bluuebunny/crossref_metadata_2025 huggingface dataset:
Formosa maritima sp. nov., isolated from coastal sediment
Authors: Cao Wen-Rui , Lu De-Chen , Li Ying-Jie , Sun Xun-Ke , Sun Yuan-Yuan , Saren Gaowa , Du Zong-Jun
Published: November 2019

A Gram-stain-negative, strictly aerobic, gliding-motile, rod-shaped and orange-pigmented bacterium, designated 1494T, was isolated from marine sediment collected off the coast of Weihai, PR China. Strain 1494T was found to grow at 4–37 °C (optimum, 30 °C), at pH 6.0–9.0 (pH 7.0) and in the presence of 0–8 % (w/v) NaCl (2 %). Cells were positive for oxidase and catalase activity. The results of 16S rRNA gene based phylogenetic analysis revealed that strain 1494T belonged to the genus

Formosa

and exhibited the highest sequence similarity to

Formosa spongicola

KCTC 22662 T (98.4 %). Menaquinone-6 (MK-6) was detected as the major respiratory quinone. The dominant cellular fatty acids were iso-C15 : 1 G and iso-C15 : 0. The DNA G+C content of strain 1494T was 31.1 mol%. The major polar lipids included phosphatidylethanolamine, one unidentified phospholipid and one unidentified lipid. Based on its phylogenetic and phenotypic characteristics, strain 1494T is considered to represent a novel species from the genus

Formosa

, for which the name Formosa maritima sp. nov. is proposed. The type strain is 1494T (=KCTC 72531T=MCCC 1H00385T).
Using Digital Surveillance Tools for Near Real-Time Mapping of the Risk of International Infectious Disease Spread: Ebola as a Case Study
Authors: Bhatia Sangeeta , Lassmann Britta , Cohn Emily , Carrion Malwina , Kraemer Moritz U. G. , Herringer Mark , Brownstein John , Madoff Larry , Cori Anne , Nouvellet Pierre
Published: November 2019

In our increasingly interconnected world, it is crucial to understand the risk of an outbreak originating in one country or region and spreading to the rest of the world. Digital disease surveillance tools such as ProMED and HealthMap have the potential to serve as important early warning systems as well as complement the field surveillance during an ongoing outbreak. Here we present a flexible statistical model that uses data produced from digital surveillance tools (ProMED and HealthMap) to forecast short term incidence trends in a spatially explicit manner. The model was applied to data collected by ProMED and HealthMap during the 2013-2016 West African Ebola epidemic. The model was able to predict each instance of international spread 1 to 4 weeks in advance. Our study highlights the potential and limitations of using publicly available digital surveillance data for assessing outbreak dynamics in real-time.
Using Mobile Phones For Computer Aided Detection Of Anomalies On Chest Radiographs: Proof Of Concept
Authors: Mitini-Nkhoma Steven
Published: November 2019

Mastering the art of interpreting chest radiographs can be a long and daunting process. We trained a neural network to classify photographs of chest radiographs into 6 groups. The trained model is hosted on a webserver. The model receives and processes photographs of chest radiographs taken using mobile phones. The system then informs the user the most probable diagnosis. Such systems could prove useful in low resource settings which do not have enough highly trained medical personnel and cannot afford the new generation of CAD based radiology equipment.
Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass- and fat mass-indexes
Authors: Scliar Marilia O , Sant Anna Hanaisa P , Santolalla Meddly L , Leal Thiago P , Araújo Nathalia M , Alvim Isabela , Borda Victor , Magalhães Wagner CS , Gouveia Mateus H , Lyra Ricardo , Machado Moara , Michelin Lucas , Rodrigues Maíra R , Araújo Gilderlanio S , Kehdy Fernanda SG , Zolini Camila , Peixoto Sérgio Viana , Luizon Marcelo , Lobo Francisco , Naslavsky Michel S , Yamamoto Guilherme L , Duarte Yeda A O , Hansen Matthew EB , Norris Shane A , Gilman Robert H , Guio Heinner , Hsing Ann W , Mbulaiteye Sam M , Mensah James , Dutil Julie , Yeager Meredith , Yeboah Edward , Tishkoff Sarah A , Choudhury Ananyo , Ramsay Michele , Passos-Bueno Maria Rita , Zatz Mayana , O’Connor Timothy D , Pereira Alexandre C , Barreto Mauricio L , Lima-Costa Maria Fernanda , Horta Bernardo L , Tarazona-Santos Eduardo
Published: November 2019

Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely under-represented in genomic studies. Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of Body Mass Index (BMI) in three population-based cohorts from Northeast (Salvador), Southeast (Bambuí) and South (Pelotas) of the country. We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p= 2.76 e-06). This variant is very rare in Europeans but with frequencies of ~3% in West Africa, and has a strong female-specific effect (95%CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat-mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among morbidly obese women from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five-times the effect size of the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects, and for which we replicated associations in Pelotas. We demonstrate how, after a decade of GWAS mostly performed in European-ancestry populations, non-European and admixed populations are a source of new relevant phenotype-associated genetic variants.
Transneuronal delivery of designer-cytokine enables functional recovery after complete spinal cord injury
Authors: Leibinger Marco , Zeitler Charlotte , Gobrecht Philipp , Andreadaki Anastasia , Fischer Dietmar
Published: November 2019

