bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the area and the number of pulmonary alveoli through the normal aging process in CD1 mouse
Authors: Ortega-Martínez Marta , Gutiérrez-Arenas Esthefania , Gutiérrez-Dávila Vanessa , Niderhauser-García Alberto , Cerda-Flores Ricardo M. , Jaramillo-Rangel Gilberto
Published: December 2020

During the aging process, the lung exhibits structural changes accompanied by a decline in its function. The related information currently available is still scarce and contradictory. In addition, changes in some pulmonary parameters through aging process are species- and strain-dependent. The aim of this study was the assessment of the area and the number of pulmonary alveoli through the normal aging process in CD1 mouse. Paraffin-embedded sections of lungs from CD1 mice at age of 2, 6, 12, 18, or 24 months were stained with hematoxylin and eosin and examined using a light microscope. Images were captured using a camera linked to an image analysis software to measure areas and count alveoli. There was a significant difference in the alveolar area among the ages analyzed (F=87.53, Sig.=0.000). The alveolar area of the 6-, 12-, 18-, and 24-month-old mice was significantly greater (allpvalues < 0.001) than in mice at 2 months of age. Also, the alveolar number was significantly different among the ages tested (F=3.21, Sig.=0.023). The number of alveoli in mice at 2 months of age was greater than in mice at all other age groups, reaching statistical significance when compared with the 6-, 12-, and 18-month-old mice (pvalues of 0.044, 0.014, and 0.002, respectively). Thus, we observed an increase in alveolar area and a decrease in alveolar number through the aging process. This information might be useful to understand pathologic changes underlying susceptibility of elderly individuals to chronic lower respiratory tract diseases.
Oligonucleotide Capture Sequencing of the SARS-CoV-2 Genome and Subgenomic Fragments from COVID-19 Individuals
Authors: Doddapaneni Harsha , Cregeen Sara Javornik , Sucgang Richard , Meng Qingchang , Qin Xiang , Avadhanula Vasanthi , Chao Hsu , Menon Vipin , Nicholson Erin , Henke David , Piedra Felipe-Andres , Rajan Anubama , Momin Zeineen , Kottapalli Kavya , Hoffman Kristi L. , Sedlazeck Fritz J. , Metcalf Ginger , Piedra Pedro A. , Muzny Donna M. , Petrosino Joseph F. , Gibbs Richard A.
Published: December 2020

The newly emerged and rapidly spreading SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). To facilitate a deeper understanding of the viral biology we developed a capture sequencing methodology to generate SARS-CoV-2 genomic and transcriptome sequences from infected patients. We utilized an oligonucleotide probe-set representing the full-length genome to obtain both genomic and transcriptome (subgenomic open reading frames [ORFs]) sequences from 45 SARS-CoV-2 clinical samples with varying viral titers. For samples with higher viral loads (cycle threshold value under 33, based on the CDC qPCR assay) complete genomes were generated. Analysis of junction reads revealed regions of differential transcriptional activity and provided evidence of expression of ORF10. Heterogeneous allelic frequencies along the 20kb ORF1ab gene suggested the presence of a defective interfering viral RNA species subpopulation in one sample. The associated workflow is straightforward, and hybridization-based capture offers an effective and scalable approach for sequencing SARS-CoV-2 from patient samples.
Ancient DNA Analysis of Archaeological Specimens Extends Chinook Salmon’s Known Historic Range to San Francisco Bay and Its Southernmost Watershed
Authors: Lanman Richard B. , Hylkema Linda , Boone Cristie M. , Allée Brian , Castillo Roger O. , Moreno Stephanie A. , Flores Mary Faith , DeSilva Upuli , Bingham Brittany , Kemp Brian M.
Published: December 2020

Understanding a species’ historic range guides contemporary management and habitat restoration. Chinook salmon (Oncorhynchus tshawytscha) are an important commercial and recreational gamefish, but nine Chinook subspecies are federally threatened or endangered due to anthropomorphic impacts. Several San Francisco Bay Area streams and rivers currently host spawning Chinook populations, but government agencies consider these non-native hatchery strays. Using ichthyofaunal analysis of 17,288 fish specimens excavated from Native American middens at Mission Santa Clara circa 1781-1834 CE, 86 salmonid vertebrae were identified. Ancient DNA sequencing identified three of these as from Chinook salmon and the remainder from steelhead trout. These findings comprise the first physical evidence of the nativity of salmon to the Guadalupe River in San Jose, California, extending their historic range to include San Francisco Bay’s southernmost watershed.

One Sentence Summary

First application of ancient DNA to extend a species’ historic range finds Chinook salmon native to San Jose, California.
Multithreaded variant calling in elPrep 5
Authors: Herzeel Charlotte , Costanza Pascal , Decap Dries , Fostier Jan , Wuyts Roel , Verachtert Wilfried
Published: December 2020

