bluuebunny/crossref_metadata_2025 huggingface dataset:
Are single peripheral measurements of baseline oxytocin in saliva and plasma reliable biomarkers of the physiology of the oxytocin system in humans?
Authors: Martins Daniel , Gabay Anthony , Mehta Mitul A. , Paloyelis Yannis
Published: July 2020

Background

Single measurements of salivary and plasmatic oxytocin are used as indicators of the physiology of the oxytocin system. However, questions remain about whether they are sufficiently stable to provide valid biomarkers of the physiology of the oxytocin system, and whether salivary oxytocin can accurately index its plasmatic concentrations.

Methods

Using radioimmunoassay, we measured baseline plasmatic and/or salivary oxytocin from two independent datasets. Dataset A comprised 17 healthy men sampled on four occasions approximately at weekly intervals. We administered exogenous oxytocin intravenously and intranasally in a triple dummy, within-subject, placebo-controlled design and compared baseline levels and the effects of routes of administration. Dataset B comprised baseline plasmatic oxytocin measurements from 20 healthy men sampled on two separate occasions. Additionally, in dataset A, we tested whether salivary oxytocin can predict plasmatic oxytocin at baseline and after intranasal and intravenous oxytocin administration.

Results

Single measurements of plasmatic and salivary oxytocin showed poor reliability across visits in both datasets. Intranasal administration of exogenous oxytocin increases salivary oxytocin, but intravenous administration of a considerable dose does not produce any changes. Saliva and plasma oxytocin did not correlate at baseline or after administration of exogenous oxytocin.

Conclusions

Our findings question the use of single measurements of baseline oxytocin concentrations in saliva and plasma as valid biomarkers of the physiology of the oxytocin system in humans. Salivary oxytocin is a weak surrogate for plasmatic oxytocin. The increases in salivary oxytocin observed after intranasal oxytocin most likely reflect unabsorbed peptide and should not be used to predict treatment effects.
Cortical Presynaptic Boutons Progressively Engulf Spinules As They Mature
Authors: Campbell Charles , Lindhartsen Sarah , Knyaz Adam , Erisir Alev , Nahmani Marc
Published: July 2020

Despite decades of discussion in the neuroanatomical literature, the role of the synaptic ‘spinule’ in synaptic development and function remains elusive. Canonically, spinules are finger-like projections that emerge from postsynaptic spines and can become enveloped by presynaptic boutons. When a presynaptic bouton encapsulates a spinule in this manner, the membrane apposition between the spinule and surrounding bouton can be significantly larger than the membrane interface at the synaptic active zone. Hence, spinules may represent a mechanism for extrasynaptic neuronal communication, and/or may function as structural ‘anchors’ that increase the stability of cortical synapses. Yet despite their potential to impact synaptic function, we have little information on the percentages of developing and adult cortical bouton populations that contain spinules, the percentages of these cortical spinule-bearing boutons (SBBs) that contain spinules from distinct neuronal/glial origins, or whether the onset of activity or cortical plasticity are correlated with increased prevalence of cortical SBBs. Here, we employed 2D and 3D electron microscopy to determine the prevalence of spinules in excitatory presynaptic boutons at key developmental time points in the primary visual cortex (V1) of female and male ferrets. We find that the prevalence of SBBs in V1 increases across postnatal development, such that ~25% of excitatory boutons in late adolescent ferret V1 contain spinules. In addition, we find that a majority of spinules within SBBs at later developmental time points emerge from postsynaptic spines and adjacent boutons/axons, suggesting that synaptic spinules may enhance synaptic stability and allow for axo-axonal communication in mature sensory cortex.

Significance Statement

Synaptic spinules are finger-like projections from neurites that can become completely embedded within presynaptic boutons, potentially enhancing synaptic communication and stability. Yet while their existence has been discussed for decades, spinule prevalence, projection origins, and relationship to neocortical sensory activity remain unknown. In this study, we employed 2D and 3D electron microscopy techniques to characterize the development of excitatory cortical spinule-bearing boutons (SBBs) and their relationship to sensory activity and plasticity. Our results demonstrate that neocortical presynaptic SBB prevalence is not correlated with the onset of sensory activity or heightened cortical plasticity, and that by late adolescence nearly one-quarter of presynaptic boutons contain a spinule. Hence, synaptic spinules may play progressively important roles in cortical function as these synapses mature.
Transcription factor recruitment by parallel G-quadruplexes to promote transcription: the case of herpes simplex virus-1 ICP4
Authors: Frasson Ilaria , Soldà Paola , Nadai Matteo , Lago Sara , Richter Sara N.
Published: July 2020

