bluuebunny/crossref_metadata_2025 huggingface dataset:
Is there any incremental benefit to conducting neuroimaging and neurocognitive assessments in the diagnosis of ADHD in young children? A machine learning investigation
Authors: Öztekin Ilke , Finlayson Mark A. , Graziano Paulo A. , Dick Anthony S.
Published: August 2020

Given the negative trajectories of early behavior problems associated with Attention-Deficit/Hyperactivity Disorder (ADHD), early diagnosis of ADHD is considered critical to enable early intervention and treatment. To this end, the current investigation employed machine learning to evaluate the relative predictive value of parent/teacher ratings, as well as behavioral and neural measures of executive function in predicting ADHD diagnostic category in a sample consisting of 162 young children (53.7% ADHD, ages 4 to 7, mean age 5.55, 67.9% male, 82.6% Hispanic/Latino). Among all the target measures assessed in the study, teacher ratings of executive function were identified as by far the most important measure in predicting ADHD diagnostic category. While a more extensive evaluation of neural measures, such as diffusion-weighted imaging, may provide more information as they relate to the underlying cognitive deficits associated with ADHD, the current study indicates that commonly used structural imaging measures of cortical thickness, as well as widely used cognitive measures of executive function, have little incremental value in differentiating typically developing children from those diagnosed with ADHD. Future research evaluating the importance of such measures in predicting children’s functional impairment in academic and social areas would provide additional insight into their contributing role in ADHD.
Inferring protein sequence-function relationships with large-scale positive-unlabeled learning
Authors: Song Hyebin , Bremer Bennett J. , Hinds Emily C. , Raskutti Garvesh , Romero Philip A.
Published: August 2020

Machine learning can infer how protein sequence maps to function without requiring a detailed understanding of the underlying physical or biological mechanisms. It’s challenging to apply existing supervised learning frameworks to large-scale experimental data generated by deep mutational scanning (DMS) and related methods. DMS data often contain high dimensional and correlated sequence variables, experimental sampling error and bias, and the presence of missing data. Importantly, most DMS data do not contain examples of negative sequences, making it challenging to directly estimate how sequence affects function. Here, we develop a positive-unlabeled (PU) learning framework to infer sequence-function relationships from large-scale DMS data. Our PU learning method displays excellent predictive performance across ten large-scale sequence-function data sets, representing proteins of different folds, functions, and library types. The estimated parameters pinpoint key residues that dictate protein structure and function. Finally, we apply our statistical sequence-function model to design highly stabilized enzymes.
Thalamic encoding of complex sensory patterns and its possible role in cognition
Authors: Castejon Carlos , Martin-Cortecero Jesus , Nuñez Angel
Published: August 2020

The function of the higher-order sensory thalamus remains unresolved. Here, POm nucleus was examined byin vivoextracellular recordings across a range of complex sensory patterns. We found that POm was highly sensitive to multiwhisker stimuli involving complex spatiotemporal interactions. The dynamical spatiotemporal structure of sensory patterns and the different complexity of their parts were accurately reflected in precise POm activity changes. Importantly, POm was also able to respond to ipsilateral stimulation and was implicated in the representation of bilateral tactile events by integrating simultaneous signals arising from both whisker pads. We found that POm nuclei are mutually connected through the cortex forming a functional POm-POm loop. We unravelled the nature and content of the messages travelling through this loop showing that they were ‘structured patterns of sustained activity’. These structured messages were transmitted preserving their integrated structure. The implication of different cortical areas was investigated revealing that S1 plays a protagonist role in this functional loop. Our results also demonstrated different laminar implication in the processing of sustained activity in this cortical area and its transmission between hemispheres. We propose a theoretical model in which these ‘structured patterns of sustained activity’ generated by POm may play important roles in perceptual, motor and cognitive functions. From a functional perspective, this proposal, supported by the results described here, provides a novel theoretical framework to understand the implication of the thalamus in cognition. In addition, a profound difference was found between VPM and POm functioning. The hypothesis of Complementary Components is proposed here to explain it.

Highlights

POm is implicated in the representation of complex sensory patterns.

POm is implicated in the encoding of bilateral tactile events.

POm nuclei are mutually connected through the cortex forming a functional POm-POm loop.

‘Structured patterns of sustained activity’ travelling through the loop

Abstract Figure
White matter connectivity of uncinate fasciculus and inferior fronto-occipital fasciculus: A possible early biomarker for callous-unemotional behaviors in young children with ADHD
Authors: Graziano Paulo A. , Garic Dea , Dick Anthony S.
Published: August 2020

Background

Callous-unemotional (CU) behaviors are important for identifying severe patterns of conduct problems (CP). One major fiber tract implicated in the development of CP is the uncinate fasciculus (UF), which connects amygdala and orbitofrontal cortex (OFC). The goals of the current study were to 1) explore differences in the white matter microstructure in the UF and other major fiber tracks (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus [IFOF], cingulum, and corticospinal tract [CST]) betweenyoungtypically developing (TD) children and those with Attention-Deficit/Hyperactivity Disorder (ADHD), and 2) explore, within the ADHD group, whether individual differences in these white matter microstructures relate to co-occurring CP and CU behaviors, respectively.

