bluuebunny/crossref_metadata_2025 huggingface dataset:
Two opposite voltage-dependent currents control the unusual early development pattern of embryonic Renshaw cell electrical activity
Authors: Boeri Juliette , Meunier Claude , Corronc Hervé Le , Branchereau Pascal , Timofeeva Yulia , Lejeune François Xavier , Mouffle Christine , Arulkandarajah Hervé , Mangin Jean Marie , Legendre Pascal , Czarnecki Antonny
Published: June 2020

Renshaw cells (V1R) are excitable as soon as they reach their final location next to the spinal motoneurons and are functionally heterogeneous. Using multiple experimental approaches, in combination with biophysical modeling and dynamical systems theory, we analyzed, for the first time, the mechanisms underlying the electrophysiological properties of V1R during early embryonic development of the spinal cord locomotor networks (E11.5-E16.5). We found that these interneurons are subdivided into several functional clusters from E11.5 and then display an unexpected transitory involution process during which they lose their ability to sustain tonic firing. We demonstrated that the essential factor controlling the diversity of the discharge pattern of embryonic V1Ris the ratio of a persistent sodium conductance to a delayed rectifier potassium conductance. Taken together, our results reveal how a simple mechanism, based on the synergy of two voltage-dependent conductances that are ubiquitous in neurons, can produce functional diversity in V1Rand control their early developmental trajectory.
Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1+/- mice
Authors: Cabana-Domínguez Judit , Martín-García Elena , Gallego-Roman Ana , Maldonado Rafael , Fernàndez-Castillo Noèlia , Cormand Bru
Published: June 2020

Background and Purpose

Cocaine addiction causes serious health problems and no effective treatment is available yet. We previously identified a genetic risk variant for cocaine addiction in thePLCB1gene and found this gene upregulated in postmortem brains of cocaine abusers and in human dopaminergic neuron-like cells after an acute cocaine exposure. Here, we functionally tested the contribution ofPLCB1gene to cocaine addictive properties in mice.

Experimental approach

We used heterozygousPlcb1knockout mice (Plcb1+/-) and characterized their behavioral phenotype. Subsequently, mice were trained for operant conditioning and self-administered cocaine for 10 days.Plcb1+/- mice were assessed for cocaine motivation, followed by 26 days of extinction and finally evaluated for cue-induced reinstatement of cocaine seeking. Gene expression alterations after reinstatement were assessed in medial prefrontal cortex (mPFC) and hippocampus (HPC) by RNAseq.

Key Results

Plcb1+/- mice showed normal behavior, although they had increased anxiety and impaired short-term memory. Importantly, after cocaine self-administration and extinction, we found a reduction in the cue-induced reinstatement of cocaine-seeking behavior inPlcb1+/- mice. After reinstatement, we identified transcriptomic alterations in the medial prefrontal cortex ofPlcb1+/- mice, mostly related to pathways relevant to addiction like the dopaminergic synapse and long-term potentiation.

Conclusions and Implications

To conclude, we found that heterozygous deletion of thePlcb1gene decreases cue-induced reinstatement of cocaine seeking, pointing at PLCB1 as a possible therapeutic target for preventing relapse and treating cocaine addiction.
Whole-genome sequence analysis reveals evolution of antimicrobial resistance in a Ugandan colistin resistantAcinetobacter baumannii
Authors: Aruhomukama Dickson , Sserwadda Ivan , Mboowa Gerald
Published: June 2020

In recent times, pan-drug resistantAcinetobacter baumanniihave emerged and continue to spread among critically ill patients, this poses an urgent risk to global and local human health. This study sought to provide the first genomic analysis of a pan-drug resistantAcinetobacter baumanniifrom Uganda and Africa, and to tell a story of mobile genetic element-mediated antibiotic resistance evolution in the isolate. It was an in-silico study in which intrinsic and acquired antibiotic resistance genes, and/or chromosomal resistance mutations were identified using PATRIC, CARD, NDARO and ResFinder. Screening for insertion sequences was done using ISfinder. Also, plasmid screening, phylogenetic analysis and sequence typing were performed using PlasmidFinder, PATRIC and Gubbin, and MLST respectively.

The isolate belonged to the Sequence type 136, belonging to Clonal complex 208 and Global complex 2. This isolate shared close homology with strains from Tanzania. Resistance in the isolate was chromosomally and mobile genetic element-mediated byAcinetobacter-derived cephalosporinases and carbapenem hydrolyzing class D β-lactamses,blaOXA-2, 51, 5 88, 317,blaADC-2, 25. Colistin resistance was associated with previously documented mutants,lpxAandlpxC. Other key resistance genes identified were:aph(3”)-lb, aph(6)-ld, aph(3’)-la, aac(3)-lld, aac(3)-lla, aph(3’)-l, aph(3”)-l, aph(6)-lc, aph(6)-ld, aac(3)-II, III, IV, VI, VIII, IX, X, macA, macB, tetA, tetB, tetR, dfrA, and those of thefloRfamily. RSF1010 like IncQ broad-host-range plasmids and features of pACICU1, pACICU2, and p3ABAYEAcinetobacter baumanniiplasmids namely partitioning proteins ParA and B were present. Insertion sequences present included IS3, IS5, IS66and those of the ISLre2families.

