bluuebunny/crossref_metadata_2025 huggingface dataset:
GTShark: Genotype compression in large project
Authors: Deorowicz Sebastian , Danek Agnieszka
Published: December 2018

Nowadays large sequencing projects handle tens of thousands of individuals. The huge files summarizing the findings definitely require compression. We propose a tool able to compress large collections of genotypes as well as single samples in such projects to sizes not achievable to date.

Availability and Implementation

https://github.com/refresh-bio/GTShark

Contact

sebastian.deorowicz@polsl.pl

Supplementary information

Supplementary data are available at publisher’s Web site.
Fast and Flexible Sequence Induction In Spiking Neural Networks Via Rapid Excitability Changes
Authors: Pang Rich , Fairhall Adrienne
Published: December 2018

Cognitive flexibility, the adaptation of mental processing to changes in task demands, is thought to depend on biological neural networks’ ability to rapidly modulate the dynamics governing how they process information. While extensive work has elucidated how network dynamics can be reshaped by slowly occurring structural changes, e.g. the gradual modification of recurrent synaptic patterns, much less is known about how dynamics might be reconfigured over faster timescales of seconds. One compelling example of rapid and selective modulation of network dynamics potentially involved in cognitive flexibility is observed in rodent hippocampus, where short bouts of exploratory behavior cause new activity sequences to preferentially “replay” during subsequent awake rest periods without continued sensory input. Fast mechanisms for selectively biasing sequential activity through networks, however, remain unknown. Using a spiking neural network model, we asked whether a simplified version of sequence replay could arise from three biophysically plausible components: recurrent, spatially organized connectivity; homogeneous, stochastic “gating” inputs; and rapid, activity-dependent scaling of gating input strengths, based on a phenomenon known as long-term potentiation of intrinsic excitability (LTP-IE). Indeed, these enabled both forward and reverse replay of flexible sequences reflecting recent behavior, despite unchanged recurrent weights. Specifically, activation-triggered LTP-IE “tags” neurons in the recurrent network by increasing their spiking probability when gating input is applied, and the sequential ordering of spikes is reconstructed by the existing recurrent connectivity. In a proof-of-concept demonstration, we also show how LTP-IE-based sequences can implement temporary stimulus-response mappings in a straightforward manner. These results elucidate a simple yet previously unexplored combination of biological mechanisms that converge in hippocampus and suffice for fast and flexible reconfiguration of sequential network dynamics, suggesting their potential role in cognitive flexibility over rapid timescales.
Benchmarking miniaturized microscopy against two-photon calcium imaging using single-cell orientation tuning in mouse visual cortex
Authors: Glas Annet , Huebener Mark , Bonhoeffer Tobias , Goltstein Pieter M
Published: December 2018

Miniaturized microscopes are lightweight imaging devices that allow optical recordings from neurons in freely moving animals over the course of weeks. Despite their ubiquitous use, individual neuronal responses measured with these microscopes have not been directly compared to those obtained with established in vivo imaging techniques such as bench-top two-photon microscopes. To achieve this, we performed calcium imaging in mouse primary visual cortex while presenting animals with drifting gratings. We identified the same neurons in image stacks acquired with both microscopy methods and quantified orientation tuning of individual neurons. The response amplitude and signal-to-noise ratio of calcium transients recorded upon visual stimulation were highly correlated between both microscopy methods, although influenced by neuropil contamination in miniaturized microscopy. Tuning properties, calculated for individual orientation tuned neurons, were strongly correlated between imaging techniques. Thus, neuronal tuning features measured with a miniaturized microscope are quantitatively similar to those obtained with a two-photon microscope.
Expanding the repertoire of glucocorticoid receptor target genes by engineering genomic response elements
Authors: Thormann Verena , Glaser Laura V. , Rothkegel Maika C. , Borschiwer Marina , Bothe Melissa , Fuchs Alisa , Meijsing Sebastiaan H.
Published: December 2018

The glucocorticoid receptor (GR), a hormone-activated transcription factor, binds to a myriad of genomic binding sites yet seems to regulate a much smaller number of genes. Genome-wide analysis of GR binding and gene regulation has shown that the likelihood of GR-dependent regulation increases with decreased distance of its binding to the transcriptional start site of a gene. To test if we can adopt this knowledge to expand the repertoire of GR target genes, we used homology directed repair (HDR)-mediated genome editing to add a single GR binding site directly upstream of the transcriptional start site of four genes. To our surprise, we found that the addition of a single GR binding site can be enough to convert a gene into a GR target. The gain of GR-dependent regulation was observed for two out of four genes analyzed and coincided with acquired GR binding at the introduced binding site. However, the gene-specific gain of GR-dependent regulation could not be explained by obvious differences in chromatin accessibility between converted genes and their non-converted counterparts. Further, by introducing GR binding sequences with different nucleotide compositions, we show that activation can be facilitated by distinct sequences without obvious differences in activity between the GR binding sequence variants we tested. The approach to use genome engineering to build genomic response elements facilitates the generation of cell lines with tailored repertoires of GR-responsive genes and a framework to test and refine our understanding of the cis-regulatory logic of gene regulation by testing if engineered response elements behave as predicted.
Eigenvector centrality mapping for ultrahigh resolution fMRI data of the human brain
Authors: Lohmann Gabriele , Loktyushin Alexander , Stelzer Johannes , Scheffler Klaus
Published: December 2018

