bluuebunny/crossref_metadata_2025 huggingface dataset:
Psoas abscess associated with aortic endograft infection caused by bacteremia of Listeria monocytogenes
Authors: Ma Jen-Wen , Hu Sung-Yuan , Lin Tzu-Chieh , Tsai Che-An
Published: November 2019

Rationale:

Endograft infection following endovascular stent for aortic aneurysm is rare (0.6%–3%), but it results in high mortality rate of 25% to 88%.

Patient concerns:

A 66-year-old hypertensive man underwent an endovascular stent graft for abdominal aortic aneurysm 18 months ago. Recurrent episodes of fever, chills, and abdominal fullness occurred 6 months ago before this admission. Laboratory data showed 20 mg/dL of C-reactive protein and abdominal computed tomography (CT) revealed an aortic endoleak at an urban hospital, so 4-day course of intravenous (IV) amoxicillin/clavulanic acid was given and he was discharged after fever subsided. He was admitted to our hospital due to fever, chills, and watery diarrhea for 1 day. Abdominal CT showed left psoas abscess associated with endograft infection. Blood culture grew Listeria monocytogenes.

Diagnosis:

Left psoas abscess associated with endograft infection caused by bacteremia of Listeria monocytogenes.

Interventions:

IV ampicillin with 8 days of synergistic gentamicin was prescribed and it created satisfactory response. Ampicillin was continued for 30 days and then shifted to IV co-trimoxazole for 12 days.

Outcomes:

He remained asymptomatic with a decline of CRP to 0.36 mg/dL and ESR to 39 mm/h. He was discharged on the 44th hospital day. Orally SMX/TMP was prescribed for 13.5 months.

Lessons:

Only few cases of aortic endograft infection caused by Listeria monocytogenes had been reported. In selected cases, particularly with smoldering presentations and high operative risk, endograft retention with a prolonged antimicrobial therapy seem plausible as an initial therapeutic option, complemented with percutaneous drainage or surgical debridement if necessary.
Characteristics of nocardiosis patients with different immune status from a Chinese tertiary general hospital during 8-year period
Authors: Huang Lei , Sun Liying , Yan Yan
Published: November 2019

Nocardia is an opportunistic pathogen from environment, which is generally thought to infect immunosuppressed patients (ISPs), but recent studies showed it could also cause infections in immunocompetent patients (ICPs).

The aim of this study was to compare the clinical characteristics, patients’ outcome, Nocardia species’ identification, and antibiotic susceptibility profiles of nocardiosis between ICPs and ISPs.

The detailed clinical data were collected from all the nonrepetitive nocardiosis patients during 2011 and 2018, from a tertiary general hospital in Beijing, China. Then each Nocardia isolate was identified to species level by DNA sequencing. The antibiotic susceptibility testing was performed by E test method, and interpreted following CLSI M24 document. The clinical and microbiological characteristics between ICPs and ISPs were compared statistically.

A total of 23 nonrepetitive nocardiosis patients with detailed clinical data were enrolled in this study. Among them, 9 were ICPs and 14 were ISPs. All the skin and soft tissue infections occurred in ICPs (33.3% vs 0%, P < .05). Bronchiectasis occurred more frequently in ICPs (44.4% vs 21.4%), whereas chronic kidney diseases and coinfection with aspergillosis occurred more frequently in ISPs (35.7% vs 0%, 35.7% vs 0%, respectively), although they did not reach the statistical significance. There were no significant differences in other clinical characteristics, Nocardia species’ identification, and antibiotic susceptibility between ISPs and ICPs (P > .05).

Nocardiosis could occur in both ISPs and ICPs. Skin and soft tissue infection and bronchiectasis occurred more frequently in ICPs. Chronic kidney diseases and co-infection with aspergillosis occurred more frequently in ISPs. These characteristics should be noticed by physicians in diagnosis of nocardiosis.
Plasma proteome analysis of patients with hereditary transthyretin-mediated (hATTR) amyloidosis establishes neurofilament light chain (NfL) as a biomarker of disease and treatment response
Authors: Ticau Simina , Sridharan Gautham V , Tsour Shira , Cantley William L , Chan Amy , Gilbert Jason A , Erbe David , Aldinc Emre , Reilly Mary M , Adams David , Polydefkis Michael , Fitzgerald Kevin , Vaishnaw Akshay , Nioi Paul
Published: November 2019

Background

Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, progressively debilitating, and fatal disease caused by deposition of aggregated transthyretin amyloid in multiple organs and tissues. Highly variable disease penetrance has made it difficult to predict disease onset and progression. Clinically validated, non-invasive plasma biomarkers may facilitate earlier diagnosis and aid monitoring of disease progression.

Methods

Plasma levels of >1000 proteins were measured in patients with hATTR amyloidosis with polyneuropathy who received either placebo or patisiran in the phase 3 APOLLO study (NCT01960348) and in a cohort of healthy individuals. The impact of patisiran treatment on the time profile of each protein was determined by a linear mixed model at 0, 9, and 18 months. Neurofilament light chain (NfL) protein was further assessed using an orthogonal quantitative approach.