Spinal cord injury (SCI) often causes severe and permanent disabilities. The current study uses a transneuronal approach to stimulate spinal cord regeneration by AAV-hyper-IL-6 (hIL-6) application after injury. While preinjury PTEN knockout in cortical motoneurons fails to improve functional recovery after complete spinal cord crush, a single, postinjury injection of hIL-6 into the sensorimotor cortex markedly promotes axon regeneration in the corticospinal and, remarkably, raphespinal tracts enabling significant locomotion recovery of both hindlimbs. Moreover, transduced cortical motoneurons directly innervate serotonergic neurons in both sides of the raphe nuclei equally, enabling the synaptic release of hIL-6 and the transneuronal stimulation of raphe neurons in the brain stem. Functional recovery depends on the regeneration of serotonergic neurons as their degeneration induced by a toxin abolishes the hIL-6-mediated recovery. Thus, the transneuronal application of highly potent cytokines enables functional regeneration by stimulating neurons in the deep brain stem that are otherwise challenging to access, yet highly relevant for functional recovery after SCI.
Application of long-read sequencing for robust identification of correct alleles in genome edited animals
Authors: McCabe Christopher V. , Codner Gemma F. , Allan Alasdair J. , Caulder Adam , Christou Skevoulla , Loeffler Jorik , Mackenzie Matthew , Malzer Elke , Mianné Joffrey , Pike Fran J. , Hutchison Marie , Stewart Michelle E. , Gates Hilary , Wells Sara , Sanderson Nicholas D. , Teboul Lydia
Published: November 2019

Recent developments in CRISPR/Cas9 genome editing tools have facilitated the introduction of more complex alleles, often spanning genetic intervals of several kilobases, directly into the embryo. These techniques often produce mosaic founder animals and the introduction of donor templates, via homologous directed repair, can be erroneous or incomplete. Newly generated alleles must be verified at the sequence level across the targeted locus. Screening for the presence of the desired mutant allele using traditional sequencing methods can be challenging due to the size of the desired edit(s) together with founder mosaicism. In order to help disentangle the genetic complexity of these animals, we tested the application of Oxford Nanopore long read sequencing of the targeted locus. Taking advantage of sequencing the entire length of the segment in each single read, we were able to determine whether the entire intended mutant sequence was present in both mosaic founders and their offspring.
AMELIE 2 speeds up Mendelian diagnosis by matching patient phenotype & genotype to primary literature
Authors: Birgmeier Johannes , Haeussler Maximilian , Deisseroth Cole A. , Steinberg Ethan H. , Jagadeesh Karthik A. , Ratner Alexander J. , Guturu Harendra , Wenger Aaron M. , Diekhans Mark E. , Stenson Peter D. , Cooper David N. , Ré Christopher ,   The Manton Center, Beggs Alan H. , Bernstein Jonathan A. , Bejerano Gill
Published: November 2019

The diagnosis of Mendelian disorders requires labor-intensive literature research. Trained clinicians can spend hours looking for the right publication/s supporting a single gene that best explains a patient’s disease. AMELIE (Automatic Mendelian Literature Evaluation) greatly accelerates this process. AMELIE parses all 29 million PubMed abstracts, downloads and further parses hundreds of thousands of full text articles in search of information supporting the causality and associated phenotypes of any published genetic variant. AMELIE then prioritizes patient candidate variants for their likelihood of explaining any patient’s given set of phenotypes. Diagnosis of singleton patients (without relatives’ exomes) is the most time-consuming scenario. AMELIE ranked the causative gene at the very top in 2/3 of 215 diagnosed singleton Mendelian patients. Evaluating only the top 11 AMELIE scored genes of 127 (median) candidate genes per patient results in rapid diagnosis for 90+% of cases. AMELIE-based evaluation of all cases is 3-19x more efficient than hand-curated database-based approaches. We replicate these results on a cohort of clinical cases from Stanford Children’s Health and the Manton Center for Orphan Disease Research. An analysis web portal with our most recent update, programmatic interface and code will be available at AMELIE.stanford.edu. A pilot run of the web portal has already served many thousands of job submissions from dozens of countries.
Family permutation profiling identifies a dynamic protein domain as functionally tolerant to increased conformational entropy
Authors: Atkinson Joshua T. , Jones Alicia M. , Nanda Vikas , Silberg Jonathan J.
Published: November 2019

To investigate whether adenylate kinase (AK) homologs differ in their functional tolerance to mutational lesions that alter dynamics, we subjected three homologs having a range of thermostabilities to random circular permutation and evaluated where new protein termini were non-disruptive to activity using a cellular selection and deep mutational scanning. Analysis of the positional tolerance to new termini, which increase local conformational entropy by breaking peptide bonds, showed that bonds were either functionally sensitive to cleavage across all three homologs, differentially sensitive, or uniformly tolerant. The mobile AMP binding domain, which displays the highest calculated contact energies (frustration), presented the greatest tolerance to new termini across all AKs. In contrast, retention of function in the lid and core domains was more dependent upon AK melting temperature. Thus, regions of high energetic frustration tolerated increases in conformational entropy in a manner that was less dependent on thermostability than regions of lower frustration. Our results suggest that family permutation profiling identifies primary structure that has been selected by evolution for high frustration that is critical to enzymatic activity. They also illustrate how deep mutational scanning can be applied to protein homologs in parallel to learn how topology and function govern mutational tolerance.
The Subsystem Mechanism of Default Mode Network Underlying Rumination: a Reproducible Neuroimaging Study
Authors: Chen Xiao , Chen Ning-Xuan , Shen Yang-Qian , Li Hui-Xian , Li Le , Lu Bin , Zhu Zhi-Chen , Fan Zhen , Yan Chao-Gan
Published: November 2019

