bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rice embryogenic trigger BABY BOOM1 promotes somatic embryogenesis by upregulation of auxin biosynthesis genes
Authors: Khanday Imtiyaz , Santos-Medellín Christian , Sundaresan Venkatesan 
Published: August 2020

ABSTRACTSomatic embryogenesis, a powerful tool for clonal propagation and for plant transformation, involves cellular reprogramming of differentiated somatic cells to acquire pluripotency. Somatic embryogenesis can be induced by treating explants with plant growth regulators. However, several plant species including agronomically important cereal crops remain recalcitrant to dedifferentiation and transformation except from embryonic tissues. Somatic embryogenesis can also be induced by ectopic expression of select embryonic factors, including in cereals byBABY BOOM (BBM)transcription factors. HowBBMgenes bypass the need for exogenous hormones is not well understood. Here, we investigated downstream targets during induction of somatic embryogenesis in rice byOsBBM1((Oryza sativa BABY BOOM1). Transient induction ofOsBBM1led to the upregulation of auxin biosynthesisOsYUCCAgenes. Continued induction ofOsBBM1resulted in somatic embryogenesis without the need for exogenous auxins. Genetic mutant analysis ofOsBBM1downstream targets,OsYUCCA6, OsYUCCA7andOsYUCCA9, show that they are required for normal rice development including root and shoot development. Somatic embryogenic potential ofOsYUCCAtriple mutants was highly compromised despite the presence of exogenous auxin. Additionally, we show that somatic embryogenesis induction by exogenous auxin in rice requires functionalBBMgenes. Thus,OsBBM1mediated cellular reprogramming and somatic embryogenesis likely involves increased localized auxin through direct upregulation ofOsYUCCAgenes. This study reveals mechanistic details of how somatic embryogenesis is established in differentiated tissues in rice, a monocot model and agronomically important cereal crop, with the potential utility to improve regeneration from tissue culture for recalcitrant plants in future.One-sentence summaryRice BABY BOOM1 induces somatic embryogenesis from differentiated tissues by promoting auxin biosynthesis through direct upregulation ofYUCCAgenes.
Lamellar cells in Pacinian and Meissner corpuscles are touch sensors
Authors: Nikolaev Yury A. , Feketa Viktor V. , Anderson Evan O. , Gracheva Elena O. , Bagriantsev Sviatoslav N. 
Published: August 2020

AbstractThe skin covering the human palm and other specialized tactile organs contains a high density of mechanosensory corpuscles tuned to detect transient pressure and vibration. These corpuscles comprise a sensory afferent neuron surrounded by lamellar cells1-3. The neuronal afferent is thought to be the mechanical sensor within the corpuscle, whereas the function of lamellar cells is unknown2,4,5. Here we show that lamellar cells within Meissner and Pacinian corpuscles detect tactile stimuli. We develop a preparation of bill skin from tactile-specialist ducks that permits electrophysiological recordings from lamellar cells and demonstrate that they contain mechanically-gated ion channels. We also show that lamellar cells from Meissner corpuscles generate mechanically-evoked action potentials using R-type voltage-gated calcium channels. These findings provide the first evidence for R-type channel-dependent action potentials in non-neuronal cells and demonstrate that lamellar cells are active detectors of touch. We propose that Meissner and Pacinian corpuscles use both neuronal and non-neuronal mechanoreception to detect mechanical signals.
Click evoked middle ear muscle reflex: Spectral and temporal aspectsa)
Authors: Boothalingam Sriram , Goodman Shawn S. 
Published: August 2020