Methods

Participants included 198 young children (78% boys,Mage= 4.95 years; 80% Latinx; 49% TD). CU behaviors and CP were measured via a combination of teacher/parent ratings. Non-invasive diffusion-weighted imaging (DWI) was used to measure fractional anisotropy (FA), an indirect indicator of white matter properties.

Results

Relative to TD children, children with ADHD had reduced FA on four out of the five fiber tracks we examined (except for cingulum). Within the ADHD group, no associations were found between CP and reduced white matter integrity across any of the fiber tracks examined. However, we found that even after accounting for CP and a host of covariates including whole brain FA, CU behaviors were independently related to reduced FA in bilateral UF and left IFOF.

Conclusions

The bilateral UF and IFOF may be a biomarker of CU behaviors, even in very young children.
The nanoscale anatomy of exocytic dense-core vesicles in neuroendocrine cells
Authors: Prasai Bijeta , Haber Gideon J. , Strub Marie-Paule , Ciemniecki John A. , Sochacki Kem A. , Taraska Justin W.
Published: August 2020

Rab-GTPases and their interacting partners are key regulators of secretory vesicle trafficking, docking, and fusion to the plasma membrane in neurons and neuroendocrine cells. Where and how these proteins are positioned and organized with respect to the vesicle and plasma membrane are unknown. Here, we use correlative super-resolution light and platinum replica electron microscopy to map Rab-GTPases (Rab27a and Rab3a) and their effectors (Granuphilin-a, Rabphilin3a, and Rim2) at the nanoscale in 2D. Next, we develop a targetable genetically-encoded electron microscopy labeling method that uses histidine based affinity-tags and metal-binding gold-nanoparticles to determine the axial location of exocytic proteins using electron tomography. Our data show that Rab-GTPases and their effectors are distributed across the entire surface of individual docked vesicles. This circumferential distribution likely aids in the efficient transport, capture, docking, and rapid fusion of vesicles in excitable cells. The nanoscale molecular model of dense core vesicles generated from our methods reveals how key proteins assemble at the plasma membrane to regulate membrane trafficking and exocytosis.
InhA inhibitors have activity against non-replicatingMycobacterium tuberculosis
Authors: Flint Lindsay , Korkegian Aaron , Parish Tanya
Published: August 2020

We previously identified a diazaborine series with potential for development as a new tuberculosis drug. This series has activityin vitroandin vivoand targets cell wall biosynthesis via inhibition of InhA. We tested the ability of two molecules of the diazaborine series to kill non-replicatingMycobacterium tuberculosisin the nutrient starvation model; both molecules were bactericidal, reducing viability by >3 logs in 21 days. Activity was not inoculum-dependent and showed similar kill rates to other InhA inhibitors (isoniazid and NITD-916). We conclude that inhibition of InhA is bactericidal against nutrient-starved non-replicatingM. tuberculosis.
Impaired miRNA degradation by post-transcriptional addition of 3’ cytosine and adenine in T cell activation
Authors: Rodríguez-Galán Ana , Dosil Sara G , Gómez Manuel José , Fernández-Delgado Irene , Sánchez-Cabo Fátima , Sánchez-Madrid Francisco
Published: August 2020

MiRNA repertoire of T cells undergoes extensive changes in response to activation. Whereas global miRNA downregulation occurs few hours after activation, some individual miRNAs are specifically up- or down-regulated. In this study, we have assessed miRNA expression and post-transcriptional modification kinetics in human primary CD4+ T cells upon short-term stimulation with αCD3αCD28 or IFN I using Next Generation Sequencing. Multiple miRNAs not related before with T cell activation profile have been identified as differentially expressed. Downregulated miRNAs presented higher 3’ uridylation. Dis3L2 and Eri1 (3’ to 5’ exoribonucleases that prefer uridylated RNA as substrates) increased their expression upon TCR stimulation, probably generating an adverse environment for miRNAs. Remarkably, non-templated cytosine additions to 3’ end, previously unknown to be a relevant post-transcriptional modification mechanism, were overrepresented in upregulated miRNAs, together with high levels of adenylation. In the midst of an increasing presence of exoribonucleases, miRNAs multiplying their levels may successfully escape degradation due to 3’ cytosine and adenine addition. These protective signals open a new avenue to improve miRNA stability for therapy in T cells.
Distinct aging-vulnerable trajectories of motor circuit functions in oxidation- and temperature-stressedDrosophila
Authors: Ram Iyengar Atulya Srisudarshan , Ruan Hongyu , Wu Chun-Fang
Published: August 2020

We examined several sensory-motor processing circuits inDrosophilaacross the lifespan and uncovered distinctive age-resilient and age-vulnerable trajectories in their established functional properties. We observed relatively little deterioration toward the end of lifespan in the giant-fiber (GF) and downstream circuit elements responsible for the jump-and-flight escape reflex. In contrast, we found substantial age-dependent modifications in the performance of GF inputs and other circuits driving flight motoneuron activities. Importantly, in high temperature (HT)-reared flies (29 °C), the characteristic age-dependent progression of these properties was largely maintained, albeit over a compressed time scale, lending support for the common practice of expeditingDrosophilaaging studies by HT rearing. We discovered shortened lifespans inCu2+/Zn2+Superoxide Dismutase 1(Sod) mutant flies were accompanied by alterations distinct from HT-reared flies, highlighting differential effects of oxidative vs temperature stressors. This work also establishes several age-vulnerable parameters that may serve as quantitative neurophysiological landmarks for aging inDrosophila.
The genetic architecture and genomic context of glyphosate resistance inAmaranthus tuberculatus
Authors: Kreiner J.M. , Tranel P.J. , Weigel D. , Stinchcombe J.R. , Wright S.I.
Published: August 2020