Rumination is a repetitive self-referential thinking style and posited to be an expression of abnormalities in the default mode network (DMN) in major depressive disorder (MDD). Recent evidences indicate DMN is not a unitary network but can be further divided into 3 functionally heterogenous subsystems. However, the subsystem mechanism through which DMN underlie rumination remain unclear. Here, with a modified continuous state-like paradigm, we induced healthy participants to ruminate or imagine objective scenarios (as a distraction control condition) on 3 different MRI scanners. We compared functional connectivities (FC) and inter-subject correlations (ISC) of the DMN and its 3 subsystems between rumination and distraction states. Results yielded a highly reproducible and dissociated pattern. During rumination, within-DMN FC was generally decreased compared to the distraction state. At the subsystem level, we found increased FC between the core and medial temporal lobe (MTL) subsystem and decreased FC between the core and dorsal medial prefrontal cortex (DMPFC) subsystem and within the MTL subsystem. Furthermore, we found decreased ISC within the MTL subsystem. These results suggest a specific and less synchronous activity pattern of DMN during rumination and shed new light on the association between rumination and DMN substrates regarding MDD.
Functional insights from the GC-poor genomes of two aphid parasitoids,Aphidius erviandLysiphlebus fabarum
Authors: Dennis Alice B. , Ballesteros Gabriel I. , Robin Stéphanie , Schrader Lukas , Bast Jens , Berghöfer Jan , Beukeboom Leo , Belghazi Maya , Bretaudeau Anthony , Büllesbach Jan , Cash Elizabeth , Colinet Dominique , Dumas Zoé , Falabella Patrizia , Gatti Jean-Luc , Geuverink Elzemiek , Gibson Joshua D. , Hertäg Corinne , Hartmann Stefanie , Jacquin-Joly Emmanuelle , Lammers Mark , Lavandero Blas I. , Lindenbaum Ina , Massardier-Galata Lauriane , Meslin Camille , Montagné Nicolas , Pak Nina , Poirié Marylène , Salvia Rosanna , Smith Chris R. , Tagu Denis , Tares Sophie , Vogel Heiko , Schwander Tanja , Simon Jean-Christophe , Figueroa Christian C. , Vorburger Christoph , Legeai Fabrice , Gadau Jürgen
Published: November 2019

Background

Parasitoid wasps have fascinating life cycles and play an important role in trophic networks, yet little is known about their genome content and function. Parasitoids that infect aphids are an important group with the potential for biocontrol, and infecting aphids requires overcoming both aphid defenses and their defensive endosymbionts.

Results

We present thede novogenome assemblies, detailed annotation, and comparative analysis of two closely related parasitoid wasps that target pest aphids:Aphidius erviandLysiphlebus fabarum(Hymenoptera: Braconidae: Aphidiinae). The genomes are small (139 and 141 Mbp), highly syntenic, and the most AT-rich reported thus far for any arthropod (GC content: 25.8% and 23.8%). This nucleotide bias is accompanied by skewed codon usage, and is stronger in genes with adult-biased expression. AT-richness may be the consequence of reduced genome size, a near absence of DNA methylation, and age-specific energy demands. We identify expansions of F-box/Leucine-rich-repeat proteins, suggesting that diversification in this gene family may be associated with their broad host range or with countering defenses from aphids’ endosymbionts. The absence of some immune genes (Toll and Imd pathways) resembles similar losses in their aphid hosts, highlighting the potential impact of symbiosis on both aphids and their parasitoids.

Conclusions

These findings are of fundamental interest for insect evolution and beyond. This will provide a strong foundation for further functional studies including coevolution with respect to their hosts, the basis of successful infection, and biocontrol. Both genomes are available athttps://bipaa.genouest.org.
Cell volume homeostatically controls the rDNA repeat copy number and rRNA synthesis rate in yeast
Authors: Pérez-Ortín José E. , Mena Adriana , Barba-Aliaga Marina , Alonso-Monge Rebeca , Singh Abhyudai , Chávez Sebastián , García-Martínez José
Published: November 2019