AbstractThis study describes a time series-based method of middle ear muscle reflex (MEMR) detection using bilateral clicks. Although many methods can detect changes in the OAE evoking stimulus to monitor the MEMR, they do not discriminate between true MEMR-mediated vs. artifactual changes in the stimulus. We measured MEMR in 20 young clinically normal hearing individuals using 1-second-long click trains presented at six levels (65 to 95 dB peak-to-peak SPL in 6 dB steps). Changes in the stimulus levels over the 1 second period were well-approximated by two-term exponential functions. The magnitude of ear canal pressure changes due to MEMR increased monotonically as a function of click level but non-monotonically with frequency when separated into 1/3rd-octave wide bands between 1 and 3.2 kHz. MEMR thresholds estimated using this method were lower than that obtained from a clinical tympanometer in ∼94% of the participants. A time series-based method, along with statistical tests, may provide additional confidence in detecting the MEMR. MEMR effects were smallest at 2 kHz, between 1 and 3.2 kHz, which may provide avenues for minimizing the MEMR influence while measuring other responses (e.g., the medial olivocochlear reflex).
Enhancing c-MYC degradation via 20S proteasome activation inducesin vivoanti-tumor efficacy
Authors: Njomen Evert , Lansdell Theresa A. , Vanecek Allison , Benham Vanessa , Bernard Matt P. , Yang Ya-Ting , Schall Peter Z. , Isaac Daniel , Alkharabsheh Omar , Al-Janadi Anas , Giletto Matthew B. , Ellsworth Edmund , Taylor Catherine , Tang Terence , Lau Sarah , Bailie Marc , Bernard Jamie J. , Yuzbasiyan-Gurkan Vilma , Tepe Jetze J. 
Published: August 2020

SUMMARYEnhancing proteasome activity is a potential new therapeutic strategy to prevent the accumulation of aberrant high levels of protein that drive the pathogenesis of many diseases. Herein, we examine the use of small molecules to activate the 20S proteasome to reduce aberrant signaling by the undruggable oncoprotein c-MYC, to treat c-MYC driven oncogenesis. Overexpression of c-MYC is found in more than 50% of all human cancer but remains undruggable because of its highly dynamic intrinsically disordered 3-D conformation, which renders traditional therapeutic strategies largely ineffective. We demonstrate herein that small molecule activation of the 20S proteasome targets dysregulated intrinsically disordered proteins (IDPs), including c-MYC, and reduces cancer growthin vitroandin vivomodels of multiple myeloma, and is even effective in bortezomib resistant cells and unresponsive patient samples. Genomic analysis of various cancer pathways showed that proteasome activation results in downregulation of many c-MYC target genes. Moreover, proteasome enhancement was well tolerated in mice and dogs. These data support the therapeutic potential of 20S proteasome activation in targeting IDP-driven proteotoxic disorders, including cancer, and demonstrate that this new therapeutic strategy is well toleratedin vivo.
Identification of an N-acetylneuraminic acid-presenting bacteria isolated from a healthy human microbiome
Authors: Han Zhen , Thuy-Boun Peter S. , Pfeiffer Wayne , Vartabedian Vincent F. , Torkamani Ali , Teijaro John R. , Wolan Dennis W. 
Published: August 2020

AbstractN-acetylneuraminic acid is the most abundant sialic acid in humans and is generally expressed as the terminal sugar on intestinal mucus glycans. Several pathogenic bacterial species harvest sialic acid from the mucus, diet, as well as other intestinal sources and display this sugar on their own surface to evade sialic acid-binding immunoglobulin-type lectin (Siglec)-mediated host immune surveillance. While previous studies have identified bacterial enzymes associated with sialic acid catabolism, no reported methods permit the selective labeling, tracking, and quantitation of sialic acid-presenting microbes within complex multi-microbial systems. Here, we apply an interdisciplinary approach combining metabolic labeling, click chemistry, metagenomic, and whole-genome sequencing to selectively track and identify sialic acid-presenting microbes from a cultured healthy human fecal microbiome. We isolated and identified a new strain ofEscherichia colithat incorporates sialic acid onto its own surface. Analysis of the sequence data reveals that thisE. colistrain encodes for the NanT, NeuA, and NeuS genes necessary for harvesting environmental sialic acid and generating the capsular polysialic acid. We envision that this method is applicable to the detection and quantitation of sialic acid-presenting bacteria from human, animal, and environmental microbiomes, as well as investigating the importance of other carbohydrates to commensal and pathogenic bacteria.
Genomic diversity generated by a transposable element burst in a rice recombinant inbred population
Authors: Chen Jinfeng , Lu Lu , Robb Sofia M.C. , Collin Matthew , Okumoto Yutaka , Stajich Jason E. , Wessler Susan R. 
Published: August 2020