Findings

A significant change in the levels of 66 proteins was observed with patisiran vs placebo, with change in NfL, a marker of neuronal damage, most significant (p<10−20). Analysis of the changes in protein levels demonstrated that the proteome of patients treated with patisiran trended towards healthy individuals at 18 months. Plasma NfL levels in healthy controls were four-fold lower than in patients with hATTR amyloidosis with polyneuropathy (16·3 [SD 12·0] pg/mL vs 69·4 [SD 42·1] pg/mL, p<10−16). Levels of NfL at 18 months increased with placebo (99·5 [SD 60·1] pg/mL) and decreased with patisiran treatment (48·8 [SD 29·9] pg/mL). At 18 months, improvement in modified Neuropathy Impairment Score+7 (mNIS+7) in patisiran-treated patients significantly correlated with a reduction in NfL levels (R=0·43, p<10−7).

Interpretation

The observed correlation of NfL reduction with patisiran treatment and improvement in mNIS+7 suggests it may serve as a biomarker of nerve damage and polyneuropathy in hATTR amyloidosis. This biomarker may enable earlier diagnosis of polyneuropathy in patients with hATTR amyloidosis and facilitate monitoring of disease progression.
Structural basis for the binding selectivity of human CDY chromodomains
Authors: Dong Cheng , Liu Yanli , Lyu Tian-Jie , Beldar Serap , Lamb Kelsey N. , Tempel Wolfram , Li Yanjun , Li Zoey , James Lindsey I. , Qin Su , Wang Yun , Min Jinrong
Published: November 2019

The CDY (Chromodomain on the Y) family is a small family of chromodomain containing proteins, whose chromodomains closely resemble those in HP1 and Polycomb. The CDY proteins play an essential role in normal spermatogenesis and brain development. Dysregulation of their expression has been linked to male infertility and various neurological diseases. Like the chromodomains of HP1 and Polycomb, the CDY chromodomains also recognize the lysine-methylated ARKS motif embedded in histone and non-histone proteins. Interestingly, the CDY chromodomains exhibit different binding preferences for the lysine-methylated ARKS motif in different sequence contexts. Here, we present the structural basis for selective binding of CDY1 to H3K9me3 and preferential binding of CDYL2 to H3tK27me3 over H3K27me3. Based on our structural, binding and mutagenesis data, we synthesized a more CDYL1/2 selective peptidic ligand UNC4850. Our work provides critical implications that CDYL1b’s role in the regulation of neural development is dependent on its recognition of lysine-methylated ARKS motifs.
Stochastic model of T Cell repolarization during target elimination (I)
Authors: Hornak I. , Rieger H.
Published: November 2019

Cytotoxic T lymphocytes (T) and natural killer (NK) cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (i.e. target cells). Once a NK or T cell has identified a target cell, they form a tight contact zone, the immunological synapse (IS). One then observes a re-polarization of the cell involving the rotation of the microtubule (MT) half-spindle and a movement of the microtubule organizing center (MTOC) to a position that is just underneath the plasma membrane at the center of the IS. Concomitantly a massive relocation of organelles attached to MTs is observed, including the Golgi apparatus, lytic granules and mitochondria. Since the mechanism of this relocation is still elusive we devise a theoretical model for the molecular motor driven motion of the MT half-spindle confined between plasma membrane and nucleus during T cell polarization. We analyze different scenarios currently discussed in the literature, the cortical sliding and the capture-shrinkage mechanisms, and compare quantitative predictions about the spatio-temporal evolution of MTOC position and spindle morphology with experimental observations. The model predicts the experimentally observed biphasic nature of the repositioning process due to an interplay between spindle geometry and motor forces and confirms the dominance of the capture-shrinkage over the cortical sliding mechanism when MTOC and IS are initially diametrically opposed. We also find that the two mechanisms act synergetically, thereby reducing the resources necessary for repositioning. Moreover, it turns out that the localization of dyneins in the pSMAC facilitates their interaction with the MTs. Our model also opens a way to infer details of the dynein distribution from the experimentally observed features of the MT half-spindle dynamics. In a subsequent publication we will address the issue of general initial configurations and situations in which the T cell established two immunological synapses.
A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers
Authors: Flies Andrew S. , Darby Jocelyn M. , Lennard Patrick R. , Murphy Peter R. , Ong Chrissie E. B. , Pinfold Terry L. , Lyons A. Bruce , Woods Gregory M. , Patchett Amanda L.
Published: November 2019

Immune checkpoint immunotherapy has revolutionized medicine, but translational success for new treatments remains low. Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. Additionally, devils are affected by two of the three known transmissible cancers in mammals. Unfortunately, little is known about of immune checkpoints in devils and other non-model species, largely due to a lack of species-specific reagents. We developed a simple cut-and-paste reagent development method applicable to any vertebrate species and show that immune checkpoint interactions are conserved across 160 million years of evolution. The inhibitory checkpoint molecule CD200 is highly expressed on devil facial tumor cells. We are the first to demonstrate that co-expression of CD200R1 can block CD200 expression. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can serve as models for understanding cancer and immunological tolerance.