The adjustment of transcription and translation rates to variable needs is of utmost importance for the fitness and survival of living cells. We have previously shown that the global transcription rate for RNA polymerase II is regulated differently in cells presenting symmetrical or asymmetrical cell division. The budding yeast Saccharomyces cerevisiae adopts a particular strategy to avoid that the smaller daughter cells increase their total mRNA concentration with every generation. The global mRNA synthesis rate lowers with a growing cell volume, but global mRNA stability increases. In this paper, we address what the solution is to the same theoretical problem for the RNA polymerase I synthesis rate. We find that the RNA polymerase I synthesis rate strictly depends on the copy number of its 35S rRNA gene. For cells with larger cell sizes, such as a mutant cln3 strain, the rDNA repeat copy number is increased by a mechanism based on a feed-back mechanism in which Sir2 histone deacetylase homeostatically controls the amplification of the rRNA genes at the rDNA locus in a volume-dependent manner.
Genomic architecture of artificially and sexually selected traits in a wild cervid
Authors: Anderson S. J. , Côté S. D. , Richard J. H. , Shafer A. B. A.
Published: November 2019

Characterization of the genomic architecture of fitness-related traits such as body size and male ornamentation in mammals provides tools for conservation and management: as both indicators of quality and health, these traits are often subject to sexual and artificial selective pressures. Here we performed high-depth whole genome re-sequencing on pools of individuals representing the phenotypic extremes in our study system for antler and body size in white-tailed deer (Odocoileus virginianus). Samples were selected from a tissue repository containing phenotypic data for 4,466 male white-tailed deer from Anticosti Island, Quebec, with four pools representing the extreme phenotypes for antler and body size in the population, after controlling for age. Our results revealed a largely panmictic population, but detected highly diverged windows between pools for both traits with high shifts in allele frequency (mean allele frequency difference of 14% for and 13% for antler and body SNPs in outlier windows). These regions often contained putative genes of small-to-moderate effect consistent with a polygenic model of quantitative traits. Genes in outlier antler windows had known direct or indirect effects on growth and pathogen defence, while body genes, overall GO terms, and transposable element analyses were more varied and nuanced. Through qPCR analysis we validated both a body and antler gene. Overall, this study revealed the polygenic nature of both antler morphology and body size in free-ranging white-tailed deer and identified target loci for additional analyses.
Blocking mitochondrial pyruvate import causes energy wasting via futile lipid cycling in brown fat
Authors: Veliova Michaela , Ferreira Caroline M. , Benador Ilan Y. , Jones Anthony E. , Desousa Brandon R. , Mahdaviani Kiana , Acín-Pérez Rebeca , Petcherski Anton , Divakaruni Ajit S. , Prentki Marc , Corkey Barbara E. , Liesa Marc , Oliveira Marcus F. , Shirihai Orian S.
Published: November 2019

Futile lipid cycling is an ATP-wasting process proposed to participate in energy expenditure of mature fat-storing white adipocytes, given their inability to oxidize fat. The hallmark of activated brown adipocytes is to increase fat oxidation by uncoupling respiration from ATP synthesis. Whether ATP-consuming lipid cycling can contribute to BAT energy expenditure has been largely unexplored. Here we find that pharmacological inhibition of the mitochondrial pyruvate carrier (MPC) in brown adipocytes is sufficient to increase ATP-synthesis fueled by fatty acid oxidation, even in the absence of adrenergic stimulation. We find that elevated ATP-demand induced by MPC inhibition results from activation of futile lipid cycling. Furthermore, we identify that glutamine consumption and theMalate-AspartateShuttle are required for the increase inEnergyExpenditure induced by MPC inhibition inBrownAdipocytes (MAShEEBA). These data demonstrate that futile energy expenditure through lipid cycling can be activated in BAT by altering fuel availability to mitochondria. Therefore, we identify a new mechanism to increase fat oxidation and energy expenditure in BAT that bypasses the need for adrenergic stimulation of mitochondrial uncoupling.
Neuromodulation of astrocytic K+ clearance
Authors: Bellot-Saez Alba , Kékesi Orsolya , Ben-Abu Yuval , Morley John W. , Buskila Yossi
Published: November 2019

Potassium homeostasis is a fundamental requirement for normal brain function. Therefore, effective removal of excessive K+accumulation from the synaptic cleft during neuronal activity is paramount. Astrocytes, one of the most common subtype of glial cells in the brain, play a key role in K+clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]°) or impairments of the astrocytic clearance mechanism effect the resonance and oscillatory behaviour of both individual and networks of neurons recorded from C57/BL6 mice of both sexes. These results indicate that astrocytes have the potential to modulate neuronal network activity, however the cellular effectors that may affect the astrocytic K+clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behaviour, on the astrocytic clearance process. Our results suggest that some neuromodulators (5-HT; NA) affect astrocytic spatial buffering via gap-junctions, while others (DA; Histamine) affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to recruitment of neurons into ensamble of networks to maximise the synchronous network activity.

