bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hippocampal theta and episodic memory
Authors: Rudoler Joseph H. , Herweg Nora A. , Kahana Michael J. 
Published: March 2022

AbstractComputational models of rodent physiology implicate hippocampal theta as a key modulator of learning and memory (Buzsaki & Moser, 2013; J. E. Lisman & Jensen, 2013), yet human hippocampal recordings have shown divergent theta correlates of memory formation. Herweg et al. (2020) suggest that decreases in memory-related broadband power mask narrowband theta increases. Their survey also notes that theta’s role in memory appears strongest in contrasts that isolate retrieval processes and when aggregating signals across large brain regions. We evaluate these hypotheses by analyzing human hippocampal recordings captured as 162 neurosurgical patients (N= 86 female) performed a free recall task. Using the irregular-resampling auto-spectral analysis to separate broad and narrow-band components of the field potential we show: 1) Broadband and narrowband components of theta exhibit opposite effects, with broadband signals decreasing and narrow-band theta increasing during successful encoding; 2) Whereas low-frequency theta oscillations increase prior to successful recall, higher-frequency theta and alpha oscillations decrease, masking theta’s positive effect when aggregating across the full band; 3) Theta’s effects on memory encoding and retrieval do not differ between reference schemes that accentuate local signals (bipolar) and those that aggregate across large reference (whole brain average). In line with computational models that ascribe a fundamental role for hippocampal theta in memory, our large-scale study of human hippocampal recordings shows that 3-4 Hz theta oscillations reliably increase during successful memory encoding and prior to spontaneous recall of previously studied items.Significance statementAnalyzing recordings from 162 patients we resolve a long-standing question regarding the role of hippocampal theta oscillations in the formation and retrieval of episodic memories. We show that broadband spectral changes confound estimates of narrowband theta activity, thereby accounting for inconsistent results in the literature. After accounting for broadband effects, we find that increased theta activity marks successful encoding and retrieval of episodic memories, supporting rodent models that ascribe a key role for hippocampal theta in memory function.
HIV-1 infection induces functional reprogramming of female plasmacytoid dendritic cells associated with enhanced TLR7 expression
Authors: Abbas Flora , Youness Ali , Azar Pascal , Cenac Claire , Delobel Pierre , Guéry Jean-Charles 
Published: March 2022

AbstractPlasmacytoid dendritic cells (pDCs) express TLR7, a ssRNA-sensor encoded on the X chromosome, which escapes X chromosome inactivation (XCI) in females. pDCs are specialized in the production of type 1 interferons (IFN-I) through TLR7 activation which mediates both immune cell activation and also reactivation of latent HIV-1. The effect of HIV-1 infection in women under antiretroviral therapy (ART) on pDC functional responses remains poorly understood. Here, we show that pDCs from HIV/ART women exhibit exacerbated production of IFN-α and TNF-α as compared to uninfected controls (UC) upon TLR7-activation. Because TLR7 can escape XCI in female pDCs, we measured the contribution of TLR7 allelic expression using SNP haplotypic markers to rigorously tag the allele of origin of TLR7 gene at single cell resolution. Herein, we provide evidence that the functional reprogramming of pDCs in HIV/ART women is associated with enhanced transcriptional activity of the TLR7 locus from both X chromosomes, rather than differences in the frequency of TLR7 bi-allelic cells. These data reinforce the interest in targeting the HIV-1 reservoir using TLR7 agonists in women.
The French Early Breast Cancer Cohort (FRESH): a resource for breast cancer research and evaluations of oncology practices based on the French National Healthcare System Database (SNDS)
Authors: Dumas Elise , Laot Lucie , Coussy Florence , Rejo Beatriz Grandal , Daoud Eric , Laas Enora , Kassara Amyn , Majdling Alena , Kabirian Rayan , Jochum Floriane , Gougis Paul , Michel Sophie , Houzard Sophie , Le Bihan-Benjamin Christine , Bousquet Philippe-Jean , Hotton Judicaël , Azencott Chloé-Agathe , Reyal Fabien , Hamy Anne-Sophie 
Published: March 2022