Eigenvector centrality mapping (ECM) is a popular technique for analyzing fMRI data of the human brain. It is used to obtain maps of functional hubs in networks of the brain in a manner similar to Google's PageRank algorithm. ECM attributes a score to the time course of each voxel that reflects its centrality within the network. Voxels that are strongly correlated with many other voxels that are themselves strongly correlated with other voxels receive high scores. Currently, there exist two different implementations ECM, one of which is very fast but limited to one particular type of correlation metric whose interpretation can be problematic. The second implementation supports many different metrics, but it is computationally costly and requires a very large main memory. Here we propose two new implementations of the ECM approach that resolve these issues. The first is based on a new correlation metric that we call "ReLU correlation (RLC)". The second method is based on matrix projections. We demonstrate the use of both techniques on standard fMRI data, as well as on high-resolution fMRI data acquired at 9.4 Tesla.
Reproducibility of the correlative triad among aging, dopamine receptor availability, and cognition
Authors: Juarez Eric J. , Castrellon Jaime J. , Green Mikella A. , Crawford Jennifer L. , Seaman Kendra L. , Smith Christopher T. , Dang Linh C. , Matuskey David , Morris Evan D. , Cowan Ronald L. , Zald David H. , Samanez-Larkin Gregory R.
Published: December 2018

The evidence that dopamine function mediates the association between aging and cognition is one of the most cited findings in the cognitive neuroscience of aging. However, few and relatively small studies have directly examined these associations. Here we examined correlations among adult age, dopamine D2-like receptor (D2R) availability, and cognition in two cross-sectional studies of healthy human adults. Participants completed a short cognitive test battery and, on a separate day, a PET scan with either the high-affinity D2R tracer [18F]Fallypride (Study 1) or [11C]FLB457 (Study 2). Digit span, a measure of short-term memory maintenance and working memory, was the only cognitive test for which dopamine D2R availability partially mediated the age effect on cognition. In Study 1, age was negatively correlated with digit span. Striatal D2R availability was positively correlated with digit span controlling for age. The age effect on digit span was smaller when controlling for striatal D2R availability. Although other cognitive measures used here have individually been associated with age and D2R availability in prior studies, we found no consistent evidence for significant associations between low D2R availability and low cognitive performance on these measures. These results at best only partially supported the correlative triad of age, dopamine D2R availability, and cognition. While a wealth of other research in human and non-human animals demonstrates that dopamine makes critical contributions to cognition, the present studies suggest caution in interpreting PET findings as evidence that dopamine D2R loss is a primary cause of broad age-related declines in fluid cognition.
Population structure of modern-day Italians reveals patterns of ancient and archaic ancestries in Southern Europe
Authors: Raveane Alessandro , Aneli Serena , Montinaro Francesco , Athanasiadis Georgios , Barlera Simona , Birolo Giovanni , Boncoraglio Giorgio , Di Blasio Anna Maria , Di Gaetano Cornelia , Pagani Luca , Parolo Silvia , Paschou Peristera , Piazza Alberto , Stamatoyannopoulos George , Angius Andrea , Brucato Nicolas , Cucca Francesco , Hellenthal Garrett , Mulas Antonella , Peyret-Guzzon Marine , Zoledziewska Madzia , Baali Abdellatif , Bycroft Clare , Cherkaoui Mohammed , Dina Christian , Dugoujon Jean-Michel , Galan Pilar , Giemza Joanna , Kivisild Toomas , Melhaoui Mohammed , Metspalu Mait , Myers Simon , Pereira Luisa Mesquita , Ricaut Francois-Xavier , Brisighelli Francesca , Cardinali Irene , Grugni Viola , Lancioni Hovirag , Pascali Vincenzo Lorenzo , Torroni Antonio , Semino Ornella , Matullo Giuseppe , Achilli Alessandro , Olivieri Anna , Capelli Cristian
Published: December 2018

European populations display low genetic diversity as the result of long term blending of the small number of ancient founding ancestries. However it is still unclear how the combination of ancient ancestries related to early European foragers, Neolithic farmers and Bronze Age nomadic pastoralists can fully explain genetic variation across Europe. Populations in natural crossroads like the Italian peninsula are expected to recapitulate the overall continental diversity, but to date have been systematically understudied. Here we characterised the ancestry profiles of modern-day Italian populations using a genome-wide dataset representative of modern and ancient samples from across Italy, Europe and the rest of the world. Italian genomes captured several ancient signatures, including a non-steppe related substantial ancestry contribution ultimately from the Caucasus. Differences in ancestry composition as the result of migration and admixture generated in Italy the largest degree of population structure detected so far in the continent and shaped the amount of Neanderthal DNA present in modern-day populations.
Assessing the effect of hypoxia on cardiac metabolism using hyperpolarized 13C magnetic resonance spectroscopy
Authors: Le Page Lydia M , Rider Oliver J , Lewis Andrew J , Noden Victoria , Kerr Matthew , Giles Lucia , Ambrose Lucy J A , Ball Vicky , Mansor Latt , Heather Lisa C , Tyler Damian J
Published: December 2018

