bluuebunny/crossref_metadata_2025 huggingface dataset:
SPARC regulation of PMN clearance protects from pristane induced lupus and rheumatoid arthritis
Authors: Sangaletti Sabina , Botti Laura , Gulino Alessandro , Lecis Daniele , Bassani Barbara , Portararo Paola , Milani Matteo , De Cecco Loris , Dugo Matteo , Tripodo Claudio , Colombo Mario P.
Published: August 2020

One step along the pathogenesis of Systemic lupus erythematosus (SLE) is associated with polymorphonuclear leukocyte (PMN) death and their ineffective removal by M2-macrophages. The secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein with unexpected immunosuppressive function in M2-macrophages and myeloid cells. To investigate the role of SPARC in autoimmunity, we adopted a pristane–induced model of lupus in mice, which recapitulates clinical manifestations of human SLE.Sparc-/-mice developed earlier and more severe renal disease, lung and liver parenchymal damage than the WT counterpart. Most prominently,Sparc-/-mice had anticipated and severe occurrence of arthritis. An intermediate phenotype was obtained inSparc+/-hemizygous mice, a result that suggestsSparcgene-dosage as relevant in autoimmune-related events. Mechanistically, a defectiveSparcexpression in PMN blocks their clearance by macrophages, through a defective delivery of eat-me and don’t eat-me signals.Sparc-/-PMN that escape macrophage scavenging becomes a source of autoantigens for dendritic cell (DC) presentation and a direct stimulus for IL-17 expression in γδ-T-cells. Gene profile analysis of synovial biopsies of knees affected by SLE-associated arthritis showed an inverse correlation between SPARC and key autoimmune genes. These results point to SPARC down-regulation as a key event characterizing SLE and associated rheumatoid arthritis pathogenesis.
Heterotrophic flagellates and centrohelid heliozoans from marine waters of Curacao, the Netherlands Antilles
Authors: Prokina Kristina I. , Keeling Patrick J. , Tikhonenkov Denis V.
Published: August 2020

Recent progress in understanding the early evolution of eukaryotes was tied to morphological identification of flagellates and heliozoans in the natural samples, isolation of their cultures and genomic and ultrastructural investigations. These protists are the smallest and least studied microbial eukaryotes but play an important role in functioning of microbial food webs. Using light and electron microscopy, we have studied the diversity of heterotrophic flagellates and centrohelid heliozoans from marine waters of Curacao (The Netherlands Antilles), and provide micrographs and morphological descriptions of observed species. Among 86 flagellates and 3 centrohelids encountered in this survey, five heterotrophic flagellates and one Centrohelid heliozoan were not identified even to the genus. Some flagellate protists have a unique morphology, and may represent undescribed lineages of eukaryotes of high taxonomic rank. The vast majority (89%) of identified flagellates are characterized by wide geographical distribution and had been reported previously from all hemispheres and various climatic regions. More than half of the species were previously observed not only from marine, but also from freshwater habitats. The parameters of the species accumulation curve indicate that our species list obtained for the Curacao study sites is far from complete, and each new sample should yield new species.
Identification of limb-specificLmx1bauto-regulatory modules with Nail-Patella Syndrome pathogenicity
Authors: Haro Endika , Petit Florence , Pira Charmaine U. , Spady Conor D. , Ivey Lauren A. , Gray Austin L. , Escande Fabienne , Jourdain Anne-Sophie , Nguyen Andy , Fellmann Florence , Good Jean-Marc , Francannet Christine , Manouvrier-Hanu Sylvie , Ros Marian A. , Oberg Kerby C.
Published: August 2020

LMX1Bhaploinsufficiency causes Nail-patella syndrome (NPS; MIM 161200), characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma. Accordingly, in miceLmx1bhas been shown to play crucial roles in the development of the limb, kidney and eye. Although one functional allele of murineLmx1bappears adequate for development,Lmx1bnull mice display ventral-ventral distal limbs with abnormal kidney, eye and cerebellar development, more disruptive, but fully concordant with NPS. Interestingly, inLmx1bfunctional knockouts (KOs),Lmx1btranscription in the limb is decreased nearly 6-fold indicating autoregulation. Herein, we report on two conservedLmx1b-associatedcis-regulatorymodules (LARM1andLARM2)that are bound by Lmx1b, amplifyLmx1bexpression in the limb and are necessary for Lmx1b-mediated limb dorsalization. Remarkably, we also report on two NPS patient families with normalLMX1Bcoding sequence, but loss-of-function variations in theLARM1/2region, stressing the role of regulatory modules in disease pathogenesis.
Genome-wide analysis of DNA replication and DNA double strand breaks by TrAEL-seq
Authors: Kara Neesha , Krueger Felix , Rugg-Gunn Peter , Houseley Jonathan
Published: August 2020