G-quadruplexes (G4s), four-stranded nucleic acid structures that adopt several distinctive conformations, are abundant at gene promoters and have been proposed as transcription regulatory elements. G4s form in the herpes simplex virus-1 (HSV-1) genome during its viral cycle. Here by cross-linking/pull-down assay we identified ICP4 as the protein that most interacts with viral G4s during infection. In vitro and in infected cells, ICP4 specifically and directly bound and unfolded parallel G4s, including those present in HSV-1 immediate early gene promoters, and consequently induced transcription. This mechanism was also exploited by ICP4 to promote its own transcription. By proximity ligation assay we visualized ICP4 interaction at the single G4 in cells. G4 ligands inhibited ICP4 binding to G4s. Our results indicate the existence of a well-defined G4-viral protein network that regulates the productive HSV-1 cycle. They also point to G4s as elements that recruit transcription factors to activate transcription in cells.
A standardized broad host range inverter package for genetic circuitry design in Gram-negative bacteria
Authors: Tas Huseyin , Goñi-Moreno Ángel , de Lorenzo Víctor
Published: July 2020

Genetically encoded logic gates, especially inverters—NOT gates—are the building blocks for designing circuits, engineering biosensors or decision-making devices in synthetic biology. However, the repertoire of inverters readily available for different species is rather limited. In this work, a large whole of NOT gates that was shown to function previously in a specific strain ofEscherichia coli, was recreated as broad host range (BHR) collection of constructs assembled in low, medium and high copy number plasmid backbones of the SEVA (Standard European Vector Architecture) collection. The input/output function of each of the gates was characterized and parameterized in the environmental bacterium and metabolic engineering chassisPseudomonas putida. Comparisons of the resulting fluorescence cytometry data with those published for the same gates inEscherichia coliprovided useful hints on the portability of the corresponding gates. The hereby described BHR inverter package (20 different versions of 12 distinct gates) thus becomes a toolbox of choice for designing genetic circuitries in a variety of Gram-negative species other thanE. coli.
The Nesprin-1/-2 ortholog ANC-1 regulates organelle positioning inC. eleganswithout its KASH or actin-binding domains
Authors: Hao Hongyan , Kalra Shilpi , Jameson Laura E. , Guerrero Leslie A. , Cain Natalie E. , Bolivar Jessica , Starr Daniel A.
Published: July 2020

KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of LINC complexes that connect nuclei to the cytoskeleton.Caenorhabditis elegansANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the trans-membrane span. Inanc-1mutants, the ER was unanchored, moving throughout the cytoplasm, and often fragmented. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and likely other organelles in place.
Glutathione S-transferase: A Candidate Gene for Berry Color in Muscadine Grapes (Vitis rotundifolia)
Authors: Varanasi Aruna , Worthington Margaret , Nelson Lacy , Brown Autumn , Threlfall Renee , Howard Luke , Clark John R.
Published: July 2020

Muscadine grapes (Vitis rotundifoliaMichx.) are a specialty crop cultivated in the southern United States. Muscadines (2n=40) belong to theMuscadiniasubgenus ofVitis,while all other cultivated grape species belong to the subgenusEuvitis(2n=38). The berry color locus in muscadines has been mapped to a 0.8 Mbp region syntenic with chromosome 4 ofV. vinifera. In this study, we identified glutathione S-transferase4 (GST4) as a likely candidate gene for anthocyanin transport within the berry color locus. PCR and KASP genotyping identified a single intragenic SNP (C/T) marker corresponding to a proline to leucine mutation within the muscadineGST4(VrGST4) that differentiated black (CC and CT) from bronze (TT) muscadines in 65 breeding selections, 14 cultivars, and 320 progeny from two mapping populations. Anthocyanin profiling on a subset of the progeny indicated a dominantVrGST4action, with no allele dosage effect on total anthocyanin content or composition of individual anthocyanins. Proanthocyanidin content was similar in the seeds of both black and bronze genotypes, and seeds had much higherVrGST3expression and lowerVrGST4expression than skins.VrGST4expression was higher in post-veraison berries of black muscadines compared to pre-veraison berries, but no changes in gene expression in pre- and post-veraison berries were observed in the bronze muscadine cultivar.VrMybA1expression was higher in post-veraison berries of both black and bronze muscadines. These results suggest that berry pigmentation in muscadines is regulated by a mechanism distinct from theMybAgene cluster that is responsible for berry color variation inV. vinifera.
Bacterial quorum sensing signal arrests phytoplankton cell division and protects against virus-induced mortality
Authors: Pollara Scott B. , Becker Jamie W. , Nunn Brook L. , Boiteau Rene , Repeta Daniel , Mudge Miranda C. , Downing Grayton , Chase Davis , Harvey Elizabeth L. , Whalen Kristen E.
Published: July 2020

Interactions between phytoplankton and heterotrophic bacteria fundamentally shape marine ecosystems. These interactions are driven by the exchange of compounds, however, linking these chemical signals, their mechanisms of action, and resultant ecological consequences remains a fundamental challenge. The bacterial signal 2-heptyl-4-quinolone (HHQ), induces immediate cellular stasis in the coccolithophore,Emiliania huxleyi, however, the mechanism responsible remains unknown. Here, we show that HHQ exposure leads to the accumulation of DNA damage in phytoplankton and prevents its repair. While this effect is reversible, HHQ-exposed phytoplankton are also protected from viral mortality, ascribing a new role of quorum sensing signals in regulating multi-trophic interactions. Further results demonstrate global HHQ production potential and the firstin situmeasurements of HHQ which coincide with areas of enhanced micro- and nanoplankton biomass. Our results support bacterial communication signals as emerging players, providing a new mechanistic framework for how compounds may contribute to structure complex marine microbial communities.
MetaWorks: A flexible, scalable bioinformatic pipeline for high-throughput multi-marker biodiversity assessments
Authors: Porter Teresita M. , Hajibabaei Mehrdad
Published: July 2020