Hypoxia plays a role in many diseases and can have a wide range of effects on cardiac metabolism depending on the extent of the hypoxic insult. Non-invasive imaging methods could shed valuable light on the metabolic effects of hypoxia on the heart in vivo. Hyperpolarized carbon-13 magnetic resonance spectroscopy (HP 13C MRS) in particular is an exciting technique for imaging metabolism that could provide such information. The aim of our work was, therefore, to establish whether hyperpolarized 13C MRS can be used to assess the in vivo response of cardiac metabolism to systemic acute and chronic hypoxic exposure. Groups of healthy male Wistar rats were exposed to either acute (30 minutes), one week or three weeks of hypoxia. In vivo MRS of hyperpolarized [1-13C] pyruvate was carried out along with assessments of physiological parameters and ejection fraction. No significant changes in heart rate, respiration rate, or ejection fraction were observed at any timepoint. Haematocrit was elevated after one week and three weeks of hypoxia. Thirty minutes of hypoxia resulted in a significant reduction in pyruvate dehydrogenase (PDH) flux, whereas one or three weeks of hypoxia resulted in a PDH flux that was not different to normoxic animals. Conversion of hyperpolarized [1-13C] pyruvate into [1-13C] lactate was elevated following acute hypoxia, suggestive of enhanced anaerobic glycolysis. Elevated HP pyruvate to lactate conversion was also seen at the one-week timepoint, in concert with an increase in lactate dehydrogenase (LDH) expression. Following three weeks of hypoxic exposure, cardiac metabolism was comparable to that observed in normoxia. We have successfully visualized of the effects of systemic hypoxia on cardiac metabolism using hyperpolarized 13C MRS, with differences observed following 30 minutes and 1 week of hypoxia. This demonstrates the potential of in vivo hyperpolarized 13C MRS data for assessing the cardiometabolic effects of hypoxia in disease.
Oncogenic PIK3CA promotes cellular stemness in an allele dose-dependent manner
Authors: Madsen Ralitsa R. , Knox Rachel G. , Pearce Wayne , Lopez Saioa , Mahler-Araujo Betania , McGranahan Nicholas , Vanhaesebroeck Bart , Semple Robert K.
Published: December 2018

The PIK3CA gene, which encodes the p110α catalytic subunit of PI3-kinase (PI3K), is mutationally activated in cancer and in overgrowth disorders known as PIK3CA-related overgrowth spectrum (PROS). To determine the consequences of genetic PIK3CA activation in a developmental context of relevance to both PROS and cancer, we engineered isogenic human induced pluripotent stem cells (iPSCs) with heterozygous or homozygous knock-in of PIK3CAH1047R. While heterozygous iPSCs remained largely similar to wild-type cells, homozygosity for PIK3CAH1047R caused widespread, cancer-like transcriptional remodeling, partial loss of epithelial morphology, upregulation of stemness markers and impaired differentiation to all three germ layers in vitro and in vivo. Genetic analysis of PIK3CA-associated cancers revealed that 64 % had multiple oncogenic PIK3CA copies (39 %) or additional PI3K signaling pathway-activating “hits” (25 %). This contrasts with the prevailing view that PIK3CA mutations occur heterozygously in cancer. Our findings suggest that a PI3K activity threshold determines pathological consequences of oncogenic PIK3CA activation and provide the first insight into the specific role of this pathway in human pluripotent stem cells.
Forces and constraints controlling podosome assembly and disassembly
Authors: Mohd Rafiq Nisha , Grenci Gianluca , Kozlov Michael M , Jones Gareth E , Viasnoff Virgile , Bershadsky Alexander D
Published: December 2018