We present elPrep 5, which updates the elPrep framework for processing sequencing alignment/map files with variant calling. elPrep 5 can now execute the full pipeline described by the GATK Best Practices for variant calling, which consists of PCR and optical duplicate marking, sorting by coordinate order, base quality score recalibration, and variant calling using the haplotype caller algorithm. elPrep 5 produces identical BAM and VCF output as GATK4 while significantly reducing the runtime by parallelizing and merging the execution of the pipeline steps. Our benchmarks show that elPrep 5 speeds up the runtime of the variant calling pipeline by a factor 8-16x on both whole-exome and whole-genome data while using the same hardware resources as GATK 4. This makes elPrep 5 a suitable drop-in replacement for GATK 4 when faster execution times are needed.
Real-time Synthesis of Imagined Speech Processes from Minimally Invasive Recordings of Neural Activity
Authors: Angrick Miguel , Ottenhoff Maarten , Diener Lorenz , Ivucic Darius , Ivucic Gabriel , Goulis Sofoklis , Saal Jeremy , Colon Albert J. , Wagner Louis , Krusienski Dean J. , Kubben Pieter L. , Schultz Tanja , Herff Christian
Published: December 2020

Speech neuroprosthetics aim to provide a natural communication channel to individuals who are unable to speak due to physical or neurological impairments. Real-time synthesis of acoustic speech directly from measured neural activity could enable natural conversations and significantly improve quality of life, particularly for individuals who have severely limited means of communication. Recent advances in decoding approaches have led to high quality reconstructions of acoustic speech from invasively measured neural activity. However, most prior research utilizes data collected during open-loop experiments of articulated speech, which neglects the critical human-in-the-loop aspect of a practical speech neuroprosthetic.

Here we present an approach that synthesizes audible speech in real-time for both imagined and whispered speech conditions. Using a participant implanted with stereotactic depth electrodes, we were able to reliably generate audible speech in real-time. The decoding models rely predominately on frontal activity suggesting that speech processes have similar representations when vocalized, whispered, or imagined. Our real-time synthesis approach represents an essential step towards investigating how patients will learn to operate a closed-loop speech neuroprosthesis, as well as the development of techniques that incorporate co-adaptation of the user and system for optimized performance.
Physiological and pathological changes in the enteric nervous system of rotenone-exposed mice as early biomarkers for Parkinson’s disease
Authors: Schaffernicht Gabriela , Shang Qi , Stievenard Alicia , Bötzel Kai , Dening Yanina , Kempe Romy , Toussaint Magali , Gündel Daniel , Kranz Mathias , Reichmann Heinz , Vanbesien-Mailliot Christel , Brust Peter , Dieterich Marianne , Funk Richard H.W. , Ravens Ursula , Pan-Montojo Francisco
Published: December 2020

Parkinson’s disease (PD) is known to involve the peripheral nervous system (PNS) and the enteric nervous system (ENS). Functional changes in PNS and ENS appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients like constipation, that can precede the appearance of motor symptoms by years. We have shown that environmental toxins can trigger the disease by acting on the ENS and on the autonomic nervous system. Oral exposure to the pesticide rotenone, a mitochondrial Complex I inhibitor, leads to decreased stool depositions in mice. Here we analyzed the effect of rotenone on the function and structure of the ENS by measuring intestinal contractility in a tissue bath and by analyzing related protein expression. Our results show that rotenone changes the normal physiological response of the intestine to carbachol, dopamine and electric field stimulation. The magnitude and direction of these alterations varies between intestinal regions and exposure times and is associated with an early up-regulation of dopaminergic, cholinergic and adrenergic receptors and an irregular reduction in the amount of enteric neurons in rotenone-exposed mice. The early appearance of these alterations makes them ideal candidates to be used as biomarkers for the detection of Parkinson’s disease in its early stages.
CEDAR, an online resource for the reporting and exploration of complexome profiling data
Authors: van Strien Joeri , Haupt Alexander , Schulte Uwe , Braun Hans-Peter , Cabrera-Orefice Alfredo , Choudhary Jyoti S. , Evers Felix , Fernandez-Vizarra Erika , Guerrero-Castillo Sergio , Kooij Taco W.A. , Páleníková Petra , Pardo Mercedes , Ugalde Cristina , Wittig Ilka , Wöhlbrand Lars , Brandt Ulrich , Arnold Susanne , Huynen Martijn A.
Published: December 2020

Complexome profiling is an emerging ‘omics approach that systematically interrogates the composition of protein complexes (the complexome) of a sample, by combining biochemical separation of native protein complexes with mass-spectrometry based quantitation proteomics. The resulting fractionation profiles hold comprehensive information on the abundance and composition of the complexome, and have a high potential for reuse by experimental and computational researchers. However, the lack of a central resource that provides access to these data, reported with adequate descriptions and an analysis tool, has limited their reuse. Therefore, we established the ComplexomE profiling DAta Resource (CEDAR,www3.cmbi.umcn.nl/cedar/), an openly accessible database for depositing and exploring mass spectrometry data from complexome profiling studies. Compatibility and reusability of the data is ensured by a standardized data and reporting format containing the “minimum information required for a complexome profiling experiment” (MIACE). The data can be accessed through a user-friendly web interface, as well as programmatically using the REST API portal. Additionally, all complexome profiles available on CEDAR can be inspected directly on the website with the profile viewer tool that allows the detection of correlated profiles and inference of potential complexes. In conclusion, CEDAR is a unique, growing and invaluable resource for the study of protein complex composition and dynamics across biological systems.
NPRL3: Direct Effects on Human Phenotypic Variability, mTOR Signaling, Subcellular mTOR Localization, Cortical Lamination, and Seizure Susceptibility
Authors: Iffland Philip H. , Everett Mariah E. , Cobb-Pitstick Katherine M. , Bowser Lauren E. , Barnes Allan E. , Babus Janice K. , Romanowski Andrea , Baybis Marianna , Puffenberger Erik G. , Gonzaga-Jauregui Claudia , Poulopoulos Alexandros , Carson Vincent J. , Crino Peter B.
Published: December 2020