AbstractGenomes of all characterized higher eukaryotes harbor examples of transposable element (TE) bursts - the rapid amplification of TE copies throughout a genome. Despite their prevalence, understanding how bursts diversify genomes requires the characterization of actively transposing TEs before insertion sites and structural rearrangements have been obscured by selection acting over evolutionary time. In this study rice recombinant inbred lines (RILs), generated by crossing a bursting accession and the reference Nipponbare accession were exploited to characterize the spread of the very activePing/mPingfamily through a small population and the resulting impact on genome diversity. Comparative sequence analysis of 272 individuals led to the identification of over 14,000 new insertions of themPingminiature inverted-repeat transposable element (MITE) with no evidence for silencing of the transposase-encodingPingelement. In addition to new insertions,Ping-encoded transposase was found to preferentially catalyze the excision ofmPingloci tightly linked to a secondmPinginsertion. Similarly, structural variations, including deletion of rice exons or regulatory regions, were enriched for those with breakpoints at one or both ends of linkedmPingelements. Taken together, these results indicate that structural variations are generated during a TE burst as transposase catalyzes both the high copy numbers needed to distribute linked elements throughout the genome and the DNA cuts at the TE ends known to dramatically increase the frequency of recombination.Significance StatementTransposable elements (TEs) represent the largest component of the genomes of higher eukaryotes. Among this component are some TEs that have attained very high copy numbers with hundreds, even thousands of elements. By documenting the spread ofmPingelements throughout the genomes of a rice population we demonstrate that such bursts of amplification generate functionally relevant genomic variations upon which selection can act. Specifically, continuedmPingamplification increases the number of tightly linked elements that, in turn, increases the frequency of structural variations that appear to be derived from aberrant transposition events. The significance of this finding is that it provides a TE-mediated mechanism that may generate much of the structural variation represented by pan-genomes in plants and other organisms.
Origin and evolutionary dynamics of multi-drug resistant and highly virulent community-associated methicillin-resistantStaphylococcus aureusST772-SCCmecV lineage
Authors: Bakthavatchalam Yamuna Devi , Vasudevan Karthick , Rao ShomaVinay , Varughese Santosh , Rupali Priscilla , Gina Maki , Zervos Marcus , Peter John Victor , Veeraraghavan Balaji 
Published: August 2020

BackgroundCommunity-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) are increasing in prevalence across the world. However, studies on the molecular epidemiology and the genomic investigation of MRSA are limited in India.ObjectivesTo understand the molecular epidemiology of MRSA and to reconstruct the origin and evolution ofS. aureusbelonged to the sequence type (ST772).MethodsA total of 233 non-repetitive MRSA isolates were screened for the presence staphylococcal cassette chromosome (SCCmec) types, multi-locus sequence types (MLST) and staphylococcal protein A (spa) types. Whole genome sequence data of ST772-SCCmecV (n=32) isolates were generated and analysed along with the publically available ST772-SCCmecV (n=273) genome.ResultsST772 (27%), ST22 (19%) and ST239 (16%) were found as the predominant STs. Analysis of the core SNPs using Bayesian time scaled phylogenetic analysis showed ST772-SCCmecV was emerged on the Indian subcontinent in 1960s. The acquisition of integrated resistance plasmid (IRP) in the ST772-SCCmecV lineage during 1990s, fixation of SCCmecV (5C2) and the double serine mutations (S84L, S80Y) appears to have played a key role in the successful expansion. The IRP carries the loci for multiple antibiotic resistant genes: beta-lactam (blaZ), aminoglycosides (aphA3-sat-aadE), macrolide (mphC), macrolide-lincosamide-streptogramin B (msrA) and bacitracin (bacA,bacB).ConclusionThe Panton Valentine Leukocidin (PVL) positive ST772 and ST22 MRSA lineages are observed in the hospital settings. ST772-SCCmecV has the multi-drug resistance trait of hospital-associated (HA) MRSA and the epidemiological characteristics of CA-MRSA. The antimicrobial use pattern may have driven the spread and survival of ST772 MRSA in hospitals.
Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting
Authors: Tantale Katiana , Garcia-Oliver Encarnation , L’Hostis Adèle , Yang Yueyuxio , Robert Marie-Cécile , Gostan Thierry , Basu Meenakshi , Kozulic-Pirher Alja , Andrau Jean-Christophe , Muller Florian , Basyuk Eugenia , Radulescu Ovidiu , Bertrand Edouard 
Published: August 2020