Understanding the distribution of sites at which replication forks stall, and the ensuing fork processing events, requires genome-wide methods sensitive to both changes in replication fork structure and the formation of recombinogenic DNA ends. Here we describeTransferase-ActivatedEndLigationsequencing (TrAEL-seq), a method that captures single stranded DNA 3’ ends genome-wide and with base pair resolution. TrAEL-seq labels DNA breaks, and profiles both stalled and processive replication forks in yeast and mammalian cells. Replication forks stalling at defined barriers and expressed genes are detected by TrAEL-seq with exceptional signal-to-noise, most likely through labelling of DNA 3’ ends exposed during fork reversal. TrAEL-seq also labels unperturbed processive replication forks to yield maps of replication fork direction similar to those obtained by Okazaki fragment sequencing, however TrAEL-seq is performed on asynchronous populations of wild-type cells without incorporation of labels, cell sorting, or biochemical purification of replication intermediates, rendering TrAEL-seq simpler and more widely applicable than existing replication fork direction profiling methods. The specificity of TrAEL-seq for DNA 3’ ends also allows accurate detection of double strand break sites after the initiation of DNA end resection, which we demonstrate by genome-wide mapping of meiotic double strand break hotspots in admc1Δ mutant. Overall, TrAEL-seq provides a flexible and robust methodology with high sensitivity and resolution for studying DNA replication and repair, which will be of significant use in determining mechanisms of genome instability.
Gut microbial communities associated with phenotypically divergent populations of the striped stem borerChilo suppressalis
Authors: Zhong Haiying , Chen Jianming , Zhang Juefeng , Li Fang
Published: August 2020

Chilo suppressalisis a serious stem borer of rice and water-oat, however, little is known about the effect of diet and gut compartments on the gut microbial communities of this species. We analyzed the microbial communities in phenotypically divergent populations ofC. suppressalis. In original and cross-rearing populations, the most dominant phyla were Proteobacteria (16.0% to 96.4%) and Firmicutes (2.3% to 78.9%); the most abundant family were Enterobacteriaceae (8.0% to 78%), followed by Enterococcaceae (1.7% to 64.2%) and Halomonadaceae (0.3% to 69.8%). The genera distribution showed great differences due to diet types and gut compartments. The fewest microbial species were shared by original populations, whereas the highest bacteria diversity was found for midgut of rice population feeding on water-oat. The bacterial communities in the midgut were more diverse than those in the hindgut. A comparison among phenotypically divergent populations ofC. suppressalisshows that gut microbial communities vary with diet types and gut compartment.
A comparison of non-magnetic and magnetic beads for measuring IgG antibodies againstP. vivaxantigens in a multiplexed bead-based assay using Luminex®technology (Bio-Plex®200 or MAGPIX®)
Authors: Mazhari Ramin , Brewster Jessica , Fong Rich , Bourke Caitlin , Liu Zoe SJ , Takashima Eizo , Tsuboi Takafumi , Tham Wai-Hong , Harbers Matthias , Chitnis Chetan , Healer Julie , Ome-Kaius Maria , Sattabongkot Jetsumon , Kazura James , Robinson Leanne J. , King Christopher , Mueller Ivo , Longley Rhea J.
Published: August 2020

Multiplexed bead-based assays that use Luminex xMAP®technology have become popular for measuring antibodies against proteins of interest in many fields, including malaria and more recently SARS-CoV-2/COVID-19. There are currently two formats that are widely used: non-magnetic beads or magnetic beads. Data is lacking regarding the comparability of results obtained using these two types of beads, and for assays run on different instruments. Whilst non-magnetic beads can only be run on flow-based instruments (such as the Luminex®100/200™ or Bio-Plex®200), magnetic beads can be run on both these and the newer MAGPIX®instruments. In this study we utilized a panel of purified recombinantPlasmodium vivaxproteins and samples from malaria-endemic areas to measureP. vivax-specific IgG responses using different combinations of beads and instruments. We directly compared: i) non-magnetic versus magnetic beads run on a Bio-Plex®200, ii) magnetic beads run on the Bio-Plex®200 versus MAGPIX®and iii) non-magnetic beads run on a Bio-Plex®200 versus magnetic beads run on the MAGPIX®. We also performed an external validation of our optimized assay. We observed that IgG antibody responses, measured against our panel ofP. vivaxproteins, were strongly correlated in all three of our comparisons, however higher amounts of protein were required for coupling to magnetic beads. Our external validation indicated that results generated in different laboratories using the same coupled beads are also highly comparable, particularly if a reference standard curve is used.
CoRhythMo: A Computational Framework for Modeling Biobehavioral Rhythms from Mobile and Wearable Data Streams
Authors: Yan Runze , Liu Xinwen , Dutcher Janine M , Tumminia Michael J , Villalba Daniella , Cohen Sheldon , Creswell David , Creswell Kasey , Mankoff Jennifer , Dey Anind K , Doryab Afsaneh
Published: August 2020

This paper presents CoRhythMo, the first computational framework for modeling biobehavioral rhythms - the repeating cycles of physiological, psychological, social, and environmental events - from mobile and wearable data streams. The framework incorporates four main components: mobile data processing, rhythm discovery, rhythm modeling, and machine learning. We use a dataset of smartphone and Fitbit data collected from 138 college students over a semester to evaluate the framework’s ability to 1) model biobehavioral rhythms of students, 2) measure the stability of their rhythms over the course of the semester, 3) model differences between rhythms of students with different health status, and 4) predict the mental health status in students using the model of their biobehavioral rhythms. Our evaluation provides evidence for the feasibility of using CoRhythMo for modeling and discovering human rhythms and using them to assess and predict different life and health outcomes.
Scanned optogenetic control of mammalian somatosensory input to map input-specific behavioral outputs
Authors: Schorscher-Petcu Ara , Takács Flóra , Browne Liam E.
Published: August 2020