Nitrogen Permease Regulator Like 3(NPRL3)variants are associated with malformations of cortical development (MCD) and epilepsy. We report a large (n=133) founderNPRL3(c.349delG, p.Glu117LysFS) pedigree dating to 1727, with heterogeneous epilepsy and MCD phenotypes. Whole exome analysis in individuals with and without seizures in this cohort did not identify a genetic modifier to explain the variability in seizure phenotype. Then as a strategy to investigate the developmental effects of NPRL3 loss in human brain, we show that CRISPR/Cas9Nprl3knockout (KO) in Neuro2a cells (N2aC)in vitrocauses mechanistic target of rapamycin (mTOR) pathway hyperactivation, cell soma enlargement, and excessive cellular aggregation. Amino acid starvation caused mTOR inhibition and cytoplasmic mTOR localization in wildtype cells, whereas followingNprl3KO, mTOR remained inappropriately localized on the lysosome and activated, evidenced by persistent ribosomal S6 and 4E-BP1 phosphorylation, demonstrating thatNprl3loss decouples mTOR activation from metabolic state.Nprl3KO byin uteroelectroporation in fetal (E14) mouse cortex resulted in mTOR-dependent cortical dyslamination with ectopic neurons in subcortical white matter. EEG recordings of these mice showed hyperexcitability in the electroporated hemisphere.NPRL3variants are linked to a highly variable clinical phenotype likely as a consequence of mTOR-dependent effects on cell structure, cortical development, and network organization.
Distinct protocerebral neuropils associated with attractive and aversive female-produced odorants in the male moth brain
Authors: Kymre Jonas Hansen , Liu XiaoLan , Ian Elena , Berge Christoffer Nerland , Zhao XinCheng , Wang GuiRong , Berg Bente G. , Chu Xi
Published: December 2020

The pheromone system of heliothine moths is an optimal model for studying principles underlying higher-order olfactory processing. InHelicoverpa armigera, three male-specific glomeruli receive input about three female-produced signals, the primary pheromone component, serving as an attractant, and two minor constituents, serving a dual function, i.e. attraction versus inhibition of attraction. From the antennal-lobe glomeruli, the information is conveyed to higher olfactory centers, including the lateral protocerebrum, via three main paths – of which the medial tract is the most prominent. In this study, we traced physiologically identified medial-tract projection neurons from each of the three male-specific glomeruli with the aim of mapping their terminal branches in the lateral protocerebrum. Our data suggest that the neurons’ wide-spread projections are organized according to behavioral significance, including a spatial separation of signals representing attraction versus inhibition – however, with a unique capacity of switching behavioral consequence based on the amount of the minor components.
Introducingselfisher: open source software for statistical analyses of fishing gear selectivity
Authors: Brooks Mollie E , Melli Valentina , Savina Esther , Santos Juan , Millar Russell , O’Neill Finbarr Gerard , Veiga-Malta Tiago , Krag Ludvig Ahm , Feekings Jordan Paul
Published: December 2020

Fishing gear is constantly being improved to select certain sizes and species while excluding others. Experiments are conducted to quantify the selectivity and the resulting data needs to be analyzed using specialized statistical methods in many cases. Here, we present a new estimation tool for analyzing this type of data: an R package namedselfisher. It can be used for both active and passive gears, and can handle different trial designs. It allows fitting models containing multiple fixed effects (e.g. length, total catch weight, mesh size, water turbidity) and random effects (e.g. haul). A bootstrapping procedure is provided to account for between and within haul variability and overdispersion. We demonstrate its use via four case studies including (1) covered codend analyses of four gears, (2) a paired gear study with numerous potential covariates, (3) a catch comparison study of unpaired hauls of gillnets and (4) a catch comparison study of paired hauls using polynomials and splines. This free and open source software will make it easier to model fishing gear selectivity, teach the statistical methods, and make analyses more repeatable.
Cell type-specific isolation and transcriptomic profiling informs glial pathology in human temporal lobe epilepsy
Authors: Tome-Garcia Jessica , Nudelman German , Mussa Zarmeen , Caballero Elodia , Jiang Yan , Beaumont Kristin G. , Wang Ying-Chih , Sebra Robert , Akbarian Schahram , Pinto Dalila , Zaslavsky Elena , Tsankova Nadejda M.
Published: December 2020

The pathophysiology of epilepsy underlies complex network dysfunction, the cell-type-specific contributions of which remain poorly defined in human disease. In this study, we developed a strategy that simultaneously isolates neuronal, astrocyte and oligodendroglial progenitor (OPC)-enriched nuclei from human fresh-frozen neocortex and applied it to characterize the distinct transcriptome of each cell type in temporal lobe epilepsy (TLE) surgical samples. Differential RNA-seq analysis revealed several dysregulated pathways in neurons, OPCs, and astrocytes, and disclosed an immature phenotype switch in TLE astrocytes. An independent single cell RNA-seq TLE dataset uncovered a hybrid population of cells aberrantly co-expressing canonical astrocyte and OPC-like progenitor markers (GFAP+OLIG2+ glia), which we corroborated in-situ in human TLE samples, and further demonstrated their emergence after chronic seizure injury in a mouse model of status epilepticus. In line with their immature signature, a subset of human TLE glia were also abnormally proliferative, both in-vivo and in-vitro. Generally, this analysis validates the utility of the proposed cell type-specific isolation strategy to study glia-specific changes ex vivo using fresh-frozen human samples, and specifically, it delineates an aberrant glial phenotype in human TLE specimens.
The hidden pangenome: comparative genomics reveals pervasive diversity in symbiotic and free-living sulfur-oxidizing bacteria
Authors: Ansorge Rebecca , Romano Stefano , Sayavedra Lizbeth , Rubin-Blum Maxim , Gruber-Vodicka Harald , Scilipoti Stefano , Molari Massimiliano , Dubilier Nicole , Petersen Jillian
Published: December 2020