Podosomes are a singular category of integrin-mediated adhesions important in the processes of cell migration, matrix degradation, and cancer cell invasion. Despite a wealth of biochemical studies, the effects of mechanical forces on podosome integrity and dynamics are poorly understood. Here, we show that podosomes are highly sensitive to two groups of physical factors. First, we describe the process of podosome disassembly induced by activation of myosin- IIA filament assembly. Next, we find that podosome integrity and dynamics depends upon membrane tension and can be experimentally perturbed by osmotic swelling and deoxycholate treatment. We have also found that podosomes can be disrupted in a reversible manner by single or cyclic radial stretching of the substratum. We show that disruption of podosomes induced by osmotic swelling is independent of myosin-II filaments. Inhibition of the membrane sculpting protein, dynamin-II, but not clathrin, resulted in activation of myosin-IIA filament formation and disruption of podosomes. The effect of dynamin-II inhibition on podosomes was however independent of myosin-II filaments. Moreover, formation of organized arrays of podosomes in response to microtopographic cues (the ridges with triangular profile) was not accompanied by reorganization of myosin-II filaments. Thus, mechanical elements such as myosin-II filaments and factors affecting membrane tension/sculpting independently modulate podosome formation and dynamics, underlying a versatile response of these adhesion structures to intracellular and extracellular cues.
Antibiotic usage promotes the evolution of resistance against gepotidacin, a novel multi-targeting drug
Authors: Szili Petra , Draskovits Gabor , Revesz Tamas , Bogar Ferenc , Balogh David , Martinek Tamas , Daruka Lejla , Spohn Reka , Vasarhelyi Balint Mark , Czikkely Marton , Kintses Balint , Grezal Gabor , Ferenc Gyorgyi , Pal Csaba , Nyerges Akos
Published: December 2018

Multi-targeting antibiotics, i.e. single compounds capable to inhibit two or more bacterial targets offer a promising therapeutic strategy, but information on resistance evolution against such drugs is scarce. Gepotidacin is an antibiotic candidate that selectively inhibits both bacterial DNA gyrase and topoisomerase IV. In a susceptible organism, Klebsiella pneumoniae, a combination of two specific mutations in these target proteins provide an over 2000-fold increment in resistance, while individually none of these mutations affect resistance significantly. Alarmingly, gepotidacin-resistant strains are found to be as virulent as the wild-type K. pneumoniae strain in a murine model, and extensive cross-resistance was demonstrated between gepotidacin and ciprofloxacin, a fluoroquinolone antibiotic widely employed in clinical practice. This suggests that numerous fluoroquinolone-resistant pathogenic isolates carry mutations which would promote the evolution of clinically significant resistance against gepotidacin in the future. We conclude that prolonged antibiotic usage could select for mutations that serve as stepping-stones towards resistance against antimicrobial compounds still under development. More generally, our research indicates that even balanced multi-targeting antibiotics are prone to resistance evolution.
Differentiation of mild cognitive impairment using an entorhinal cortex-based test of VR navigation
Authors: Howett David , Castegnaro Andrea , Krzywicka Katarzyna , Hagman Johanna , Henson Richard , Rio Miguel , King John A , Burgess Neil , Chan Dennis
Published: December 2018

The entorhinal cortex is one of the first regions to exhibit neurodegeneration in Alzheimer’s disease, and as such identification of entorhinal cortex dysfunction may aid detection of the disease in its earliest stages. Extensive evidence demonstrates that the entorhinal cortex is critically implicated in navigation underpinned by the firing of spatially modulated neurons. This study tested the hypothesis that entorhinal-dependent navigation is impaired in pre-dementia Alzheimer’s disease.

Forty-five patients with mild cognitive impairment (26 with CSF Alzheimer’s disease biomarker data: 12 biomarker-positive and 14 biomarker-negative) and 41 healthy control participants undertook an immersive virtual reality path integration test, as a measure of entorhinal-dependent navigation. Behavioural performance was correlated with MRI measures of entorhinal cortex volume, and the classification accuracy of the path integration task was compared with a battery of cognitive tests considered sensitive and specific for early Alzheimer’s Disease.

Biomarker-positive patients exhibited larger errors in the navigation task than biomarker-negative patients, whose performance did not significantly differ from controls participants. Path-integration errors were negatively correlated with the volumes of the total entorhinal cortex and of its posteromedial subdivision. The path integration task demonstrated higher diagnostic sensitivity and specificity for differentiating biomarker positive versus negative patients (area under the curve = 0.90) than was achieved by the best of the cognitive tests (area under the curve = 0.57).

This study demonstrates that an entorhinal cortex-based virtual reality navigation task can differentiate patients with mild cognitive impairment at low and high risk of developing dementia, with classification accuracy superior to reference cognitive tests considered to be highly sensitive to early Alzheimer’s disease. This study provides evidence that navigation tasks may aid early diagnosis of Alzheimer’s disease, and the basis of this in animal cellular and behavioural studies provides the opportunity to answer the unmet need for translatable outcome measures for comparing treatment effect across preclinical and clinical trial phases of future anti-Alzheimer’s drugs.
Neural activity in a hippocampus-like region of the teleost pallium are associated with navigation and active sensing
Authors: Fotowat H , Lee C , Jun JJ , Maler L
Published: December 2018