Somatosensory stimuli guide and shape behavior, from immediate protective reflexes to longer-term learning and high-order processes related to pain and touch. However, somatosensory inputs are challenging to control in awake mammals due to the diversity and nature of contact stimuli. Application of cutaneous stimuli is currently limited to relatively imprecise methods as well as subjective behavioral measures. The strategy we present here overcomes these difficulties by achieving spatiotemporally precise, remote and dynamic optogenetic stimulation of skin by projecting light to a small defined area in freely-behaving mice. We mapped behavioral responses to specific nociceptive inputs and revealed a sparse code for stimulus intensity: using the first action potential, the number of activated nociceptors governs the timing and magnitude of rapid protective pain-related behavior. The strategy can be used to define specific behavioral repertoires, examine the timing and nature of reflexes, and dissect sensory, motor, cognitive and motivational processes guiding behavior.
The record of Deinotheriidae from the Miocene of the Swiss Jura Mountains (Jura Canton, Switzerland)
Authors: Gagliardi Fanny , Maridet Olivier , Becker Damien
Published: August 2020

The Miocene sands of the Swiss Jura Mountains, long exploited in quarries for the construction industry, have yielded abundant fossil remains of large mammals. Among Deinotheriidae (Proboscidea), two species,Prodeinotherium bavaricumandDeinotherium giganteum, had previously been identified in the Delémont valley, but never described. A third species,Deinotherium levius, from the locality of Charmoille in Ajoie, is reported herein for the first time in Switzerland. These occurrences are dated from the middle to the late Miocene, correlating to the European Mammal biozones MN5 to MN9. The study is completed by a discussion on the palaeobiogeography of deinotheres at the European scale.
Anti-oxidant andin-vitroalpha amylase inhibitory activities of leaves and barks ofRandia dumetorum
Authors: Timalsina Deepak
Published: August 2020

The process of drug discovery and development in the world over a recent year has been increasingly shaped by the formulaic approaches and natural products, prioritized by popular pharmaceutical industries. In many countries like Nepal,Randia dumetorum(Maidal) is one of the popular alternatives for overcoming various symptoms such as acidity, food poisoning ulcers, diabetes and ulcers. It has been using by the people because of its wide range of therapeutic uses. Though, the considerable research had been conducted to reveal the biologically active compounds and its pharmacological effect, the rich constituent of this plant and its major biological perspective was yet to be studied comprehensively. Accordingly, the main focus of this study was the alpha amylase inhibition of methanolic extracts obtained from leaves and barks ofRandia dumetorumplant. The plant extracts were obtained by dissolving dried plant with 100% methanol overnight and evaporating to the dryness. The obtained plant extract was used to study mentioned biological activities. The results obtained showed that the extract obtained from leaves and barks showed antioxidant and alpha amylase inhibition activities. This research can be helpful to discover new types of therapeutics in the future.
RNA secondary structure prediction using deep learning with thermodynamic integration
Authors: Sato Kengo , Akiyama Manato , Sakakibara Yasubumi
Published: August 2020

RNA secondary structure prediction is one of the key technologies for revealing the essential roles of functional non-coding RNAs. Although machine learning-based rich-parametrized models have achieved extremely high performance in terms of prediction accuracy, the risk of overfitting for such models has been reported. In this work, we propose a new algorithm for predicting RNA secondary structures that uses deep learning with thermodynamic integration, thereby enabling robust predictions. Similar to our previous work, the folding scores, which are computed by a deep neural network, are integrated with traditional thermodynamic parameters to enable robust predictions. We also propose thermodynamic regularization for training our model without overfitting it to the training data. Our algorithm (MXfold2) achieved the most robust and accurate predictions in computational experiments designed for newly discovered non-coding RNAs, with significant 2–10 % improvements over our previous algorithm (MXfold) and standard algorithms for predicting RNA secondary structures in terms ofF-value.
A Broadly Neutralizing Macaque Monoclonal Antibody Against the HIV-1 V3-Glycan Patch
Authors: Wang Zijun , Barnes Christopher O. , Gautam Rajeev , Lorenzi Julio C. C. , Mayer Christian T. , Oliveira Thiago Y. , Ramos Victor , Cipolla Melissa , Gordon Kristie M. , Gristick Harry B. , West Anthony P. , Nishimura Yoshiaki , Raina Henna , Seaman Michael S. , Gazumyan Anna , Martin Malcolm A. , Bjorkman Pamela J. , Escolano Amelia , Nussenzweig Michel C.
Published: August 2020

A small fraction of HIV-1 infected humans develop potent broadly neutralizing antibodies (bNAbs) against HIV-1 that can protect macaques from infection with simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a small number of macaques infected with SHIVs also develop broadly neutralizing serologic activity, but less is known about the nature of these simian antibodies. Here we report on a monoclonal antibody, Ab1485, isolated from a macaque infected with SHIVAD8that developed broadly neutralizing serologic activity mapping to the V3-glycan region of HIV-1 Env. Ab1485 neutralizes 38.1 % of HIV-1 isolates in a panel of 42 pseudoviruses with a geometric mean IC50of 0.055 μg/ml and SHIVAD8with an IC50of 0.028 μg/ml. Ab1485 binds to the V3-glycan epitope in a glycan-dependent manner as determined by ELISA and neutralization assays with JRCSF mutant viruses. A 3.5 Å cryo-electron microscopy structure of Ab1485 in complex with a native-like SOSIP Env trimer showed conserved contacts with the N332gp120glycan and gp120 GDIR peptide motif, but in a distinct Env-binding orientation relative to human V3/N332gp120glycan-targeting bNAbs. Finally, intravenous infusion of Ab1485 protected macaques from a high dose intrarectal challenge with SHIVAD8. We conclude that macaques can develop bNAbs against the V3-glycan patch that resemble human V3-glycan bNAbs.