The study described for the first time a pan-drug resistantAcinetobacter baumanniifrom Uganda, and told a story of mobile genetic element-mediated antibiotic resistance evolution in the isolate despite being limited by pan-drug resistance phenotypic data. It provides a basis to track trends in antibiotic resistance and identification of emerging resistance patterns inAcinetobacter baumanniiin Uganda.
Nucleotide binding, evolutionary insights and interaction partners of the pseudokinase Unc-51-like kinase 4
Authors: Preuss Franziska , Chatterjee Deep , Mathea Sebastian , Shrestha Safal , St-Germain Jonathan , Saha Manipa , Kannan Natarajan , Raught Brian , Rottapel Robert , Knapp Stefan
Published: June 2020

Unc-51-like kinase 4 (ULK4) is a pseudokinase that has been linked to the development of several diseases. Even though sequence motifs required for ATP binding in kinases are lacking, ULK4 still tightly binds ATP and the presence of the cofactor is required for structural stability of ULK4. Here we present a high-resolution structure of a ULK4-ATPγS complex revealing a highly unusual ATP binding mode in which the lack of the canonical VAIK motif lysine is compensated by K39, located N-terminal to αC. Evolutionary analysis suggests that degradation of active site motifs in metazoan ULK4 has co-occurred with an ULK4 specific activation loop, which stabilizes the C-helix. In addition, cellular interaction studies using BioID and biochemical validation data revealed high confidence interactors of the pseudokinase and armadillo repeat domains. Many of the identified ULK4 interaction partners were centrosomal and tubulin associated proteins and several active kinases suggesting new roles for ULK4.

Highlights

Structure of the ULK4 ATP complex reveals a unique ATP binding mode.

Disease associated mutations modulate ATP binding and ULK4 stability

Degradation of active site motifs co-occurred in evolution with an ULK4 specific activation loop

BioID suggests a role of ULK4 regulating centrosomal and cytoskeletal functions
Role of misfolded tau in the onset and progression of brain toxicity after trauma
Authors: Zanier Elisa R. , Barzago Maria Monica , Vegliante Gloria , Romeo Margherita , Bertani Ilaria , Natale Carmina , Colnaghi Luca , Colombo Laura , Russo Luca , Micotti Edoardo , Fioriti Luana , Chiesa Roberto , Diomede Luisa
Published: June 2020

Traumatic brain injury (TBI) is associated with widespread tau pathology in about one third of patients. We previously found that TBI induces a transmissible tau pathology (tauTBI), with late cognitive decline and synaptic dysfunction. To understand whether tauTBIis a marker of ongoing neurodegeneration or a driver of functional decline, we employedC. elegans. Brain homogenates from chronic TBI mice, or from mice in which tauTBIhad been transmitted by intracerebral inoculation, impairedC. elegansmotility and neuromuscular synaptic transmission. Brain homogenates from tau P301L transgenic mice, or pre-aggregated recombinant tau, induced a similar toxic response. Protease digestion or pre-incubation of homogenates with anti-tau antibodies abolished toxicity, and TBI brain homogenates from tau knock-out mice had no toxic effect. These results support a vital role of abnormal tau species in chronic neurodegeneration after TBI and set the groundwork for the development of aC. elegans-based platform for screening anti-tau compounds.
Nonlinear spatial integration underlies the diversity of retinal ganglion cell responses to natural stimuli
Authors: Karamanlis Dimokratis , Gollisch Tim
Published: June 2020

How neurons encode natural stimuli is a fundamental question for sensory neuroscience. In the early visual system, standard encoding models assume that neurons linearly filter incoming stimuli through their receptive fields, but artificial stimuli, such as reversing gratings, often reveal nonlinear spatial processing. We investigated whether such nonlinear processing is relevant for the encoding of natural images in ganglion cells of the mouse retina. We found that standard linear receptive field models fail to capture the spiking activity for a large proportion of cells. These cells displayed pronounced sensitivity to fine spatial contrast, and local signal rectification was identified as the dominant nonlinearity. In addition, we also observed a class of nonlinear ganglion cells with opposite tuning for spatial contrast and a particular sensitivity for spatially homogeneous stimuli. Our work highlights receptive field nonlinearities as a crucial component for understanding early sensory encoding in the context of natural stimuli.
Optimised cell systems for the investigation of hepatitis C virus E1E2 glycoproteins
Authors: Kalemera Mphatso D. , Cappella-Pujol Joan , Chumbe Ana , Underwood Alexander , Bull Rowena A. , Schinkel Janke , Sliepen Kwinten , Grove Joe
Published: June 2020