GRAPHICAL ABSTRACT
Reward certainty and preference bias selectively shape voluntary decisions
Authors: Zajkowski Wojciech , Krzemiński Dominik , Barone Jacopo , Evans Lisa , Zhang Jiaxiang
Published: November 2019

Choosing between equally valued options can be a conundrum, for which classical decision theories predicted a prolonged response time (RT). Paradoxically, a rational decision-maker would need no deliberative thinking in this scenario, as outcomes of alternatives are indifferent. How individuals choose between equal options remain unclear. Here, we characterized the neurocognitive processes underlying such voluntary decisions, by integrating advanced cognitive modelling and EEG recording in a probabilistic reward task, in which human participants chose between pairs of cues associated with identical reward probabilities at different levels. We showed that higher reward certainty accelerated RT. At each certainty level, participants preferred to choose one cue faster and more frequently over the other. The behavioral effects on RT persisted in simple reactions to reward cues. By using hierarchical Bayesian parameter estimation for an accumulator model, we showed that the certainty and preference effects were independently associated with the rate of evidence accumulation during decisions, but not with visual encoding or motor execution latencies. Time-resolved multivariate pattern classification of EEG evoked response identified significant representations of reward certainty and preference choices as early as 120 ms after stimulus onset, with spatial relevance patterns maximal in middle central and parietal electrodes. Furthermore, EEG-informed computational modelling showed that the rate of change between N100 and P300 event-related potentials reflected changes in the model-derived rate of evidence accumulation on a trial-by-trial basis. Our findings suggested that reward certainty and preference collectively shaped voluntary decisions between equal options, providing a mechanism to prevent indecision or random behavior.
Modeling phylogenetic biome shifts on a planet with a past
Authors: Landis Michael J. , Edwards Erika J. , Donoghue Michael J.
Published: November 2019

The spatial distribution of biomes has changed considerably over deep time, so the geographical opportunity for an evolutionary lineage to shift into a new biome may depend on how the availability and connectivity of biomes has varied temporally. To better understand how lineages shift between biomes in space and time, we developed a phylogenetic biome shift model in which each lineage shifts between biomes and disperses between regions at rates that depend on the lineage’s biome affinity and location relative to the spatiotemporal distribution of biomes at any given time. To study the behavior of the biome shift model in an empirical setting, we developed a literature-based representation of paleobiome structure for three mesic forest biomes, six regions, and eight time strata, ranging from the Late Cretaceous (100 Ma) through the present. We then fitted the model to a time-calibrated phylogeny of 119Viburnumspecies to compare how the results responded to various realistic or unrealistic assumptions about paleobiome structure.

Ancestral biome estimates that account for paleobiome dynamics reconstructed a warm temperate (or tropical) origin ofViburnum, which is consistent with previous fossil-based estimates of ancestral biomes. Imposing unrealistic paleobiome distributions led to ancestral biome estimates that eliminated support for tropical origins, and instead inflated support for cold temperate ancestry throughout the warmer Paleocene and Eocene. The biome shift model we describe is applicable to the study of evolutionary systems beyondViburnum, and the core mechanisms of our model are extensible to the design of richer phylogenetic models of historical biogeography and/or lineage diversification. We conclude that biome shift models that account for dynamic geographical opportunities are important for inferring ancestral biomes that are compatible with our understanding of Earth history.
Host-dependent induction of disease tolerance to infection by tetracycline antibiotics
Authors: Colaço Henrique G. , Barros André , Neves-Costa Ana , Seixas Elsa , Pedroso Dora , Velho Tiago R. , Willmann Katharina , Yi Hyon-Seung , Shong Minho , Benes Vladimir , Weis Sebastian , Köcher Thomas , Moita Luís F.
Published: November 2019

Synergy of resistance and disease tolerance mechanisms is necessary for an effective immune response leading to survival and return to homeostasis when an organism is challenged by infection. Antibiotics are used for their resistance enhancement capabilities by decreasing pathogen load, but several classes have long been known to have beneficial effects that cannot be explained strictly on the basis of their capacity to control the infectious agent. Here we report that tetracycline antibiotics, a class of ribosome-targeting drugs, robustly protects against sepsis by inducing disease tolerance, independently from their direct antibiotic properties. Mechanistically, we find that mitochondrial inhibition of protein synthesis perturbs the electron transfer chain and leads to improved damage repair in the lung and fatty acid oxidation and glucocorticoid sensitivity in the liver. Using a partial and acute deletion ofCRIF1in the liver, a critical mitoribosomal component for protein synthesis, we find that mice are protected against bacterial sepsis, an observation which is phenocopied by the transient inhibition of complex I of ETC by phenformin. Together, we demonstrate that ribosome-targeting antibiotics are beneficial beyond their antibacterial activity and that mitochondrial protein synthesis inhibition leading to ETC perturbation is a novel mechanism for the induction of disease tolerance.
How Array Design affects SNP Ascertainment Bias
Authors: Geibel Johannes , Reimer Christian , Weigend Steffen , Weigend Annett , Pook Torsten , Simianer Henner
Published: November 2019