Multi-marker metabarcoding is increasingly being used to generate biodiversity information across different domains of life from microbes to fungi to animals such as for molecular ecology and biomonitoring applications in different sectors from academic research to regulatory agencies and industry. Current popular bioinformatic pipelines support microbial and fungal marker analysis, while ad hoc methods are often used to process animal metabarcode markers from the same study. MetaWorks provides a harmonized processing environment, pipeline, and taxonomic assignment approach for demultiplexed Illumina reads for all biota using a wide range of metabarcoding markers such as 16S, ITS, and COI. A Conda environment is provided to quickly gather most of the programs and dependencies for the pipeline. Several workflows are provided such as: taxonomically assigning exact sequence variants, provides an option to generate operational taxonomic units, and facilitates single-read processing. Pipelines are automated using Snakemake to minimize user intervention and facilitate scalability. All pipelines use the RDP classifier to provide taxonomic assignments with confidence measures. We extend the functionality of the RDP classifier for taxonomically assigning 16S (bacteria), ITS (fungi), and 28S (fungi), to also support COI (animals), rbcL (eukaryotes, land plants, diatoms), 12S (fish), 18S (eukaryotes, diatoms) and ITS (fungi, plants). MetaWorks properly handles ITS by trimming flanking conserved rRNA gene regions as well as protein coding genes by providing two options for removing obvious pseudogenes. MetaWorks is available athttps://github.com/terrimporter/MetaWorksalong with quick-start instructions using test data, detailed workflow descriptions, and a tutorial for new users.
Mitogenome reconstruction of an endangered African seahorse from a Traditional Chinese Medicine market was based on a misidentification
Authors: Teske Peter R.
Published: July 2020

The recently published complete mitochondrial genome of the endangered Knysna seahorse,Hippocampus capensisBoulenger, 1900, was based on a specimen obtained from a Traditional Chinese Medicine market. AsH. capensisis endemic to temperate South Africa and exceptionally rare, illegal trade to supply Asian markets would constitute a considerable extinction risk. I investigated the phylogenetic placement of the Chinese specimen using mitochondrial DNA control region and cytochromebsequences from theH. capensismitogenome among corresponding published sequences ofH. capensisand a number of closely related seahorse species. The Chinese specimen was distinct fromH. capensisand instead clustered withH. casscsio, a seahorse that was recently described from the South China Sea. The sequences ofH. casscsioclustered randomly among those of specimens identified asH. fuscus, a species whose taxonomic validity is disputed, and which is considered to be a synonym of the widespread Indo-Pacific seahorseH. kuda. Given that the morphological identification of seahorses is difficult, it is recommended that the publication of new species descriptions and genomic resources be preceded by a comprehensive comparison with the available molecular data. The taxonomy of seahorses is far from resolved, and cutting-edge molecular studies will not improve this situation if they do not take existing information into consideration.
Repression of interrupted and intact rDNA by the SUMO pathway inDrosophila melanogaster
Authors: Luo Yicheng , Fefelova Elena , Ninova Maria , Chen Yung-Chia Ariel , Aravin Alexei A.
Published: July 2020

Ribosomal RNAs (rRNAs) are essential components of the ribosome and are among the most abundant macromolecules in the cell. To ensure high rRNA level, eukaryotic genomes contain dozens to hundreds of rDNA genes, however, only a fraction of the rRNA genes seems to be active, while others are transcriptionally silent. We found that individual rDNA genes have high level of cell-to-cell heterogeneity in their expression inDrosophila melanogaster. Insertion of heterologous sequences into rDNA leads to repression associated with reduced expression in individual cells and decreased number of cells expressing rDNA with insertions. We found that SUMO (Small Ubiquitin-like Modifier) and SUMO ligase Ubc9 are required for efficient repression of interrupted rDNA units and variable expression of intact rDNA. Disruption of the SUMO pathway abolishes discrimination of interrupted and intact rDNAs and removes cell-to-cell heterogeneity leading to uniformly high expression of individual rDNA in single cells. Our results suggest that the SUMO pathway is responsible for both repression of interrupted units and control of intact rDNA expression.
Modeling alcoholic liver disease in a human Liver-Chip
Authors: Nawroth Janna C. , Petropolis Debora B. , Manatakis Dimitris V. , Maulana Tengku Ibrahim , Burchett Gabriel , Schlünder Katharina , Witt Anke , Shukla Abhishek , Hamilton Geraldine , Seki Ekihiro , Lu Shelley , Karalis Katia
Published: July 2020