Great strides have been made in understanding and treating Hepatitis C virus (HCV) thanks in part to the development of the full-length cell-culture system, the pseudoparticle system and soluble envelope glycoproteins. The HCV pseudoparticle (HCVpp) system is a platform used extensively in studies of cell entry, screening of novel entry inhibitors, assessing the phenotypes of clinically observed E1 and E2 glycoproteins and, most pertinently, in characterising neutralizing antibody breadth induced upon vaccination and natural infection in patients. Nonetheless, some patient-derived clones fail to produce infectious particles or produce particles that exhibit infectivity too low for meaningful phenotyping. The mechanisms governing whether any particular clone produces infectious pseudoparticles are poorly understood. Here we show that endogenous expression of CD81, an HCV receptor and a cognate binding partner of E2, in producer HEK 293T cells is detrimental to the infectivity of recovered HCVpp for most strains. Many HCVpp clones exhibited increased infectivity or had their infectivity rescued when they were produced in HEK 293T cells CRISPR/Cas9 engineered to ablate CD81 expression (293TCD81KO). Clones made in 293TCD81KOcells were antigenically very similar to their matched counterparts made parental cells and appear to honour the accepted HCV entry pathway. Deletion of CD81 did not appreciably increase the recovered titres of soluble E2 (sE2). However, we did, unexpectedly, find that monomeric sE2 made in 293T and 293F exhibit important differences. We found that 293F-produced sE2 harbours mostly complex type glycans whilst 293T-produced sE2 displays a heterogeneous mixture of both complex type glycans and highmannose or hybrid type glycans. Moreover, sE2 produced in HEK 293T cells is antigenically superior; exhibiting increased binding to conformational antibodies and the large extracellular loop of CD81. In summary, this work describes an optimal cell line for the production of HCVpp and reveals that sE2 made in 293T and 293F cells are not antigenic equals. Our findings have implications for functional studies of E1E2 and the production of candidate immunogens.
Global pleiotropic effects in adaptively evolvedEscherichia colilacking CRP reveal molecular mechanisms that define growth physiology
Authors: Pal Ankita , Iyer Mahesh S. , Srinivasan Sumana , Seshasayee Aswin S , Venkatesh K.V.
Published: June 2020

Evolution entails the orchestration of cellular resources together with mutations to achieve fitter phenotypes. Here, we determined the system-wide pleiotropic effects that redress the significant perturbations caused by the deletion of global transcriptional regulator CRP inEscherichia coliwhen evolved in the presence of glucose. We elucidated that absence of CRP results in alterations in key metabolic pathways instrumental for the precise functioning of protein biosynthesis machinery that subsequently corroborated with intracellular metabolite profiles. Apart from acquiring mutations in the promoter of glucose transporterptsG, the evolved populations recovered the metabolic pathways to their pre-perturbed state with amelioration of protein biosynthesis machinery coupled with fine-tuned proteome re-allocation that enabled growth recovery. However, ineffective utilization of carbon towards biomass as perceived from ATP maintenance flux and costly amino acid accumulations poses a limitation. Overall, we comprehensively illustrate the genetic and metabolic adjustments underlying adaptive evolvability, fundamental for understanding the growth physiology.
A Mild Keratin 1 Decrease Leads to Cell Death and Increased Oxidative Stress in B16-F10 Melanoma Cell Lines
Authors: Li Yujia , Zhang Mingchao , Ying Weihai
Published: June 2020

Keratins play multiple significant biological roles in epithelium. K1 / keratin 10 (K10) heterodimer is a hallmarker for keratinocyte differentiation. While keratins are absent in normal melanocyte, keratins have been found in both melanoma cell lines and human melanoma. The biological significance of the keratins in melanoma cells has remained unclear. In our current study we applied K1 siRNA to investigate the biological significance of the K1 in B16-F10 melanoma cells. We found that as low as a 16% decrease in the K1 level led to significant increases in both apoptosis and necrosis of the cells. Moreover, the mild K1 decrease led to significant increases in both dichlorofluorescein (DCF) and ethidium signals - two indicators of oxidative stress - in the cells. Collectively, our findings have provided the first evidence indicating both a critical role of the K1 in maintaining the survival of melanoma cells and an important role of the K1 in modulating the oxidative stress state of the cells. These findings have exposed new functions of keratins in cancer cells, suggesting that K1 may become a novel therapeutic target for melanoma.
Large cognitive fluctuations surrounding sleep in daily living
Authors: Huber Reto , Ghosh Arko
Published: June 2020

It is well recognized that cognitive output fluctuates surrounding sleep. Such fluctuations are rarely investigated in subjects’ daily living, partially due to the inaccessibility of sleep laboratory technology and cognitive testing. Here we leverage the continuous and long-term smartphone touchscreen interaction logs to study the patterns of cognitive output surrounding sleep and contrasted these to the patterns underlying physical activity captured from wrist-worn actigraphy. According to spectral density analysis, both cognitive and physical activity was dominated by diurnal (∼24 h) and infra-radian (∼7 days) rhythms. However, these rhythms differed in a domain-specific manner. The proxy measures of cognitive performance – tapping speed, unlocking speed, and app locating speed – contained lower-powered diurnal rhythm than physical activity. Still, the amount of smartphone usage showed the strongest diurnal rhythm – even when compared to the ambient luminescence levels experienced according to actigraphy. Interestingly, the cognitive rhythms were not in sync with physical activity, as cognitive measures peaked later in the day and on weekdays rather than weekends. The difference between cognitive and physical activity became vivid during bedtime and subjects routinely interacted with their smartphones during the actigraphy labelled sleep period. The cognitive measures in this period were worse in comparison to the hour before or after sleep. Therefore, smartphones can seamlessly capture the dynamic fluctuations in cognitive output including during spontaneous awakenings. We conclude that the rhythms underlying cognitive activity in the real world are distinct from physical activity and this discord may be a hallmark of modern human behaviour.
Germanium nanospheres for ultraresolution picotensiometry of kinesin motors
Authors: Sudhakar Swathi , Abdosamadi Mohammad Kazem , Jachowski Tobias Jörg , Bugiel Michael , Jannasch Anita , Schäffer Erik
Published: June 2020