Neural mechanisms underlying spatial navigation in fish are unknown and little is known, for any vertebrate, about the relationship between active sensing and the formation of spatial maps. The weakly electric fish, Gymnotus Carapo, uses their active electric sense for spatial navigation. The electric organ discharge rate (EODr) undergoes transient increases during navigation to enhance electrosensory sampling. Gymnotus also uses stereotyped forward/ backward swimming as a second form of active sensing that brings objects towards the electroreceptor-dense head region. We wirelessly recorded neural activity from the pallium of freely swimming Gymnotus. Spiking activity was sparse and occurred only during swimming. Notably, some units exhibited significant place specificity and/or association with both forms of active sensing. Our results provide the first characterization of neural activity in a hippocampal-like region of a teleost fish brain and connects active sensing via sensory sampling rate and directed movements to higher order encoding of spatial information.
Age-Related Modulations of Alpha and Gamma Brain Activities Underlying Anticipation and Distraction
Authors: ElShafei Hesham A. , Fornoni Lesly , Masson Rémy , Bertrand Olivier , Bidet-Caulet Aurélie
Published: December 2018

Attention operates through top-down (TD) and bottom-up (BU) mechanisms. Recently, it has been shown that slow (alpha) frequencies index facilitatory and suppressive mechanisms of TD attention and faster (gamma) frequencies signal BU attentional capture. Ageing is characterized by increased behavioral distractibility, resulting from either a reduced efficiency of TD attention or an enhanced triggering of BU attention. However, only few studies have investigated the impact of ageing upon the oscillatory activities involved in TD and BU attention. MEG data were collected from 14 elderly and 14 matched young healthy human participants while performing the Competitive Attention Task. Elderly participants displayed (1) exacerbated behavioral distractibility, (2) altered TD suppressive mechanisms, indexed by a reduced alpha synchronization in task-irrelevant regions, (3) less prominent alpha peak-frequency differences between cortical regions, (4) a similar BU system activation indexed by gamma activity, and (5) a reduced activation of lateral prefrontal inhibitory control regions. These results show that the ageing-related increased distractibility is of TD origin.
In trans variant calling reveals enrichment for compound heterozygous variants in genes involved in neuronal development and growth.
Authors: Cox Allison J , Grady Fillan , Velez Gabriel , Mahajan Vinit B , Ferguson Polly J , Kitchen Andrew , Darbro Benjamin W , Bassuk Alexander G
Published: December 2018

Compound heterozygotes occur when different mutations at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of mutations at the individual level. We used VarCount to characterize compound heterozygous coding variants in patients with epileptic encephalopathy and in the 1000 genomes participants. The Epi4k data contains variants identified by whole exome sequencing in patients with either Lennox-Gastaut Syndrome (LGS) or Infantile Spasms (IS), as well as their parents. We queried the Epi4k dataset (264 trios) and the phased 1000 genomes data (2504 participants) for recessive variants. To assess enrichment, transcript counts were compared between the Epi4k and 1000 genomes participants using minor allele frequency (MAF) cutoffs of 0.5% and 1.0%, and including all ancestries or only probands of European ancestry. In the Epi4k participants, we found enrichment for rare, compound heterozygous mutations in six genes, including three involved in neuronal growth and development; PRTG (p=0.00086, 1% MAF, combined ancestries), TNC (p=0.0221% MAF, combined ancestries), and MACF1 (p=0.0245, 0.5% MAF, EU ancestry). Due the total number of transcripts considered in these analyses, the enrichment detected was not significant after correction for multiple testing and higher powered or prospective studies are necessary to validate the candidacy of these genes. However, PRTG, TNC, and MACF1 are potential novel recessive epilepsy genes and our results highlight that compound heterozygous mutations should be considered in sporadic epilepsy.
Methyl ketone production byPseudomonas putidais enhanced by plant-derived amino acids
Authors: Dong Jie , Chen Yan , Benites Veronica Teixeira , Baidoo Edward E.K. , Petzold Christopher J. , Beller Harry R. , Eudes Aymerick , Scheller Henrik V. , Adams Paul D. , Mukhopadhyay Aindrila , Simmons Blake A. , Singer Steven W.
Published: December 2018

Plant biomass is an attractive source of renewable carbon for conversion to biofuels and bio-based chemicals. Conversion strategies often use a fraction of the total biomass, focusing on sugars from cellulose and hemicellulose. Strategies that use plant components such as plant-derived aromatics and amino acids have the potential to improve the efficiency of overall biomass conversion.Pseudomonas putidais a promising host for biomass conversion for its ability to metabolize a wide variety of organic compounds, including aromatics derived from lignin.P. putidawas engineered to produce medium chain methyl ketones, which are promising diesel blendstocks and potential platform chemicals, from glucose and lignin-related aromatics, 4-hydroxybenzoate (4-HB) and protocatechuate (PCA). Unexpectedly,P. putidamethyl ketone production was enhanced 2-to 5-fold compared to sugar controls whenArabidopsis thalianahydrolysates derived from engineered plants that overproduce 4-HB and PCA, whileE. coliproduction was lowered in these hydrolysates. This enhancement was more pronounced (~7-fold increase) with hydrolysates derived from non-engineered switchgrass (Panicum virgatumL.) suggesting it did not arise from overproduction of 4-HB and PCA. Global proteomic analysis of the methyl ketone-producingP. putidasuggested that plant-derived amino acids may be the source of this enhancement. Mass spectrometry-based measurements of plant-derived amino acids demonstrated a high correlation between methyl ketone production and amino acid concentration in plant hydrolysates. Amendment of glucose-containing minimal media with a defined mixture of amino acids similar to those found in the hydrolysates studied led to a 9-fold increase in methyl ketone titer (1.1 g/L).
Using neural distance to predict reaction time for categorizing the animacy, shape, and abstract properties of objects
Authors: Ritchie J.Brendan , Op de Beeck Hans
Published: December 2018