Significance statement

Rhesus macaques infected with SHIV are an important model for evaluating HIV-1 prevention and therapy strategies and can also be used to evaluate humoral immune responses to candidate HIV-1 vaccines, but whether macaques produce human-like bNAbs has not been evaluated. Like HIV-1 infected humans, 10-20% of the SHIVAD8challenged macaques develop low levels of neutralizing antibodies, and only one macaque has developed broad and potent serologic neutralizing activity. We have examined the antibody response of this macaque (CE8J) and we report on the cloning and molecular characterization of a bNAb produced in this elite neutralizing non-human primate, its structure bound to an HIV-1 Env trimer, and the implications for development of vaccines targeting the V3-glycan patch of Env.
ViruSurf: an integrated database to investigate viral sequences
Authors: Canakoglu Arif , Pinoli Pietro , Bernasconi Anna , Alfonsi Tommaso , Melidis Damianos P. , Ceri Stefano
Published: August 2020

ViruSurf, available athttp://gmql.eu/virusurf/, is a large public database of viral sequences and integrated and curated metadata from heterogeneous sources (GenBank, COG-UK and NMDC); it also exposes computed nucleotide and amino acid variants, called from original sequences. A GISAID-specific ViruSurf database, available athttp://gmql.eu/virusurf_gisaid/, offers a subset of these functionalities. Given the current pandemic outbreak, SARS-CoV-2 data are collected from the four sources; but ViruSurf contains other virus species harmful to humans, including SARS-CoV, MERS-CoV, Ebola, and Dengue.

The database is centered on sequences, described from their biological, technological, and organizational dimensions. In addition, the analytical dimension characterizes the sequence in terms of its annotations and variants. The web interface enables expressing complex search queries in a simple way; arbitrary search queries can freely combine conditions on attributes from the four dimensions, extracting the resulting sequences.

Several example queries on the database confirm and possibly improve results from recent research papers; results can be recomputed over time and upon selected populations. Effective search over large and curated sequence data may enable faster responses to future threats that could arise from new viruses.
Characterizing and controlling nanoscale self-assembly of suckerin-12
Authors: Hershewe Jasmine M. , Wiseman William D. , Kath James E. , Buck Chelsea C. , Gupta Maneesh K. , Dennis Patrick B. , Naik Rajesh R. , Jewett Michael C.
Published: August 2020

Structural proteins such as the “suckerins” present promising avenues for fabricating functional materials. Suckerins are a family of naturally occurring block copolymer-type proteins that comprise the sucker ring teeth of cephalopods and are known to self-assemble into supramolecular networks of nanoconfinedβ-sheets. Here, we report characterization and controllable, nanoscale self-assembly of suckerin-12 (S12). We characterize impacts of salt, pH, and protein concentration on S12 solubility, secondary structure, and self-assembly. In doing so, we identify conditions for fabricating ~100 nm nanoassemblies (NAs) with narrow size distributions. Finally, by installing a non-canonical amino acid (ncAA) into S12, we demonstrate the assembly of NAs that are covalently conjugated with a hydrophobic fluorophore, and the ability to change self-assembly andβ-sheet content by PEGylation. This work presents new insights into the biochemistry of suckerin-12 and demonstrates how ncAAs can be used to expedite and fine-tune the design of protein materials.
Reconciling functional differences in populations of neurons recorded with two-photon imaging and electrophysiology
Authors: Siegle Joshua H. , Ledochowitsch Peter , Jia Xiaoxuan , Millman Daniel , Ocker Gabriel K. , Caldejon Shiella , Casal Linzy , Cho Andrew , Denman Daniel J. , Durand Séverine , Groblewski Peter A. , Heller Greggory , Kato India , Kivikas Sara , Lecoq Jerome , Nayan Chelsea , Ngo Kiet , Nicovich Philip R. , North Kat R. , Ramirez Tamina K. , Swapp Jackie , Waughman Xana , Williford Ali , Olsen Shawn R. , Koch Christof , Buice Michael A. , de Vries Saskia E. J.
Published: August 2020

Extracellular electrophysiology and two-photon calcium imaging are widely used methods for measuring physiological activity with single-cell resolution across large populations of neurons in the brain. While these two modalities have distinct advantages and disadvantages, neither provides complete, unbiased information about the underlying neural population. Here, we compare evoked responses in visual cortex recorded in awake mice under highly standardized conditions using either imaging or electrophysiology. Across all stimulus conditions tested, we observe a larger fraction of responsive neurons in electrophysiology and higher stimulus selectivity in calcium imaging. This work explores which data transformations are most useful for explaining these modality-specific discrepancies. We show that the higher selectivity in imaging can be partially reconciled by applying a spikes-to-calcium forward model to the electrophysiology data. However, the forward model could not reconcile differences in responsiveness without sub-selecting neurons based on event rate or level of signal contamination. This suggests that differences in responsiveness more likely reflect neuronal sampling bias or cluster-merging artifacts during spike sorting of electrophysiological recordings, rather than flaws in event detection from fluorescence time series. This work establishes the dominant impacts of the two modalities’ respective biases on a set of functional metrics that are fundamental for characterizing sensory-evoked responses.
An RNA-centric global view ofClostridioides difficilereveals broad activity of Hfq in a clinically important Gram-positive bacterium
Authors: Fuchs Manuela , Lamm-Schmidt Vanessa , Ponath Falk , Jenniches Laura , Barquist Lars , Vogel Jörg , Faber Franziska
Published: August 2020