Kinesin motors are essential for transport of cellular cargo along cytoskeletal microtubule filaments. How motors step, detach, and cooperate is still unclear. To dissect the molecular motion of kinesin-1, we have developed germanium nanospheres as ultraresolution optical trapping probes. We found that single motors took 4-nm-center-of-mass steps. Furthermore, motors never detached from microtubules under native hindering load conditions. Instead, motors slid on microtubules with microsecond-long, 8-nm steps and remained in this slip state before detaching or reengaging in directed motion. Surprisingly, reengagement and, thus, rescue of directed motion was prevailing. We argue that teams of motors may be synchronized through this slip state and rescues need to be accounted for to understand long-range transport.

One Sentence Summary

Optical trapping of high-refractive-index semiconductor nanoparticles shows how motors detach and walk with 4-nm steps.
Private Antibody Repertoires Are Public
Authors: Arora Rohit , Arnaout Ramy
Published: June 2020

When faced with a given pathogen, the antibody response generally functions similarly across different people,1–4but the source of this similarity has been unclear. One hypothesis was that people share a high proportion of the same VDJ-recombined antibody genes, but this has been disproven.5,6An alternative is that people share a high proportion offunctionally similarantibodies,7,8but testing this hypothesis requires a method for measuring functional similarity that scales to the millions of antibodies per repertoire and across multiple repertoires, which is impossible experimentally. We recently described a framework for doing so computationally,9which revealed that repertoires consist of loose overlapping functional classes of antibodies with similar antigen-binding capacities;10–12this framework allowed us to estimate a repertoire’s antigen-binding capacity,τ, for the ideal target of any given antibody. Here, we show that this framework supports the second hypothesis, and provide the first comprehensive demonstration of overwhelming functional overlap between repertoires from 20 different individuals directly from sequence, without need of binding studies. Overlap is highest among the young and falls with age, due to the selective loss of antibodies that represent a core set of shared or “public” antigen-binding capacities. We reveal considerable heterogeneity in antigen-binding capacities for antibodies against influenza, HIV, and SARS-CoV-2, and show that while some of these classes shrink with age, others persist across individuals. These discoveries change our understanding of repertoire diversity and have implications for vaccine and therapeutic-antibody development, especially for the aged.
Testing evolutionary explanations for the lifespan benefit of dietary restriction inDrosophila melanogaster
Authors: Savola Eevi , Montgomery Clara , Waldron Fergal M. , Monteith Katy , Vale Pedro , Walling Craig
Published: June 2020

Dietary restriction (DR), limiting calories or specific nutrients, extends lifespan across diverse taxa. This lifespan extension has been explained as diet-mediated changes in the trade-off between lifespan and reproduction, with survival favoured with scarce resources. Another evolutionary hypothesis suggests the selective benefit of the response is the maintenance of reproduction. This hypothesis predicts that lifespan extension is a side effect of benign laboratory conditions, where DR individuals are frailer and unable to deal with additional stressors, and thus lifespan extension should disappear under more stressful conditions. We tested this by rearing outbred femaleDrosophila melanogasteron 10 different protein:carbohydrate diets. Flies were either infected with a bacterial pathogen (Pseudomonas entomophila), injured or unstressed. We monitored lifespan, fecundity and ageing measures. DR extended lifespan and reduced reproduction irrespective of injury and infection. These results do not support lifespan extension under DR being a side effect of benign laboratory conditions.
Learning a latent representation of human genomics using Avocado
Authors: Schreiber Jacob , Noble William
Published: June 2020

In the past decade, the use of high-throughput sequencing assays has allowed researchers to experimentally acquire thousands of functional measurements for each basepair in the human genome. Despite their value, these measurements are only a small fraction of the potential experiments that could be performed while also being too numerous to easily visualize or compute on. In a recent pair of publications, we address both of these challenges with a deep neural network tensor factorization method, Avocado, that compresses these measurements into dense, information-rich representations. We demonstrate that these learned representations can be used to impute with high accuracy the output of experimental assays that have not yet been performed and that machine learning models that leverage these representations outperform those trained directly on the functional measurements on a variety of genomics tasks. The code is publicly available athttps://github.com/jmschrei/avocado.
HIV-1 Gag protein with or without p6 specifically dimerizes on the viral RNA packaging signal
Authors: Sarni Samantha , Biswas Banhi , Liu Shuohui , Olson Erik D. , Kitzrow Jonathan P. , Rein Alan , Wysocki Vicki H. , Musier-Forsyth Karin
Published: June 2020