A large number of neuroimaging studies have shown that information about object category can be decoded from regions of the ventral visual pathway. One question is how this information might be functionally exploited in the brain. In an attempt to answer this question, some studies have adopted a neural distance-to-bound approach, and shown that distance to a classifier decision boundary through neural activation space can be used to predict reaction times (RT) on animacy categorization tasks. However, these experiments have not controlled for possible visual confounds, such as shape, in their stimulus design. In the present study we sought to determine whether, when animacy and shape properties are orthogonal, neural distance in low- and high-level visual cortex would predict categorization RTs. We also investigated whether a combination of animacy and shape distance might predict RTs when categories crisscrossed the two stimulus dimensions, and so were not linearly separable. In line with previous results, we found that RTs correlated with neural distance, but only for animate stimuli, with similar, though weaker, asymmetric effects for the shape and crisscrossing tasks. Taken together, these results suggest there is potential to expand the neural distance-to-bound approach to other divisions beyond animacy and object category.
E74 like ETS transcription factor 3 (ELF3) is a negative regulator of epithelial-mesenchymal transition in bladder carcinoma
Authors: Gondkar Kirti , Patel Krishna , Krishnappa Shoba , Patil Akkamahadevi , Nair Bipin , Sundaram Gopinath Meenakshi , Zea Tan Tuan , Kumar Prashant
Published: December 2018

Transcription factors are known to be commonly deregulated in various cancers. The E74 like ETS transcription factor 3 (ELF3) expression is restricted to epithelial tissue. In the present study, we evaluated the role of ELF3 in the pathogenesis of bladder carcinoma (BCa) using cell line model. The cell lines with low expression of ELF3 showed increased expression of mesenchymal markers and decreased expression of epithelial markers. Immunofluorescence and immunohistochemical analysis of ELF3 showed selective expression in low-grade BCa cell lines and tumor tissues, respectively. We demonstrated that overexpression of ELF3 in UMUC3, a mesenchymal BCa cell line resulted in reduced invasion and decreased expression of mesenchymal markers. Furthermore, using publicly available data, we found that low expression of ELF3 was associated with increased risk and poor overall survival rate in BCa. In conclusion, ELF3-modulated reversal of EMT might be a useful strategy in the treatment of bladder cancer.
Prevalence, Characteristics, and Clinical Significance of Concomitant Cardiomyopathies in Subjects with Bicuspid Aortic Valve
Authors: Jeong Hyeonju , Shim Chi Young , Kim Darae , Choi Jah Yeon , Choi Kang-Un , Lee Soo Youn , Hong Geu-Ru , Ha Jong-Won
Published: December 2018

Background: In this study, the prevalence, characteristics, and clinical significance of concomitant specific cardiomyopathies (CMs) were investigated in subjects with bicuspid aortic valve (BAV).
Methods: We retrospectively evaluated 1,186 adults with BAV (850 males, mean age 56 ± 14 years). Left ventricular noncompaction (LVNC), hypertrophic CM (HCM), and idiopathic dilated CM (DCM) were diagnosed when patients fulfilled current clinical and echocardiographic criteria. Clinical and echocardiographic characteristics including comorbidities, heart failure presentation, BAV morphology, function, and aorta phenotypes in BAV subjects with or without specific CM were compared.
Results: Overall, 67 subjects (5.6 %) had concomitant CMs: 40 (3.4%) patients with LVNC, 17 (1.4%) with HCM, and 10 (0.8%) with DCM. BAV subjects with HCM had a higher prevalence of diabetes mellitus, heart failure with preserved ejection fraction (HFPEF), and tended to have type 0 phenotype, while BAV subjects with DCM showed a higher prevalence of chronic kidney disease and heart failure with reduced ejection fraction (HFREF). BAV subjects with LVNC were significantly younger, predominantly male, and had greater BAV dysfunction and a higher prevalence of normal aorta shape. In multiple regression analysis, presence of CM was independently associated with heart failure (odds ratio (OR) 2.866, 95% confidential interval (CI) 1.652–4.974, p < 0.001) even after controlling confounding factors.
Conclusion: Concomitant CMs were observed in 5.6% of subjects with BAV. A few clinical and echocardiographic characteristics including comorbidities, heart failure presentation, BAV morphology, function, and presence of aortopathy were found. The presence of CM was independently associated with heart failure.
Optimization of accelerated solvent extraction of fatty acids from Coix seeds using chemometrics methods
Authors: Liu Xing , Fan Kai , Song Wei-Guo , Wang Zhengwu
Published: December 2018