Fatty liver disease (FLD), is a major public health burden that affects up to 30% of people in Western countries and leads to progressive liver injury, comorbidities, and increased mortality. Key risk factors for developing FLD are obesity and alcohol consumption, both of which are growing in prevalence worldwide. There is an urgent need for human-relevant preclinical models to improve our understanding of FLD progression to steatohepatitis and for the development of sensitive noninvasive diagnostics and therapies. Alcohol-induced liver disease (ALD) represents an ideal case for modeling FDL as ethanol exposure is a comparatively simpler trigger for experimental induction of the pathology, as opposed to the complexity of modeling the diet- and life-style induced FLD. Further, despite their different root causes, the two pathologies share several common characteristics in disease progression and deterioration of liver function, highlighting the potential of an ALD microphysiological model for broad application in translational research. Here, we leverage our recently reported human Liver-Chip for toxicity applications, to expand the capabilities of the platform for broad application in translational research. We report the firstin vitromodeling of ALD that uses human relevant blood alcohol concentrations (BAC) and affords multimodal profiling of clinically relevant endpoints. Our ALD Liver-Chip recapitulates established FLD markers in response to ethanol in a concentration-dependent manner, including lipid accumulation and oxidative stress. Importantly, we show that the ALD Liver-Chip supports the study of secondary insults common in patients with advanced ALD, such as high blood endotoxin levels due to alcohol-associated increased intestinal permeability and barrier dysfunction. Moreover, owing to new developments in the design, the ALD Liver-Chip enables the measurement of structural changes of the bile canaliculi (BC) network as a novelin vitroquantitative readout of alcoholic liver toxicity. In summary, we report the development of a human ALD Liver-Chip as a new platform for modeling the progression of alcohol-induced liver injury with direct translation to clinical research.
Metastatic Site Prediction in Breast Cancer using Omics Knowledge Graph and Pattern Mining with Kirchhoff’s Law Traversal
Authors: Jha Alokkumar , Khan Yasar , Sahay Ratnesh , d’Aquin Mathieu
Published: July 2020

Prediction of metastatic sites from the primary site of origin is a impugn task in breast cancer (BRCA). Multi-dimensionality of such metastatic sites - bone, lung, kidney, and brain, using large-scale multi-dimensional Poly-Omics (Transcriptomics, Proteomics and Metabolomics) data of various type, for example, CNV (Copy number variation), GE (Gene expression), DNA methylation, path-ways, and drugs with clinical associations makes classification of metastasis a multi-faceted challenge. In this paper, we have approached the above problem in three steps; 1) Applied Linked data and semantic web to build Poly-Omics data as knowledge graphs and termed them as cancer decision network; 2) Reduced the dimensionality of data using Graph Pattern Mining and explained gene rewiring in cancer decision network by first time using Kirchhoff’s law for knowledge or any graph traversal; 3) Established ruled based modeling to understand the essential -Omics data from poly-Omics for breast cancer progression 4) Predicted the disease’s metastatic site using Kirchhoff’s knowledge graphs as a hidden layer in the graph convolution neural network(GCNN). The features (genes) extracted by applying Kirchhoff’s law on knowledge graphs are used to predict disease relapse site with 91.9% AUC (Area Under Curve) and performed detailed evaluation against the state-of-the-art approaches. The novelty of our approach is in the creation of RDF knowledge graphs from the poly-omics, such as the drug, disease, target(gene/protein), pathways and application of Kirchhoff’s law on knowledge graph to and the first approach to predict metastatic site from the primary tumor. Further, we have applied the rule-based knowledge graph using graph convolution neural network for metastasis site prediction makes the even classification novel.
Antibody Escape by Polyomavirus Capsid Mutation Facilitates Neurovirulence
Authors: Lauver Matthew D. , Goetschius Daniel J. , Netherby-Winslow Colleen S. , Ayers Katelyn N. , Jin Ge , Haas Daniel G. , Frost Elizabeth L. , Cho Sung Hyun , Bator Carol M. , Bywaters Stephanie M. , Christensen Neil D. , Hafenstein Susan L. , Lukacher Aron E.
Published: July 2020

JCPyV polyomavirus, a member of the human virome, causes Progressive Multifocal Leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb)in vivois unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo EM and a custom subvolume refinement approach, we resolved an MuPyV:Fab complex map to 3.1 Å resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulencein vivoby a frequent JCPyV-PML VP1 mutation.
The FlgN chaperone activates the Na+-driven engine of the flagellar protein export apparatus
Authors: Minamino Tohru , Kinoshita Miki , Morimoto Yusuke V. , Namba Keiichi
Published: July 2020

The bacterial flagellar protein export machinery promotes H+-coupled translocation of flagellar proteins to the cell exterior. When the cytoplasmic ATPase complex does not function, the transmembrane export gate complex opens its Na+channel and continues protein transport. However, it remains unknown how. Here we report that the FlgN chaperone acts as a switch to activate a backup export mechanism for the ATPase complex by activating the Na+-driven engine. Impaired interaction of FlhA with the FliJ subunit of the ATPase complex increased Na+-dependence of flagellar protein export. Deletion of FlgN inhibited protein export in the absence of the ATPase complex but not in its presence. Gain-of-function mutations in FlhA restored not only the FlgN defect but also the FliJ defect. We propose that the interaction of FlgN with FlhA opens the Na+channel in the export engine, thereby maintaining the protein export activity in the absence of the active ATPase complex.
Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex
Authors: Huang Xiawei , Hu Hongmiao , Webster Alexandre , Zou Fan , Du Jiamu , Toth Katalin Fejes , Aravin Alexei A. , Li Sisi
Published: July 2020