SummaryPromoter-proximal polymerase pausing is a key process regulating gene expression. In latent HIV-1 cells, it prevents viral transcription and is essential for latency maintenance, while in acutely infected cells the viral factor Tat releases paused polymerase to induce viral expression. Pausing is fundamental for HIV-1, but how it contributes to bursting and stochastic viral reactivation is unclear. Here, we performed single molecule imaging of HIV-1 transcription, and we developed a quantitative analysis method that manages multiple time scales from seconds to days, and that rapidly fits many models of promoter dynamics. We found that RNA polymerases enter a long-lived pause at latent HIV-1 promoters (>20 minutes), thereby effectively limiting viral transcription. Surprisingly and in contrast to current models, pausing appears stochastic and not obligatory, with only a small fraction of the polymerases undergoing long-lived pausing in absence of Tat. One consequence of stochastic pausing is that HIV-1 transcription occurs in bursts in latent cells, thereby facilitating latency exit and providing a rationale for the stochasticity of viral rebounds.
Exogenous disturbances and endogenous self-organized processes are not mutually exclusive drivers of spatial patterns in macroalgal assemblages
Authors: He J. , Rindi L. , Mintrone C. , Benedetti-Cecchi L. 
Published: August 2020

AbstractComplex spatial patterns are common in coastal marine systems, but mechanisms underlying their formation are disputed. Most empirical work has focused on exogeneous spatially structured disturbances as the leading cause of pattern formation in species assemblages. However, theoretical and observational studies suggest that complex spatial patterns, such as power laws in gap-size distribution, may result from endogenous self-organized processes involving local-scale interactions. The lack of studies simultaneously assessing the influence of spatially variable disturbances and local-scale interactions has fuelled the idea that exogenous and endogenous processes are mutually exclusive explanations of spatial patterns in marine ecosystems. To assess the relative contribution of endogenous and exogenous processes in the emergence of spatial patterns, an intertidal assemblage of algae and invertebrates was exposed for 2 years to various combinations of intensity and spatial patterns of disturbance. Localized disturbances impinging at the margins of previously disturbed clearings and homogenous disturbances without any spatial pattern generated heterogeneous distributions of disturbed gaps and macroalgal patches, characterized by a truncated or a pure power-law scaling. Spatially varying disturbances produced a spatial gradient in the distribution of algal patches and, to a lesser extent, also a power-scaling in both patch- and gap-size distributions. These results suggest that exogenous and endogenous processes are not mutually exclusive forces that can lead to the formation of similar spatial patterns in species assemblages.
No exploitation of temporal predictive context during visual search
Authors: Bouwkamp Floortje G. , de Lange Floris P. , Spaak Eelke 
Published: August 2020

AbstractThe human visual system can rapidly extract regularities from our visual environment, generating predictive context. It has been shown that spatial predictive context can be used during visual search. We set out to see whether observers can additionally exploit temporal predictive context, using an extended version of a contextual cueing paradigm. Though we replicated the contextual cueing effect, repeating search scenes in a structured order versus a random order yielded no additional behavioural benefit. This was true both for participants who were sensitive to spatial predictive context, and for those who were not. We argue that spatial predictive context during visual search is more readily learned and subsequently exploited than temporal predictive context, potentially rendering the latter redundant. In conclusion, unlike spatial context, temporal context is not automatically extracted and used during visual search.
Using Multilayer Heterogeneous Networks to Infer Functions of Phosphorylated Sites
Authors: Watson Joanne , Schwartz Jean-Marc , Francavilla Chiara 
Published: August 2020

