bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery and Characterization of Low-Molecular Weight Inhibitors of Erwinia tracheiphila
Authors: Vrisman Cláudio M. , Deblais Loïc , Helmy Yosra A. , Johnson Reed , Rajashekara Gireesh , Miller Sally A.
Published: January 2020

Plant pathogenic bacteria in the genus Erwinia cause economically important diseases, including bacterial wilt of cucurbits caused by Erwinia tracheiphila. Conventional bactericides are insufficient to control this disease. Using high-throughput screening, 464 small molecules (SMs) with either cidal or static activity at 100 µM against a cucumber strain of E. tracheiphila were identified. Among them, 20 SMs (SM1 to SM20), composed of nine distinct chemical moiety structures, were cidal to multiple E. tracheiphila strains at 100 µM. These lead SMs had low toxicity to human cells and honey bees at 100 µM. No phytotoxicity was observed on melon plants at 100 µM, except when SM12 was either mixed with Silwet L-77 and foliar sprayed or when delivered through the roots. Lead SMs did not inhibit the growth of beneficial Pseudomonas and Enterobacter species but inhibited the growth of Bacillus species. Nineteen SMs were cidal to Xanthomonas cucurbitae and showed >50% growth inhibition against Pseudomonas syringae pv. lachrymans. In addition, 19 SMs were cidal or static against Erwinia amylovora in vitro. Five SMs demonstrated potential to suppress E. tracheiphila when foliar sprayed on melon plants at 2× the minimum bactericidal concentration. Thirteen SMs reduced Et load in melon plants when delivered via roots. Temperature and light did not affect the activity of SMs. In vitro cidal activity was observed after 3 to 10 h of exposure to these five SMs. Here, we report 19 SMs that provide chemical scaffolds for future development of bactericides against plant pathogenic bacterial species.
Predicting Alcohol Dependence from Multi-Site Brain Structural Measures
Authors: Hahn Sage , Mackey Scott , Cousijn Janna , Foxe John J. , Hester Robert , Hutchinson Kent , Korucuoglu Ozlem , London Edythe , Lorenzetti Valentina , Luijten Maartje , Momenan Reza , Orr Catherine , Paulus Martin , Schmaal Lianne , Sinha Rajita , Sjoerds Zsuzsika , Stein Dan J. , Stein Elliot , van Holst Ruth J. , Veltman Dick , Wiers Reinout W. , Yucel Murat , Thompson Paul M. , Conrod Patricia , Allgaier Nicholas , Garavan Hugh
Published: January 2020

Background

The search for neuroimaging biomarkers of alcohol use disorder (AUD) has primarily been restricted to significance testing in small datasets of low diversity. To identify neurobiological markers beyond individual differences, it may be useful to develop classification models for AUD. The ever-increasing quantity of neuroimaging data demands methods that are robust to the complexities of multi-site designs and are generalizable to data from new scanners.

Methods

This study represents a mega-analysis of previously published datasets from 2,034 AUD and comparison participants spanning 27 sites, coordinated by the ENIGMA Addiction Working Group. Data were grouped into a training set including 1,652 participants (692 AUD, 24 sites), and test set with 382 participants (146 AUD, 3 sites). A battery of machine learning classifiers was evaluated using repeated random cross-validation (CV) and leave-site-out CV. Area under the receiver operating characteristic curve (AUC) was our base metric of performance.

Results

Multi-objective evolutionary search was conducted to identify sparse, generalizable, and high performing subsets of brain measurements. Cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume, appeared most frequently across searches. Restricting a regularized logistic regression model to these four features yielded a test-set AUC of .768.

Conclusions

Developing classification models on multi-site data with varied underlying class distributions poses unique challenges. Supplementing datasets with controls from new sites and performing feature selection increases generalizability. Four features identified by evolutionary search may serve as specific biomarkers for individuals with current AUD.
Accurate CNV identification from only a few cells with low GC bias in a single-molecule sequencing platform
Authors: Hu Liang , Lin Qunting , Xie Pingyuan , Zeng Lidong , Liu Lichun , Huang Mengxian , Yan Qin , Zhang Meng , Lin Ge
Published: January 2020

A technical problem of characterizing copy number variation of several cells with next-generation sequencing is the whole genome amplification induced bias. The result of CNVs and mosaicism detection is affected by the GC bias. Here, we report a rapid non-WGA sample preparation strategy for a single-molecule sequencing platform GenoCare1600. This approach, combined with a single-molecule sequencing platform that avoids the use of WGA and bridge PCR processes, can provide higher reliability with its lower GC bias. By combining our optimized Tn5-based transposon insertion approach with GenoCare, we successfully detected CNVs as small as 1.29M and mosaicism as small as 20%, which is consistent with next-generation sequencing (NGS) data. Moreover, our GenoCare-TTI protocol showed less GC bias and less Mad of Diff. These results suggest that the optimized TTI approach, together with the GenoCare1600 sequencing platform, is a promising option for CNV characterization from maybe one single cell.
ARF1 dimerization is essential for vesicle trafficking and dependent on activation by ARF-GEF dimers in Arabidopsis
Authors: Brumm Sabine , Nielsen Mads Eggert , Richter Sandra , Beckmann Hauke , Stierhof York-Dieter , Singh Manoj K. , Fischer Angela-Melanie , Sundaresan Venkatesan , Jürgens Gerd
Published: January 2020