The HIV-1 Gag protein is responsible for genomic RNA (gRNA) packaging and immature viral particle assembly. While the presence of gRNA in virions is required for viral infectivity, in its absence, Gag can assemble around cellular RNAs and form particles resembling gRNA-containing particles. When gRNA is expressed, it is selectively packaged despite the presence of excess host RNA, but how it is selectively packaged is not understood. Specific recognition of a gRNA packaging signal (Psi) has been proposed to stimulate the efficient nucleation of viral assembly. However, the heterogeneity of Gag-RNA interactions renders capturing this transient nucleation complex using traditional structural biology approaches challenging. Here, we used native mass spectrometry to investigate RNA binding of wild-type Gag and Gag lacking the p6 domain (GagΔp6). Both proteins bind to Psi RNA primarily as dimers, but to a control RNA primarily as monomers. The dimeric complexes on Psi RNA require an intact dimer interface within Gag. GagΔp6 binds to Psi RNA with high specificityin vitroand also selectively packages gRNA in particles produced in mammalian cells. These studies provide direct support for the idea that Gag binding to Psi specifically nucleates Gag-Gag interactions at the early stages of immature viral particle assembly in a p6-independent manner.
All is fish that comes to the net: metabarcoding for rapid fisheries catch assessment
Authors: Russo Tommaso , Maiello Giulia , Talarico Lorenzo , Baillie Charles , Colosimo Giuliano , D’Andrea Lorenzo , Di Maio Federico , Fiorentino Fabio , Franceschini Simone , Garofalo Germana , Scannella Danilo , Cataudella Stefano , Mariani Stefano
Published: June 2020

Monitoring marine resource exploitation is a key activity in fisheries science and biodiversity conservation. Since research surveys are time-consuming and costly, fishery-dependent data (i.e. derived directly from fishing vessels) are increasingly credited with a key role in expanding the reach of ocean monitoring. Fishing vessels may be seen as widely ranging data-collecting platforms, which could act as a fleet of sentinels for monitoring marine life, in particular exploited stocks. Here, we investigate the possibility of assessing catch composition of single hauls carried out by trawlers by applying DNA metabarcoding to the “slush” collected from fishing nets just after the end of hauling operations. We assess the performance of this approach in portraying β-diversity and examining the quantitative relationship between species abundances in the catch and DNA amount in the slush (reads counts generated by amplicon sequencing). We demonstrate that the assemblages identified using DNA in the slush mirror those returned by visual inspection of net content and detect a strong relationship between read counts and species abundances in the catch. We therefore argue that this approach could be upscaled to serve as a powerful source of information on the structure of demersal assemblages and the impact of fisheries.
Mitochondrial functional resilience after TFAM ablation in adult cardiomyocytes
Authors: Ghazal Nasab , Peoples Jessica N. , Mohuiddin Tahmina , Kwong Jennifer Q.
Published: June 2020

The adult heart is a terminally differentiated tissue that depends on mitochondria for its energy supply. Respiratory chain energy supply deficits due to alterations in the mitochondrial genome (mtDNA) or in nuclear genome (nDNA)-encoded mtDNA regulators are associated with cardiac pathologies ranging from primary mitochondrial cardiomyopathies to heart failure. Mitochondrial transcription factor A (TFAM) is an nDNA-encoded regulator of mtDNA transcription, replication, and maintenance. Insufficiency of this protein in embryonic and postnatal cardiomyocytes causes cardiomyopathy and/or lethality, establishing TFAM as indispensable to the developing heart; its role in adult tissue has been inferred from these findings. Here, we provide evidence that challenges this long-standing paradigm usingTfamablation in the adult heart. Unexpectedly, loss ofTfamin adult cardiomyocytes resulted in a prolonged period of functional resilience characterized by preserved mtDNA content, mitochondrial function, and cardiac function despite mitochondrial structural alterations and decreased transcript abundance. Remarkably, TFAM protein levels did not directly dictate mtDNA content in the adult heart, and mitochondrial translation was preserved with acute TFAM inactivation, suggesting a mechanism whereby respiratory chain assembly and function can be sustained, which we term ‘functional resilience’. Finally, long-termTfaminactivation induced a coordinated downregulation of the core mtDNA transcription and replication machinery that ultimately resulted in mitochondrial dysfunction and cardiomyopathy. Taken together, adult-onset cardiomyocyte-specificTfaminactivation reveals a striking resilience of the adult heart to acute insults to mtDNA regulatory mechanisms and provides insight into critical differences between the developing versus differentiated heart.
Brainprints: identifying individuals from magnetoencephalograms
Authors: Wu Shenghao , Ramdas Aaditya , Wehbe Leila
Published: June 2020

Magnetoencephalography (MEG) is used to study a wide variety of cognitive processes. Increasingly, researchers are adopting principles of open science and releasing their MEG data. While essential for reproducibility, sharing MEG data has unforeseen privacy risks. Individual differences may make a participant identifiable from their anonymized recordings. However, our ability to identify individuals based on these individual differences has not yet been assessed. Here, we propose interpretable MEG features to characterize individual difference. We term these features brainprints (brain fingerprints). We show through several datasets that brainprints accurately identify individuals across days, tasks, and even between MEG and Electroencephalography (EEG). Furthermore, we identify consistent brainprint components that are important for identification. We study the dependence of identifiability on the amount of data available. We also relate identifiability to the level of preprocessing, the experimental task. Our findings reveal specific aspects of individual variability in MEG. They also raise concerns about unregulated sharing of brain data, even if anonymized.

Abstract Figure

Figure 1:

Graphical abstract.