Much of what we know about the genetic basis of herbicide resistance has come from detailed investigations of monogenic adaptation at known target-sites, despite the increasingly recognized importance of polygenic resistance. Little work has been done to characterize the broader genomic basis of herbicide resistance, including the number and distribution of genes involved, their effect sizes, allele frequencies, and signatures of selection. In this work, we implemented genome-wide association (GWA) and population genomic approaches to examine the genetic architecture of glyphosate resistance in the problematic agricultural weed,Amaranthus tuberculatus. A GWA was able to correctly identify the gene targeted by glyphosate, but when we statistically controlled for two target-site genetic mechanisms, we found an additional 250 genes across all 16 chromosomes associated with non-target site resistance (NTSR). The encoded proteins had functions that have been linked to non-target site resistance (NTSR), the most significant of which is response to chemicals, but also showed pleiotropic roles in reproduction and growth. The architecture of NTSR was enriched for large effect sizes and low allele frequencies, suggesting the role of pleiotropic constraints on its evolution. The enrichment of rare alleles also suggested that the genetic architecture of NTSR may be population-specific and heterogeneous across the range. Despite their rarity, we found signals of recent positive selection on NTSR-alleles by both window- and haplotype-based statistics, and an enrichment of amino-acid changing variants. In our samples, genome-wide SNPs explain a comparable amount of the total variation in glyphosate resistance to monogenic mechanisms, even in a collection of individuals where 80% of resistant individuals have large-effect TSR mutations, indicating an underappreciated polygenic contribution to the evolution of herbicide resistance in weed populations.
Larval zebrafish use olfactory detection of sodium and chloride to avoid salt-water
Authors: Herrera Kristian J. , Panier Thomas , Guggiana-Nilo Drago , Engert Florian
Published: August 2020

Salinity levels constrain the habitable environment of all aquatic organisms. Zebrafish are freshwater fish that cannot tolerate high salt environments and would, therefore, benefit from neural mechanisms that enable the navigation of salt gradients to avoid high salinity. Yet, zebrafish lack epithelial sodium channels, the primary conduit land animals use to taste sodium. This suggests fish may possess novel, undescribed mechanisms for salt detection. In the present study, we show that zebrafish, indeed, respond to small temporal increases in salt by reorienting more frequently. Further, we use calcium imaging techniques to identify the olfactory system as the primary sense used for salt detection, and we find that a specific subset of olfactory receptor neurons encodes absolute salinity concentrations by detecting monovalent anions and cations. In summary, our study establishes that zebrafish larvae have the ability to navigate, and thus detect salinity gradients, and that this is achieved through previously undescribed sensory mechanisms for salt detection.
CRISPR-Cas9-mediated depletion ofO-GlcNAc hydrolase and transferase for functional dissection ofO-GlcNAcylation in human cells
Authors: Gorelik Andrii , Ferenbach Andrew T.
Published: August 2020

O-GlcNAcylation is an abundant post-translational modification (PTM) on serine and threonine residues of nuclear and cytoplasmic proteins. Although this PTM has been reported on thousands of proteins,O-GlcNAc transferase (OGT) and hydrolase (OGA) are the only two enzymes that perform the respective addition and removal ofO-GlcNAc on protein substrates. To examine the consequences of deregulatedO-GlcNAcylation, theO-GlcNAc field has mostly relied on the use of RNA interference to knockdown OGT/OGA and inhibitors to block their activities in cells. Here, we describe the first complete CRISPR-Cas9 knockouts of OGA and a knockdown of OGT (with a maximal decrease in expression of over 80%) in two human cell lines. Notably, constitutive depletion of oneO-GlcNAc cycling enzyme not only led to a respective increase or decrease in totalO-GlcNAcylation levels but also resulted in diminished expression of the opposing enzyme, as a compensatory mechanism, observed in previous short-term pharmacological studies. The OGA knockout system presents a convenient platform to dissect OGA mutations and was used to further characterise the single Ser405O-GlcNAc site of human OGA using theS-GlcNAc genetic recoding approach, helping to identify anS-GlcNAc-specific antibody which was previously thought to primarily detectO-GlcNAc.
BART3D: Inferring transcriptional regulators associated with differential chromatin interactions from Hi-C data
Authors: Wang Zhenjia , Zhang Yifan , Zang Chongzhi
Published: August 2020

Identification of functional transcriptional regulators associated with chromatin interactions is an important problem in studies of 3-dimensional genome organization and gene regulation. Direct inference of TR binding has been limited by the resolution of Hi-C data. Here, we present BART3D, a computational method for inferring TRs associated with genome-wide differential chromatin interactions by comparing Hi-C maps from two states, leveraging public ChIP-seq data for human and mouse. We demonstrate that BART3D can detect relevant TRs from dynamic Hi-C profiles with TR perturbation or cell differentiation. BART3D can be a useful tool in 3D genome data analysis and functional genomics research.