Membrane traffic maintains the organization of the eukaryotic cell and delivers cargo proteins to their subcellular destinations such as sites of action or degradation. Membrane vesicle formation requires ARF GTPase activation by the SEC7 domain of ARF guanine-nucleotide exchange factors (ARF-GEFs), resulting in the recruitment of coat proteins by GTP-bound ARFs.In vitroexchange assays were done with monomeric proteins, although ARF-GEFs have been shown to form dimersin vivo. This feature is conserved across the eukaryotes, however its biological significance is unknown. Here we demonstrate ARF1 dimerizationin vivoand we show that ARF-GEF dimers mediate ARF1 dimer formation. Mutational disruption of ARF1 dimers interfered with ARF1-dependent trafficking but not coat protein recruitment in Arabidopsis. Mutations disrupting simultaneous binding of two ARF1•GDPs by the two SEC7 domains of GNOM ARF-GEF dimer prevented stable interaction of ARF1 with ARF-GEF and thus, efficient ARF1 activation. Our results suggest a model of activation-dependent dimerization of membrane-inserted ARF1•GTP molecules required for coated membrane vesicle formation. Considering the evolutionary conservation of ARFs and ARF-GEFs, this initial regulatory step of membrane trafficking might well occur in eukaryotes in general.
High sensitivity (zeptomole) detection of BODIPY heparan sulfate (HS) disaccharides by ion-paired RP-HPLC and LIF detection enables analysis of HS from mosquito midguts
Authors: Maciej-Hulme Marissa L. , Leprince Anaëlle C. N. , Lavin Andre , Guimond Scott E. , Turnbull Jeremy E. , Pelletier Julien , Yates Edwin A. , Powell Andrew K. , Skidmore M. A.
Published: January 2020

The fine structure of heparan sulfate (HS), the glycosaminoglycan polysaccharide component of cell surface and extracellular matrix HS proteoglycans, coordinates the complex cell signalling processes that control homeostasis and drive development in multicellular animals. In addition, HS is involved in the infection of mammals by viruses, bacteria and parasites. The current detection limit for fluorescently labelled HS disaccharides that is in the low femtomole range (10-15mol), has effectively hampered investigations of HS composition from small, functionally-relevant populations of cells and tissues. Here, an ultra-high sensitivity method is described that utilises a combination of reverse-phase HPLC, with tetraoctylammonium bromide (TOAB) as the ion-pairing reagent and laser-induced fluorescence detection of BODIPY-FI-labelled disaccharides. The method provides an unparalleled increase in the sensitivity of detection by ∼ six orders of magnitude, to the zeptomolar range (∼10-21moles), enabling detection of <1000 labelled molecules. This facilitates determination of HS disaccharide compositional analysis from minute biological samples, as demonstrated by analysis of HS isolated from the midguts ofAnopheles gambiaemosquitoes that was achieved without approaching the limit of detection.
Capsaicin and its analogues impede nocifensive response ofCaenorhabditis elegansto noxious heat
Authors: Nkambeu Bruno , Salem Jennifer Ben , Beaudry Francis
Published: January 2020

Capsaicin is the most abundant pungent molecule identified in red chili peppers, and it is widely used for food flavoring, in pepper spray for self-defense devices and recently in ointments for the relief of neuropathic pain. Capsaicin and several other related vanilloid compounds are secondary plant metabolites. Capsaicin is a selective agonist of the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1). After exposition to vanilloid solution,C. eleganswild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index was used to phenotype each testedC. elegansexperimental groups. The data revealed for the first-time that capsaicin can impede nocifensive response ofC. elegansto noxious heat (32°C – 35°C) following a sustained exposition. The effect was reversed 6h post capsaicin exposition. Additionally, we identified the capsaicin target, theC. eleganstransient receptor potential channel OCR-2. Further experiments also undoubtedly revealed anti-nociceptive effect for capsaicin analogues, including ginger (Zingiber officinale) and turmeric (Curcuma longa) secondary metabolites.
Biomechanical Regulation of Breast Cancer Metastasis and Progression
Authors: Spencer Adrianne , Sligar Andrew D. , Chavarria Daniel , Lee Jason , Choksi Darshil , Patil Nikita P. , Lee HooWon , Veith Austin P. , Riley William J. , Desai Shubh , Abbaspour Ali , Singeetham Rohan , Baker Aaron B.
Published: January 2020