AbstractBackgroundBreast cancer (BC) is the most frequent cancer and the leading cause of cancer-related death in women. The French National Cancer Institute has created a national cancer cohort to promote cancer research and improve our understanding of cancer using the National Health Data System (SNDS). This cohort amalgamates all cancer sites, with no detailed separate data for early BC.ObjectivesWe describe the French Early Breast Cancer Cohort (FRESH).MethodsAll French women aged 18 years or over, with early-stage BC newly diagnosed between January 1, 2011 and December 31, 2017, treated by surgery and registered in the general health insurance coverage plan were included in the cohort. Patients with suspected locoregional or distant metastases at diagnosis were excluded. BC treatments (surgery, chemotherapy, targeted therapy, radiotherapy, endocrine therapy), and diagnostic procedures (biopsy, cytology, imaging) were extracted from hospital discharge reports, outpatient care notes or pharmacy drug delivery data. BC subtype was inferred from the treatments received.ResultsWe included 235,368 patients with early BC in the cohort (median age: 60 years). BC subtype distribution was as follows: luminal (80.2%), triple-negative (TNBC, 9.5%); HER2+ (10.3%), or unidentifiable (n=44,388, 18.9% of the cohort). Most patients underwent radiotherapy (n=200,685, 85.3%) and endocrine therapy (n=165,655, 70.4%), and 38.3% (n=90,252) received chemotherapy. Treatments and care pathways are described.ConclusionThe FRESH Cohort is an unprecedented population-based resource facilitating future large-scale real-life studies aiming to improve care pathways and quality of care for BC patients.
People underestimate the change of airborne Corona virus exposure when changing distance to an infected person: On interpersonal distance, exposure time, face masks and perceived virus exposure
Authors: Svenson Ola 
Published: March 2022

AbstractParticipants judged airborne Corona virus exposure following a change of inter-personal distance and time of a conversation with an infected person with and without a face mask. About 75% of the participants underestimated how much virus exposure changes when the distance to an infected person changed. The smallest average face to face distance from an infected person without a mask that a participant judged as sufficiently safe was about 12 feet (3.67 m). Correlations showed that the more a person underestimated the effects of change of distance on exposure the shorter was that person’s own safety distance. On average the effects of different lengths of a conversation on exposure were correct, but those who judged the effects of time as smaller tended to select longer safety distances. Worry of own COVID-19 infection correlated with protective behaviors: keeping longer safety distances, avoiding public gatherings, postponement of meetings with friends. The results showed that the protective effects of both distancing and wearing a face mask were under-estimated by a majority of the participants. Implications of these results were discussed last.
Super-spreaders of novel coronaviruses that cause SARS, MERS and COVID-19 : A systematic review
Authors: Brainard Julii , Jones Natalia R. , Harrison Florence , Hammer Charlotte C. , Lake Iain R. 
Published: March 2022

ABSTRACTOBJECTIVEMost index cases with novel coronavirus infections transmit disease to just 1 or 2 other individuals, but some individuals ‘super-spread’ – they are infection sources for many secondary cases. Understanding common factors that super-spreaders may share could inform outbreak models.METHODSWe conducted a comprehensive search in MEDLINE, Scopus and preprint servers to identify studies about persons who were each documented as transmitting SARS, MERS or COVID-19 to at least nine other persons. We extracted data from and applied quality assessment to eligible published scientific articles about super-spreaders to describe them demographically: by age, sex, location, occupation, activities, symptom severity, any underlying conditions and disease outcome. We included scientific reports published by mid June 2021.RESULTSThe completeness of data reporting was often limited, which meant we could not identify traits such as patient age, sex, occupation, etc. Where demographic information was available, for these coronavirus diseases, the most typical super-spreader was a male age 40+. Most SARS or MERS super-spreaders were very symptomatic and died in hospital settings. In contrast, COVID-19 super-spreaders often had a very mild disease course and most COVID-19 super-spreading happened in community settings.CONCLUSIONAlthough SARS and MERS super-spreaders were often symptomatic, middle- or older-age adults who had a high mortality rate, COVID-19 super-spreaders often had a mild disease course and were documented to be any adult age (from 18 to 91 years old). More outbreak reports should be published with anonymised but useful demographic information to improve understanding of super-spreading, super-spreaders, and the settings that super-spreading happens in.
Prospectively validated augmented intelligence for disease-agnostic predictions of clinical success for novel therapeutics
Authors: Lovetrue Bragi , Lovetrue Idonae 
Published: March 2022