Sulfur-oxidizingThioglobaceae, often referred to as SUP05 and Arctic96BD clades, are widespread and common to hydrothermal vents and oxygen minimum zones. They impact global biogeochemical cycles and exhibit a variety of host-associated and free-living lifestyles. The evolutionary driving forces that led to the versatility, adoption of multiple lifestyles and global success of this family are largely unknown. Here, we perform an in-depth comparative genomic analysis using all available and newly generatedThioglobaceaegenomes. Gene content variation was common, throughout taxonomic ranks and lifestyles. We uncovered a pool of variable genes within mostThioglobaceaepopulations in single environmental samples and we referred to this as the ‘hidden pangenome’. The ‘hidden pangenome’ is often overlooked in comparative genomic studies and our results indicate a much higher intra-specific diversity within environmental bacterial populations than previously thought. Our results show that core-community functions are different from species core genomes suggesting that core functions across populations are divided among the intra-specific members within a population. Defense mechanisms against foreign DNA and phages were enriched in symbiotic lineages, indicating an increased exchange of genetic material in symbioses. Our study suggests that genomic plasticity and frequent exchange of genetic material drives the global success of this family by increasing its evolvability in a heterogeneous environment.
Four-dimensional tractography animates neural propagations via distinct interhemispheric pathways
Authors: Mitsuhashi Takumi , Sonoda Masaki , Jeong Jeong-won , Silverstein Brian H. , Iwaki Hirotaka , Luat Aimee F. , Sood Sandeep , Asano Eishi
Published: December 2020

Objective

To visualize and validate the dynamics of interhemispheric neural propagations induced by single-pulse electrical stimulation (SPES).

Methods

This methodological study included three patients with drug-resistant focal epilepsy who underwent measurement of cortico-cortical spectral responses (CCSRs) during bilateral stereo-electroencephalography recording. We delivered SPES to 83 electrode pairs and analyzed CCSRs recorded at 268 nonepileptic electrode sites. Diffusion-weighted imaging (DWI) tractography localized the interhemispheric white matter pathways as streamlines directly connecting two electrode sites. We localized and visualized the putative SPES-related fiber activation, at each 1-ms time window, based on the propagation velocity defined as the DWI-based streamline length divided by the early CCSR peak latency.

Results

The resulting movie, herein referred to as four-dimensional tractography, delineated the spatiotemporal dynamics of fiber activation via the corpus callosum and anterior commissure. Longer streamline length was associated with delayed peak latency and smaller amplitude of CCSRs. The cortical regions adjacent to each fiber activation site indeed exhibited CCSRs at the same time window.

Conclusions

Our four-dimensional tractography successfully animated neural propagations via distinct interhemispheric pathways.

Significance

Our novel animation method has the potential to help investigators in addressing the mechanistic significance of the interhemispheric network dynamics supporting physiological function.
Native Extracellular Matrix Orientation Determines Multipotent Vascular Stem Cell Proliferation in Response to Cyclic Uniaxial Tensile Strain and Simulated Stent Indentation
Authors: Mathieu P.S. , Fitzpatrick E. , Di Luca M. , Cahill P.A. , Lally C.
Published: December 2020

Cardiovascular disease is the leading cause of death worldwide, with multipotent vascular stem cells (MVSC) implicated in contributing to diseased vessels. MVSC are mechanosensitive cells which align perpendicular to cyclic uniaxial tensile strain. Within the blood vessel wall, collagen fibers constrain cells so that they are forced to align circumferentially, in the primary direction of tensile strain. In these experiments, MVSC were seeded onto the medial layer of decellularized porcine carotid arteries, then exposed to 10%, 1 Hz cyclic tensile strain for 10 days with the collagen fiber direction either parallel or perpendicular to the direction of strain. Cells aligned with the direction of the collagen fibers regardless of the orientation to strain. Cells aligned with the direction of strain showed an increased number of proliferative Ki67 positive cells, while those strained perpendicular to the direction of cell alignment showed no change in cell proliferation. A bioreactor system was designed to simulate the indentation of a single, wire stent strut. After 10 days of cyclic loading to 10% strain, MVSC showed regions of densely packed, highly proliferative cells. Therefore, MVSC may play a significant role in in-stent restenosis, and this proliferative response could potentially be controlled by controlling MVSC orientation relative to applied strain.
Radiochemical synthesis and evaluation in nonhuman primates of 3-[11C]methoxy-4-aminopyridine: a novel PET tracer for imaging potassium channels in the CNS
Authors: Guehl Nicolas J. , Neelamegam Ramesh , Zhou Yu-Peng , Moon Sung-Hyun , Dhaynaut Maeva , El Fakhri Georges , Normandin Marc D. , Brugarolas Pedro
Published: December 2020