Physical activity has been consistently linked to decreased incidence of breast cancer and a substantial increase in the length of survival of patients with breast cancer. However, the understanding of how applied physical forces directly regulate breast cancer remains limited. We investigated the role of mechanical forces in altering the chemoresistance, proliferation and metastasis of breast cancer cells. We found that applied mechanical tension can dramatically alter gene expression in breast cancer cells, leading to decreased proliferation, increased resistance to chemotherapeutic treatment and enhanced adhesion to inflamed endothelial cells and collagen I under fluidic shear stress. A mechanistic analysis of the pathways involved in these effects supported a complex signaling network that included Abl1, Lck, Jak2 and PI3K to regulate pro-survival signaling and enhancement of adhesion under flow. Studies using mouse xenograft models demonstrated reduced proliferation of breast cancer cells with orthotopic implantation and increased metastasis to the skull when the cancer cells were treated with mechanical load. Using high throughput mechanobiological screens we identified pathways that could be targeted to reduce the effects of load on metastasis and found that the effects of mechanical load on bone colonization could be reduced through treatment with a PI3Kγ inhibitor.
Self-generated whisker movements drive state-dependent sensory input to developing barrel cortex
Authors: Dooley James C. , Glanz Ryan M. , Sokoloff Greta , Blumberg Mark S.
Published: January 2020

Summary

Cortical development is an activity-dependent process [1–3]. Regarding the role of activity in developing somatosensory cortex, one persistent debate concerns the importance of sensory feedback from self-generated movements. Specifically, recent studies claim that cortical activity is generated intrinsically, independent of movement [3, 4]. However, other studies claim that behavioral state moderates the relationship between movement and cortical activity [5–7]. Thus, perhaps inattention to behavioral state leads to failures to detect movement-driven activity [8]. Here, we resolve this issue by associating local field activity (i.e., spindle bursts) and unit activity in the barrel cortex of 5-day-old rats with whisker movements during wake and myoclonic twitches of the whiskers during active (REM) sleep. Barrel activity increased significantly within 500 ms of whisker movements, especially after twitches. Also, higher-amplitude movements were more likely to trigger barrel activity; when we controlled for movement amplitude, barrel activity was again greater after a twitch than a wake movement. We then inverted the analysis to assess the likelihood that increases in barrel activity were preceded within 500 ms by whisker movements: At least 55% of barrel activity was attributable to sensory feedback from whisker movements. Finally, when periods with and without movement were compared, 70–75% of barrel activity was movement-related. These results confirm the importance of sensory feedback from movements in driving activity in sensorimotor cortex and underscore the necessity of monitoring sleep-wake states to ensure accurate assessments of the contributions of the sensory periphery to activity in developing somatosensory cortex.
Arabidopsis ERF4 and MYB52 Transcription Factors Play Antagonistic Roles in Regulating Homogalacturonan De-methylesterification in Seed Coat Mucilage
Authors: Ding Anming , Tang Xianfeng , Han Linhe , Sun Jianlu , Ren Angyan , Sun Jinhao , Xu Zongchang , Hu Ruibo , Zhou Gongke , Kong Yingzhen
Published: January 2020

The Arabidopsis (Arabidopsis thaliana) seed coat mucilage is a specialized cell wall with pectin as its major component. Pectin is synthesized in the Golgi apparatus with homogalacturonan fully methylesterified, but it must undergo de-methylesterification by pectin methylesterase (PME) after being secreted into the cell wall. This reaction is critical for pectin maturation, but the mechanisms of its transcriptional regulation remain largely unknown. Here, we show that the Arabidopsis ERF4 transcription factor positively regulates pectin de-methylesterification during seed development and directly suppresses the expression ofPME INHIBITOR13(PMEI13),14,15andSUBTILISIN-LIKE SERINE PROTEASE 1.7(SBT1.7). Theerf4mutant seeds showed repartitioning of mucilage between soluble and adherent layers as a result of decreased PME activity and increased degree of pectin methylesterification. ERF4 physically associates with and antagonizes MYB52 in activatingPMEI6,14andSBT1.7and MYB52 also antagonizes ERF4 activity in the regulation of downstream targets. Gene expression studies revealed that ERF4 and MYB52 have opposite effects on pectin de-methylesterification. Genetic analysis indicated that theerf4-2 myb52double mutant seeds show mucilage phenotype similar to wild-type. Taken together, this study demonstrates that ERF4 and MYB52 antagonize each other’s activity to maintain the appropriate degree of pectin methylesterification, expanding our understanding of how pectin de-methylesterification is fine-tuned by the ERF4-MYB52 transcriptional complex in the seed mucilage.

One-sentence summary

Arabidopsis ERF4 and MYB52 transcription factors interact and play antagonistic roles in regulating homogalacturonan de-methylesterification related genes in the seed coat mucilage.
STAGdb: a 30K SNP genotyping array and Science Gateway for Acropora corals and their dinoflagellate symbionts
Authors: Kitchen S.A. , Von Kuster G. , Vasquez Kuntz K.L. , Reich H.G. , Miller W. , Griffin S. , Fogarty Nicole D. , Baums I.B.
Published: January 2020