Piwi proteins use guide piRNAs to repress selfish genomic elements, protecting the genomic integrity of gametes and ensuring the fertility of animal species. Efficient transposon repression depends on amplification of piRNA guides in the ping-pong cycle, which in Drosophila entails tight cooperation between two Piwi proteins, Aub and Ago3. Here we show that post-translational modification, symmetric dimethylarginine (sDMA), of Aub is essential for piRNA biogenesis, transposon silencing and fertility. Methylation is triggered by loading of a piRNA guide into Aub, which exposes its unstructured N-terminal region to the PRMT5 methylosome complex. Thus, sDMA modification is a signal that Aub is loaded with piRNA guide. Amplification of piRNA in the ping-pong cycle requires assembly of a tertiary complex scaffolded by Krimper, which simultaneously binds the N-terminal regions of Aub and Ago3. To promote generation of new piRNA, Krimp uses its two Tudor domains to bind Aub and Ago3 in opposite modification and piRNA-loading states. Our results reveal that post-translational modifications in unstructured regions of Piwi proteins and their binding by Tudor domains that are capable of discriminating between modification states is essential for piRNA biogenesis and silencing.

Highlights

sDMA modification of Aub is essential for ping-pong cycle, transposon silencing and fertility.

piRNA loading triggers Aub sDMA modification by exposing its unstructured N terminal region to the methylosome complex.

A single molecule of Krimp simultaneously binds piRNA-bound Aub and empty Ago3 to assemble ping-pong complex.

The distinct structure of two Tudor domains of Krimp ensures binding of Ago3 and Aub in opposite modification and piRNA-loading states.
Genetic basis of offspring number and body weight variation inDrosophila melanogaster
Authors: Akhund-Zade Jamilla , Lall Shraddha , Gajda Erika , Yoon Denise , de Bivort Benjamin
Published: July 2020

Drosophila melanogasteregg production, a proxy for fecundity, is an extensively studied life-history trait with a strong genetic basis. As eggs develop into larvae and adults, space and resource constraints can put pressure on the developing offspring, leading to a decrease in viability, body size, and lifespan. Our goal was to map the genetic basis of offspring number and weight under the restriction of a standard laboratory vial. We screened 143 lines from theDrosophilaGenetic Reference Panel for offspring numbers and weights to create an ‘offspring index’ that captured the number vs. weight trade-off. We found 30 associated variants in 18 genes. Validation ofhid,Sox21b,CG8312, andmubcandidate genes using gene disruption mutants demonstrated a role in adult stage viability, while mutations inIhandRbpincreased offspring number and increased weight, respectively. The polygenic basis of offspring number and weight, with many variants of small effect, as well as the involvement of genes with varied functional roles, support the notion of Fisher’s “infinitesimal model” for this life-history trait.
Stator remodeling mechanism ofBacillus subtilisflagellar motor during biofilm development
Authors: Terahara Naoya , Namba Keiichi , Minamino Tohru
Published: July 2020

Bacillus subtilispossesses two distinct types of stator protein complexes for the flagellar motor: H+-type MotAB and Na+-type MotPS. The MotPS complex is used when both the external Na+concentration and viscosity are high. Because deletion of themotPSgenes does not affect swimming motility of cells, a physiological role of MotPS-dependent motility remains unclear. Here, we report that the MotPS stator complex is required for efficient biofilm maturation. Depletion of the MotPS complex did not cause a significant delay in the initiation of biofilm formation but reduced the number of viable cells in the biofilm. The MotAB stator units were efficiently replaced by the MotPS complexes with an increase in the viscosity of the environments. Therefore, we propose that MotPS-dependent motility of motile cells in the biofilm structure is required to efficiently keep the bacterial society in the biofilm healthy.
Molecular insight into Nickel(II) binding by Her2-specific IgE: a possible mechanistic insight into the pathogenesis of Type I nickel hypersensitivity
Authors: Su Chinh Tran-To , Lua Wai-Heng , Poh Jun-Jie , Ling Wei-Li , Yeo Joshua Yi , Gan Samuel Ken-En
Published: July 2020