Demyelination, the loss of the protecting sheath of neurons, contributes to disability in many neurological diseases. In order to fully understand its role in different diseases and to monitor treatments aiming at reversing this process, it would be valuable to have PET radiotracers that can detect and quantify molecular changes involved in demyelination such as the uncovering and upregulation of the axonal potassium channels Kv1.1 and Kv1.2. Carbon-11 labeled radiotracers present the advantage of allowing for multiple scans on the same subject in the same day. Here, we describe [11C|3MeO4AP, a novel11C-labeled version of the K+channel tracer [18F]3F4AP, and characterize its imaging properties in two nonhuman primates including a monkey with a focal brain injury sustained during a surgical procedure three years prior to imaging. Our findings show that [11C]3MeO4AP is brain permeable, metabolically stable and has high plasma availability. When compared with [18F]3F4AP, [11C]3MeO4AP shows very high correlation in volumes of distribution (VT) confirming a common target. [11C]3MeO4AP shows slower washout than [18F]3F4AP suggesting stronger binding. Finally, similar to [18F]3F4AP, [11C]3MeO4AP is highly sensitive to the focal brain injury. All these features make it a promising radioligand for imaging demyelinated lesions.
Lifetime genealogical divergence within plants leads to epigenetic mosaicism in the long-lived shrubLavandula latifolia(Lamiaceae)
Authors: Herrera Carlos M. , Bazaga Pilar , Pérez Ricardo , Alonso Conchita
Published: December 2020

Epigenetic mosaicism is a possible source of within-plant phenotypic heterogeneity, yet its frequency and developmental origin remain unexplored. This study examines whether the extant epigenetic heterogeneity within long-livedLavandula latifolia(Lamiaceae) shrubs reflects recent epigenetic modifications experienced independently by different plant parts or, alternatively, it is the cumulative outcome of a steady lifetime process.

Leaf samples from different architectural modules were collected from threeL. latifoliaplants and characterized epigenetically by global DNA cytosine methylation and methylation state of methylation-sensitive amplified fragment length polymorphism markers (MS-AFLP). Epigenetic characteristics of modules were then assembled with information on the branching history of plants. Methods borrowed from phylogenetic research were used to assess genealogical signal of extant epigenetic variation and reconstruct within-plant genealogical trajectory of epigenetic traits.

Plants were epigenetically heterogeneous, as shown by differences among modules in global DNA methylation and variation in the methylation states of 6-8% of MS-AFLP markers. All epigenetic features exhibited significant genealogical signal within plants. Events of epigenetic divergence occurred throughout the lifespan of individuals and were subsequently propagated by branch divisions.

Internal epigenetic diversification ofL. latifoliaindividuals took place steadily during their development, a process which eventually led to persistent epigenetic mosaicism.
The essential role of sodium bioenergetics and ATP homeostasis in the developmental transitions of a cyanobacterium
Authors: Doello Sofia , Burkhardt Markus , Forchhammer Karl
Published: December 2020

The ability to resume growth after a dormant period is an important strategy for the survival and spreading of bacterial populations. Energy homeostasis is critical in the transition into and out of a quiescent state. Synechocystis sp. PCC 6803, a non-diazotrophic cyanobacterium, enters metabolic dormancy as a response to nitrogen starvation. We used Synechocystis as a model to investigate the regulation of ATP homeostasis during dormancy and unraveled a critical role for sodium bioenergetics in dormant cells. During nitrogen starvation, cells reduce their ATP levels and engage sodium bioenergetics to maintain the minimum ATP content required for viability. When nitrogen becomes available, energy requirements rise, and cells immediately increase ATP levels employing sodium bioenergetics and glycogen catabolism. These processes allow them to restore the photosynthetic machinery and resume photoautotrophic growth. Our work reveals a precise regulation of the energy metabolism essential for bacterial survival during periods of nutrient deprivation.
Glycomic analysis reveals a conserved response to bacterial sepsis induced by different bacterial pathogens
Authors: Heindel Daniel W. , Aziz Peter V. , Chen Shuhui , Marth Jamey D. , Mahal Lara K.
Published: December 2020

Sepsis is an extreme inflammatory response to infection (bacterial, viral, fungal) that occurs in the bloodstream and causes damage throughout the body. Currently, there are few diagnostic biomarkers of sepsis and new effective treatments have not been developed. There is a clear need to study the molecular underpinnings of this disease. Glycosylation is known to play a role in immunity and inflammation, but the role of glycans in sepsis is not well defined. Herein, we profiled the serum glycomes of experimental mouse sepsis models to identify changes induced by 4 different clinical bacterial pathogens (Gram-positive:Streptococcus pneumoniae, Staphylococcus aureus, Gram-negative:Escherichia coliandSalmonellaTyphimurium) using our lectin microarray technology. We observed global shifts in the blood sera glycome that were conserved across all four species, regardless of whether they were Gram positive or negative. Bisecting GlcNAc was decreased upon sepsis and a strong increase in core 1/3O-glycans was observed. Lectin blot analysis revealed a high molecular weight protein induced in sepsis by all four bacteria as the major cause of the core 1/3O-glycan shift. While the identity of this protein remains to be elucidated, its presence indicates a common feature of bacterial sepsis associated with this glycomic signature.
Rapid encoding of temporal sequences discovered in brain dynamics
Authors: Bonetti L. , Brattico E. , Carlomagno F. , Donati G. , Cabral J. , Haumann N.T. , Deco G. , Vuust P. , Kringelbach M.L.
Published: December 2020