Standardized identification of genotypes is necessary in animals that reproduce asexually and form large clonal populations such as coral. We developed a high-resolution hybridization-based genotype array coupled with an analysis workflow and database for the most speciose genus of coral,Acropora, and their symbionts. We designed the array to co-analyze host and symbionts based on bi-allelic single nucleotide polymorphisms (SNP) markers identified from genomic data of the two CaribbeanAcroporaspecies as well as their dominant dinoflagellate symbiont,Symbiodinium ‘fitti’.SNPs were selected to resolve multi-locus genotypes of host (called genets) and symbionts (called strains), distinguish host populations and determine ancestry of the coral hybrids in Caribbean acroporids. Pacific acroporids can also be genotyped using a subset of the SNP loci and additional markers enable the detection of symbionts belonging to the generaBreviolum, Cladocopium, andDurusdinium. Analytic tools to produce multi-locus genotypes of hosts based on these SNP markers were combined in a workflow called theStandardTools forAcroporidGenotyping (STAG). In the workflow the user’s data is compared to the database of previously genotyped samples and generates a report of genet identification. The STAG workflow and database are contained within a customized Galaxy environment (https://coralsnp.science.psu.edu/galaxy/), which allows for consistent identification of host genet and symbiont strains and serves as a template for the development of arrays for additional coral genera. STAG data can be used to track temporal and spatial changes of sampled genets necessary for restoration planning as well as be applied to downstream genomic analyses.
Geometric models for robust encoding of dynamical information into embryonic patterns
Authors: Jutras-Dubé Laurent , El-Sherif Ezzat , François Paul
Published: January 2020

During development, cells gradually assume specialized fates via changes of transcriptional dynamics, sometimes even within the same developmental stage. For anterior-posterior (AP) patterning in metazoans, it has been suggested that the gradual transition from a dynamic genetic regime to a static one is encoded by different transcriptional modules. In that case, the static regime has an essential role in pattern formation in addition to its maintenance function. In this work, we introduce a geometric approach to study such transition. We exhibit two types of genetic regime transitions, respectively arising through local or global bifurcations. We find that the global bifurcation type is more generic, more robust, and better preserves dynamical information. This could parsimoniously explain common features of metazoan segmentation, such as changes of periods leading to waves of gene expressions, “speed/frequency-gradient” dynamics, and changes of wave patterns. Geometric approaches appear as possible alternatives to gene regulatory networks to understand development.
Prenylation of axonally translated proteins controls NGF-dependent axon growth
Authors: Scott-Solomon Emily , Kuruvilla Rejji
Published: January 2020

Compartmentalized signaling is critical for cellular organization and specificity of functional outcomes in neurons. Here, we report that post-translational lipidation of newly synthesized proteins in axonal compartments allows for short-term and autonomous responses to extrinsic cues. Using conditional mutant mice, we found that protein prenylation is essential for sympathetic axon innervation of target organs. We identify a localized requirement for prenylation in sympathetic axons to promote axonal growth in response to the neurotrophin, Nerve Growth Factor (NGF). NGF triggers prenylation of proteins including the Rac1 GTPase in axons, counter to the canonical view of prenylation as constitutive, and strikingly, in a manner dependent on axonal protein synthesis. Newly prenylated proteins localize to TrkA-harboring endosomes in axons, and promote receptor trafficking necessary for axonal growth. Thus, coupling of prenylation to local protein synthesis presents a mechanism for spatially segregated cellular functions during neuronal development.
Poor hive thermoregulation produces an Allee effect and leads to colony collapse
Authors: Zeaiter Zeaiter , Myerscough Mary R.
Published: January 2020

In recent years the honey bee industry has bee experiencing increased loss of hives. The accumulation of multiple stressors on a hive potentially drives hive loss in various ways, including winter loss and colony collapse disorder. One of these stressors is the breakdown of thermoregulation inside the hive. For pupae to develop correctly into healthy adult bees, the temperature within the hive must be regulated by the hive bees to within a narrow range that ensures optimal development. Suboptimal development in adults affects their brain and flight muscles so bees becomes inefficient foragers with shorter life spans. We model the effect of thermoregulation on hive health using a system of delay differential equations that gives insights into how varying hive temperatures have an effect on the survival of the colony. We show that thermoregulatory stress has the capacity to drive colony loss in the model via a saddle-node bifurcation with an associated Allee effect.
Nipponbare and wild rice species as unexpected tolerance and susceptibility sources againstSchizotetranychus oryzae(Acari: Tetranychidae) mite infestation
Authors: Bufon Giseli , dos Reis Blasi Édina Aparecida , Lamb Thainá Inês , Adamski Janete Mariza , Schwambach Joséli , Ricachenevsky Felipe Klein , Bertolazi Amanda , Silveira Vanildo , Barbosa Lopes Mara Cristina , Sperotto Raul Antonio
Published: January 2020