Nickel (Ni) allergy has been reported in contact dermatitis Type IV (Ni-specific T cells mediated) and asthmatic Type I (IgE-mediated) hypersensitivities. Associations between the two hypersensitivities have been found in some patients, but the underlying mechanisms remain enigmatic. Using Her2-specific IgEs as models, we found additional binding to Ni-NTA without observable changes in binding to Her2 and that glutamine, together with the canonical Ni2+-binding histidine, could form Ni2+binding signatures. This mechanism may underlie Type I hypersensitivity in the selection of anti-Ni2+IgEs. This mechanism may also underlie Type IV hypersensitivity and the interaction of immunoglobulin proteins with other heavy metal ions. Our findings shed light to how Ni hypersensitivities can occur and how they can be avoided in therapeutics design, or even incorporated for biotechnological purification purposes.
The molecular basis of socially-mediated phenotypic plasticity in a eusocial paper wasp
Authors: Taylor Benjamin A. , Cini Alessandro , Wyatt Christopher D. R. , Reuter Max , Sumner Seirian
Published: July 2020

Phenotypic plasticity, the ability to produce multiple phenotypes from a single genotype, represents an excellent model with which to examine the relationship between gene expression and phenotypes. Despite this, analyses of the molecular bases of plasticity have been limited by the challenges of linking individual phenotypes with individual-level gene expression profiles, especially in the case of complex social phenotypes. Here, we tackle this challenge by analysing the individual-level gene expression profiles ofPolistes dominulapaper wasps following the loss of a queen, a perturbation that induces some individuals to undergo a significant phenotypic shift and become replacement reproductives. Using a machine learning approach, we find a strong response of caste-associated gene expression to queen loss, wherein individuals’ expression profiles become intermediate between queen and worker states. Importantly, this change occurs even in individuals that appear phenotypically unaffected. Part of this response is explained by individual attributes, most prominently age. These results demonstrate that large changes in gene expression may occur in the absence of detectable phenotypic changes, resulting here in a socially mediated de-differentiation of individuals at the transcriptomic but not the phenotypic level. Our findings also highlight the complexity of the relationship between gene expression and phenotype, where transcriptomes are neither a direct reflection of the genotype nor a proxy for the molecular underpinnings of the external phenotype.
AGC kinase members phosphorylate ubiquitin
Authors: Kolbe Carl-Christian , Latz Eicke
Published: July 2020

The posttranslational modification of proteins with ubiquitin controls most cellular processes, such as protein degradation or transport, cell signaling, or transcription1–5. Ubiquitin can be phosphorylated at multiple sites, which likely further modulates the function of protein ubiquitination6,7. However, except for PINK18–10, the kinases involved in ubiquitin phosphorylation remain unknown, which hampers our understanding of phospho-ubiquitin signaling. In this study, we performed genome-wide in vitro kinase screenings and discovered that AGC kinases phosphorylate ubiquitin. Ubiquitin phosphorylation by members of the PKA, PKC, PKG and RSK families as well as by less well-characterized kinases, such as SGK2, was not solely dependent on peptide specificity but required additional kinase recruitment to ubiquitin. The stabilization of the kinase interaction with ubiquitin resulted in phosphorylation of suboptimal kinase motifs on ubiquitin, suggesting that ubiquitin phosphorylation is dictated primarily through the recruitment of kinases to the ubiquitinated proteins. Hence, we identify AGC kinase members as enzymes that can phosphorylate ubiquitin in a mechanism regulated by protein interactions outside of the catalytic kinase domain and are only applicable to specific subsets of ubiquitinated proteins.
Myeloid deletion and therapeutic activation of AMP-activated protein kinase (AMPK) do not alter atherosclerosis in male or female mice
Authors: LeBlond Nicholas D. , Ghorbani Peyman , O’Dwyer Conor , Ambursley Nia , Nunes Julia R. C. , Smith Tyler K.T. , Trzaskalski Natasha A. , Mulvihill Erin E. , Viollet Benoit , Foretz Marc , Fullerton Morgan D.
Published: July 2020

Objective

The dysregulation of myeloid-derived cell metabolism can drive atherosclerosis. AMP-activated protein kinase (AMPK) controls various aspects of macrophage dynamics and lipid homeostasis, which are important during atherogenesis.

Approach and Results

We aimed to clarify the role of myeloid-specific AMPK signaling by using LysM-Cre to drive the deletion of both the α1 and α2 catalytic subunits (MacKO), in male and female mice made acutely atherosclerotic by PCSK9-AAV and Western diet-feeding. After 6 weeks of Western diet feeding, half received daily injection of either the AMPK activator, A-769662 or a vehicle control for a further 6 weeks. After 12 weeks, myeloid cell populations were not different between genotype or sex. Similarly, aortic sinus plaque size, lipid staining and necrotic area were not different in male and female MacKO mice compared to their littermate floxed controls. Moreover, therapeutic intervention with A-769662 had no effect. There were no differences in the amount of circulating total cholesterol or triglyceride, and only minor differences in the levels of inflammatory cytokines between groups. Finally, CD68+ area or markers of autophagy showed no effect of either lacking AMPK signaling or systemic AMPK activation.

Conclusions

Our data suggest that while defined roles for each catalytic AMPK subunit have been identified, global deletion of myeloid AMPK signaling does not significantly impact atherosclerosis. Moreover, we show that intervention with the first-generation AMPK activator, A-769662, was not able to stem the progression of atherosclerosis.