Information encoding has received a wide neuroscientific attention, but the underlying rapid spatiotemporal brain dynamics remain largely unknown. Here, we investigated the rapid brain mechanisms for encoding and prediction of sounds forming a complex temporal sequence. Specifically, we used magnetoencephalography (MEG) to record the brain activity of 68 participants while they listened to a highly structured musical prelude. Advanced analysis of the phase synchronisation and graph theoretical measures showed the rapid transition of brain activity from primary auditory cortex to higher order association areas including insula and superior temporal pole within a whole-brain network, occurring during the first 220 ms of the encoding process. We discovered individual differences, revealing the rapid unfolding of brain network dynamics responsible for the processing of the current sounds and the prediction of the forthcoming events of the sequence. This provides a first glimpse of the general mechanisms underlying pattern encoding in the human brain.
The transcriptomic landscapes of diverse rice cultivars grown under mild drought conditions
Authors: Kawakatsu Taiji , Teramoto Shota , Takayasu Satoko , Maruyama Natsuko , Nishijima Ryo , Kitomi Yuka , Uga Yusaku
Published: December 2020

Root system architecture affects plant drought tolerance and other key agronomic traits such as lodging. However, although phenotypic and genomic variation has been extensively analyzed, few field studies have integrated phenotypic and transcriptomic information, especially for below-ground traits such as root system architecture. Here, we report the phenotypic and transcriptomic landscape of 61 rice (Oryza sativa) accessions with highly diverse below-ground traits grown in an upland field under mild drought stress. We found that four principal components explained the phenotypic variation and that accessions could be classified into four admixture groups (admixed,aus,indica, andjaponica) based on their tiller numbers and crown root diameters. Transcriptome analysis revealed that differentially expressed genes associated with specific admixture groups were enriched with stress response-related genes, suggesting that admixture groups have distinct stress response mechanisms. Root growth was negatively correlated with auxin-inducible genes, suggesting an association between auxin signaling and mild drought stress. A negative correlation between crown root diameter and stress response-related genes suggested that thicker crown root diameter is associated with resistance to mild drought stress. Finally, co-expression network analysis implemented with DNA affinity purification followed by sequencing (DAP-seq) analysis identified phytohormone signaling networks and key transcription factors negatively regulating crown root diameter. Our datasets provide a useful resource for understanding the genomic and transcriptomic basis of phenotypic variation under mild drought stress.

ONE-SENTENCE SUMMARY

Catalog of the phenomes and transcriptomes of rice cultivars grown in upland fields provides a resource for further studies toward breeding climate-resilient crops.
Physiological and transcriptomic response ofMedicago truncatulato colonization with high and low benefit arbuscular mycorrhizal fungi
Authors: Cope Kevin R. , Kafle Arjun , Yakha Jaya K. , Pfeffer Philip E. , Strahan Gary D. , Garcia Kevin , Subramanian Senthil , Bücking Heike
Published: December 2020

Arbuscular mycorrhizal (AM) fungi form a root endosymbiosis with many agronomically important crop species and both enhance the ability of their host to obtain nutrients from the soil and increase host tolerance to biotic and abiotic stressors. However, AM fungal species differ in the benefits they provide to their host plants. Here, we examined the putative molecular mechanisms involved in the regulation of the physiological response ofMedicago truncatulato eitherRhizophagus irregularis or Glomus aggregatum,a high or a low benefit AM fungus, respectively. Colonization withR. irregularisled to higher growth and nutrient uptake benefits than the colonization withG. aggregatum. These benefits were linked to an elevated expression in the roots of genes involved in strigolactone biosynthesis (NSP1,NSP2,CCD7, andMAX1a), mycorrhiza-induced phosphate (PT8), ammonium (AMT2;3), and nitrate (NPF4.12) transporters and the putative ammonium transporterNIP1;5.R. irregularisalso stimulated the expression of photosynthesis-related genes in the shoot and the upregulation of the sugar transportersSWEET1.2, SWEET3.3andSWEET 12and the lipid biosynthesis geneRAM2in the roots. In contrast,G. aggregatuminduced the expression of biotic stress defense response genes in the shoots and several genes associated with abiotic stress in the roots. This suggests that either the host perceives colonization byG. aggregatumas a pathogen attack or thatG. aggregatumcan prime host defense responses. Our findings reveal novel insights into the molecular mechanisms that control the host plant response to colonization with high- and low-benefit arbuscular mycorrhizal fungal symbionts.
Importance of test-retest reliability for promoting fMRI based screening and interventions in major depressive disorder
Authors: Compère Laurie , Siegle Greg J. , Young Kymberly
Published: December 2020