Cultivated rice (Oryza sativaL.) is frequently exposed to multiple stresses, includingSchizotetranychus oryzaemite infestation. Rice domestication has narrowed the genetic diversity of the species, reducing the stress resistance and leading to a wide susceptibility. Therefore, wild rice species present an alternative to search for this lost variability. Aiming to observe the response of two wild rice species (Oryza barthiiandOryza glaberrima) and twoOryza sativagenotypes (cv. Nipponbare andO. sativaf.spontanea) toS. oryzaeinfestation, we used agronomic, physiological and molecular analyses. Surprisingly, analyses of leaf damage, histochemistry, chlorophyll concentration and chlorophyll fluorescence showed that the wild species present higher level of leaf damage, increased accumulation of H2O2and lower photosynthetic capacity when compared toO. sativagenotypes under infested conditions. Infestation did not affect plant height, but decreased tiller number, except in cv. Nipponbare, whose development was not affected. Infestation also caused the death of wild plants during the reproductive stage, unlikeO. sativagenotypes, which were able to tolerate stress and produce seeds. While infestation did not affect the weight of 1,000 grains in bothO. sativagenotypes, the number of panicles per plant was affected only inO. sativaf.spontanea, and the percentage of full seeds per panicle and seed length were increased only in cv. Nipponbare. Proteomic analysis allowed us to identify 195 differentially abundant proteins when comparing susceptible (O. barthii) and tolerant (O. sativacv. Nipponbare) genotypes under control and infested conditions. We found thatO. barthiihas a less abundant antioxidant arsenal. In addition, it is unable to modulate proteins involved with general metabolism and energy production under infested condition. In Nipponbare we found high abundance of detoxification-related proteins, general metabolic processes and energy production, which allows us to suggest that, under infested condition, the primary metabolism is maintained more active compared toO. barthii. Also, Nipponbare presents a greater abundance of defense-related proteins, such as osmotin, ricin B-like lectin, and protease inhibitors of the Bowman Birk trypsin inhibitor family, as well as higher levels of the compatible osmolyte Proline under infested condition. Identification of these differentially abundant proteins can be used as an important biotechnological tool in breeding programs that aim increased tolerance to phytophagous mite infestation.
A motor axonopathy in a mouse model of Duchenne Muscular Dystrophy
Authors: Dhindsa Justin S , McCall Angela L , Strickland Laura M , Fusco Anna F , Kahn Amanda F , Elmallah Mai K
Published: January 2020

Skeletal muscle weakness due to loss of dystrophin is a well-documented pathological hallmark of Duchenne muscular dystrophy (DMD). In contrast, the neuropathology of this disease remains understudied. Here, we characterize an axonopathy in the phrenic and hypoglossal (XII) nerves of mdx mice. We observe nerve dysfunction that we propose contributes to respiratory failure, the most common cause of death in DMD.
Quantitative microbiome profiling in lumenal and tissue samples with broad coverage and dynamic range via a single-step 16S rRNA gene DNA copy quantification and amplicon barcoding
Authors: Bogatyrev Said R. , Ismagilov Rustem F.
Published: January 2020

Current methods for detecting, accurately quantifying, and profiling complex microbial communities based on the microbial 16S rRNA marker genes are limited by a number of factors, including inconsistent extraction of microbial nucleic acids, amplification interference from contaminants and host DNA, different coverage of PCR primers utilized for quantification and sequencing, and potentially biases in PCR amplification rates among microbial taxa during amplicon barcoding. Here, we describe a single-step method that enables the quantification of microbial 16S rRNA gene DNA copies with wide dynamic range and broad microbial diversity, and simultaneous amplicon barcoding for quantitative 16S rRNA gene amplicon profiling of microbiota. The method is suitable for a variety of sample types and is robust in samples with low microbial abundance, including samples containing high levels of host mammalian DNA, as is common in human clinical samples. We demonstrate that our modification to the Earth Microbiome Project (EMP) V4 16S rRNA gene primers expands their microbial coverage while dramatically reducing non-specific mammalian mitochondrial DNA amplification, thus achieving wide dynamic range in microbial quantification and broad coverage for capturing high microbial diversity in samples with or without high host DNA background. The approach relies only on broadly available hardware (real-time PCR instruments) and standard reagents utilized for conventional 16S rRNA gene amplicon library preparation both of which make it amenable for immediate and widespread adoption. Simultaneous 16S rRNA gene DNA copy quantification and amplicon barcoding for multiplexed next-generation sequencing from the same analyzed sample, performed in a combined workflow, reduces the amount of sample needed and reduces time and reagent costs. Additionally, we demonstrate that using our modified 16S rRNA gene primers in a digital PCR (dPCR) format enables precise and exact microbial quantification in samples with very high host DNA background levels without the need for quantification standards. Potential future applications of this approach include: (1) quantitative microbiome profiling in human and animal microbiome research; (2) detection of monoinfections and profiling of polymicrobial infections in tissues, stool, and bodily fluids in human and veterinary medicine; (3) environmental sample analyses (e.g., soil and water); and (4) broad-coverage detection of microbial food contamination in products high in mammalian DNA, such as meat products. We predict that utilization of this approach primarily for quantitative microbiome profiling will be invaluable to microbiome studies, which have historically been limited to analysis of relative abundances of microbes.
Bacterial Growth Induced Biocementation Technology, ‘Space-Brick’ - A Proposal for Experiment at Microgravity and Planetary Environments
Authors: Kumar Aloke , Dikshit Rashmi , Gupta Nitin , Jain Animesh , Dey Arjun , Nandi Anuj , Venugopal I. , Viswanathan Koushik , Sridhara N. , Rajendra A.
Published: January 2020