The Gram-positive human pathogenClostridioides difficilehas emerged as the leading cause of antibiotic-associated diarrhea. Despite growing evidence for a role of Hfq in RNA-based gene regulation inC. difficile, little is known about the bacterium’s transcriptome architecture and mechanisms of post-transcriptional control. Here, we have applied a suite of RNA-centric techniques, including transcription start site mapping, transcription termination mapping and Hfq RIP-seq, to generate a single-nucleotide resolution RNA map ofC. difficile630. Our transcriptome annotation provides information about 5’ and 3’ untranslated regions, operon structures and non-coding regulators, including 42 sRNAs. These transcriptome data are accessible via an open-access browser called ‘Clost-Base’. Our results indicate functionality of many conserved riboswitches and predict novelcis-regulatory elements upstream of MDR-type ABC transporters and transcriptional regulators. Recent studies have revealed a role of sRNA-based regulation in several Gram-positive bacteria but their involvement with the RNA-binding protein Hfq remains controversial. Here, sequencing the RNA ligands of Hfq revealsin vivoassociation of many sRNAs along with hundreds of potential target mRNAs inC. difficileproviding evidence for a global role of Hfq in post-transcriptional regulation in a Gram-positive bacterium. Through integration of Hfq-bound transcripts and computational approaches we predict regulated target mRNAs for the novel sRNA AtcS encoding several adhesins and the conserved oligopeptide transporteroppBthat influences sporulation initiation inC. difficile. Overall, these findings provide a potential mechanistic explanation for increased biofilm formation and sporulation in anhfqdeletion strain and lay the foundation for understanding clostridial ribo regulation with implications for the infection process.
The intrinsically disordered protein SPE-18 promotes localized assembly of the major sperm protein inC. elegansspermatocytes
Authors: Price Kari L. , Presler Marc , Uyehara Christopher M. , Shakes Diane C.
Published: August 2020

Many specialized cells use unconventional strategies of cytoskeletal control. Nematode spermatocytes discard their actin and tubulin following meiosis, and instead employ the regulated assembly/disassembly of the Major Sperm Protein (MSP) to drive sperm motility. However prior to the meiotic divisions, MSP is effectively sequestered as it exclusively assembles into paracrystalline structures called fibrous bodies (FBs). The accessory proteins that direct this sequestration process have remained mysterious. This study reveals SPE-18 as an intrinsically disordered protein that that is essential for MSP assembly within FBs. Inspe-18mutant spermatocytes, MSP remains cytosolic, and the cells arrest in meiosis. In wildtype spermatocytes, SPE-18 localizes to pre-FB complexes and functions with the kinase SPE-6 to recruit MSP. Changing patterns of SPE-18 localization revealed unappreciated complexities in FB maturation. Later, within newly individualized spermatids, SPE −18 is rapidly lost, yet SPE-18 loss alone is insufficient for MSP disassembly. Our findings reveal an alternative strategy for sequestering cytoskeletal elements, not as monomers but in localized, bundled polymers. Additionally, these studies provide an important example of disordered proteins promoting ordered cellular structures.

Summary Statement

Intrinsically disordered proteins are increasingly recognized as key regulators of localized cytoskeletal assembly. Expanding that paradigm, SPE-18 localizes MSP assembly withinC. elegansspermatocytes.
BRAKER2: Automatic Eukaryotic Genome Annotation with GeneMark-EP+ and AUGUSTUS Supported by a Protein Database
Authors: Brůna Tomáš , Hoff Katharina J. , Lomsadze Alexandre , Stanke Mario , Borodovsky Mark
Published: August 2020

Full automation of gene prediction has become an important bioinformatics task since the advent of next generation sequencing. The eukaryotic genome annotation pipeline BRAKER1 had combined self-training GeneMark-ET with AUGUSTUS to generate genes’ coordinates with support of transcriptomic data. Here, we introduce BRAKER2, a pipeline with GeneMark-EP+ and AUGUSTUS externally supported by cross-species protein sequences aligned to the genome. Among the challenges addressed in the development of the new pipeline was generation of reliable hints to the locations of protein-coding exon boundaries from likely homologous but evolutionarily distant proteins. Under equal conditions, the gene prediction accuracy of BRAKER2 was shown to be higher than the one of MAKER2, yet another genome annotation pipeline. Also, in comparison with BRAKER1 supported by a large volume of transcript data, BRAKER2 could produce a better gene prediction accuracy if the evolutionary distances to the reference species in the protein database were rather small. All over, our tests demonstrated that fully automatic BRAKER2 is a fast and accurate method for structural annotation of novel eukaryotic genomes.
AlphaSimR: An R-package for Breeding Program Simulations
Authors: Gaynor R. Chris , Gorjanc Gregor , Hickey John M.
Published: August 2020