Availability and Implementation

Implemented in Python, source code freely available athttps://github.com/zanglab/bart3d

Contact

zang@virginia.edu

Supplementary Information

Supplementary data are available.
Neural and subjective effects of inhaled DMT in natural settings
Authors: Pallavicini Carla , Cavanna Federico , Zamberlan Federico , de la Fuente Laura Alethia , Perl Yonatan Sanz , Arias Mauricio , Romero Celeste , Carhart-Harris Robin , Timmermann Christopher , Tagliazucchi Enzo
Published: August 2020

Background

N,N-Dimethyltryptamine (DMT) is a short acting psychedelic tryptamine found naturally in many plants and animals. Few studies to date addressed the neural and psychological effects of DMT alone, either administered intravenously or inhaled in freebase form, and none conducted in natural settings.

Aims

Our primary aim was to study the acute effects of inhaled DMT in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (i.e. “set” and “setting”), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming DMT in familiar and comfortable settings.

Methods

We combined state-of-the-art wireless electroencephalography (EEG) with psychometric questionnaires to study the neural and subjective effects of naturalistic DMT use in 35 healthy and experienced participants.

Results

We observed that DMT significantly decreased the power of alpha (8-12 Hz) oscillations throughout all scalp locations, while simultaneously increasing power of delta (1-4 Hz) and gamma (30-40 Hz) oscillations. Gamma power increases correlated with subjective reports indicative of mystical-type experiences. DMT also increased/decreased global synchrony and metastability in the gamma/alpha band, and resulted in widespread increases in signal complexity.

Conclusions

Our results are consistent with previous studies of psychedelic action in the human brain, while at the same time suggesting potential EEG markers of mystical-type experiences in natural settings, thus highlighting the importance of investigating these compounds in the contexts where they are naturally consumed.
Vector manipulation by a semi-persistent plant virus through disease symptom expression
Authors: Vasquez Diego F. , Borrero-Echeverry Felipe , Rincon Diego F.
Published: August 2020

The greenhouse whitefly (GWF),Trialeurodes vaporariorum(Westwood) (Hemiptera: Aleyrodidae) is rarely associated with potato plants yet is the only known vector of thePotato yellow vein virus(PYVV). A host shift related with vector’s cognition often requires neural alterations by the virus. However, PYVV, being semi-persistent, is not supposed to directly affect vector physiology. As such, we propose that changes in potato plants caused by PYVV infection should manipulate insect behaviour to increase transmission. Here, we studied the effect of PYVV infection and symptom expression on GWF biological parameters, and attraction towards infected and uninfected potato plants. We compared survival and development rates of GWF nymphs fed with PYVV-infected plants (symptomatic and asymptomatic) and healthy plants under controlled conditions. We also carried out free-choice tests to determine host preference of GWF adults as a function of PYVV infection and disease symptom expression. We found that PYVV infection (both symptomatic and asymptomatic) reduce GWF survival while increasing development time (in symptomatic plants). Combined, a prolonged development time and reduced survival should favour viral uptake and trigger migration of vectors from symptomatic plants short after acquiring the virus. We also found that symptom expression (yellowing) causes significantly greater GWF attraction and establishment compared to healthy or asymptomatic plants. Interestingly, we found that GWF adults that have previously fed on infected plants switch their host preference choosing and establishing on healthy potato plants, which clearly increases horizontal transmission rates. The mechanism through which this behavioural manipulation takes place is not yet well understood. Our results show that symptoms associated with PYVV infection may account for a set of behavioural modifications that make an improbable vector, such as the GWF, into an efficient agent that increases horizontal transmission rates of PYVV.

Highlights

PYVD reduces the survival of GWF and increases development time when symptoms occur

PYVD symptom makes potato, a non-host plant, attractive to GWF

After feeding on infected plants, GWF preference changes to prefer uninfected plants

PYVV modulates GWF behaviour to enhance horizontal transmission between plants
Mechanistic Picture for Monomeric Human Fibroblast Growth Factor 1 Stabilization by Heparin Binding
Authors: Kumar Vivek Govind , Agrawal Shilpi , Kumar Thallapuranam Krishnaswamy Suresh , Moradi Mahmoud
Published: August 2020