1AbstractMass spectrometry-based quantitative phosphoproteomics has become an essential approach in the study of cellular processes such as signaling. Commonly used methods to analyze phosphoproteomics datasets depend on generic, gene-centric annotations such as Gene Ontology terms which do not account for the function of a protein in a particular phosphorylation state. Analysis of phosphoproteomics data is hampered by a lack of phosphorylated site-specific annotations. We propose a method that combines shotgun phosphoproteomics data, protein-protein interactions, and functional annotations into a heterogeneous multilayer network. Phosphorylation sites are associated to potential functions using a random walk on heterogeneous network (RWHN) algorithm. We validated our approach against a model of the MAPK/ERK pathway and functional annotations from PhosphoSite Plus and were able to associate differentially regulated sites on the same proteins to their previously described specific functions. We further tested the algorithm on three previously published datasets and were able to reproduce their experimentally validated conclusions and to associate phosphorylation sites with known functions based on their regulatory patterns. Our approach provides a refinement of commonly used analysis methods and accurately predicts context-specific functions for sites with similar phosphorylation profiles.For table of contents onlyWe confirm that the eTOC figure contains original material drawn by the authors.
Role of working capital management in profitability considering the connection between accounting and finance
Authors: Morshed Amer 
Published: August 2020

PurposeThe study aims to explain the relationship between accounting and finance through measuring the effect of rational working capital management on profitability.Design/methodology/approachEmploying the methodology of semi-structured interviews with sixteen financial managers.FindingsThe findings pointed out the relationship between accounting and finance is complementary, since it supports the accountant by the critical skills and information, like project evaluation, managing the company funding resources and working capital management. These skills put the accountant up to the financial manager stage. The working capital investment and financing policies have the most significant impact on profitability. These policies related to risk and return theory; since the conservative policy will reduce both the risk and return and the aggressive one will have the opposite impact.Originality/valueIt recommends accountants to be in professional stage and increase the profitability of the company to grab both accounting and finance information and skills.
Study on incentive and supervision mechanisms of technological innovation in megaprojects based on the principal-agent theory
Authors: Liu Jiawei , Ma Guanghong 
Published: August 2020

PurposeThe high uncertainty of technological innovation in megaprojects brings great challenges to the R&D institution and also acts as a trigger for moral hazard. The incentive and supervision are effective means to improve the performance of innovation. The purpose of this paper is to propose appropriate incentive and supervision mechanisms to reduce information asymmetry and improve the efficiency of incentives. Suggestions on technological innovation are put forward to megaprojects management.Design/methodology/approachAccording to the principal-agent theory, the research develops incentive models under three states, i.e. information symmetry, information asymmetry and information asymmetry based on supervision mechanism. The Bayesian theory is employed to prove the effectiveness of the novel supervision method based on risk assessment.FindingsThe results indicate that under the information asymmetry, the incentive intensity is positively correlated with the social benefits coefficient, and negatively correlated with the patent benefits coefficient. The R&D effort and the owner's incentive intensity decline with the increase of information asymmetry. The supervision of risks can effectively reduce the degree of information asymmetry, and the higher the uncertainty of innovations, the more significant the effect of supervision is. As the supervision intensity increases, the incentive intensity, the R&D effort and the innovation output will increase. In addition, the R&D institutions with high innovation capability, low unit cost of R&D and low risk-aversion are more willing to make efforts to innovate.Originality/valueThis study fills the research gap on incentive and supervision of technological innovation in megaprojects. The externality of innovation benefits is considered in the model. The traditional incentive model is extended through the introduction of supervision. Furthermore, a novel supervision method based on risk assessment is proposed. The results validate the importance of risk management in technological innovation and provide a new insight for project management.