Proponents of personalized medicine have promoted neuroimaging evaluation and treatment of major depressive disorder in three areas of clinical application: clinical prediction, outcome evaluation, and neurofeedback. Whereas psychometric considerations such as test-retest reliability are basic precursors to clinical adoption for most clinical instruments, they are often not considered for neuroimaging assessments. As an example, we consider functional magnetic resonance imaging (fMRI) of depression, a common and particularly well validated mechanistic technology for understanding disorder and guiding treatment. In this article, we review work on test-retest reliability for depression fMRI studies. We find that basic psychometrics have not been regularly attended to in this domain. For instance, no fMRI neurofeedback study has included measures of test-retest reliability despite the implicit assumption that brain signals are stable enough to train. We consider several factors that could be useful to aid clinical translation including 1) attending to how the BOLD response is parameterized, 2) identifying and promoting regions or voxels with stronger psychometric properties 3) accounting for within-individual changes (e.g., in symptomatology) across time and 4) focusing on tasks and clinical populations that are relevant for the intended clinical application. We apply these principles to published prognostic and neurofeedback data sets. The broad implication of this work is that attention to psychometrics is important for clinical adoption of mechanistic assessment, is feasible, and may improve the underlying science.
Conformational Ensembles of Non-Coding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations
Authors: Bottaro Sandro , Bussi Giovanni , Lindorff-Larsen Kresten
Published: December 2020

The 5′ untranslated region (UTR) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome is a conserved, functional and structured genomic region consisting of several RNA stem-loop elements. While the secondary structure of such elements has been determined experimentally, their three-dimensional structures are not known yet. Here, we predict structure and dynamics of five RNA stem loops in the 5′-UTR of SARS-CoV-2 by extensive atomistic molecular dynamics simulations, more than 0.5ms of aggregate simulation time, in combination with enhanced sampling techniques. We compare simulations with available experimental data, describe the resulting conformational ensembles, and identify the presence of specific structural rearrangements in apical and internal loops that may be functionally relevant. Our atomic-detailed structural predictions reveal a rich dynamics in these RNA molecules, could help the experimental characterisation of these systems, and provide putative three-dimensional models for structure-based drug design studies.
A novel allele ofSIR2reveals a heritable intermediate state of gene silencing
Authors: Farris Delaney , Saxton Daniel S , Rine Jasper
Published: December 2020

Genetic information acquires additional meaning through epigenetic regulation, the process by which genetically identical cells can exhibit heritable differences in gene expression and phenotype. Inheritance of epigenetic information is a critical step in maintaining cellular identity and organismal health. InSaccharomyces cerevisiae, one form of epigenetic regulation is the transcriptional silencing of two mating-type loci,HMLandHMR, by the SIR-protein complex. To focus on the epigenetic dimension of this gene regulation, we conducted a forward mutagenesis screen to identify mutants exhibiting an epigenetic or metastable silencing defect. We utilized fluorescent reporters atHMLandHMR, and screened yeast colonies for epigenetic silencing defects. We uncovered numerous independentsir1alleles, a gene known to be required for stable epigenetic inheritance. More interestingly, we recovered a missense mutation withinSIR2, which encodes a highly conserved histone deacetylase. In contrast tosir1Δ, which exhibits states that are either fully silenced or fully expressed, thissir2allele exhibited heritable states that were either fully silenced or expressed at an intermediate level. The heritable nature of this unique silencing defect was influenced by, but not completely dependent on, changes in rDNA copy number. Therefore, this study revealed a heritable state of intermediate silencing and linked this state to a central silencing factor, Sir2.
Evolution of the recombination regulator PRDM9 in minke whales
Authors: Damm Elena , Ullrich Kristian K , Amos William B , Odenthal-Hesse Linda
Published: December 2020

We explored the structure and variability of thePrdm9gene, which codes for the PRDM9 protein, in samples of the minke whales from the Atlantic, Pacific and Southern Oceans. The PRDM9 protein controls the reshuffling of parental genomes in most metazoans and we show that minke whale possess all the features characteristic of PRDM9-directed recombination initiation, including complete KRAB, SSXRD and SET domains and a rapidly evolving array of C2H2-type-Zincfingers (ZnF). We uncovered eighteen novel PRDM9 variants and evidence of rapid evolution, particularly at DNA-recognizing positions that evolve under positive selection. At different geographical scales, we observed extensivePrdm9allelic diversity in Antarctic minke whales (Balaenoptera bonarensis) that, conversely, lack observable population differentiation in mitochondrial DNA and microsatellites. In contrast, a single PRDM9 variant is shared between all Common Minke whales and even across subspecies boundaries of North Atlantic (B. a. acutorostrata) and North Pacific (B. a. scammoni) minke whale, which do show clear population differentiation. PRDM9 variation of whales predicts distinct recombination initiation landscapes genome-wide, which has possible consequences for speciation.
Measuring Compound Eye Optics with Microscope and MicroCT Images
Authors: Currea John Paul , Sondhi Yash , Kawahara Akito Y. , Theobald Jamie
Published: December 2020

With a great variety of shapes and sizes, compound eye morphologies give insight into visual ecology, development, and evolution, and inspire novel engineering. In contrast to our owncamera-typeeyes, compound eyes reveal their resolution, sensitivity, and field of view externally, provided they have spherical curvature and orthogonal ommatidia. Non-spherical compound eyes with skewed ommatidia require measuring internal structures, such as with MicroCT (μCT). Thus far, there is no efficient tool to characterize compound eye optics, from either 2D or 3D data, automatically. Here we present two open-source programs: (1) the ommatidia detecting algorithm (ODA), which measures ommatidia count and diameter in 2D images, and (2) a μCT pipeline (ODA-3D), which calculates anatomical acuity, sensitivity, and field of view across the eye by applying the ODA to 3D data. We validate these algorithms on images, images of replicas, and μCT eye scans from ants, fruit flies, moths, and a bee.
Choice of fluorophore affects dynamic DNA nanostructures
Authors: Jahnke Kevin , Grubmüller Helmut , Igaev Maxim , Göpfrich Kerstin
Published: December 2020