Identifying which subject a segment of MEG data belongs to is strikingly easy when other data from the same session is available for every subject. We propose three types of interpretable features that can also be used to identify individuals across sessions with high accuracy. Identifiability of individuals is influenced by factors such as resting state vs. task state, components of each feature, the sample size and the level of preprocessing. Our results reveal aspects of individual variability in MEG signals and highlight privacy risks associated with MEG data sharing.
Histone H3.3 Hira chaperone complex contributes to zygote formation in mice and humans
Authors: Smith Rowena , Pickering Sue , Kopakaki Anna , Thong K Joo , Anderson Richard A , Lin Chih-Jen
Published: June 2020

Elucidating the underlining mechanisms underpinning successful fertilisation is imperative in optimising IVF treatments, and may lead to a specific diagnosis and therefore potential treatment for some infertile couples. One of the critical steps involves paternal chromatin reprogramming, in which compacted sperm chromatin packed by protamines is removed by oocyte factors and new histones, including histone H3.3, are incorporated. This step is critical for the formation of the male pronucleus, without which the zygote contains only 1 pronucleus (1PN), in contrast to normally fertilised zygotes with two-pronuclei (2PN). 1PN zygotes are a frequently observed phenomenon in IVF treatments, therefore aberrant mechanism of action controlling paternal chromatin repackaging may be an important cause of abnormal fertilisation. Hira is the main H3.3 chaperone that governs this protamine-to-histone exchange. In this study, we investigated the maternal functions of two other molecules of the Hira complex, Cabin1 and Ubn1 in the mouse. Loss-of-function Cabin1 and Ubn1 mouse models were developed: their zygotes displayed abnormal 1PN zygote phenotypes, similar to the phenotype of Hira mutants. We then studied human 1PN zygotes, and found that the Hira complex was absent in 1PN zygotes which were lacking the male pronucleus. This result confirms that the role of the Hira complex in male pronucleus formation has coherence from mice to humans. Furthermore, rescue experiments showed that the abnormal 1PN phenotype derived from Hira mutants could be resolved by overexpression of Hira in the mouse oocytes. In summary, we have provided evidence of the role of Hira complex in regulating male pronucleus formation in both mice and humans, that both Cabin1 and Ubn1 components of the Hira complex are equally essential for male pronucleus formation, and that this can be rescued. We present a proof-of-concept experiment that could potentially lead to a personalised IVF therapy for oocyte defects.
Evidence for distinct isotopic composition of sap and tissue water in tree stems: consequences for plant water source identification
Authors: Barbeta Adrià , Burlett Régis , Martín-Gómez Paula , Fréjaville Bastien , Devert Nicolas , Wingate Lisa , Domec Jean-Christophe , Ogée Jérôme
Published: June 2020

For decades, theory has upheld that plants do not fractionate water isotopes as they move across the soil-root interface or along plant stems. This theory is now being challenged by several recent studies reporting that the water held in woody stems has an isotopic composition that cannot be attributed to any potential water source. Isotopic offsets between stem and source water still need to be explained, as they prevent identifying unambiguously tree water’s origin from water isotope measurements. Here we show that isotopic offsets between stem and source water can be explained by micrometer-scale water isotope heterogeneity within woody stems and soil micropores. Using a novel technique to extract sap water in xylem conduits separately from the water held in other xylem tissues, we show that these non-conductive xylem tissues are more depleted in deuterium than sap water. We also report that, in cut stems and well-watered potted plants, the isotopic composition of sap water reflects well that of irrigation water, demonstrating that no isotopic fractionation occurs during root water uptake or the sap water extraction process. Previous studies showed that isotopic heterogeneity also exists in soils at the pore scale where water adsorbed onto soil particles is more depleted than capillary/mobile soil water. Data collected at a beech (Fagus sylvatica) forest indicate that sap water matches best the capillary/mobile soil water from deep soil horizons, indicating that micrometer-scale water isotope heterogeneity in soils and stems must be accounted for to unambiguously identify where trees obtain their water within catchments.

Significance Statement

Forests are prime regulators of the water cycle over land. They return, via transpiration, a large fraction of precipitation back to the atmosphere, influence surface runoff, groundwater recharge or stream flow, and enhance the recycling of atmospheric moisture inland from the ocean. The isotopic composition of water in woody stems can provide unique information on the role forests play in the water cycle only if it can be unambiguously related to the isotopic composition of source water. Here, we report a previously overlooked isotopic fractionation of stem water whereby non-conductive tissues are more depleted in deuterium than sap water, and propose a new technique to extract sap water separately from bulk stem water to unambiguously identify plant water sources.
Detection of differential RNA modifications from direct RNA sequencing of human cell lines
Authors: Pratanwanich Ploy N. , Yao Fei , Chen Ying , Koh Casslynn W.Q. , Hendra Christopher , Poon Polly , Goh Yeek Teck , Yap Phoebe M. L. , Yuan Choi Jing , Chng Wee Joo , Ng Sarah , Thiery Alexandre , Goh W.S. Sho , Göke Jonathan
Published: June 2020

Differences in RNA expression can provide insights into the molecular identity of a cell, pathways involved in human diseases, and variation in RNA levels across patients associated with clinical phenotypes. RNA modifications such as m6A have been found to contribute to molecular functions of RNAs. However, quantification of differences in RNA modifications has been challenging. Here we develop a computational method (xPore) to identify differential RNA modifications from direct RNA sequencing data. We evaluate our method on transcriptome-wide m6A profiling data, demonstrating that xPore identifies positions of m6A sites at single base resolution, estimates the fraction of modified RNAs in the cell, and quantifies the differential modification rate across conditions. We apply the method to direct RNA-Sequencing data from 6 cell lines and find that many m6A sites are preserved, while a subset of m6A sites show significant differences in their modification rates across cell types. Together, we show that RNA modifications can be identified from direct RNA-sequencing with high accuracy, enabling the analysis of differential modifications and expression from a single high throughput experiment.