Significance statement

Neuromodulators are known to mediate changes in network oscillatory behaviour and thus impact on brain states. In this study we show that certain neuromodulators directly affect distinct stages of astrocytic K+clearance, promoting neuronal excitability and network oscillations through parallel activation of both neurons and astrocytes, thus establishing a synergistic mechanism to maximise the synchronous network activity.
Experts, but not novices, exhibit StartReact indicating experts use the reticulospinal system more than novices
Authors: Bartels Brandon M. , Quezada Maria Jose , Ravichandran Vengateswaran J. , Honeycutt Claire F.
Published: November 2019

Motor skill acquisition utilizes a wide array of neural structures; however, few articles evaluate how the relative contributions of these structures shift over the course of learning. Recent evidence from rodents and songbirds suggests there is a transfer from cortical to subcortical structures following intense, repetitive training. Evidence from humans indicate that the reticulospinal system is modulated over the course of skill acquisition and may be a subcortical facilitator of learning. The objective of this study was to evaluate how reticulospinal contributions are modulated by task expertise. Reticulospinal contributions were assessed using StartReact (SR). We hypothesized that expert typists would show SR during an individuated, keystroke task but SR would be absent in novices. Expert (75.2 ± 9.8 WPM) and novice typists (41.6 ± 8.2 WPM) were evaluated during an individuated, keystroke movements. In experts, SR was present in all fingers (except the middle) but was absent in novices (except the little). Together, these results suggest that experts use reticulospinal contributions more for movement than novices indicating that the reticular formation becomes increasingly important for movement execution in highly trained, skilled tasks even those that require individuated movement of the fingers.
The neocortical progenitor specification program is established through combined modulation of SHH and FGF signaling
Authors: Yabut Odessa R. , Ng Hui-Xuan , Yoon Keejung , Arela Jessica C. , Ngo Thomas , Pleasure Samuel J.
Published: November 2019

Neuronal progenitors in the developing forebrain undergo dynamic competence states to ensure timely generation of specific excitatory and inhibitory neuronal subtypes from distinct neurogenic niches of the dorsal and ventral forebrain, respectively. Here we show evidence of progenitor plasticity when Sonic hedgehog (SHH) signaling is left unmodulated in the embryonic neocortex of the dorsal forebrain. At early stages of corticogenesis, loss of Suppressor of Fused (Sufu), a potent inhibitor of SHH signaling, in neocortical progenitors, altered their transcriptomic landscape. Ectopic activation of SHH signaling occurred, via degradation of Gli3R, resulting in significant upregulation of Fibroblast Growth Factor 15 (FGF15) gene expression. Consequently, activation of FGF signaling, and its downstream effector the MAPK signaling, facilitated expression of genes characteristic of ventral forebrain progenitors. Our studies identify the importance of modulating extrinsic niche signals such as SHH and FGF15 to maintain the competency and specification program of neocortical progenitors throughout corticogenesis.

SIGNIFICANCE STATEMENT

Low levels of FGF15 control progenitor proliferation and differentiation during neocortical development but little is known on how FGF15 expression is maintained. Our studies identified SHH signaling as a critical activator of FGF15 expression during corticogenesis. We found that Sufu, via Gli3R, ensured low levels of FGF15 was expressed to prevent abnormal specification of neocortical progenitors. These studies advance our knowledge on the molecular mechanisms guiding the generation of specific neocortical neuronal lineages, their implications in neurodevelopmental diseases, and may guide future studies on how progenitor cells may be utilized for brain repair.
Specific hippocampal interneurons shape consolidation of recognition memory
Authors: Oliveira da Cruz Jose F. , Busquets-Garcia Arnau , Zhao Zhe , Varilh Marjorie , Lavanco Gianluca , Bellocchio Luigi , Robin Laurie , Cannich Astrid , Julio-Kalajzić Francisca , Drago Filippo , Marsicano Giovanni , Soria-Gomez Edgar
Published: November 2019

A complex array of different inhibitory interneurons tightly controls hippocampal activity, but how such diversity specifically impacts on memory processes is scantly known. We found that a small subclass of type-1 cannabinoid receptor (CB1)-expressing hippocampal interneurons determines episodic-like memory consolidation by linking dopamine D1 receptor signaling to GABAergic transmission.

Mice lacking CB1 in D1-positive cells (D1-CB1-KO) displayed impaired long-term, but not short-term, object recognition memory. Re-expression of CB1 in hippocampal, but not striatal, D1-positive cells rescued this memory impairment. Learning induced a facilitation of in vivo hippocampal long-term potentiation (LTP), which was abolished in mutant mice. Chemogenetic and pharmacological experiments revealed that both CB1-mediated memory and associated LTP facilitation involves the local control of GABAergic inhibition in a D1-dependent manner.

This study reveals that CB1-/D1-expressing interneurons shape hippocampal circuits to sustain recognition memory, thereby identifying a mechanism linking the diversity of hippocampal interneurons to specific behavioral and cognitive outcomes.
Inversions shape the divergence ofDrosophila pseudoobscuraandD. persimilison multiple timescales
Authors: Korunes Katharine L , Machado Carlos A , Noor Mohamed AF
Published: November 2019

By shaping meiotic recombination, chromosomal inversions can influence genetic exchange between hybridizing species. Despite the recognized importance of inversions in evolutionary processes such as divergence and speciation, teasing apart the effects of inversions over time remains challenging. For example, are their effects on sequence divergence primarily generated through creating blocks of linkage-disequilibrium pre-speciation or through preventing gene flux after speciation? We provide a comprehensive look into the influence of chromosomal inversions on gene flow throughout the evolutionary history of a classic system:Drosophila pseudoobscuraandD. persimilis. We use extensive whole-genome sequence data to report patterns of introgression and divergence with respect to chromosomal arrangements. Overall, we find evidence that inversions have contributed to divergence patterns betweenDrosophila pseudoobscuraandD. persimilisover three distinct timescales: 1) pre-speciation segregation of ancestral polymorphism, 2) post-speciation ancient gene flow, and 3) recent gene flow. We discuss these results in terms of our understanding of evolution in this classic system and provide cautions for interpreting divergence measures in similar datasets in other systems.
UPCLASS: a Deep Learning-based Classifier for UniProtKB Entry Publications
Authors: Teodoro Douglas , Knafou Julien , Naderi Nona , Pasche Emilie , Gobeill Julien , Arighi Cecilia N. , Ruch Patrick
Published: November 2019