Standalone artificial intelligence has not alleviated the long-term bottleneck of linearly extracting new knowledge from exponentially growing biological data, which has severely limited clinical success rates for drug discovery. We developed a ‘virtual patient’ augmented intelligence model that functionally reconstructed human physiology and human pathogenesis for high-fidelity simulations of drug-body interactions. We examined the clinical utility of ‘virtual patient’ in prospective predictions of clinical efficacy and safety of novel therapeutics regardless of prior clinical data availability, through a 24- month, public, prospective, large-scale, unbiased, and real-world validation study. ‘Virtual patient’ achieved 90.1% sensitivity and 82.0% precision with a 99% confidence across all major therapeutic areas, representing its capability of discovering 90.1% of all possible drug-indication pairs that could bring clinical benefits to patients, and its potential of increasing tenfold the baseline clinical success rate from 7.9% to 82.0%. ‘Virtual patient’ represents a methodological shift of drug discovery especially for age-related diseases by doing away with animal experiments whose data are hard to reproduce, virtualizing human trials whose outcomes are doomed to failure, initiating human trials whose participants are likely to benefit, and reducing R&D cycles and costs while increasing clinical efficacy and safety.One-Sentence SummaryA prospectively validated ‘virtual patient’ achieved a 10.4-fold improvement in the clinical success rate for new drugs across all major diseases with 99% confidence.
Dissecting neural computations of the human auditory pathway using deep neural networks for speech
Authors: Li Yuanning , Anumanchipalli Gopala K. , Mohamed Abdelrahman , Lu Junfeng , Wu Jinsong , Chang Edward F. 
Published: March 2022

AbstractThe human auditory system extracts rich linguistic abstractions from the speech signal. Traditional approaches to understand this complex process have used classical linear feature encoding models, with limited success. Artificial neural networks have recently achieved remarkable speech recognition performance and offer potential alternative computational models of speech processing. We used the speech representations learned by state-of-the-art deep neural network (DNN) models to investigate neural coding across the ascending auditory pathway from the peripheral auditory nerve to auditory speech cortex. We found that representations in hierarchical layers of the DNN correlated well to neural activity throughout the ascending auditory system. Unsupervised speech models achieve the optimal neural correlations among all models evaluated. Deeper DNN layers with context-dependent computations were essential for populations of high order auditory cortex encoding, and the computations were aligned to phonemic and syllabic context structures in speech. Accordingly, DNN models trained on a specific language (English or Mandarin) predicted cortical responses in native speakers of each language. These results reveal convergence between representations learned in DNN models and the biological auditory pathway and provide new approaches to modeling neural coding in the auditory cortex.
Discovery of a novel jingmenvirus in Australian sugarcane Soldier fly (Inopus flavus) larvae
Authors: Colmant Agathe M.G. , Furlong Michael , Etebari Kayvan 
Published: March 2022

AbstractIn Australia, soldier flies are major pests of sugarcane, and they can cause significant yield losses in some areas, possibly due to virus transmission to the plants. We sequenced fly larvae salivary glands and identified a novel jingmenvirus, putatively named Inopus flavus jingmenvirus 1 (IFJV1). Phylogenetic trees confirmed that IFJV1 groups with insect-associated jingmenviruses, newly identified flavivirus-like viruses with a segmented genome. After the design and validation of molecular detection systems for IFJV1, larval homogenates were passaged on insect and vertebrate cells but IFJV1 could only be detected in the first two passages in insect cells and not at all in vertebrate cells. Despite this lack of consistent replication in laboratory models, this virus does replicate in its host Inopus flavus, as sequenced small RNA from larvae match the IFJV1 sequences, are predominantly 21 nucleotides-long and map to the whole sequences on both strands, which is typical of an actively replicating virus. This discovery confirms the worldwide presence of jingmenviruses, which until now had only been detected on four continents. However, the study of IFJV1 tropism and of the possible pathogenicity to its host or the sugarcane it parasitizes requires the development of a stable replication model.
Transcriptome profiling of barley and tomato shoot and root meristems unravels physiological variations underlying photoperiodic sensitivity
Authors: Schneider Michael , Vedder Lucia , Oyiga Benedict Chijioke , Mathew Boby , Schoof Heiko , Léon Jens , Naz Ali Ahmad 
Published: March 2022