This study investigated the optimization of accelerated solvent extraction (ASE) of fatty acids (FAs) from three Coix seeds (small Coix seed, SCS; big Coix seed, BCS; translucent Coix seed, TCS) by chemometrics methods. Partial least-squares regression (PLSR) and backpropagation neural network (BPNN) were applied to build models that reflect the relationship between content of FAs and extraction conditions (temperature, time, and extraction solvent). Genetic algorithms (GAs) and particle swarm optimization (PSO) were utilized to optimize the combination of extraction conditions. The composition of FAs was analysed by gas chromatography-mass spectrometry (GC-MS). The PLSR models could reflect the relationship of FA content in both BCS and SCS and extraction conditions well, while the BPNN model was more suitable for TCS. The optimal extraction conditions for BCS and SCS were obtained by GAs, whereas those of TCS were obtained by PSO. The FA compositions of the three Coix seeds exhibited differences. The results show that ASE combined with chemometrics methods can rapidly and effectively obtain the optimal conditions for the extraction of FAs from Coix seed and there are differences in the extraction conditions and compositions of FAs among different varieties of Coix seed, but all the extraction time is shorter than other extractions methods.
Phase transition and amyloid formation by a viral protein as an additional molecular mechanism of virus-induced cell toxicity
Authors: Salladini Edoardo , Debarnot Claire , Delauzun Vincent , Murrali Maria Grazia , Sutto-Ortiz Priscila , Spinelli Silvia , Pierattelli Roberta , Bignon Christophe , Longhi Sonia
Published: December 2018

Henipaviruses are severe human pathogens responsible for severe encephalitis. Their V protein is a key player in the evasion of the host innate immune response. We have previously reported a biophysical characterization of the Henipavirus V proteins and shown that they interact with DDB1, a cellular protein that is a component of the ubiquitin ligase E3 complex. Here, we serendipitously discovered that the Hendra virus V protein undergoes a liquidhydrogel phase transition. By combining experimental and bioinformatics approaches, we have identified the V region responsible for this phenomenon. This region (referred to as PNT3), which falls within the long intrinsically disordered region of V, was further investigated using a combination of biophysical and structural approaches. ThioflavinT and Congo red binding assays, together with negative-staining electron microscopy studies, show that this region forms amyloid-like, β-enriched structures. Such structures are also formed in mammal cells transfected to express PNT3. Those cells also exhibit a reduced viability in the presence of a stress agent. Interestingly, mammal cells expressing a rationally designed, non-amyloidogenic PNT3 variant (PNT33A), appear to be much less sensitive to the stress agent, thus enabling the establishment of a link between fibril formation and cell toxicity. The present findings therefore pinpoint a so far never reported possible mechanism of virus-induced cell toxicity.
Analysing linear multivariate pattern transformations in neuroimaging data
Authors: Basti Alessio , Mur Marieke , Kriegeskorte Nikolaus , Pizzella Vittorio , Marzetti Laura , Hauk Olaf
Published: December 2018

Most connectivity metrics in neuroimaging research reduce multivariate activity patterns in regions-of-interests (ROIs) to one dimension, which leads to a loss of information. Importantly, it prevents us from investigating the transformations between patterns in different ROIs. Here, we applied linear estimation theory in order to robustly estimate the linear transformations between multivariate fMRI patterns with a cross-validated Tikhonov regularisation approach. We derived three novel metrics that describe different features of these voxel-by-voxel mappings: goodness-of-fit, sparsity and pattern deformation. The goodness-of-fit describes the degree to which the patterns in an input region can be described as a linear transformation of patterns in an output region. The sparsity metric, which relies on a Monte Carlo procedure, was introduced in order to test whether the transformation mostly consists of one-to-one mappings between voxels in different regions. Furthermore, we defined a metric for pattern deformation, i.e. the degree to which the transformation rotates or rescales the input patterns. As a proof of concept, we applied these metrics to an event-related fMRI data set consisting of four subjects that has been used in previous studies. We focused on the transformations from early visual cortex (EVC) to inferior temporal cortex (ITC), fusiform face area (FFA) and parahippocampal place area (PPA). Our results suggest that the estimated linear mappings are able to explain a significant amount of variance of the three output ROIs. The transformation from EVC to ITC shows the highest goodness-of-fit, and those from EVC to FFA and PPA show the expected preference for faces and places as well as animate and inanimate objects, respectively. The pattern transformations are sparse, but sparsity is lower than would have been expected for one-to-one mappings, thus suggesting the presence of one-to-few voxel mappings. ITC, FFA and PPA patterns are not simple rotations of an EVC pattern, indicating that the corresponding transformations amplify or dampen certain dimensions of the input patterns. While our results are only based on a small number of subjects, they show that our pattern transformation metrics can describe novel aspects of multivariate functional connectivity in neuroimaging data.
Energy use and rural poverty: empirical evidence from potato farmers in northern China
Authors: Li Zihan , Gong Yazhen , Chen Kevin Z.
Published: December 2018

Purpose

Rising energy expenditures due to more intensive use of energy in modern agriculture and increasing energy prices may affect rural households’ agricultural incomes, particularly the incomes of the rural poor in developing countries. However, the exact link between energy costs and income among the rural poor needs further empirical investigation. The purpose of this paper is to develop a deeper understanding of the relationship between energy use and family income, using household-level panel data collected from 500 potato farmers in a poor region of Northern China, where eliminating poverty by 2020 is now the top government priority.