The ability to dynamically remodel DNA origami structures or functional nanodevices is highly desired in the field of DNA nanotechnology. Concomitantly, the use of fluorophores to track and validate the dynamics of such DNA-based architectures is commonplace and often unavoidable. It is therefore crucial to be aware of the side effects of popular fluorophores, which are often exchanged without considering the potential impact on the system. Here, we show that the choice of fluorophore can strongly affect the reconfiguration of DNA nanostructures. To this end, we encapsulate a triple-stranded DNA (tsDNA) into water-in-oil compartments and functionalize their periphery with a single-stranded DNA handle (ssDNA). Thus, the tsDNA can bind and unbind from the periphery by reversible opening of the triplex and subsequent strand displacement. Using a combination of experiments, molecular dynamics (MD) simulations, and reaction-diffusion modeling, we demonstrate for twelve different fluorophore combinations that it is possible to alter or even inhibit the DNA nanostructure formation – without changing the DNA sequence. Besides its immediate importance for the design of pH-responsive switches and fluorophore labelling, our work presents a strategy to precisely tune the energy landscape of dynamic DNA nanodevices.
Barnacle-Inspired Paste for Instant Hemostatic Tissue Sealing
Authors: Yuk Hyunwoo , Wu Jingjing , Mao Xinyu , Varela Claudia E. , Roche Ellen T. , Nabzdyk Christoph S. , Zhao Xuanhe
Published: December 2020

Whilst sealing damaged tissues by adhesives has potential advantages over suturing or stapling, existing tissue adhesives cannot form rapid or robust adhesion on tissues covered with body fluids such as blood. In contrast, the glues of barnacles, consisting of a lipid-rich matrix and adhesive proteins, and can strongly adhere to wet and contaminated surfaces. Here we report a barnacle-inspired paste capable of forming instant robust hemostatic sealing of diverse tissues. The paste is composed of a hydrophobic oil matrix and bioadhesive microparticles to implement the barnacle-inspired mechanism to repel blood through the hydrophobic matrix. Subsequently, the bioadhesive microparticles crosslink with underlying tissues under gentle pressure. The barnacle-inspired paste can provide tough (interfacial toughness over 300 J m-2) and strong (shear and tensile strength over 70 kPa, burst pressure over 350 mmHg) hemostatic sealing of a broad range of tissues within five seconds. We validatein vitroandin vivobiocompatibility and biodegradability of the barnacle-inspired paste in rodent models. We further demonstrate potential applications of the barnacle-inspired paste for instant hemostatic sealing inex vivoporcine aorta,in vivorat liver and heart models.
Health education teachers' historical bodies: constructing teacher identity and teaching information evaluation
Authors: Nygård Tuula , Hirvonen Noora , Räisänen Sari , Korkeamäki Riitta-Liisa
Published: December 2020

Purpose

This article describes how Finnish health education teachers verbalise and construct their teacher identity based on their lifestyle, subject area and relationships with their students.

Design/methodology/approach

Narrative interviews were conducted amongst eight secondary and upper secondary school teachers. The nexus analysis was used to analyse teachers' methods of teaching students information-seeking, evaluation and critical thinking skills.

Findings

The teachers' historical bodies – their skills, interests, information-seeking habits and familiar sources – impacted the chosen teaching methods. The results indicate that teacher identity is constructed along different paths and is constantly performed and transformed in the classroom through interactions with students.

Originality/value

The study illustrates the reconstruction of teacher identity through interaction in interviews. Teachers act as role models, information gatekeepers and trustees who guide students to choose credible health information sources.
An experimental/numerical hydrothermal-Second law analysis of a finned/tubular heat exchanger using Bhatnagar–Gross–Krook Lattice Boltzmann (BGKLBM) and rheological-thermal behavior of Fe2O3-water
Authors: Hejri Saeid , Kamali Daryoush , Hasani Malekshah Emad
Published: December 2020

Purpose

The purpose of this study is analysis of the natural convection and entropy production in a two-dimensional section of the considered heat exchanger. For this purpose, the lattice Boltzmann method which is equipped with Bhatnagar–Gross–Krook model is used. This model proposes a significant accurate prediction for thermal and hydro-dynamical behaviors over free convection phenomenon. The heat exchanger is filled with Fe2O3-water nanofluid. To improve the accuracy of prediction, it is neglected to use the theoretical models for properties of nanofluid. At this end, some experimental observations are conducted, and the required rheological and thermal properties of nanofluid are measured based on laboratory work..

Design/methodology/approach

The present work focuses on the influence of different factors on the thermal behaviors and entropy production of a heat exchanger. The heat exchanger is consisted by an inner tube, an outer tube and some fins which are implanted at the surface of inner tube.

Findings

The effects of various factors like structure of inner fins, nanoparticle concentration and Rayleigh number over the heat transfer rate, local and volumetric entropy production, Bejan number, flow configuration and temperature distributions are provided.

Originality/value

The originality of this work is using a new-developed numerical method for treating natural convection and experimental measurements for thermal and rheological properties of nanofluid.