AbstractThe average sowing date of crops in temperate climate zones has been shifted forwards by several days, resulting in a changed photoperiod regime at the emergence stage. In the present study, we performed a global transcriptome profiling of plant development genes in the seedling stage of root and shoot apical meristems of a photoperiod-sensitive species (barley) and a photoperiod insensitive species (tomato) in short-day conditions (8h). Variant expression indicated differences in physiological development under this short day-length regime between species and tissues. The barley tissue transcriptome revealed reduced differentiation compared to tomato. In addition, decreased photosynthetic activity was observed in barley, indicating a slower physiological development of shoot meristems than in tomatoes. The photomorphogenesis controlling cryptochrome gene cry1, with an effect on physiological differentiation, showed an underexpression in barley compared to tomato shoot meristems. This might lead to a cascade of suspended sink-source activities, which ultimately delay organ development and differentiation in barley shoot meristems under short photoperiods.
TNIP1 inhibits Mitophagy via interaction with FIP200 and TAX1BP1
Authors: Le Guerroué François , Werner Achim , Wang Chunxin , Youle Richard 
Published: March 2022

SummaryMitophagy is a form of selective autophagy that disposes of superfluous and potentially damage-inducing organelles in a tightly controlled manner. While the machinery involved in mitophagy induction is well known, the regulation of the components is less clear. For example, it is still unknown how the ULK1 complex is dissociated prior to closing of the autophagosome. Here, using Chemically Inducible Dimerization (CID) and mitophagy assays with the fluorescent probe mtKeima, we reveal that the ubiquitin binding domain-containing protein TNIP1 is able to induce mitophagy when ectopically targeted to mitochondria. Conversely, we demonstrate that TNIP1 knock down accelerates mitophagy rates, and that ectopic TNIP1 negatively regulates the rate of mitophagy. These functions of TNIP1 depend on a previously unrecognized, evolutionarily conserved LIR motif as well as its AHD3 domain, which are required for binding to the ULK1 complex member FIP200 and the autophagy receptor TAX1BP1, respectively. Taken together, our findings identify a novel negative regulator of mitophagy that acts at the early steps of autophagosome biogenesis and provide a molecular rationale for how the ULK1 complex might be dissociated from the closing autophagosome.
Expression and Purification of BsaXI Restriction Endonuclease and Engineering New Specificity from BsaXI Specificity (S) Subunit
Authors: Gidwani Sonal , Heiter Daniel , Xu Shuang-yong 
Published: March 2022

AbstractBsaXI is a Type IIB restriction endonuclease (REase) that cleaves both sides of its recognition sequence 5’ ↓N9 AC N5 CTCC N10↓ 3’ (complement strand 5’ ↓N7 GGAG N5 GT N12↓ 3’), creating 3-base 3’ overhangs. Here we report the cloning and expression of bsaXIS and bsaXIRM genes in E. coli. BsaXI activity was successfully reconstituted by mixing the BsaXI RM fusion subunit with the BsaXI S subunit and the enzyme complex further purified by chromatography over 6 columns. As expected, the S subunit consisted of two subdomains encoding TRD1-CR1 (TRD, target recognition domain, CR, conserved region) for 5’ AC 3’, and TRD2-CR2 presumably specifying 5’ CTCC 3’. TRD1-CR1 (TRD2-CR2 deletion) or duplication of TRD1 (TRD1-CR1-TRD1-CR2) both generated a new specificity 5’ AC N5 GT 3’ when the S variants were complexed with the RM subunits. Circular permutation of TRD1 and TRD2, i.e. relocation of TRD2-CR2 to the N-terminus and TRD1-CR1 to the C-terminus generated the same specificity with the RM subunits, although some wobble cleavage was detected. The TRD2 domain in the BsaXI S subunit can be substituted by a close homolog (∼59% sequence identity) and generated the same specificity. However, TRD2-CR2 domain alone failed to express in E. coli, but CR1-TRD2-CR2 protein could be expressed and purified which showed partial nicking activity with the RM subunits. This work demonstrated that like Type I restriction systems, the S subunit of a Type IIB system could also be manipulated to create new specificities. Genome mining of BsaXI TRD2 homologs in GenBank found more than 36 orphan TRD2 homologs, implying that quite a few orphan TRD2s are present in microbial genomes that may be potentially paired with other TRDs to create new restriction specificities.
Individual neurophysiological signatures of spontaneous rhythm processing
Authors: Criscuolo A. , Schwartze M. , Henry M.J. , Obermeier C. , Kotz S.A. 
Published: March 2022