We present results of our investigation of microbial induced calcite precipitation for manufacturing ‘space bricks’ and a proposal for study of this activity in low-earth orbit (LEO).Sporosarcina pasteurii, a urease producing bacterial strain was used to consolidate lunar simulant soil (LSS) in the form of a ‘brick’ with non-trivial strength properties. Potential of a naturally occurring polymer namely, guar gum, as an additive was investigated for enhancement in compressive strength of bio-consolidated samples. Experimental results of bio-brick exhibited an approximate 10-fold increase in compressive strength with guar gum supplementation in soil. We present results of microstructural analysis of the ‘space bricks’ and also propose a payload design for related experiments in LEO.
The combination of lipopolysaccharide and D-galactosamine administration show positive genotoxic effect in mice liver
Authors: Dong Wenjing , Song Erqun , Song Yang
Published: January 2020

Lipopolysaccharide (LPS)/D-galactosamine (D-GalN) co-administration induced acute liver injury (ALI) and hepatic fibrosis have been extensively studied. However, whether LPS/D-GalN show genotoxic effect is current unknown. Male mice were divided into eight groups and each group contain eight animals. For the acute administration of LPS/D-GalN, the mice were given a single intraperitoneal (i.p.) injection of LPS/D-GalN (25 μg/kg + 250 mg/kg, 25 μg/kg + 500 mg/kg, 50 μg/kg + 500 mg/kg body weight) for 6 h, respectively. The chronic administration was conduct by thei.p.injection of LPS/D-GalN (10 μg/kg + 100 mg/kg) every other day for 8 weeks. Saline solution (0.9%) and cyclophosphamide (CTX) (50 mg/kg body weight) injection were used as negative and positive control, respectively. Using single cell gel electrophoresis (SCGE) assay, we found that the acute administration of LPS/D-GalN induces severe DNA damage in mice hepatic cells, but not in brain, sperm and bone marrow cells, implied the genotoxicity of LPS/D-GalN. Interestingly, the chronic treatment of LPS/D-GalN causes significant genotoxic effect in both hepatic and brain cells, but not sperm and bone marrow cells. Histopathological examination in liver and brain section consistent with SCGE results, accordingly. Our study, for the first time, reported the genotoxic potential of LPS/D-GalN co-administration. In addition, LPS/D-GalN administration may serve as an experimental model for further genotoxic study.
Role of the medial prefrontal cortex in the effects of rapid acting antidepressants on decision-making biases in rodents
Authors: Hales CA , Bartlett JM , Arban R , Hengerer B , Robinson ESJ
Published: January 2020

Major Depressive Disorder is a significant and costly cause of global disability. Until the discovery of the rapid acting antidepressant (RAAD) effects of ketamine, treatments were limited to drugs that have delayed clinical benefits. The mechanism of action of ketamine is currently unclear but one hypothesis is that it may involve neuropsychological effects mediated through modulation of affective biases (where cognitive processes such as learning and memory and decision-making are modified by emotional state). Previous work has shown that affective biases in a rodent decision-making task are differentially altered by ketamine, compared to conventional, delayed onset antidepressants. This study sought to further investigate these effects by comparing ketamine with other NMDA antagonists using this decision-making task. We also investigated the subtype selective GluN2B antagonist, CP-101,606 and muscarinic antagonist scopolamine which have both been shown to have RAAD effects. Both CP-101,606 and scopolamine induced similar positive biases in decision-making to ketamine, but the same effects were not seen with other NMDA antagonists. Using targeted medial prefrontal cortex (mPFC) infusions, these effects were localised to the mPFC. In contrast, the GABAAagonist, muscimol, induced general disruptions to behaviour. These data suggest that ketamine and other RAADs mediate a specific effect on affective bias which involves the mPFC. Non-ketamine NMDA antagonists lacked efficacy and we also found that temporary inactivation of the mPFC did not fully recapitulate the effects of ketamine, suggesting a specific mechanism.
Speech-in-noise detection is related to auditory working memory precision for frequency
Authors: Lad Meher , Holmes Emma , Chu Agatha , Griffiths Timothy D
Published: January 2020

Speech-in-noise (SiN) perception is a critical aspect of natural listening, deficits in which are a major contributor to the hearing handicap in cochlear hearing loss. Studies suggest that SiN perception correlates with cognitive skills, particularly phonological working memory: the ability to hold and manipulate phonemes or words in mind. We consider here the idea that SiN perception is linked to a more general ability to hold sound objects in mind, auditory working memory, irrespective of whether the objects are speech sounds. This process might help combine foreground elements, like speech, over seconds to aid their separation from the background of an auditory scene.

We investigated the relationship between auditory working memory precision and SiN thresholds in listeners with normal hearing. We used a novel paradigm that tests auditory working memory for non-speech sounds that vary in frequency and amplitude modulation (AM) rate. The paradigm yields measures of precision in frequency and AM domains, based on the distribution of participants’ estimates of the target. Across participants, frequency precision correlated significantly with SiN thresholds. Frequency precision also correlated with the number of years of musical training. Measures of phonological working memory did not correlate with SiN detection ability.