In the UniProt Knowledgebase (UniProtKB), publications providing evidence for a specific protein annotation entry are organized across different categories, such as function, interaction and expression, based on the type of data they contain. To provide a systematic way of categorizing computationally mapped bibliography in UniProt, we investigate a Convolution Neural Network (CNN) model to classify publications with accession annotations according to UniProtKB categories. The main challenge to categorize publications at the accession annotation level is that the same publication can be annotated with multiple proteins, and thus be associated to different category sets according to the evidence provided for the protein. We propose a model that divides the document into parts containing and not containing evidence for the protein annotation. Then, we use these parts to create different feature sets for each accession and feed them to separate layers of the network. The CNN model achieved a F1-score of 0.72, outperforming baseline models based on logistic regression and support vector machine by up to 22 and 18 percentage points, respectively. We believe that such approach could be used to systematically categorize the computationally mapped bibliography in UniProtKB, which represents a significant set of the publications, and help curators to decide whether a publication is relevant for further curation for a protein accession.
Motif V acts as a Regulator of Energy Transduction Between the Flavivirus NS3 ATPase and RNA Binding Cleft
Authors: Du Pont Kelly E. , Davidson Russell , McCullagh Martin , Geiss Brian J.
Published: November 2019

The unwinding of double-stranded RNA intermediates is a critical component for the replication of flavivirus RNA genomes. This function is achieved by the C-terminal helicase domain of nonstructural protein 3 (NS3). As a member of the superfamily 2 (SF2) helicases, NS3 is known to require the binding and hydrolysis of ATP/NTP to translocate along and unwind double-stranded nucleic acids. However, the mechanism of energy transduction between the ATP and RNA binding pockets is not well understood. Previous molecular dynamics simulations published by our group have identified Motif V as a potential “communication hub” for this energy transduction pathway. In order to investigate the role of Motif V in this process, a study combining molecular dynamics, biochemistry and virology has been employed. Mutations of Motif V were tested in both replicon and recombinant protein systems to investigate viral genome replication, RNA binding affinity, ATP hydrolysis activity and helicase unwinding activity. Using these analyses, we found that T407A and S411A in Motif V demonstrated increased turnover rates, suggesting that the mutations causes the helicase to unwind dsRNA more quickly than WT. Additionally, simulations of each mutant were used to probe structural changes within NS3 caused by each mutation. These simulations indicate that Motif V controls communication between the ATP binding pocket and the helical gate. These data help define the linkage between ATP hydrolysis and helicase activity within NS3 and provide insight into the biophysical mechanisms for ATPase driven NS3 helicase function.
Dimensions of passerine biodiversity along an elevational gradient: a nexus for historical biogeography and contemporary ecology
Authors: Burgio Kevin R. , Presley Steven J. , Cisneros Laura M. , Davis Katie E. , Dreiss Lindsay M. , Klingbeil Brian T. , Willig Michael R.
Published: November 2019

Aim

The incorporation of functional and phylogenetic information is necessary to comprehensively characterize spatial patterns of biodiversity and to evaluate the relative importance of ecological and evolutionary mechanisms in molding such patterns. We evaluated the relative importance of mechanisms that shape passerine biodiversity along an extensive elevational gradient.

Location

Manu Biosphere Reserve in the Peruvian Andes

Taxon

Songbirds (order Passeriformes)

Methods

We quantified elevational gradients of species richness, phylogenetic biodiversity, and functional biodiversity for all passerines as well as separately for suboscines and oscines; determined if phylogenetic or functional biodiversity was consistent with random selection or if there was evidence of particular mechanisms dominating community assembly; and compared patterns for each dimension of biodiversity for the two suborders.

Results

For all passerines and for suboscines, species richness decreased in a saturating fashion, phylogenetic biodiversity declined linearly, and functional biodiversity was stochastic along the elevation gradient. For oscines, species richness and phylogenetic biodiversity decreased linearly, and functional biodiversity decreased in a saturating fashion.