Highlights

- The deletion of both catalytic subunits of AMPK in myeloid cells has no significant effect on the progression of atherosclerosis in either male or female mice

- Therapeutic delivery of a first-generation AMPK activator (A-769662) for the last 6 weeks of 12-week study had no beneficial effect in either male or female mice

- Studying total AMPK deletion may mask specific effects of each isoform and highlights the need for targeted disruption of AMPK phosphorylation sites via knock-in mutations, rather than the traditional “sledgehammer” knockout approach
NATURAL ENEMIES OF HERBIVORES MAINTAIN THEIR BIOLOGICAL CONTROL POTENTIAL UNDER FUTURE CO2, TEMPERATURE AND PRECIPITATION PATTERNS
Authors: Van Doan Cong , Pfander Marc , Guyer Anouk , Zhang Xi , Maurer Corina , Robert Christelle A.M.
Published: July 2020

Climate change will profoundly alter the physiology and ecology of plants, insect herbivores and their natural enemies, resulting in strong effects on multitrophic interactions. Yet, manipulative studies that investigate the direct combined impacts of changes in CO2, temperature, and precipitation on this group of organisms remain rare. Here, we assessed how three day exposure to elevated CO2, increased temperature, and decreased precipitation affect the performance and predation success on species from four major groups of natural enemies of insect herbivores: an entomopathogenic nematode, a wolf spider, a ladybug and a parasitoid wasp. Future climatic conditions (RCP 8.5), entailing a 28% decrease in precipitation, a 3.4°C raise in temperature and a 400 ppm increase in CO2levels, slightly reduced the survival of entomopathogenic nematodes, but had no effect on the survival of other species. Predation success was not negatively affected in any of the tested species, but was even increased for wolf spiders and entomopathogenic nematodes. Factorial manipulation of climate variables revealed a positive effect of reduced soil moisture on nematode infectivity, but not of increased temperature or elevated CO2. These results suggest that natural enemies of herbivores are well adapted to short term changes in climatic conditions and may not suffer from direct negative effects of future climates. These findings provide mechanistic insights that will inform future efforts to disentangle the complex interplay of biotic and abiotic factors that drive climate-dependent changes in multitrophic interaction networks.
The effective volumes of waters of crystallization: general organic solids
Authors: Glasser Leslie
Published: July 2020

Using a list of compatible hydrate/anhydrate pairs prepared by van de Streek and Motherwell [CrystEngComm (2007), 9, 55–64], we have examined the effective volume per water of crystallization for 179 pairs of organic solids using current data from the Cambridge Crystallographic Structural Database (CSD). The effective volume is the difference per water molecule between the asymmetric unit volumes of the hydrate and parent anhydrate, and has the mean value 24 Å3. The conformational changes in the reference molecule between the hydrate and its anhydrate are shown in two figures: one for a relatively rigid standard organic molecule and (in the supplementary file) one for a more flexible linear molecule. Using data from Nyman and Day [Phys. Chem. Chem. Phys. (2016), 18, 31132–31143], we have also established a generic volumetric coefficient of thermal expansion of organic solids with a value of 147 ± 56 × 10−6 K−1. There is a significant number of outliers to the data, negative, near zero, and large and positive. Some explanation for the existence of these outliers is attempted.
Electrical properties of graphite-glass thick-film resistors
Authors: Matusiak Tomasz , Dabrowski Arkadiusz , Golonka Leszek
Published: July 2020

Purpose

The purpose of this paper is to present the properties of thick-film resistors made of novel pastes prepared from glass and graphite.

Design/methodology/approach

Graphite-based resistors were made of thick-film pastes with different graphite-to-glass mass fraction were prepared and examined. Sheet resistance, temperature coefficient of resistance, impact of humidity and short-term overload were investigated. The properties of the layers fired in atmospheres of air at 550°C and nitrogen at 875°C were compared.

Findings

Graphite-based resistors with various graphite-to-glass ratios made possible to obtain a wide range of sheet resistance from single O/square to few kO/square. These values were dependent on firing atmosphere, paste composition and the number of screen-printed layers. The samples made of paste with 1:1 graphite-to-glass ratio exhibited the temperature coefficient of resistance of about −1,000 ppm/°C, almost independently on the firing atmosphere and presence of a top coating. The resistors fired in the air after coating with overglaze, exhibited significantly lower sheet resistance, reduced impact of humidity and improved power capabilities.

Originality/value

In this paper, graphite-based resistors for applications in typical high-temperature cermet thick-film circuits were presented, whereas typical graphite-based resistors were fabricated in polymer thick-film technology. Owing to very low cost of the graphite, the material is suitable for low-power passive circuits, where components are not subjected into high temperature, above the typical temperature of operation of standard electronic components.
FPGA-based experiments for demonstrating bi-stability in tabu learning neuron model
Authors: Zhu Dong , Hou Liping , Chen Mo , Bao Bocheng
Published: July 2020

Purpose

The purpose of this paper is to develop an field programmable gate array (FPGA)-based neuron circuit to mimic dynamical behaviors of tabu learning neuron model.