Our results demonstrate a specific relationship between working memory for frequency and SiN. We suggest that working memory for frequency facilitates the identification and tracking of foreground objects like speech during natural listening. Working memory performance for frequency also correlated with years of musical instrument experience suggesting that the former is potentially modifiable.
Cancer-associated HIF-2α impacts trunk neural crest stemness
Authors: Mohlin Sofie , Persson Camilla U. , Fredlund Elina , Monni Emanuela , Lindvall Jessica M. , Kokaia Zaal , Hammarlund Emma , Bronner Marianne E.
Published: January 2020

The neural crest is a stem cell population that gives rise to sympathetic ganglia, the cell type of origin of neuroblastoma. Hypoxia Inducible Factor (HIF)-2α is associated with high risk neuroblastoma, however, little is known about its role in normal neural crest development. To address this important question, here we show that HIF-2α is expressed in trunk neural crest cells of human, murine and avian embryos. Modulating HIF-2α in vivonot only causes developmental delays but also induces proliferation and stemness of neural crest cells while altering the number of cells migrating ventrally to sympathoadrenal sites. Transcriptome changes after loss of HIF-2α reflect thein vivophenotype. The results suggest that expression levels of HIF-2α must be strictly controlled and abnormal levels increase stemness and may promote metastasis. Our findings help elucidate the role of HIF-2α during normal development with implications also in tumor initiation at the onset of neuroblastoma.
Epithelial organ shape is generated by patterned actomyosin contractility and maintained by the extracellular matrix
Authors: Nematbakhsh Ali , Levis Megan , Kumar Nilay , Chen Weitao , Zartman Jeremiah , Alber Mark
Published: January 2020

Epithelial sheets play important roles in defining organ architecture during development. Here, we employed an iterative experimental and multi-scale computational modeling approach to decouple direct and indirect effects of actomyosin-generated forces, nuclear positioning, extracellular matrix (ECM), and cell-cell adhesion in shapingDrosophilawing imaginal discs, a powerful system for elucidating general principles of epithelial morphogenesis. Basally generated actomyosin forces are found to regulate apically biased nuclear positioning and are required for generating epithelial bending and cell elongation of the wing disc pouch. Surprisingly, however, short-term pharmacological inhibition of ROCK-driven actomyosin contractility does not impact the maintenance of tissue height or curved shape. In comparison, the relative tautness of the extracellular basement membrane is also patterned between regions of the wing disc. However, computational simulations show that patterning of ECM tautness provides only a minor contribution to modulating tissue shape. Instead, the buildup of a passive ECM pre-strain serves a principle role in shape maintenance. Surprisingly, this is independent from the maintenance of actomyosin contractility. Furthermore, localized apical adhesion between the two cell layers within the wing disc requires ROCK-driven actomyosin activity in the absence of the basal extracellular matrix. This apical adhesion between the two cell layers provides additional mechanical support to help maintain tissue integrity. The combined experimental and computational approach provides general insight into how the subcellular forces are generated and maintained within individual cells to induce tissue curvature and suggests an important design principle of epithelial organogenesis whereby forces generated by actomyosin followed by maintenance as pre-strain within the ECM are interconnected, but functionally separable.

Significance statement

A major outstanding question in developmental biology is the elucidation of general principles of organ shape formation and maintenance. Here, an iterative experimental and multi-scale computational modeling approach reveals that actomyosin contractility generates the bent profile along the anterior-posterior axis while tension within the ECM is sufficient and necessary for preserving the bent shape even in the absence of continued actomyosin contractility once the shape is generated. The mechanisms tested in this study define the necessary factors for establishing the shape of the wing disc, which later everts to form the adult wing during pupal development. The method can be extended to test novel mechanisms of other epithelial systems that consist of several cellular and ECM layers.
A Bayesian and efficient observer model explains concurrent attractive and repulsive history biases in visual perception
Authors: Fritsche Matthias , Spaak Eelke , de Lange Floris P.
Published: January 2020

Perceptual decisions can be repelled away from (repulsive adaptation) or attracted towards recent visual experience (attractive serial dependence). It is currently unclear whether and how these repulsive and attractive biases interact during visual processing and what computational principles may underlie these history dependencies. In the current study, we disentangle repulsive and attractive biases by exploring the respective timescales over which current visual processing is influenced by previous experience. Across four experiments, we find that perceptual decisions about stimulus orientation are concurrently attracted towards the short-term perceptual history and repelled from stimuli experienced up to minutes into the past. We show that the temporal pattern of short-term attraction and long-term repulsion cannot be captured by an ideal Bayesian observer model alone. Instead, it is well captured by an ideal observer model with efficientencodingand Bayesiandecodingof visual information in a slowly changing environment. Concurrent attractive and repulsive history biases in perceptual decisions may thus be the consequence of the need for visual processing to simultaneously satisfy constraints of both efficiency and stability.
Ginseng Ameliorates Effect of Prolonged Use of Omeprazole in Rat Renal Cortex through Decreasing Inflammation, Fibrosis and Apoptosis
Authors: Abdel Dayem Dina Ali Maher , Mahmoud Ahmed Sayed , Ali Azza Hussein , El-Tahawy Nashwa Fathy Gamal
Published: January 2020

Omeprazole is used in acid-related gastrointestinal disorders but has prolonged usage adverse effects. The aim was to study changes in renal cortex following chronic Omeprazole administration and the possible protective role of ginseng. Rats were divided into control (C-), Ginseng (G-), omeprazole (OM-), and omeprazole-ginseng (OM-G) groups. Serum urea and creatinine levels and 24-hours urine-protein were determined. Kidneys were processed for histological study. Serum urea and creatinine and 24-hours protein were significantly higher in OM-group compared to controls and significantly decreased in OM-G group comparing to OM-group. OM-group showed significant glomerular and tubulointerstitial injury with vascular congestion, inflammatory cell infiltration, partial or complete damage of apical brush border of most tubules, interrupted basement membranes of glomerular capillaries and tubules, marked increase in collagen deposition, and significant increases in COX-2 and caspase-3 immune-expression. Co-administration of ginseng with omeprazole resulted in marked and significant improvement of these morphological changes.