This paper introduces AlphaSimR, an R package for stochastic simulations of plant and animal breeding programs. AlphaSimR is a highly flexible software package able to simulate a wide range of plant and animal breeding programs for diploid and autopolyploid species. AlphaSimR is ideal for testing the overall strategy and detailed design of breeding programs. AlphaSimR utilizes a scripting approach to building simulations that is particularly well suited for modeling highly complex breeding programs, such as commercial breeding programs. The primary benefit of this scripting approach is that it frees users from preset breeding program designs and allows them to model nearly any breeding program design. This paper lists the main features of AlphaSimR and provides a brief example simulation to show how to use the software.
Perceptual difficulty modulates the direction of information flow in familiar face recognition
Authors: Karimi-Rouzbahani Hamid , Ramezani Farzad , Woolgar Alexandra , Rich Anina , Ghodrati Masoud
Published: August 2020

Humans are fast and accurate when they recognize familiar faces. Previous neurophysiological studies have shown enhanced representations for the dichotomy of familiar vs. unfamiliar faces. As familiarity is a spectrum, however, any neural correlate should reflect graded representations for more vs. less familiar faces along the spectrum. By systematically varying familiarity across stimuli, we show a neural familiarity spectrum using electroencephalography. We then evaluated the spatiotemporal dynamics of familiar face recognition across the brain. Specifically, we developed a novel informational connectivity method to test whether peri-frontal brain areas contribute to familiar face recognition. Results showed that feed-forward flow dominates for the most familiar faces and top-down flow was only dominant when sensory evidence was insufficient to support face recognition. These results demonstrate that perceptual difficulty and the level of familiarity influence the neural representation of familiar faces and the degree to which peri-frontal neural networks contribute to familiar face recognition.
Uncovering the geometry of color space with magnetoencephalography (MEG)
Authors: Rosenthal Isabelle , Singh Shridhar , Hermann Katherine , Pantazis Dimitrios , Conway Bevil R.
Published: August 2020

The geometry that describes the relationship among colors is unsettled despite centuries of study. Here we present a new approach, using multivariate analyses of direct measurements of brain activity obtained with magnetoencephalography to reverse-engineer the geometry of the neural representation of color space. The analyses depend upon determining similarity relationships among the neural responses to different colors and assessing how these relationships change in time. To evaluate the approach, we relate patterns of neural activity to universal patterns in color naming. Control experiments showed that responses to color words could not decode activity elicited by color stimuli. The results suggest that three patterns of color naming can be accounted for by decoding the similarity relationships in the neural representation of color: the association of warm colors such as reds and oranges with “light” and cool colors such as blues and greens with “dark”; the greater precision among all languages in naming warm colors compared to cool colors; and the preeminence of red.
Dietary propionate induces intestinal oxidative stress via inhibition of SIRT3-mediated SOD2 depropionylation
Authors: Ding Qian-wen , Zhang Zhen , Li Yu , Liu Hong-liang , Hao Qiang , Yang Ya-lin , Ringø Einar , Olsen Rolf Erik , Clarke Jihong Liu , Ran Chao , Zhou Zhi-gang
Published: August 2020

Propionate is a commonly used preservative in various food and feedstuffs and has been regarded as a food additive without safety concerns. However, we observed that dietary propionate supplementation induced intestinal damage in the context of high fat diet (HFD) in zebrafish. The intestinal damage was attributable to oxidative stress owing to impaired antioxidant capacity, which was caused by compromised SOD2 activity in the intestine. Global lysine propionylation analysis of the intestinal samples showed that SOD2 was propionylated at K132, and further biochemical assays demonstrated that K132 propionylation suppressed SOD2 activity. In addition, SIRT3 could directly interact with SOD2 and played an important role in regulating SOD2 activity via modulating depropionylation, and the enhanced SOD2 propionylation in zebrafish fed high fat plus propionate diet was attributable to reduced SIRT3 expression. Finally, we reveal that intestinal oxidative stress resulting from SOD2 propionylation contributed to the compositional change of gut microbiota, which further deteriorated intestinal oxidative stress independent of SIRT3. Collectively, the results in this study reveal a link between protein propionylation and intestine health, and suggest potential risk of a widely used food preservative in HFD context.
Naturally acquired immunity among Kenyan adults suppresses the West African P. falciparum NF54 strain in controlled human malaria infection (CHMI)
Authors: Kapulu Melissa C , Njuguna Patricia , Hamaluba Mainga , Kimani Domtila , Ngoi Joyce M. , Musembi Janet , Ngoto Omar , Otieno Edward , Billingsley Peter F ,   CHMI-SIKA Study Team
Published: August 2020

We used controlled human malaria infection (CHMI) to study naturally acquired immunity of Kenyan adults. We administered 3.2×103 cryopreserved Plasmodium falciparum sporozoites (SPZ, NF54 West African strain) and undertook clinical monitoring and serial quantitative PCR (qPCR). Of the 142 volunteers who were eligible for analysis: 26 (18.3%) had febrile symptoms and were treated; 30 (21.1%) reached ≥500 parasites/μl and were treated; 53 (37.3%) had parasitaemia without meeting thresholds for treatment and; 33 (23.2%) remained qPCR negative. We find that the immunity acquired by some Kenyan adults can completely suppress in vivo growth of a parasite strain originating from outside Kenya.
Proteomics reveals synergy in biomass conversion between fungal enzymes and inorganic Fenton chemistry in leaf-cutting ant colonies
Authors: Schiøtt Morten , Boomsma Jacobus J.
Published: August 2020

