approaches. We found PrL-P neurons to exert a tonic inhibitory control on thermal withdrawal thresholds in uninjured animals. Following nerve injury, ongoing activity in PrL-P neurons masked latent hypersensitivity and improved affective state. However, this function is lost as the development of sensory hypersensitivity emerges. Despite this loss of tonic control, opto-activation of PrL-P neurons at late post-injury timepoints could restore the anti-allodynic effects by inhibition of spinal nociceptive processing. We suggest that the loss of cortical drive to the descending pain modulatory system underpins the expression of neuropathic sensitisation after nerve injury.
Protein Detection and Localization in Plant Cells Using Spot-Tagging
Authors: Mentzelopoulou Andriani , Liu Chen , Moschou Panagiotis Nikolaou 
Published: November 2020

ABSTRACTFluorescent labelling of proteins without compromising their activity is crucial for determining their spatiotemporal localization while retaining their functionality. Spot-tag is a 12-amino acid peptide recognized by a single-domain nanobody. Here we introduce the spot-tag as a labelling strategy for proteins in fixed and living plant cells, using as an example the microtubule motor centromeric protein E-related Kinesin 7.3. Spot-tagging of ectopically introduced Kinesin 7.3 does not interfere with microtubules and spot staining results in a close-grained fluorophore labelling revealing a localization pattern that resembles “beads-on-a-string”. We anticipate that our protocol will apply to many more demanding protein cellular targets, offsetting activity perturbations and low photon quantum yields imposed by other protein-tagging approaches.
Cortical processing of reference in language revealed by computational models
Authors: Li Jixing , Wang Shaonan , Luh Wen-Ming , Pylkkänen Liina , Yang Yiming , Hale John 
Published: November 2020

AbstractHuman language processing involves not only combining word meanings in accordance with semantic and syntactic constraints, but also figuring out who and what is being referred to. Here we present a first study towards a mechanistic understanding of the neural basis for referential processing. Using both functional MRI and magnetoencephalography (MEG), we identified a consistent increase of activity in a network spanning the anterior and posterior left middle temporal gyrus and the angular gyrus for pronoun processing during naturalistic listening for both English and Chinese speakers. We then adopted a “reverse-engineering” approach to examine the cognitive processes underlying pronoun resolution. We evaluated the neural fit of three symbolic models that each formalizes a different strand of explanation for pronoun resolution in the cognitive and linguistic literature, as well as two deep neural network models with an LSTM or a Transformer architecture. Our results favor the memory-based symbolic model, suggesting a domain-general mechanism of pronoun resolution that resembles memory retrieval.
Structural basis of resistance to lincosamide, streptogramin A, and pleuromutilin antibiotics by ABCF ATPases in Gram-positive pathogens
Authors: Crowe-McAuliffe Caillan , Murina Victoriia , Turnbull Kathryn Jane , Kasari Marje , Mohamad Merianne , Polte Christine , Takada Hiraku , Vaitkevicius Karolis , Johansson Jörgen , Ignatova Zoya , Atkinson Gemma C. , O’Neill Alex J. , Hauryliuk Vasili , Wilson Daniel N. 
Published: November 2020

AbstractTarget protection proteins bind to antibiotic targets and confer resistance to the host organism. One class of such proteins, termedantibioticresistance (ARE) ATP binding cassette (ABC) proteins of the F-subtype (ARE ABCFs), are widely distributed throughout Gram-positive bacteria and bind the ribosome to alleviate translational inhibition by antibiotics that target the large ribosomal subunit. Using single-particle cryo-EM, we have solved the structure of ARE ABCF–ribosome complexes from three Gram-positive pathogens:Enterococcus faecalisLsaA,Staphylococcus haemolyticusVgaALCandListeria monocytogenesVgaL. Supported by extensive mutagenesis analysis, these structures enable a comparative approach to understanding how these proteins mediate antibiotic resistance on the ribosome. We present evidence of mechanistically diverse allosteric relays converging on a few peptidyltransferase center (PTC) nucleotides, and propose a general model of antibiotic resistance mediated by these ARE ABCFs.