Human fibroblast growth factor (FGF) 1 or hFGF1 is a member of the FGF family that is involved in various vital processes such as cell proliferation, cell differentiation, angiogenesis and wound healing. hFGF1, which is associated with low stabilityin vivo, is known to be stabilized by binding heparin sulfate, a glycosaminoglycan that aids the protein in the activation of its cell surface receptor. The poor thermal and proteolytic stability of hFGF1 and the stabilizing role of heparin have long been observed experimentally; however, the mechanistic details of these phenomena are not well understood. Here, we have used a combination of microsecond-level equilibrium molecular dynamics (MD) simulations, and state-of-the-art enhanced sampling MD simulations to quantitatively characterize the structural dynamics of monomeric hFGF1 in the presence and absence of heparin hexasaccharide. We have observed a conformational change in the heparin-binding pocket of hFGF1 that occurs only in the absence of heparin. Several intramolecular hydrogen bonds were also identified within the heparin-binding pocket, that form only when hFGF1 interacts with heparin. The loss of both intermolecular and intramolecular electrostatic interactions in the absence of heparin plausibly leads to the observed conformational change. This conformational transition results in increased flexibility of the heparin-binding pocket and provides an explanation for the susceptibility ofapohFGF1 to proteolytic degradation and thermal instability. The hFGF1-heparin interaction has also been quantified using absolute binding free energy calculations. Binding affinity (Kd) estimates determined computationally using our novel MD approach are in good quantitative agreement with experimental Kdvalues from isothermal titration calorimetry experiments. The successful application of a combination of microsecond-level MD and accurate free energy calculations to explain the heparin-mediated stabilization of hFGF1 at a quantitative level, represents a promising approach for studying complex biomolecular interactions between proteins and their binding partners at a detailed molecular level using rigorous physics-based simulation techniques.
PACAP induces light aversion in mice by an inheritable mechanism independent of CGRP
Authors: Kuburas Adisa , Mason Bianca N. , Hing Benjamin , Reis Alyssa S. , Sowers Levi P. , Moldovan Loomis Cristina , Garcia-Martinez Leon F. , Russo Andrew F.
Published: August 2020

The neuropeptides CGRP and PACAP have emerged as mediators of migraine, yet the potential overlap of their mechanisms remains unknown. Infusion of PACAP, like CGRP, can cause migraine in people, and both peptides share similar vasodilatory and nociceptive functions. In this study, we have used light aversion in mice as a surrogate for migraine-like photophobia to compare CGRP and PACAP and ask whether CGRP or PACAP actions were dependent on each other. Similar to CGRP, PACAP induced light aversion in outbred CD-1 mice. The light aversion was accompanied by increased resting in the dark, but not anxiety in a light-independent open field assay. Unexpectedly, about a third of the CD-1 mice did not respond to PACAP, which was not seen with CGRP. The responder and nonresponder phenotypes were stable, inheritable, and not sex-linked, although there was generally a trend for greater responses among male mice. RNA-seq analysis of trigeminal ganglia yielded hieriechial clustering of responder and nonresponder mice and revealed a number of candidate genes, including greater expression of pituitary hormones and receptors in a subset of responder mice. Importantly, an anti-PACAP monoclonal antibody could block PACAP-induced light aversion but not CGRP-induced light aversion. Conversely, an anti-CGRP antibody could not block PACAP-induced light aversion. Thus, we propose that CGRP and PACAP act by independent convergent pathways that cause a migraine-like symptom in mice.

Significance

The relationship between the neuropeptides CGRP and PACAP in migraine is relevant given that both peptides can induce migraine in people, yet to date only drugs that target CGRP are available. Using an outbred strain of mice, we were able to show that most, but not all, mice respond to PACAP in a preclinical photophobia assay. Our finding that CGRP and PACAP monoclonal antibodies do not cross-inhibit the other peptide indicates that CGRP and PACAP actions are independent and suggests that PACAP-targeted drugs may be effective in patients who do not respond to CGRP-based therapeutics.
TNFα reduces inhibitory transmission in youngTrem2R47HSporadic Alzheimer rats before observable Aβ and brain pathology
Authors: Ren Siqiang , Breuillaud Lionel , Yao Wen , Yin Tao , Norris Kelly A. , Zehntner Simone P. , D’Adamio Luciano
Published: August 2020

Trem2R47Hrats, which carry the Alzheimer’s disease (AD) risk factor p.R47H variant of the microglia geneTREM2and produce human Aβ. Previously, we demonstrated that supraphysiological TNF-α boost glutamatergic transmission and suppresses Long-term-Potentiation (LTP), a surrogate of learning and memory, in peri-adolescentTrem2R47Hrats (Ren et al., 2020). Here we tested the effect of the p.R47HTREM2variant on GABA transmission. We report that GABAergic transmission is decreased inTrem2R47H/R47Hrats. This decrease is due to the acute and reversable action of TNF-α and is not associated whit changes in human Aβ levels and pathological brain lesions. Thus, the p.R47HTREM2variant changes the excitatory/inhibitory balance between glutamate and GABA transmission, favoring excitation. This unbalance could potentiate glutamate excitotoxicity and, over time, contribute to neuronal dysfunction, enhanced neuronal cells death and neurodegeneration. Future studies will determine whether this unbalance represents an early, Aβ-independent pathway leading to dementia.
A novel oxidase fromAlcaligenessp. HO-1 oxidizes hydroxylamine to N2
Authors: Wu Meng-Ru , Miao Li-Li , Liu Ying , Hou Ting-Ting , Ai Guo-Min , Ma Lan , Zhu Hai-Zhen , Zhu Ya-Xin , Gao Xi-Yan , Qian Xin-Xin , Qin Ya-Ling , Wu Tong , Shen Xi-Hui , Jiang Cheng-Ying , Herbold Craig W. , Wagner Michael , Li De-Feng , Liu Zhi-Pei , Liu Shuang-Jiang
Published: August 2020