Single nucleotide polymorphisms (SNPs), genotyped with SNP arrays, have become a widely used marker type in population genetic analyses over the last 10 years. However, compared to whole genome re-sequencing data, arrays are known to lack a substantial proportion of globally rare variants and tend to be biased towards variants present in populations involved in the development process of the respective array. This affects population genetic estimators and is known as SNP ascertainment bias. We investigated factors contributing to ascertainment bias in array development by redesigning the Axiom™ Genome-Wide Chicken Arrayin silicoand evaluating changes in allele frequency spectra and heterozygosity estimates in a stepwise manner. A sequential reduction of rare alleles during the development process was shown with main influencing factors being the identification of SNPs in a limited set of populations and a within-population selection of common SNPs when aiming for equidistant spacing. These effects were shown to be less severe with a larger discovery panel. Additionally, a generally massive overestimation of expected heterozygosity for the ascertained SNP sets was shown. This overestimation was 24% higher for populations involved in the discovery process than not involved populations in case of the original array. The same was observed after the SNP discovery step in the redesign. However, an unequal contribution of populations during the SNP selection can mask this effect but also adds uncertainty. Finally, we make suggestions for the design of specialized arrays for large scale projects where whole genome re-sequencing techniques are still too expensive.
A statistical nonparametric method for identifying consistently important features across samples
Authors: Sauerwald Natalie , Kingsford Carl
Published: November 2019

In many applications, a consistently high measurement across many samples can indicate particularly meaningful or useful information for quality control or biological interpretation. Identification of these strong features among many others can be challenging especially when the samples cannot be expected to have the same distribution or range of values. We present a general method called conserved feature discovery (CFD) for identifying features with consistently strong signals across multiple conditions or samples. Given any real-valued data, CFD requires no parameters, makes no assumptions on the shape of the underlying sample distributions, and is robust to differences across these distributions.We show that with high probability CFD identifies all true positives and no false positives under certain assumptions on the median and variance distributions of the feature measurements. Using simulated data, we show that CFD is tolerant to a small percentage of poor quality samples and robust to false positives. Applying CFD to RNA sequencing data from the Human Body Map project and GTEx, we identify housekeeping genes as highly expressed genes across tissue types and compare to housekeeping gene lists from previous methods. CFD is consistent between the Human Body Map and GTEx data sets, and identifies lists of genes enriched for basic cellular processes as expected. The framework can be easily adapted for many data types and desired feature properties.

Availability

Code for CFD and scripts to reproduce the figures and analysis in this work are available at https://github.com/Kingsford-Group/cfd.

Supplementary information

Supplementary data are available at https://github.com/Kingsford-Group/cfd.
The thermodynamics of thinking: connections between neural activity, energy metabolism and blood flow
Authors: Buxton Richard B.
Published: November 2019

Several current functional neuroimaging methods are sensitive to cerebral metabolism and cerebral blood flow (CBF) rather than the underlying neural activity itself. Empirically, the connections between metabolism, flow and neural activity are complex and somewhat counterintuitive: CBF and glycolysis increase more than seems to be needed to provide oxygen and pyruvate for oxidative metabolism, and the oxygen extraction fraction is relatively low in the brain anddecreaseswhen oxygen metabolism increases. This work lays a foundation for the idea that this unexpected pattern of physiological changes is consistent with basic thermodynamic considerations related to metabolism. In the context of this thermodynamic framework, the apparent mismatches in metabolic rates and CBF are related to preserving the entropy change of oxidative metabolism, specifically the O2/CO2ratio in the mitochondria. However, the mechanism supporting this CBF response is likely not due to feedback from a hypothetical O2sensor in tissue, but rather is consistent with feed-forward control by signals from both excitatory and inhibitory neural activity. Quantitative predictions of the thermodynamic framework, based on models of O2and CO2transport and possible neural drivers of CBF control, are in good agreement with a wide range of experimental data, including responses to neural activation, hypercapnia, hypoxia and high-altitude acclimatization.
A tradeoff between robustness to environmental fluctuations and speed of evolution
Authors: Schmid Max , Paniw Maria , Postuma Maarten , Ozgul Arpat , Guillaume Frédéric
Published: November 2019

Organisms must cope with both short- and long-term environmental changes to persist. In this study we investigated whether life histories trade-off between their robustness to short-term environmental perturbations and their ability to evolve directional trait changes. We could confirm the tradeoff by modeling the eco-evolutionary dynamics of life-histories along the fast-slow pace-of-life continuum. Offspring dormancy and high adult survival rates allowed for large population sizes to be maintained in face of interannual environmental fluctuations but limited the speed of trait evolution with ongoing environmental change. In contrast, precocious offspring maturation and short-living adults promoted evolvability while lowering demographic robustness. This tradeoff had immediate consequences on extinction dynamics in variable environments. High evolvability allowed short-lived species to cope with long-lasting gradual environmental change, but came at the expense of more pronounced population declines and extinction rates from environmental variability. Higher robustness of slow life-histories helped them persist better on short timescales.
Detection of interictal epileptiform discharges: A comparison of on-scalp MEG and conventional MEG measurements
Authors: Westin Karin , Pfeiffer Christoph , Andersen Lau M. , Ruffieux Silvia , Cooray Gerald , Kalaboukhov Alexei , Winkler Dag , Ingvar Martin , Schneiderman Justin , Lundqvist Daniel
Published: November 2019