Conclusion

Omeprazole induced renal functional and morphological changes through inflammatory reaction, induction of fibrosis, cellular degeneration and apoptosis. Co-administration of ginseng ameliorated these effects through its anti-inflammatory, anti-fibrotic, and anti-apoptotic effects.
Ketamine blocks morphine-induced conditioned place preference and anxiety-like behaviors in mice
Authors: McKendrick Greer , Garrett Hannah , Jones Holly E. , McDevitt Dillon S. , Sharma Sonakshi , Silberman Yuval , Graziane Nicholas M.
Published: January 2020

Patients suffering from opioid use disorder often relapse during periods of abstinence, which is posited to be caused by negative affective states that drive motivated behaviors. Here, we explored whether conditioning mice with morphine in a CPP training paradigm evoked anxietylike behavior during morphine abstinence. To do this, mice were conditioned with morphine (10 mg/kg, i.p.) for five days. 24 h following conditioning, anxiety levels were tested by measuring time in the open arms of the elevated plus maze. The next day, mice were placed in the three compartment chamber to measure morphine-induced conditioned place preference (CPP). Our results show that following morphine conditioning, mice spent significantly less time in the open arm of the elevated plus maze and expressed robust morphine CPP on CPP test day. Furthermore, we found that an acute treatment with (R,S)-ketamine (10 mg/kg, i.p.), a medication demonstrating promise for preventing anxiety-related phenotypes, 30 min. prior to testing on post conditioning day 1, increased time spent in the open arm of the elevated plus maze in saline- and morphine-conditioned mice. Additionally, we found that a second injection of ketamine 30 min. prior to CPP tests on post conditioning day 2 prevented morphine-induced CPP, which lasted for up to 28 d post conditioning. Furthermore, we found that conditioning mice with 10% (w/v) sucrose using an oral self-administration procedure did not evoke anxietylike behavior, but elicited robust CPP, which was attenuated by ketamine treatment 30 min. prior to CPP tests. Overall, our results suggest that the ketamine-induced block of morphine CPP may not be attributed solely to alleviating negative affective states, but potentially through impaired memory of morphine-context associations.
Report of the Executive Committee for 2018
Authors: Ashcroft A. T.
Published: January 2020

The report of the Executive Committee for 2018 is presented.
A new optimization model for design of traditional cockpit interfaces
Authors: Şenol Mehmet Burak
Published: January 2020

Purpose

Real flight is cognitively demanding; accordingly, both indicators and display panel layout should be user-friendly to improve pilot-aircraft interaction. Poor pilot-interface interactions in aircrafts could result in accidents. Although a general reason of accidents is improper displays, relatively few studies were conducted on interfaces. This study aims to present an optimization model to create intuitively integrated user-friendly cockpit interfaces.

Design/methodology/approach

Subjectivity within most usability evaluation techniques could bring about interface design problems.A prioriinformation about indicator’s possible locations may be available or unavailable. Thus different analytical approaches must be applied for modifications and new interface designs. Relative layout design (RLD) model was developed and used in new interface designs to optimize locations of indicators. This model was based on layout optimization and constructed in accordance with design requirements, ergonomic considerations with the pilot preferences. RLD model optimizes interface design by deploying indicators to the best locations to improve usability of display panel, pilot-aircraft interaction and flight safety.

Findings

Optimum interfaces for two problem instances were gathered by RLD model in 15.77 CPU(s) with 10 indicators and 542.51 CPU(s) with 19 indicators. A comparison between relative and existing cockpit interfaces reveals that locations of six navigation and four mechanical system indicators are different. The differences may stem from pilots’ preferences and relativity constraints. Both interfaces are more similar for the central part of the display panel. The objective function value of relative interface design (Opt: 527938) is far better than existing interface (737100). The RLD model improved usability of existing interface (28.61 per cent considering decrease in the objective function values from 737100 to 527938.

Practical implications

Future cockpit and new helicopter interface designs may involve RLD model as an alternative interface design tool. Furthermore, other layout optimization problems, e.g. circuit boards, microchips and engines, etc. could be handled in a more realistic manner by RLD model.

Originality/value

Originality and impact of this study related to development and employment of a new optimization model (RLD) on cockpit interface design for the first time. Engineering requirements, human factors, ergonomics and pilots’ preferences are simultaneously considered in the RLD model. The subjectivity within usability evaluation techniques could be diminished in this way. The contributions of RLD model to classical facility layout models are relativity constraints with the physical constrictions and ergonomic objective function weights. Novelty of this paper is the development and employment of a new optimization model (RLD) to locate indicators.