Hydroxylamine is a key intermediate of microbial ammonia oxidation and plays an important role in the biogeochemical cycling of N-compounds. Hydroxylamine is oxidized to NO or N2O by hydroxylamine oxidases or cytochrome P460 from heterotrophic or autotrophic bacteria, but its enzymatic oxidation to N2has not yet been observed. Here, we report on the discovery of a novel oxidase that converts hydroxylamine to N2from the newly isolated heterotrophic nitrifierAlcaligenesstrain HO-1. Strain HO-1 accumulated hydroxylamine and produced N2from ammonia oxidation. Using transcriptome analysis and heterologous expression via fosmid library screening, we identified three genes (dnfABC) of strain HO-1 that enabledE. colicells not only to produce hydroxylamine from15N-labelled ammonium but also to further convert it to15N2. The three genes were individually cloned and expressed, and their translational products DnfA, DnfB, and DnfC were purified.In vitroDnfA bound to hydroxylamine and catalyzed the conversion of hydroxylamine to N2in the presence of FAD, NADH and O2. Thus, DnfA was identified as a novel hydroxylamine oxidase and catalyzed a previously unknown N-N bond forming reaction with a yet-to-be discovered mechanism. DnfA homologs were detected in different bacterial groups, suggesting that hydroxylamine oxidation to nitrogen might occur in additional microbial taxa.
Functional loss of a noncanonical BCOR–PRC1.1 complex accelerates SHH-driven medulloblastoma formation
Authors: Kutscher Lena M. , Okonechnikov Konstantin , Batora Nadja V. , Clark Jessica , Silva Patricia B.G. , Vouri Mikaella , van Rijn Sjoerd , Sieber Laura , Statz Britta , Gearhart Micah D. , Shiraishi Ryo , Mack Norman , Orr Brent A. , Korshunov Andrey , Gudenas Brian L. , Smith Kyle S. , Mercier Audrey L. , Ayrault Olivier , Hoshino Mikio , Kool Marcel , von Hoff Katja , Graf Norbert , Fleischhack Gudrun , Bardwell Vivian J. , Pfister Stefan M. , Northcott Paul A. , Kawauchi Daisuke
Published: August 2020

Medulloblastoma is a malignant childhood brain tumor arising from the developing cerebellum. In Sonic Hedgehog (SHH) subgroup medulloblastoma, aberrant activation of SHH signaling causes increased proliferation of granule neuron progenitors (GNPs), and predisposes these cells to tumorigenesis. A second, cooperating genetic hit is often required to push these hyperplastic cells to malignancy and confer mutation-specific characteristics associated with oncogenic signaling. Somatic loss-of-function mutations of the transcriptional corepressor BCOR are recurrent and enriched in SHH medulloblastoma. To investigate BCOR as a putative tumor suppressor, we used a genetically engineered mouse model to delete exons 9/10 of Bcor (BcorΔE9–10) in GNPs during development. This mutation leads to reduced expression of C-terminally truncated BCOR (BCORΔE9–10). While BcorΔE9–10 alone did not promote tumorigenesis or affect GNP differentiation, BcorΔE9–10 combined with loss of the SHH receptor gene Ptch1 resulted in fully penetrant medulloblastomas. In Ptch1+/−;BcorΔE9–10 tumors, the growth factor gene Igf2 was aberrantly up-regulated, and ectopic Igf2 overexpression was sufficient to drive tumorigenesis in Ptch1+/− GNPs. BCOR directly regulates Igf2, likely through the PRC1.1 complex; the repressive histone mark H2AK119Ub is decreased at the Igf2 promoter in Ptch1+/−;BcorΔE9–10 tumors. Overall, our data suggests that BCOR–PRC1.1 disruption leads to Igf2 overexpression, which transforms preneoplastic cells to malignant tumors.
Accurate and time-saving quantification of a component present in a very small amount in a mixture by the direct derivation method
Authors: Toraya Hideo
Published: August 2020

In quantitative phase analysis (QPA) using the direct derivation (DD) method, total sums of diffracted/scattered intensities for individual components are used as observed quantities. Fluctuation in their relative intensity ratios induces errors in derived weight fractions, and it ought to be suppressed for improving the accuracy in QPA, in particular, of a component that is present in a small amount. The fluctuation is primarily caused by the termination in summing/integrating diffracted/scattered intensities on the high-angle side. It is usually associated with changing the 2θ range in whole-powder-pattern fitting (WPPF) used to decompose the mixture pattern into individual component patterns. In this study, calculated patterns for individual components, fitted in WPPF, are normalized so as to give the unit area when they are separately integrated over their definition ranges in 2θ. The termination effect could effectively be reduced by extending the definition range to a certain high-angle limit. Scale parameters for adjusting the calculated patterns become non-fluctuating against the change of the 2θ range in WPPF. Thus, the time spent for intensity data collection of mixture patterns can be reduced by shortening the scan range. The present procedure has been tested with binary mixtures containing small amounts of crystalline phases of 0.02–0.4 wt%. QPA could be conducted with errors of 0.01–0.03 wt% for both inorganic materials chosen as ideal samples and pharmaceutical materials as practical ones. QPA of an amorphous component present in a small amount is also discussed.
Generalizing small-angle scattering form factors with linear transformations
Authors: Thompson Matt
Published: August 2020