The herbivorous symbiosis between leaf-cutting ants and fungal cultivars processes biomass via ant fecal fluid mixed with munched plant substrate before fungal degradation. Here we present a full proteome of the fecal fluid ofAcromyrmexleaf-cutting ants, showing that most proteins function as biomass degrading enzymes and that ca. 80% are produced by the fungal cultivar and ingested, but not digested, by the ants. Hydrogen peroxide producing oxidoreductases were remarkably common in the fecal proteome, inspiring us to test a scenario in which hydrogen peroxide reacts with iron in the fecal fluid to form reactive oxygen radicals after which oxidized iron is reduced by other fecal-fluid enzymes. Our biochemical assays confirmed that these cyclical Fenton reactions do indeed take place in special substrate pellets, presumably to degrade recalcitrant lignocellulose. This implies that the symbiosis manages a combination of chemical and enzymatic degradation, an achievement that surpasses current human bioconversion technology.
Genetic-substructure and complex demographic history of South African Bantu speakers
Authors: Sengupta Dhriti , Choudhury Ananyo , Fortes-Lima Cesar , Aron Shaun , Whitelaw Gavin , Bostoen Koen , Gunnink Hilde , Chousou-Polydouri Natalia , Delius Peter , Tollman Stephen , Casas F Gomez-Olive , Norris Shane , Mashinya Felistas , Alberts Marianne , Hazelhurst Scott , Schlebusch Carina M. , Ramsay Michèle ,   as members and collaborators of AWI-Gen and the H3Africa Consortium
Published: August 2020

South Eastern Bantu-speaking (SEB) groups constitute more than 80% of the population in South Africa. Despite clear linguistic and geographic diversity, the genetic differences between these groups have not been systematically investigated. Based on genome-wide data of over 5000 individuals, representing eight major SEB groups, we provide strong evidence for fine-scale population structure that broadly aligns with geographic distribution and is also congruent with linguistic phylogeny (separation of Nguni, Sotho-Tswana and Tsonga speakers). Although differential Khoe-San admixture plays a key role, the structure persists after Khoe-San ancestry-masking. The timing of admixture, levels of sex-biased gene flow and population size dynamics also highlight differences in the demographic histories of individual groups. The comparisons with five Iron Age farmer genomes further support genetic continuity over ∼400 years in certain regions of the country. Simulated trait genome-wide association studies further show that the observed population structure could have major implications for biomedical genomics research in South Africa.
Mapping multicellular programs from single-cell profiles
Authors: Jerby-Arnon Livnat , Regev Aviv
Published: August 2020

Tissue homeostasis relies on orchestrated multicellular circuits, where interactions between different cell types dynamically balance tissue function. While single-cell genomics identifies tissues’ cellular components, deciphering their coordinated action remains a major challenge. Here, we tackle this problem through a new framework of multicellular programs: combinations of distinct cellular programs in different cell types that are coordinatedtogetherin the tissue, thus forming a higher order functional unit at the tissue, rather than only cell, level. We develop the open-access DIALOGUE algorithm to systematically uncover such multi-cellular programs not only from spatial data, but even from tissue dissociated and profiled as single cells,e.g., by single-cell RNA-Seq. Tested on spatial transcriptomes from the mouse hypothalamus, DIALOGUE recovered spatial information, predicted the properties of a cell’s environment only based on its transcriptome, and identified multicellular programs that mark animal behavior. Applied to brain samples and colon biopsies profiled by scRNA-Seq, DIALOGUE identified multicellular configurations that mark Alzheimer’s disease and ulcerative colitis (UC), including a program spanning five cell types that is predictive of response to anti-TNF therapy in UC patients and enriched for UC risk genes from GWAS, each acting in different cell types, but all cells acting in concert. Taken together, our study provides a novel conceptual and methodological framework to unravel multicellular regulation in health and disease.
Synthesis and crystal structures of manganese(I) carbonyl complexes bearing ester-substituted α-diimine ligands
Authors: Kanno Takatoshi , Takase Tsugiko , Oyama Dai
Published: August 2020

The crystal structures of two manganese(I) complexes with ester-substituted bipyridine or biquinoline supporting ligands are reported, namely, fac-bromidotricarbonyl(diethyl 2,2′-bipyridine-4,4′-dicarboxylate-κ2
N,N′)manganese(I), [MnBr(C16H16N2O4)(CO)3], I, and fac-bromidotricarbonyl(diethyl 2,2′-biquinoline-4,4′-dicarboxylate-κ2
N,N′)manganese(I), [MnBr(C24H20N2O4)(CO)3], II. In both complexes, the manganese(I) atom adopts a distorted octahedral coordination sphere defined by three carbonyl C atoms, a Br− anion and two N atoms from the chelating α-diimine ligand. Both complexes show fac configurations of the carbonyl ligands. In I, the complex molecules are linked by C—H...Br hydrogen bonds and aromatic π–π contacts. In II, intramolecular C—H...O hydrogen bonds are present as well as intermolecular C—H...O and C—H...Br hydrogen bonds and π–π interactions.
Real-time transient stability assessment using stacked auto-encoders
Authors: Azarbik Masoud , Sarlak Mostafa
Published: August 2020

Purpose

This paper aims to report how one can assess the transient stability of a power system by using stacked auto-encoders.