Design/methodology/approach

Numerical investigations for the tabu learning neuron model show the coexisting behaviors of bi-stability. To reproduce the numerical results by hardware experiments, a digitally FPGA-based neuron circuit is constructed by pure floating-point operations to guarantee high computational accuracy. Based on the common floating-point operators provided by Xilinx Vivado software, the specific functions used in the neuron model are designed in hardware description language programs. Thus, by using the fourth-order Runge-Kutta algorithm and loading the specific functions orderly, the tabu learning neuron model is implemented on the Xilinx FPGA board.

Findings

With the variation of the activation gradient, the initial-related coexisting attractors with bi-stability are found in the tabu learning neuron model, which are experimentally demonstrated by a digitally FPGA-based neuron circuit.

Originality/value

Without any piecewise linear approximations, a digitally FPGA-based neuron circuit is implemented using pure floating-point operations, from which the initial conditions-related coexisting behaviors are experimentally demonstrated in the tabu learning neuron model.
Topological asymptotic analysis of a diffusive–convective–reactive problem
Authors: Ruscheinsky Dirlei , Carvalho Fernando , Anflor Carla , Novotny Andre Antonio
Published: July 2020

Purpose

The purpose of this study is sensitivity analysis of the L2-norm and H1-seminorm of the solution of a diffusive–convective–reactive problem to topological changes of the underlying material.

Design/methodology/approach

The topological derivative method is used to devise a simple and efficient topology design algorithm based on a level-set domain representation method.

Findings

Remarkably simple analytical expressions for the sensitivities are derived, which are useful for practical applications including heat exchange topology design and membrane eigenvalue maximization.

Originality/value

The topological asymptotic expansion associated with a diffusive–convective–reactive equation is rigorously derived, which is not available in the literature yet.
Highly mature sediments in the tropical monsoonal environment of southwestern India: an appraisal based on weathering indices
Authors: Babu Linu , Mohan S. Vishnu , Mohan Mahesh , Pradeepkumar A.P.
Published: July 2020

Purpose

This paper aims to examine the geochemical change experienced by laterites in Kerala, India, subjected to tropical monsoonal climate. These sediments are underlain by hard rock. The source rock characteristics have a major stake on the ultimate composition of sediments, as also the climatic conditions which an area experience.

Design/methodology/approach

Core samples have been obtained from several locations in a lateritic plateau. The upper portions of the borehole cores are composed of the lateritic hard cap, followed by lateritic soils. The soil samples were subjected to sediment texture analysis and XRF analysis (Bruker S4 Pioneer Sequential Wavelength-Dispersive XRF) for the determination of major elements ((in oxide form).

Findings

Major element geochemistry has revealed the following order of relative proportions of elements (in oxide form) SiO2 > Al2O3 > Fe2O3 > TiO2 >> Na2O > P2O5 > CaO > K2O > MgO > MnO. Even though the concentrations of SiO2, Al2O3 and Fe2O3 contribute 90% of major element chemistry, there is no significant correlation found for these elements within themselves or with others.

Research limitations/implications

Microscale movement of elements could not be characterised in this study. This requires access to an electron probe micro analyzer.

Practical implications

The practical implication of tropical weathering is that enhanced chemical leaching leads to movement of most elements out of the system, except for Al, leading to the possible formation of bauxite, or aluminous laterite.

Social implications

The weathered products in this study provide livelihood sustenance for many of the local households, through manual production of laterite bricks, which are used in construction.

Originality/value

The indices of the intensity of chemical alteration/weathering like chemical index of alteration (CIA), chemical index of weathering (CIW) and weathering index of parker (WIP) reveal that the sediments indicate intense weathering of the source area prior to being deposited in the present location. This indicates enhanced monsoonal activity in the provenance areas, than that obtained today.
Forecasting the wind direction by using time series models with long-term memory (case study: Nayer region)
Authors: Soleimani Paria , Emami Bahareh , Rafei Meysam , Shahrasbi Hooman
Published: July 2020

Purpose

Today, because of the increasing need for the energy resources and the reduction of fossil fuels, renewable energy, especially wind energy, has attracted special attention. The precise forecasting of such energy will be the main factor in designing and investing in this field. On the other hand, the wind energy forecast provides the possibility of optimal use of available resources. In addition, the produce maximum energy would be possible by identifying wind direction and putting wind turbines in the best position.

Design/methodology/approach

Time series forecasting methods with long-term memory in this research have been used.

Findings

Eventually, the autoregressive fractionally integrated moving average (3,0,0)-FIGARCH (1,0,1) long-term memory model has more acceptable performance. The obtained error is based on the RMSE (0.2889) and the TIC (0.2605) values.

Practical implications

In this paper, the forecast wind direction belongs to Ardebil province and Nayer city in Iran.

Originality/value

The speed and direction of wind are variables that constantly change; hence, it will be difficult to predict the exact wind energy. In recent years, some studies have been conducted on wind speed forecasting, whereas wind direction forecasting has been done in a fewer number of studies. Most studies are related to low-lying areas. As the height of the wind turbine is directly related to the energy generation, 78 m height has been considered in this study.