AbstractWhen sensory input conveys rhythmic regularity, we can form predictions about the timing of upcoming events. Although rhythm processing capacities differ considerably between individuals, these differences are often obscured by participant- and trial-level data averaging procedures in M/EEG research. Here, we systematically assessed the neurophysiological variability displayed by individuals listening to isochronous equitone sequences interspersed with unexpected deviant tones. We first focused on rhythm tracking and tested the anticipatory phase alignment of delta-band activity to expected tone onsets. These analyses confirmed that individuals encode temporal regularities and form temporal predictions, but highlight clear inter- and intra-participant variability. This observation may indicate individual and flexible tracking mechanisms, which show consistency at the single-trial level, but variability over trials. We then modelled single-trial time-locked neural responses in the beta-band to investigate individual tendencies to spontaneously employ binary grouping (“tic-toc effect”). This approach identified binary (strong-weak), ternary (strong-weak-weak), and mixed accentuation patterns, confirming the superimposition of a basic beat pattern. Furthermore, we characterized individual grouping preferences and tendencies to use binary, ternary, or combined patterns over trials. Importantly, the processing of standard and deviant tones was modulated by the employed pattern. The current approach supports individualized neurophysiological profiling as a sensitive strategy to identify dynamically evolving neural signatures of rhythm and beat processing. We further suggest that close examination of neurophysiological variability is critical to improve our understanding of the individual and flexible mechanisms underlying the capacities to rapidly evaluate and adapt to environmental rhythms.Significance statementFor decades, music, speech and rhythm research investigated how humans process, predict, and adapt to environmental rhythms. By adopting a single-trial and -participant approach, we avert the common pooling of EEG data in favor of individual time-varying neural signatures of rhythm tracking and beat processing. The results highlight large inter- and intra-individual differences in rhythm tracking, arguing against the typically documented phase-specificity for entrainment. On top of that, we characterize individual variability in beat processing, by showing that binary, ternary and other accentuation patterns are used over time, and ultimately affect the processing of (un-)expected auditory events. The approach aids individual neural profiling and may therefore allow identifying altered neural activity and its consequences in natural listening contexts.
Altered integration of excitatory inputs onto the basal dendrites of layer 5 pyramidal neurons in a mouse model of Fragile X Syndrome
Authors: Mitchell Diana E. , Miranda-Rottmann Soledad , Blanchard Maxime , Araya Roberto 
Published: March 2022

ABSTRACTTo uncover how synaptic integration of feedforward sensory inputs is affected in autism spectrum disorders (ASD), we used two-photon uncaging of caged glutamate to activate two clustered spines in the basal dendrites of layer 5 (L5) pyramidal neurons from a mouse model of Fragile X syndrome (FXS), the most common genetic cause of ASD. While subthreshold excitatory inputs integrate linearly in wild-type animals, surprisingly those with FXS summate sublinearly, contradicting what would be expected of a hyperexcitable cortex typically associated with ASD. Knockdown of the regulatory β4 subunit of BK channels, rescues the synaptic integration, a result that was corroborated with numerical simulations. Taken together, these findings suggest that there is a differential impairment in the integration of feedforward sensory and feedback predictive inputs in L5 pyramidal neurons in FXS and potentially other forms of ASD. These results challenge the traditional view that FXS and other ASD are characterized by sensory hypersensitivity, but instead by hyposensitivity of sensory inputs and hypersensitivity of predictive inputs onto cortical neurons.