Magnetoencephalography (MEG) is an important part of epilepsy evaluations because of its unsurpassed ability to detect interictal epileptiform discharges (IEDs). This ability may be improved by next-generation MEG sensors, where sensors are placed directly on the scalp instead of in a fixed-size helmet, as in today’s conventional MEG systems. In order to investigate the usefulness of on-scalp MEG measurements we performed the first-ever measurements of on-scalp MEG on an epilepsy patient. The measurement was conducted as a benchmarking study, with special focus on IED detection. An on-scalp high-temperature SQUID system was utilized alongside a conventional low-temperature “in-helmet” SQUID system. EEG was co-registered during both recordings. Visual inspection of IEDs in the raw on-scalp MEG data was unfeasible why a novel machine learning-based IED-detection algorithm was developed to guide IED detection in the on-scalp MEG data. A total of 24 IEDs were identified visually from the conventional in-helmet MEG session (of these, 16 were also seen in the EEG data; eight were detected only by MEG). The on-scalp MEG data contained a total of 47 probable IEDs of which 16 IEDs were co-registered by the EEG, and 31 IEDs were on-scalp MEG-unique IEDs found by the IED detection algorithm. We present a successful benchmarking study where on-scalp MEG are compared to conventional in-helmet MEG in a temporal lobe epilepsy patient. Our results demonstrate that on-scalp MEG measurements are feasible on epilepsy patients, and indicate that on-scalp MEG might capture IEDs not seen by other non-invasive modalities.
NF1 regulates mesenchymal glioblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1
Authors: Marques Carolina , Unterkircher Thomas , Kroon Paula , Izzo Annalisa , Dramaretska Yuliia , Kling Eva , Oldrini Barbara , Schnell Oliver , Nelander Sven , Wagner Erwin F. , Bakiri Latifa , Gargiulo Gaetano , Carro Maria Stella , Squatrito Massimo
Published: November 2019

The molecular basis underlying Glioblastoma (GBM) heterogeneity and plasticity are not fully understood. Using transcriptomic data of patient-derived brain tumor stem cell lines (BTSCs), classified based on GBM-intrinsic signatures, we identify the AP-1 transcription factorFOSL1as a key regulator of the mesenchymal (MES) subtype. We provide a mechanistic basis to the role of the Neurofibromatosis type 1 gene (NF1), a negative regulator of the RAS/MAPK pathway, in GBM mesenchymal transformation through the modulation ofFOSL1expression. Depletion ofFOSL1inNF1-mutant human BTSCs andKras-mutant mouse neural stem cells results in loss of the mesenchymal gene signature, reduction in stem cell properties andin vivotumorigenic potential. Our data demonstrate thatFOSL1controls GBM plasticity and aggressiveness in response toNF1alterations.
Polycysteine-encoding leaderless short ORFs function as cysteine-responsive attenuators of operonic gene expression in mycobacteria
Authors: Canestrari Jill G. , Lasek-Nesselquist Erica , Upadhyay Ashutosh , Rofaeil Martina , Champion Matthew M. , Wade Joseph T. , Derbyshire Keith M. , Gray Todd A.
Published: November 2019

Genome-wide transcriptomic analyses have revealed abundant expressed short open reading frames (ORFs) in bacteria. Whether these short ORFs, or the small proteins they encode, are functional remains an open question. One quarter of mycobacterial mRNAs are leaderless, beginning with a 5’-AUG or GUG initiation codon. Leaderless mRNAs often encode unannotated short ORFs as the first gene of a polycistronic transcript. Here we show that polycysteine-encoding leaderless short ORFs function as cysteine-responsive attenuators of operonic gene expression. Detailed mutational analysis shows that one polycysteine short ORF controls expression of the downstream genes. Our data indicate that ribosomes stalled in the polycysteine tract block mRNA structures that otherwise sequester the ribosome-binding site of the 3’gene. We assessed endogenous proteomic responses to cysteine limitation inMycobacterium smegmatisusing mass spectrometry. Six cysteine metabolic loci having unannotated polycysteine-encoding leaderless short ORF architectures responded to cysteine limitation, revealing widespread cysteine-responsive attenuation in mycobacteria. Individual leaderless short ORFs confer independent operon-level control, while their shared dependence on cysteine ensures a collective response mediated by ribosome pausing. We propose the term ribulon to classify ribosome-directed regulons. Regulon-level coordination by ribosomes on sensory short ORFs illustrates one utility of the many unannotated short ORFs expressed in bacterial genomes.
Stochastic Sampling of Structural Contexts Improves the Scalability and Accuracy of RNA 3D Module Identification
Authors: Sarrazin-Gendron Roman , Yao Hua-Ting , Reinharz Vladimir , Oliver Carlos G. , Ponty Yann , Waldispühl Jérôme
Published: November 2019