Availability

xPore is available as open source software (https://github.com/GoekeLab/xpore)
Measuring the accuracy of gridded human population density surfaces: a case study in Bioko Island, Equatorial Guinea
Authors: Fries Brendan F , Guerra Carlos A , García Guillermo A , Wu Sean L , Smith Jordan M , Oyono Jeremias Nzamio Mba , Donfack Olivier T , Nfumu José Osá Osá , Hay Simon I , Smith David L , Dolgert Andrew J
Published: June 2020

Geospatial datasets of population are becoming more common in models used for health policy. Publicly-available maps of human population in sub-Saharan Africa make a consistent picture from inconsistent census data, and the techniques they use to impute data makes each population map unique. Each mapping model explains its methods, but it can be difficult to know which map is appropriate for which policy work. Gold-standard census datasets, where available, are a unique opportunity to characterize maps by comparing them with truth. We use census data from Bioko Island, in Equatorial Guinea, to evaluate LandScan (LS), WorldPop (WP), and the High-Resolution Settlement Layer (HRSL). Each layer is compared to the gold-standard using statistical measures to evaluate distribution, error, and bias. We investigated how map choice affects burden estimates from a malaria prevalence model. Specific population layers were able to match the gold-standard distribution at different population densities. LandScan was able to most accurately capture highly urban distribution, HRSL matched best at all other lower population densities and WorldPop performed poorly everywhere. Correctly capturing empty pixels is key, and smaller pixel sizes (100 m vs 1 km) improve this. Normalizing areas based on known district populations increased performance. The use of differing population layers in a malaria model showed a disparity in results around transition points between endemicity levels. The metrics in this paper, some of them novel in this context, characterize how these population maps differ from the gold standard census and from each other. We show that the metrics help understand the performance of a population map within a malaria model. The closest match to the census data would combine LandScan within urban areas and the HRSL for rural areas. Researchers should prefer particular maps if health calculations have a strong dependency on knowing where people are not, or if it is important to categorize variation in density within a city.
Short-lived plants have stronger demographic responses to climate
Authors: Compagnoni Aldo , Levin Sam , Childs Dylan Z. , Harpole Stan , Paniw Maria , Römer Gesa , Burns Jean H. , Che-Castaldo Judy , Rüger Nadja , Kunstler Georges , Bennett Joanne M , Archer C. Ruth , Jones Owen R. , Salguero-Gómez Roberto , Knight Tiffany M.
Published: June 2020

To mitigate and adapt to climate change, there is an urgent need to synthesize the state of our knowledge on plant responses to climate. The availability of open-access data, combined with our understanding of plant physiology and life history theory provide opportunities to examine quantitative generalizations regarding which biomes and species are most responsive to climate drivers. Here, we synthesized time series of structured population models from 165 populations from 62 plants around the globe to link plant population growth rates to precipitation and temperature drivers. We expected: (1) more pronounced demographic responses to precipitation than temperature, especially in arid biomes; (2) a higher climate sensitivity in short-lived rather than long-lived species; and (3) a stronger response to climate by species that reproduce more frequently. We found that precipitation anomalies have a nearly three-fold larger effect onλthan temperature. Precipitation has substantially more pronounced effects in more arid sites, but large noise makes this relationship non-significant. Species with shorter generation time have much stronger absolute responses to climate anomalies, while the degree of iteroparity does not correlate with population responses to climate. We conclude that key species-level traits can predict plant population responses to climate, and discuss the relevance of this generalization for conservation planning and evolutionary theory.
miR156-independent repression of the ageing pathway by longevity-promoting AHL proteins in Arabidopsis
Authors: Rahimi Arezoo , Karami Omid , Offringa Remko
Published: June 2020