Main conclusions

Elevational gradients of biodiversity at Manu result from a combination of adaptations associated with radiations that occurred elsewhere (suboscines in Amazonian lowlands, oscines in colder climes of North America) and an in situ radiation in the Andes (tanagers). Our results suggest a combination of temperature-related physiological constraints and a reduction in functional redundancy associated with decreasing resource abundance at higher elevations molded the passerine assemblages along this elevational gradient. Explicit consideration of historical biogeography and conservatism of ancestral niches is necessary to comprehensively understand the mechanisms that mold gradients of biodiversity.
Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs
Authors: Kumar Narendra , Wang Wenjian , Ortiz-Marquez Juan C. , Catalano Matthew , Gray Mason , Biglari Nadia , Hikari Kitadai , Ling Xi , Gao Jianmin , Opijnen Tim van , Burch Kenneth S
Published: November 2019

The rapid increase in antibiotic resistant pathogenic bacteria has become a global threat, which besides the development of new drugs, requires rapid, cheap, scalable, and accurate diagnostics. Label free biosensors relying on electrochemical, mechanical, and mass based detection of whole bacterial cells have attempted to meet these requirements. However, the trade-off between selectivity and sensitivity of such sensors remains a key challenge. In particular, point-of-care diagnostics that are able to reduce and/or prevent unneeded antibiotic prescriptions require highly specific probes with sensitive and accurate transducers that can be miniaturized and multiplexed, and that are easy to operate and cheap. Towards achieving this goal, we present a number of advances in the use of graphene field effect transistors (G-FET) including the first use of peptide probes to electrically detect antibiotic resistant bacteria in a highly specific manner. In addition, we dramatically reduce the needed concentration for detection by employing dielectrophoresis for the first time in a G-FET, allowing us to monitor changes in the Dirac point due to individual bacterial cells. Specifically, we realized rapid binding of bacterial cells to a G-FET by electrical field guiding to the device to realize an overall 3 order of magnitude decrease in cell-concentration enabling a single-cell detection limit, and 9-fold reduction in needed time to 5 minutes. Utilizing our new biosensor and procedures, we demonstrate the first selective, electrical detection of the pathogenic bacterial species Staphylococcus aureus and antibiotic resistant Acinetobacter baumannii on a single platform.
Deletion ofcftrleads to an excessive neutrophilic response and defective tissue repair in a zebrafish model of sterile inflammation
Authors: Bernut Audrey , Loynes Catherine A. , Floto R. Andres , Renshaw Stephen A.
Published: November 2019

Inflammation-related progressive lung destruction is the leading causes of premature death in cystic fibrosis (CF), a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. However, therapeutic targeting of inflammation has been hampered by a lack of understanding of the links between a dysfunctional CFTR and the deleterious innate immune response in CF. Herein, we used CFTR-depleted zebrafish larvae as an innovativein vivovertebrate model, mimicking aspects of the inflammatory pathology of CF-related lung, to understand how CFTR dysfunction leads to abnormal inflammatory status in CF.

We show that impaired CFTR-mediated inflammation correlates with an exuberant neutrophilic response after injury: CF zebrafish exhibit enhanced and sustained accumulation of neutrophils at wounds. Excessive epithelial oxidative responses drive enhanced neutrophil recruitment towards wounds. Persistence of neutrophils at inflamed sites is associated with impaired reverse migration of neutrophils and reduction in neutrophil apoptosis. As a consequence, the increased number of neutrophils at wound sites causes tissue damage and abnormal tissue repair. Importantly, the pro-resolution molecule Tanshinone IIA successfully re-balances inflammation both by accelerating inflammation resolution and by improving tissue repair in CFTR-deficient animal.

Larval zebrafish giving a unique insight into innate immune cell function in CFTR deficiency, our findings bring important new understanding of the mechanisms underlying the inflammatory pathology in CF, which could be addressed therapeutically to prevent inflammatory lung damage in CF patients with potential improvements in disease outcomes.
Species-level microbiome composition of activated sludge - introducing the MiDAS 3 ecosystem-specific reference database and taxonomy
Authors: Nierychlo Marta , Andersen Kasper Skytte , Xu Yijuan , Green Nick , Albertsen Mads , Dueholm Morten S. , Nielsen Per Halkjær
Published: November 2019

The function of microbial communities in wastewater treatment systems and anaerobic digesters is dictated by the physiological activity of its members and complex interactions between them. Since functional traits are often conserved at low taxonomic ranks (genus, species, strain), the development of high taxonomic resolution and reliable classification is the first crucial step towards understanding the role of microbes in any ecosystem. Here we present MiDAS 3, a comprehensive 16S rRNA gene reference database based on high-quality full-length sequences derived from activated sludge and anaerobic digester systems. The MiDAS 3 taxonomy proposes unique provisional names for all microorganisms down to species level. MiDAS 3 was applied for the detailed analysis of microbial communities in 20 Danish wastewater treatment plants with nutrient removal, sampled over 12 years, demonstrating community stability and many abundant core taxa. The top 50 most abundant species belonged to genera, of which >50% have no known function in the system, emphasizing the need for more efforts towards elucidating the role of important members of wastewater treatment ecosystems. The MiDAS 3 taxonomic database guided an update of the MiDAS Field Guide – an online resource linking the identity of microorganisms in wastewater treatment systems to available data related to their functional importance. The new field guide contains a complete list of genera (>1,800) and species (>4,200) found in activated sludge and anaerobic digesters. The identity of the microbes is linked to functional information, where available. The website also provides the possibility to BLAST the sequences against MiDAS 3 taxonomy directly online. The MiDAS Field Guide is a collaborative platform acting as an online knowledge repository and facilitating understanding of wastewater treatment ecosystem function.
Sex differences in Variability of Brain Structure Across the Lifespan
Authors: Forde Natalie J , Jeyachandra Jerrold , Joseph Michael , Jacobs Grace R , Dickie Erin , Satterthwaite Theodore D , Shinohara Russell T , Ameis Stephanie H , Voineskos Aristotle N
Published: November 2019