RNA structures possess multiple levels of structural organization. Secondary structures are made of canonical (i.e. Watson-Crick and Wobble) helices, connected by loops whose local conformations are critical determinants of global 3D architectures. Such local 3D structures consist of conserved sets of non-canonical base pairs, called RNA modules. Their prediction from sequence data is thus a milestone toward 3D structure modelling. Unfortunately, the computational efficiency and scope of the current 3D module identification methods are too limited yet to benefit from all the knowledge accumulated in modules databases. Here, we introduceBayesPairing 2, a new sequence search algorithm leveraging secondary structure tree decomposition which allows to reduce the computational complexity and improve predictions on new sequences. We benchmarked our methods on 75 modules and 6380 RNA sequences, and report accuracies that are comparable to the state of the art, with considerable running time improvements. When identifying 200 modules on a single sequence,BayesPairing 2is over 100 times faster than its previous version, opening new doors for genome-wide applications.
The Hippo pathway oncoprotein YAP promotes melanoma cell invasion and spontaneous metastasis
Authors: Zhang Xiaomeng , Yang Lie , Szeto Pacman , Zhang Youfang , Amarasinghe Kaushalya , Li Jason , McLean Catriona , Shackleton Mark , Harvey Kieran F.
Published: November 2019

Melanoma is a deadly form of skin cancer that accounts for a disproportionally large proportion of cancer-related deaths in younger people. Compared to most other skin cancers, a feature of melanoma is its high metastatic capacity, although molecular mechanisms that confer this are not well understood. The Hippo pathway is a key regulator of organ growth and cell fate that is deregulated in many cancers. To analyse the Hippo pathway in cutaneous melanoma, we generated a transcriptional signature of pathway activity in melanoma cells. Hippo-mediated transcriptional activity varied in melanoma cell lines but failed to cluster with known genetic drivers of melanomagenesis such asBRAFandNRASmutation status. Instead, it correlated strongly with published gene expression profiles linked to melanoma cell invasiveness. Consistent with this, the central Hippo oncogene, YAP, was both necessary and sufficient for melanoma cell invasion in vitro. In in vivo murine studies, YAP promoted spontaneous melanoma metastasis, whilst the growth of YAP-expressing primary tumours was impeded. Finally, we identified the YAP target genesAXL,THBS1andCYR61as key mediators of YAP-induced melanoma cell invasion. These data suggest that the Hippo pathway is a critical regulator of melanoma metastasis.
An extensively optimized chromatin immunoprecipitation protocol for quantitatively comparable and robust results
Authors: de Jonge Wim J. , Brok Mariël , Kemmeren Patrick , Holstege Frank C.P.
Published: November 2019

Chromatin immunoprecipitation (ChIP) is a commonly used technique to investigate which parts of a genome are bound by a particular protein. The result of ChIP is often interpreted in a binary manner: bound or not bound. Due to this focus, ChIP protocols frequently lack the ability to quantitatively compare samples with each other, for example in a time series or under different growth conditions. Here, using the yeast S. cerevisiae transcription factors Cbf1, Abf1, Reb1, Mcm1 and Sum1, we optimized the five major steps of a commonly used ChIP protocol: cross-linking, quenching, cell lysis, fragmentation and immunoprecipitation. Quenching with glycine is inefficient and can lead to large degrees of variability, an issue that is resolved by using tris(hydroxymethyl)aminomethane (Tris). Another source of variability is degradation of the protein of interest during the procedure. Enzymatic cell lysis with zymolyase can lead to extensive protein degradation, which is greatly reduced by mechanical lysis through bead beating. Degradation also occurs during sonication of chromatin, affecting large proteins in particular. An optimal mix of protease inhibitors and cross-linking with a higher percentage of formaldehyde reduces the extent of this degradation. Finally we also show that the immunoprecipitation step itself can be greatly improved with magnetic beads and optimized incubation/washing steps. The study results in a highly optimized protocol, which is shorter, easier to perform and has a stronger, more reproducible signal with less background. This protocol is presented in detail. In addition, the results highlight the greatest sources of variability in many other protocols, showing which steps are important to focus on for reproducible and quantitatively comparable ChIP experiments.
Fast fitting of reflectivity data of growing thin films using neural networks
Authors: Greco Alessandro , Starostin Vladimir , Karapanagiotis Christos , Hinderhofer Alexander , Gerlach Alexander , Pithan Linus , Liehr Sascha , Schreiber Frank , Kowarik Stefan
Published: November 2019

X-ray reflectivity (XRR) is a powerful and popular scattering technique that can give valuable insight into the growth behavior of thin films. This study shows how a simple artificial neural network model can be used to determine the thickness, roughness and density of thin films of different organic semiconductors [diindenoperylene, copper(II) phthalocyanine and α-sexithiophene] on silica from their XRR data with millisecond computation time and with minimal user input ora prioriknowledge. For a large experimental data set of 372 XRR curves, it is shown that a simple fully connected model can provide good results with a mean absolute percentage error of 8–18% when compared with the results obtained by a genetic least mean squares fit using the classical Parratt formalism. Furthermore, current drawbacks and prospects for improvement are discussed.
Quantification of amorphous siliceous fly ash in hydrated blended cement pastes by X-ray powder diffraction
Authors: Li Xuerun , Snellings Ruben , Scrivener Karen L.
Published: November 2019