Plants age by transition through distinct developmental phases, with the juvenile- to adult vegetative and the adult vegetative to reproductive phase change as two consecutive important post-embryonic phase transitions. During the transition from the juvenile- to adult vegetative phase, also known as the vegetative phase change (VPC), many plants undergo specific morphological and physiological changes. In the model plantArabidopsis thaliana(Arabidopsis), for example, the VPC is marked by clear heteroblastic changes in leaf shape and size and the appearance of trichomes on the abaxial side of leaves. The VPC and the vegetative to reproductive transition are promoted by the SQUAMOSA PROMOTOR BINDING PROTEIN-LIKE (SPL) family of transcription factors and repressed by miR156 and miR157 that target theSPLtranscripts. Here we present data that the plant longevity promoting AT-HOOK MOTIF NUCLEAR LOCALIZED protein 15 (AHL15) and family members also repress the SPL-driven ageing pathway. Arabidopsisahlloss-of-function mutants showed an accelerated VPC and flowering time, whereasAHL15overexpression dramatically delayed the VPC and flowering time in both Arabidopsis andNicotiana tabacum. Expression analysis and tissue-specificAHL15overexpression revealed thatAHL15affects the VPC and flowering time directly through its expression in the shoot apical meristem and young leaves. In addition, we found evidence that AHL15 repressesSPLgene expression in a miR156/157-independent manner. The juvenile traits ofsplloss-of-function mutants appeared to be dependent on the enhanced expression of theAHL15gene, providing evidence for a reciprocal negative feedback betweenAHL15andSPLgenes. Antagonistically to AHLs, SPLs promote axillary meristem (AM) maturation and thus prevent vegetative growth from these meristems by repressingAHL15expression. Taken together, our results place AHL15 and family members at a central position in the SPL-driven ageing pathway as suppressors of the VPC, flowering time and AM maturation.
Neuronal Classification from Network Connectivity via Adjacency Spectral Embedding
Authors: Mehta Ketan , Goldin Rebecca F. , Marchette David , Vogelstein Joshua T. , Priebe Carey E. , Ascoli Giorgio A.
Published: June 2020

This work presents a novel strategy for classifying neurons, represented by nodes of a directed graph, based on their circuitry (edge connectivity). We assume a stochastic block model (SBM) where neurons belong together if they connect to neurons of other groups according to the same probability distributions. Following adjacency spectral embedding (ASE) of the SBM graph, we derive the number of classes and assign each neuron to a class with a Gaussian mixture model-based expectation-maximization (EM) clustering algorithm. To improve accuracy, we introduce a simple variation using random hierarchical agglomerative clustering to initialize the EM algorithm and picking the best solution over multiple EM restarts. We test this procedure on a large (n~ 212− 215neurons), sparse, biologically inspired connectome with eight neuron classes. The simulation results demonstrate that the proposed approach is broadly stable to the choice of dimensional embedding and scales extremely well as the number of neurons in the network increases. Clustering accuracy is robust to variations in model parameters and highly tolerant to simulated experimental noise, achieving perfect classifications with up to 40% of swapped edges. Thus, this approach may be useful to analyze and interpret large-scale brain connectomics data in terms of underlying cellular components.
Long-read RNA sequencing of human and animal filarial parasites improves gene models and discovers operons
Authors: Wheeler Nicolas J , Airs Paul M. , Zamanian Mostafa
Published: June 2020

Filarial nematodes (Filarioidea) cause substantial disease burden to humans and animals around the world. Recently there has been a coordinated global effort to generate and curate genomic data from nematode species of medical and veterinary importance. This has resulted in two chromosome-level assemblies (Brugia malayiandOnchocerca volvulus) and 10 additional draft genomes from Filarioidea. These reference assemblies facilitate comparative genomics to explore basic helminth biology and prioritize new drug and vaccine targets. While the continual improvement of genome contiguity and completeness advances these goals, experimental functional annotation of genes is often hindered by poor gene models. Short-read RNA sequencing data and expressed sequence tags, in cooperation withab initioprediction algorithms, are employed for gene prediction, but these can result in missing clade-specific genes, fragmented models, imperfect mapping of gene ends, and lack of isoform resolution. Long-read RNA sequencing can overcome these drawbacks and greatly improve gene model quality. Here, we present Iso-Seq data forB. malayiandDirofilaria immitis, etiological agents of lymphatic filariasis and canine heartworm disease, respectively. These data cover approximately half of the known coding genomes and substantially improve gene models by extending untranslated regions, cataloging novel splice junctions from novel isoforms, and correcting mispredicted junctions. Furthermore, we validated computationally predicted operons, identified new operons, and merged fragmented gene models. We carried out analyses of poly(A) tails in both species, leading to the identification of non-canonical poly(A) signals. Finally, we prioritized and assessed known and putative anthelmintic targets, correcting or validating gene models for molecular cloning and target-based antiparasitic screening efforts. Overall, these data significantly improve the catalog of gene models for two important parasites, and they demonstrate how long-read RNA sequencing should be prioritized for future improvement of parasitic nematode genome assemblies.
Wolbachiaand virus alter the host transcriptome at the interface of nucleotide metabolism pathways
Authors: Lindsey Amelia RI , Bhattacharya Tamanash , Hardy Richard W , Newton Irene LG
Published: June 2020

Wolbachiais a maternally transmitted bacterium that manipulates arthropod and nematode biology in myriad ways. TheWolbachiastrain colonizingDrosophila melanogastercreates sperm-egg incompatibilities and protects its host against RNA viruses, making it a promising tool for vector control. Despite successful trials usingWolbachia-transfected mosquitoes for Dengue control, knowledge of howWolbachiaand viruses jointly affect insect biology remains limited. Using theDrosophilamodel, transcriptomics and gene expression network analyses revealed pathways with altered expression and splicing due toWolbachiacolonization and virus infection. Included are metabolic pathways previously unknown to be important forWolbachia-host interactions. Additionally,Wolbachia-colonized flies exhibit a dampened transcriptomic response to virus infection, consistent with early blocking of virus replication. Finally, usingDrosophilagenetics, we showWolbachiaand expression of nucleotide metabolism genes have interactive effects on virus replication. Understanding the mechanisms of pathogen blocking will contribute to the effective development ofWolbachia-mediated vector control programs.