Nanostructure characterization using small-angle scattering is often performed by iteratively fitting a scattering model to experimental data. These scattering models are usually derived in part from the form factors of the expected shapes of the particles. Most small-angle-scattering pattern-fitting software is well equipped with form factor libraries for high-symmetry models, yet there is more limited support for distortions to these ideals that are more typically found in nature. Here, a means of generalizing high-symmetry form factors to these lower-symmetry cases via linear transformations is introduced, significantly expanding the range of form factors available to researchers. These linear transformations are composed of a series of scaling, shear, rotation and inversion operations, enabling particle distortions to be understood in a straightforward and intuitive way. This approach is expected to be especially useful for in situ studies of nanostructure growth where anisotropic structures change continuously and large data sets must be analysed.
The ripple effect of credit accessibility on the technical efficiency of maize farmers in Ghana
Authors: Siaw Anthony , Jiang Yuansheng , Ankrah Twumasi Martinson , Agbenyo Wonder , Ntim-Amo Gideon , Osei Danquah Frank , Ankrah Ernest Kwarko
Published: August 2020

Purpose

The purpose of this study is to examine the impact of access to credit on technical efficiency (TE) of maize farmers in a developing country, Ghana.

Design/methodology/approach

The study employed an instrumental variable approach and the stochastic frontier analysis (SFA) method for the estimation of the results.

Findings

The study found that farmers who have access to agricultural credit stand the chance of increasing TE by a margin of 8%, which also influences the maize production than those who did not have access to credit. The average TE score of the farmers was 74%. The study also found out that factors like membership, gender, farmers' access to credit, age and social network determine farmers' possibility of accessing agricultural credit. The study finds out that returns to size are increasing among the maize farmers and that significant improvement in efficiency can be realized by increasing the level of input used in production. Also, factors such as farm size, labor, seeds and fertilizer are the essential determinants of maize production output. Also, gender, extension, age, off-farm income, access to credit and membership were significant factors influencing technical inefficiency (TI).

Originality/value

The paper contributes to the existing literature on agricultural credit on rural agricultural development. The problem of endogeneity associated with access to credit, which has been considered by other researchers, is dealt with this study. This paper also provides information to government policymakers, practitioners and all other stakeholders in the maize sub-sectors and also will benefit small farmers outside the study area.
The effect of auditor type on audit quality in emerging markets: evidence from Egypt
Authors: El-Dyasty Mohamed M. , Elamer Ahmed A.
Published: August 2020

Purpose

Although a number of studies suggest that big audit firms provide higher audit quality in strict legal environments, empirical evidence remains inconclusive. As little is known about the effect of auditor type on audit quality in less strictly legal environments, this study aims to investigate the impact of auditor type on audit quality in the Egyptian market.

Design/methodology/approach

Data of Egyptian-listed companies during the period 2011–2018 are used. To examine the impact of auditor type on audit quality, ordinary least square regression and robust standard errors clustered at year and industry level are used. This study uses discretionary accruals as a proxy for audit quality. Several additional analyzes are conducted to assess the robustness of the main results, including alternative measures of audit quality and auditor type.

Findings

The results show that audit firms tend to provide higher audit quality when they are affiliated with a foreign audit firm. However, Big 4 auditors do not provide higher audit quality compare to their counterparts. Additionally, the governmental agency, accountability state authority, that monopolize audit function in state-owned companies do not appear to be associated with higher audit quality. Finally, local audit firms have a negative association with audit quality. This may be their strategy to secure future clients that seek low-quality audits.

Research limitations/implications

This study suggests that affiliation with foreign audit firms will help the Egyptian firms to develop their abilities by using advanced technology and techniques and transfer rare expertize to the Egyptian auditors. This study also shows that the strategy adopted by many Egyptian audit firms to affiliate with foreign auditors reflects the desire of these firms to be included in one tier alongside Big 4 audit firms to increase their market share under a claim of providing a higher audit quality.

Originality/value

This study adds to the rare but growing body of literature by investigating how auditor type affects audit quality in the context of less strictly legal environments. The results are important, as investors, standards-setters and regulators have growing concerns over audit quality since the Enron scandal. The findings suggest that audit quality depends on auditor type. These findings have important implications for investors, standards-setters and auditors interested in auditor oversight, audit quality and auditor choice.
Supplier flexibility in the order-to-delivery process – a customer perspective
Authors: Forslund Helena , Jonsson Patrik , Mattsson Stig-Arne
Published: August 2020

Purpose

Flexibility is one enabler of efficient use of resources and is therefore an antecedent to sustainability. The purpose of this article is to identify supplier flexibility variables in, and related to, the order-to-delivery (OTD) process and categorize them into a framework, followed by empirically exploring the framework.

Design/methodology/approach

A perception-based survey was sent to Swedish purchasing managers. 289 responses were received. After descriptive gap analysis, exploratory factor analysis was applied to structure the responses into factors. This formed the basis for hierarchical linear regression analysis, explaining supplier flexibility.

Findings

A conceptual framework, specifying supplier flexibility into volume, delivery and information exchange dimensions and relating these dimensions to the OTD process, was developed. Significant negative gaps between actual and demanded volume flexibility and delivery flexibility were identified, while positive gaps were found for information exchange flexibility. The factor analysis revealed three factors. The regression analysis verified that OTD-related information exchange flexibility and OTD-related volume and delivery flexibility explain the variation in OTD-specific flexibility and are important antecedents for supplier flexibility in the OTD process.