X-ray powder diffraction (XRPD)-based quantitative phase analysis is a common technique for studying the hydration of cementitious systems. Hydrated cements often comprise several amorphous or nanocrystalline phases. This paper presents a protocol for the quantification of amorphous siliceous fly ash in hydrated cement using XRPD based on the Rietveld PONKCS (partial or no known crystal structure) method. The protocol is validated by comparison against independent measurements, such as Ca(OH)2content by thermogravimetry and isothermal calorimetry to evaluate the fly ash degree of reaction. A sensitivity analysis of the protocol was carried out to test the robustness of the results with regard to sample preparation, data collection strategies and refinement model parameters. The key sensitive aspects of the protocol are (i) the preservation and preparation of the hydrated cement sample for XRPD measurement, (ii) the selection of a 2θ angular range for the Rietveld analysis that avoids low-angle scattering interferences, and (iii) the use of the peak profile to account for the contribution of other amorphous phases such as the diffraction pattern of nanocrystalline calcium silicate hydrate (C–S–H). The results show good accuracy in terms of quantification if the initial fly ash content is more than 10 wt%. ExampleTOPASfly ash and C–S–H codes, as well as the raw XRPD data set, are provided.
A scanning reflection X-ray microscope for magnetic imaging in the EUV range
Authors: Schümmer Andreas , Mertins H.-Ch. , Schneider Claus Michael , Adam Roman , Trellenkamp Stefan , Borowski Rene , Bürgler Daniel Emil , Juschkin Larissa , Berges Ulf
Published: November 2019

The mechanical setup of a novel scanning reflection X-ray microscope is presented. It is based on zone plate optics optimized for reflection mode in the EUV spectral range. The microscope can operate at synchrotron radiation beamlines as well as at laboratory-based plasma light sources. In contrast to established X-ray transmission microscopes that use thin foil samples, the new microscope design presented here allows the investigation of any type of bulk materials. Importantly, this permits the investigation of magnetic materials by employing experimental techniques based on X-ray magnetic circular dichroism, X-ray linear magnetic dichroism or the transversal magneto-optical Kerr effect (T-MOKE). The reliable functionality of the new microscope design has been demonstrated by T-MOKE microscopy spectra of Fe/Cr-wedge/Fe trilayer samples. The spectra were recorded at various photon energies across the Fe 3p edge revealing the orientation of magnetic domains in the sample.
Crystal structure and Hirshfeld surface analysis of poly[tris(μ4-benzene-1,4-dicarboxylato)tetrakis(dimethylformamide)trinickel(II)]: a two-dimensional coordination network
Authors: Ajpi Cesario , Suescun Leopoldo , Leiva Naviana , Lundblad Anders , Lindbergh Göran , Cabrera Saul
Published: November 2019

The crystal structure of the title compound, [Ni3(C8H4O4)3(C3H7NO)4], is a two-dimensional coordination network formed by trinuclear linear Ni3(tp)3(DMF)4 units (tp = terephthalate = benzene-1,4-dicarboxylate and DMF = dimethylformamide) displaying a characteristic coordination mode of acetate groups in polynuclear metal–organic compounds. Individual trinuclear units are connected through tp anions in a triangular network that forms layers. One of the DMF ligands points outwards and provides interactions with equivalent planes above and below, leaving the second ligand in a structural void much larger than the DMF molecule, which shows positional disorder. Parallel planes are connected mainly through weak C—H...O, H...H and H...C interactions between DMF molecules, as shown by Hirshfeld surface analysis.
IFRS adoption and accounting regulation in Ethiopia
Authors: Wagaw Yitayew Mihret , Mihret Dessalegn Getie , Obo Degefe Duressa
Published: November 2019

Purpose

The purpose of this study is to examine international financial reporting standards (IFRSs) adoption in Ethiopia to explain transnational political-economic antecedents of this change and its associated consequences on the regulatory landscape of accounting.

Design/methodology/approach

Using a neo-Gramscian theory of globalization and the state, the study examines interview and document review evidence pertaining to IFRS adoption in Ethiopia by focusing on the period from 1991 to 2014.

Findings

The study illustrates that a dialectical rather than deterministic interaction between global and national forces explains IFRS adoption in Ethiopia, i.e. IFRS adoption falls within the broader scheme of universalizing regulatory institutions in the globalizing world economy. Compared to the commonly understood trends of IFRS adoption circumscribed within a pre-existing regulatory framework, this study illustrates IFRS adoption as a primary driver of major reforms to the accounting regulatory landscape.

Originality/value

This study contributes original theoretically grounded insights into the transnational political-economic rationale for IFRS adoption and consequences of the adoption on the accounting regulatory landscape.
Stock price synchronicity and dividend policy: evidence from an emerging market
Authors: Farooq Omar , ElBannan Mona A.
Published: November 2019

Purpose

The purpose of this paper is to document the impact of stock price synchronicity (SYNCH) on the dividend payout ratio.

Design/methodology/approach

The authors use data from India for the period between 2000 and 2012 and the panel regression approach to test their arguments.