Several brain disorders exhibit sex differences in onset, presentation, and prevalence. Increased understanding of the neurobiology of sex-based differences across the lifespan can provide insight into potential disease risk and protective mechanisms. We focused on sex-related differences in variability, which may be indicative of both disease vulnerability and resilience. In n=3,069 participants, from 8-95 years of age, we first analyzed the variance ratio in females vs. males of cortical surface area and global and subcortical volumes for discrete brain regions, and found widespread greater variability in males. In contrast, variance in cortical thickness was similar for males and females. Multivariate analysis that accounts for structural covariance supported variance ratio findings. Findings were present from early life and stable with age. We then examined variability among brain regions by sex. We found significant age-by-sex interactions across neuroimaging metrics, whereby in very early life males had reduced among-region variability compared to females, while in very late life this was reversed. Overall, our findings of greater regional variability but less among-region variability in males in early life may aid our understanding of sex-based risk for neurodevelopmental disorders. In contrast, our findings in late life may provide a potential sex-based risk mechanism for dementia.
Recycling of energy dissipated as heat accounts for high activity of Photosystem II
Authors: Zubik Monika , Luchowski Rafal , Kluczyk Dariusz , Grudzinski Wojciech , Maksim Magdalena , Nosalewicz Artur , Gruszecki Wieslaw I.
Published: November 2019

Photosystem II (PSII) converts light into chemical energy powering almost entire life on Earth. The primary photovoltaic reaction in the PSII reaction centre requires energy corresponding to 680 nm that is significantly higher than in the case of the low-energy states in the antenna complexes involved in the harvesting of excitations driving PSII. Here we show that despite seemingly insufficient energy, the low-energy excited states can power PSII thanks to the activity of the thermally-driven up-conversion. We demonstrate the operation of this mechanism both in intact leaves and in isolated pigment-protein complex LHCII. A mechanism is proposed, according to which the effective utilization of thermal energy in the photosynthetic apparatus is possible owing to the formation of LHCII supramolecular structures, leading to the coupled energy levels, corresponding to approx. 680 nm and 700 nm, capable of exchanging excitation energy through the spontaneous relaxation and the thermal up-conversion.

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Vortex fluidics-mediated DNA rescue from formalin-fixed museum specimens
Authors: Totoiu Christian A. , Phillips Jessica M. , Reese Aspen T. , Majumdar Sudipta , Girguis Peter R. , Raston Colin L. , Weiss Gregory A.
Published: November 2019

DNA from formalin-preserved tissue could unlock a vast repository of genetic information stored in museums worldwide. However, formaldehyde crosslinks proteins and DNA, and prevents ready amplification and DNA sequencing. Formaldehyde acylation also fragments the DNA. Treatment with proteinase K proteolyzes crosslinked proteins to rescue the DNA, though the process is quite slow. To reduce processing time and improve rescue efficiency, we applied the mechanical energy of a vortex fluidic device (VFD) to drive the catalytic activity of proteinase K and recover DNA from American lobster tissue (Homarus americanus) fixed in 3.7% formalin for >1-year. A scan of VFD rotational speeds identified the optimal rotational speed for recovery of PCR-amplifiable DNA and while 500+ base pairs were sequenced, shorter read lengths were more consistently obtained. This VFD-based method also effectively recovered DNA from formalin-preserved samples. The results provide a roadmap for exploring DNA from millions of historical and even extinct species.
Microtubule Nucleation Promoters Mto1 and Mto2 Regulate Cytokinesis in Fission Yeast
Authors: Dundon Samantha E. R. , Pollard Thomas D.
Published: November 2019

Microtubules of the mitotic spindle direct cytokinesis in metazoans but this has not been documented in fungi. We report evidence that astral microtubules help coordinate cytokinetic furrow formation in fission yeast. The temperature-sensitivecps1-191strain (Liu et al., 1999) with a D277N substitution in β-glucan synthase 1 (Cps1/Bgs1) was reported to arrest with an unconstricted contractile ring. We discovered that contractile rings incps1-191cells do constrict slowly and that an S338N mutation in themto2gene is required with thebgs1D277Nmutation to reproduce thecps1-191phenotype. Complexes of Mto2 and Mto1 with γ-tubulin regulate microtubule assembly. Deletion of Mto1 along with thebgs1D277Nmutation also gives thecps1-191phenotype, which is not observed inmto2S338Normto1Δcells expressingbgs1+. Bothmto2S338Nandmto1Δcells nucleate fewer astral microtubules than normal and have higher levels of Rho1-GTP at the division site than wild-type cells. We report multiple conditions that sensitizemto1Δandmto2S338Ncells to furrow ingression phenotypes.

Dundon and Pollard show that compromising the Mto1 or Mto2 regulators of the fission yeast γ-tubulin complex reduces or eliminates astral microtubules, exaggerates the effects of a D277N substitution in β-glucan synthase 1 (Cps1/Bgs1) on the rate of cytokinetic furrow formation, and increases Rho1-GTP at the cleavage site.