Research limitations/implications

A contribution to research is the framework – with defined, related and empirically validated flexibility types.

Practical implications

The study proposes a perception-based way to capture supplier flexibility in the OTD process, which is of practical relevance when evaluating suppliers.

Originality/value

Identifying, conceptualizing and capturing types of supplier flexibility in the OTD process is new related to academic literature. Also the wide empirical study mapping supplier flexibility gaps is unique in its focus.
Punitive discontinuation of opioid agonist therapy during incarceration
Authors: Marmel Allison , Bozinoff Nikki
Published: August 2020

Purpose

The prevalence of substance use disorders among incarcerated individuals in Canada is substantially higher than in the general population. Many incarcerated individuals with opioid use disorder remain untreated due to inadequate access to opioid agonist therapy (OAT). A considerable proportion of overdose-related deaths in the province of Ontario are individuals who have recently been released from prison. The purpose of this paper is to highlight that discontinuation of OAT as a disciplinary measure remains an active concern within prisons in Canada and places individuals with opioid use disorder at increased risk of relapse and resultant overdose death.

Design/methodology/approach

This case report describes an incarcerated client with opioid use disorder who was initially stable on OAT, but was forcibly tapered off OAT as a disciplinary measure and subsequently relapsed to illicit opioid use while in custody.

Findings

This case calls attention to concerns regarding treatment of opioid use disorder during incarceration, as forcible detoxification from OAT as a disciplinary measure is a highly dangerous practice. The authors discuss concerns regarding diversion and ways in which prison-based OAT programs can be improved to increase their safety and acceptability among correctional staff. Ongoing advocacy is required on the part of health-care workers and policymakers to ensure that individuals are able to appropriately access this life-saving therapy while incarcerated.

Originality/value

To the best of the authors’ knowledge, this is the first case report to describe forcible tapering of OAT as a disciplinary measure during incarceration. Despite existing evidence emphasizing the significant risk of overdose associated with detoxification from opioids, this case highlights the need for further research into the causes and prevalence of this practice.
Privacy-deprived e-commerce: the efficacy of consumer privacy policies on China's e-commerce websites from a legal perspective
Authors: Zhu Ruilin , Srivastava Aashish , Sutanto Juliana
Published: August 2020

Purpose

Despite grave public concerns over information privacy and ongoing academic explorations of privacy policy, there is a general lack of understanding toward this issue in the legal context in China, the largest e-commerce market in the world. Departing from the extant literature of general discussion in nature, the authors undertook an exploratory study on the efficacy of e-commerce websites' privacy policies in China from the legal perspective.

Design/methodology/approach

The authors drew on a qualitative grounded theory approach to identify selective codes relating to the focal issue and established a theoretical framework therefrom. The authors then conducted theoretical integration by linking them to the Theory of Development Blocks and the System Justification Theory.

Findings

The research identifies a general distrust of Chinese consumers toward privacy policies and highlights that despite their growing concerns about privacy, the privacy policies are largely ineffective in reflecting legal enforcement, changing their perceptions or influencing purchase behaviors. It also reveals that the current Chinese legislation is unable to fully render consumers' confidence in e-commerce websites' privacy policies effectiveness and privacy protection due to its limited recognition and influences among them.

Originality/value

The research has multiple ramifications. The authors empirically confirmed a mismatch between customers' perception of privacy policies and their actual behaviors and then theoretically explained the seemingly conflicting scenario in the context of development block of legal enforcement and system justification. The authors theorized the absence of the legal enforcement in privacy policies to supplement the legal perspective to the literature. The research further leads us to suggest that the time has come to update and strongly enforce privacy regulation in China to fuel the further development of e-commerce sector in practice.
Data breaches in hospitality: is the industry different?
Authors: Gwebu Kholekile , Barrows Clayton W.
Published: August 2020

Purpose

The purpose of this study is to expand on the existing literature by specifically examining data security incidents within the hospitality industry, assessing origins and causes, comparing breaches within the industry with those of other industries and identifying areas of concern.

Design/methodology/approach

A sample of data breach incidents is drawn from the Verizon VERIS Community Database (VCDB). Statistical comparisons between hospitality and non-hospitality industry firms are conducted following the Verizon A4 threat framework.

Findings

The results reveal that breaches between hospitality and non-hospitality firms differ significantly in terms of actors, actions, assets and attributes. Specifically, proportions of breaches in the hospitality industry are larger in terms of external actors, hacking and malware, user devices compromised and integrity violations. Additionally, compared to other industries, point-of-sales (POS) system breaches occur at a higher rate in the hospitality industry. The study finds that company size, hacking and malware predict the likelihood of a POS breach.

Research limitations/implications

The study uses secondary data and does not include the entire universe of data breaches.

Originality/value

In the quest to reduce data breach incidents, it is imperative to identify and assess the nature of data breach incidents between industries. Doing so permits the development of targeted industry-specific solutions rather than generic ones. This study systematically identifies differences between hospitality and non-hospitality data security incidents and then suggests areas where hospitality companies should focus future attention to mitigate breach incidents.