Findings

This paper documents that the relationship between synchronicity and dividend payout ratio is positive until a turning point is reached. After that point, synchronicity has a negative impact on dividend payout ratio. The authors argue that firms with low synchronicity have higher information asymmetries. As a result, they have an incentive to develop a reputation as better-governed firms by paying high dividends. However, as synchronicity increases further, information asymmetries go down and as a result incentive to use dividend payouts as a mechanism to reduce information asymmetries goes down. Therefore, positive relationship between synchronicity and dividend payout ratios breaks down at high levels of synchronicity.

Originality/value

The authors provide evidence regarding the role played by SYNCH – a publicly available measure – on dividend polices adopted by firms within the context of emerging markets.
CSR and reconciliation with Indigenous peoples in Canada
Authors: Long Brad S.
Published: November 2019

Purpose

This paper aims to highlight blind spots in the discourse of corporate social responsibility (CSR) and stretch the boundaries of existent CSR frameworks within the particular context of resource extraction and with regard to the particular stakeholder group of Indigenous peoples in Canada. This context is important in light of the recommendations from the recent Truth and Reconciliation Commission (TRC), as they relate to initiatives that businesses may take towards reconciliation with Indigenous people.

Design/methodology/approach

This paper brings together a disparate body of literature on CSR, Indigenous spiritual values and experiences of extractive practices on Indigenous ancestral lands. Suggestions are offered for empirical research and projects that may advance the project of reconciliation.

Findings

CSR may not be an appropriate framework for reconciliation without alteration to its managerial biases and ideological assumptions. The CSR discourse needs to accommodate the “free prior and informed consent” of Indigenous peoples and their spiritual values and knowledge vis-à-vis the land for resource extractive practices to edge towards being socially responsible when they occur on Canadian ancestral territories.

Originality/value

Canadian society exists in a post-TRC world, which demands that we reconcile with our past of denying Indigenous values and suppressing the cultures of Indigenous peoples from flourishing. This paper aspires to respond to the TRC’s recommendation for how businesses in the resource extractive industries may engage meaningfully and authentically with Indigenous people in Canada as a step towards reconciliation.
Innovation dimensions and business performance under environmental uncertainty
Authors: Kafetzopoulos Dimitrios , Psomas Evangelos , Skalkos Dimitris
Published: November 2019

Purpose

The purpose of this paper is to examine the impact of the dimensions of innovation on manufacturing firm performance taking into consideration the moderating role of environmental uncertainty among these relationships.

Design/methodology/approach

A research study was carried out using a sample of 580 Greek manufacturing firms. Exploratory and confirmatory factor analyses were applied to extract and validate the latent factors. K-means cluster analysis was also applied in order to group the responding firms. Finally, the structural relationships among the latent factors were determined through structural equation modeling.

Findings

According to the study findings, only three dimensions of innovation performance directly contributes to business performance. Moreover, this paper shows the differential effects of firm innovativeness on business performance under the influence of environmental uncertainty.

Research limitations/implications

The sample of the responding firms which is limited to the Greek manufacturing sector and the subjective business evidence coming from only one firm representative constitute the main limitations of the present study.

Practical implications

Firms can properly manage innovation dimensions. In case of high uncertainty, they should focus on product, marketing and process innovation, while in case of low uncertainty the focus should be on process, organization and product innovation.

Originality/value

Based on the multi-dimensional structure, this empirical study determines the contribution of innovation performance to business performance taking into consideration the role of environmental uncertainty as moderator on this relationship.
Transformational leadership and employee knowledge sharing: explore the mediating roles of psychological safety and team efficacy
Authors: Yin Jielin , Ma Zhenzhong , Yu Haiyun , Jia Muxiao , Liao Ganli
Published: November 2019

Purpose

This paper aims—based on past research works which have shown that transformational leadership has positive impact on knowledge sharing—to explore the impact of different leadership dimensions of transformational leadership on knowledge sharing and further to explore the mechanism through which transformational leadership affects employee knowledge sharing in China.

Design/methodology/approach

Based on the transformational leadership theory and the team learning theory, it is proposed that all four dimensions of transformational leadership, including intellectual stimulation, individualized consideration, inspirational motivation and idealized influence, have unique impact on employee knowledge sharing. It is further proposed that psychology safety and team efficacy mediate these relationships. Then data were collected from over 400 employees from knowledge-based companies in China to empirically test the proposed relationships with the method of structural equation modeling.

Findings

The results show that psychological safety fully mediated the impact of intellectual stimulation on knowledge sharing, and team efficacy fully mediated the impact of inspirational motivation on knowledge sharing. Both factors also mediated the impact of individualized consideration on knowledge sharing. The results thus provide empirical support for the impact of transformational leadership on employee knowledge sharing in an international context.

Originality/value

The past years have seen increasing interest in leadership and knowledge sharing in emerging markets, yet the mechanism through which leadership affects employee knowledge sharing remains understudied. This study explores the impact of different dimensions of transformational leadership on employee knowledge sharing, and further shows that psychological safety and team efficacy mediate these relationships in a collectivistic society where knowledge sharing is consistent with cultural norms. The findings help develop more robust knowledge sharing theories in the international context and provide insightful suggestions for management practitioners in emerging markets.