Design/methodology/approach

The proposed algorithm works in a power system equipped with the wide area measurement system. To be more exact, it needs pre- and post-disturbance values of frequency sent from phasor measurement units.

Findings

The authors have investigated the performance of the proposed method. Going through details, the authors have simulated many contingencies, and then have predicted the transient stability in each of which by using the proposed algorithm.

Originality/value

The results demonstrate that the algorithm is fast, and it has acceptable performance under different circumstances including the change of system topology and failures of telecommunication channels.
Quality of working life and career engagement of cancer survivors: the mediating role of effect of disease and treatment
Authors: Hamzah Siti Raba’ah , Musa Siti Nur Syuhada , Muda Zulaiha , Ismail Maimunah
Published: August 2020

Purpose

This study aims at investigating the relationship between the quality of working life and career engagement of cancer survivors and the mediating role of the effect of disease and treatment.

Design/methodology/approach

A cross-sectional study was conducted on 400 cancer survivors in Malaysia. The participants, aged between 18 and 40, were Malaysian citizens undergoing follow-up sessions at the Kuala Lumpur General Hospital and the National Cancer Institute of Malaysia. Data were analysed using descriptive statistics, Pearson’s correlation coefficient and regression analysis that implemented Baron and Kenny’s method for mediation were used for analyses.

Findings

The effect of treatment and disease was found to significantly mediate the relationship between quality of work-life and career engagement of cancer survivors.

Research limitations/implications

The instrument for this study was a self-reported questionnaire, with participants responding to specific items on a five-point Likert scale under the supervision of the researchers. As results from the survey were subjective in nature, the bias in the participants could not be eliminated completely. This study was also limited to the two main parameters, namely, quality of working life and career engagement and a mediator, namely, effects of the disease and treatment. Moreover, as the survey was conducted in only two hospitals in the Klang Valley area, the results cannot be generalized to other cancer survivors in other regions of Malaysia.

Practical implications

The results of this study indicated that the mediating role of the effects of disease and treatment on the relationship of the quality of working life subscales with career engagement. Practical implications, cancer survivor consciousness of the effects of disease and treatment is very important and should be addressed and could be notable to improve the quality of working life.

Originality/value

This study gives valuable insight to managers and practitioners by investigating the relationship between the quality of working life and career engagement and mediates by the effects of disease and treatment. The findings highlight the challenges cancer survivors face on their return to working life. The findings also highlight the need for management to take steps to help cancer survivors cope with career engagement for better work performance.
From displacement to resettlement: how current policies shape eviction narratives among urban poor in the Philippines
Authors: Collado Zaldy C. , Orozco Noella May-i G.
Published: August 2020

Purpose

This study aims to examine the experiences of urban poor relocatees in their resettlement communities, specifically those who were relocated from the Caloocan, Malabon, Navotas, Valenzuela and Quezon City areas to the province of Bulacan, Philippines. This study hopes to convey the importance of revisiting the law on socialized housing in the Philippines.

Design/methodology/approach

This study gathered qualitative data through 2 focus group discussions among 28 participants who came from 3 resettlement sites in San Jose del Monte City, Bulacan Province, Philippines. The resettlement areas are owned and managed by the National Housing Authority of the Philippine Government.

Findings

Results show that resettlement experiences are stories of survival under impoverished conditions. Lack of housing facilities or poorly built units characterize their relocation experience aside from having no immediate access to basic utilities such as electricity and water, despite a law that supposedly secures these rights to relocatees. The expensive cost of transportation and the lack of livelihood also heavily strain the lives of the relocated population.

Originality/value

This study illustrates that involuntary displacement predicts poor living conditions upon resettlement. This study is an inquiry not only of existing conditions of socialized housing in resettlement areas but also past realities of these housing communities at the onset of the displacees’ relocation.
Does information disclosure reduce stock price volatility? A comparison of Islamic and conventional banks in Gulf countries
Authors: Azrak Tawfik , Saiti Buerhan , Kutan Ali , Engku Ali Engku Rabiah Adawiah
Published: August 2020

Purpose

The purpose of this paper is to investigate whether higher disclosure levels at both Islamic and conventional banks are associated with higher stock price volatility in the member countries of the Gulf Cooperation Council (GCC).

Design/methodology/approach

To do this, the authors build a disclosure index (DI) for both types of banks and compare their transparency levels. After that, the authors evaluate the relationship between disclosure and stock price volatility for both conventional and Islamic banks (IBs) and include macro- and bank-level control factors to isolate the effect of disclosure from potentially confounding influences by employing panel data.

Findings

The author find that the significance of the DI on stock price volatility is economically negligible at both types of banks, suggesting that injecting more information into markets would raise stock price volatility only slightly and hence will not have much economically significant effect on stock price volatility in our sample countries. The authors discuss the policy implications of the findings.

Originality/value

The study fills the gap in the literature and assists in formulating appropriate regulation policies for corporate governance disclosure requirements. To the best of our knowledge, this is the first empirical study to investigate the impact of disclosure on reducing stock price volatility in the dual banking system of the GCC countries.