Design/methodology/approach

The paper uses household survey data collected from six counties in a poor region in northern China in 2013 to measure the relationship between energy cost and family income. A fixed effect model is employed to estimate the relationship.

Findings

The findings indicate that potatoes play an important role in the surveyed families’ incomes, and that the energy costs of potato production have a significant negative relationship with family income. However, this negative relationship is only significant for farmers with low economic standing, such as those living below or just above the poverty line. The negative relationship between energy costs and family income is only significant for those cultivating a certain size of potato-sown area; it is insignificant for those cultivating smaller areas.

Originality/value

These findings indicate that, in general, reducing energy costs helps the poor increase their income but is not necessarily helpful to those with high economic standing or a relatively small potato-sown area. If rural development policies are to support poverty reduction and energy savings (at least in major potato production regions), interventions aimed at energy cost reduction may be effective only for the poor whose family income depends, to a relatively high degree, on potato production.
Multiscale concurrent topology optimization of structures and microscopic multi-phase materials for thermal conductivity
Authors: Da Daicong , Cui Xiangyang , Long Kai , Cai Yong , Li Guangyao
Published: December 2018

Purpose

The optimal material microstructures in pure material design are no longer efficient or optimal when accounting macroscopic structure performance with specific boundary conditions. Therefore, it is important to provide a novel multiscale topology optimization framework to tailor the topology of structure and the material to achieve specific applications. In comparison with porous materials, composites consisting of two or more phase materials are more attractive and advantageous from the perspective of engineering application. This paper aims to provide a novel concurrent topological design of structures and microscopic materials for thermal conductivity involving multi-material topology optimization (material distribution) at the lower scale.

Design/methodology/approach

In this work, the effective thermal conductivity properties of microscopic three or more phase materials are obtained via homogenization theory, which serves as a bridge of the macrostructure and the periodic material microstructures. The optimization problem, including the topological design of macrostructures and inverse homogenization of microscopic materials, are solved by bi-directional evolutionary structure optimization method.

Findings

As a result, the presented framework shows high stability during the optimization process and requires little iterations for convergence. A number of interesting and valid macrostructures and material microstructures are obtained in terms of optimal thermal conductive path, which verify the effectiveness of the proposed mutliscale topology optimization method. Numerical examples adequately consider effects of initial guesses of the representative unit cell and of the volume constraints of adopted base materials at the microscopic scale on the final design. The resultant structures at both the scales with clear and distinctive boundary between different phases, making the manufacturing straightforward.

Originality/value

This paper presents a novel multiscale concurrent topology optimization method for structures and the underlying multi-phase materials for thermal conductivity. The authors have carried out the concurrent multi-phase topology optimization for both 2D and 3D cases, which makes this work distinguished from existing references. In addition, some interesting and efficient multi-phase material microstructures and macrostructures have been obtained in terms of optimal thermal conductive path.
Effects of feature selection on lane-change maneuver recognition: an analysis of naturalistic driving data
Authors: Li Xiaohan , Wang Wenshuo , Zhang Zhang , Rötting Matthias
Published: December 2018

Purpose

Feature selection is crucial for machine learning to recognize lane-change (LC) maneuver as there exist a large number of feature candidates. Blindly using feature could take up large storage and excessive computation time, while insufficient feature selection would cause poor performance. Selecting high contributive features to classify LC and lane-keep behavior is effective for maneuver recognition. This paper aims to propose a feature selection method from a statistical view based on an analysis from naturalistic driving data.

Design/methodology/approach

In total, 1,375 LC cases are analyzed. To comprehensively select features, the authors extract the feature candidates from both time and frequency domains with various LC scenarios segmented by an occupancy schedule grid. Then the effect size (Cohen’s d) and p-value of every feature are computed to assess their contribution for each scenario.

Findings

It has been found that the common lateral features, e.g. yaw rate, lateral acceleration and time-to-lane crossing, are not strong features for recognition of LC maneuver as empirical knowledge. Finally, cross-validation tests are conducted to evaluate model performance using metrics of receiver operating characteristic. Experimental results show that the selected features can achieve better recognition performance than using all the features without purification.

Originality/value

In this paper, the authors investigate the contributions of each feature from the perspective of statistics based on big naturalistic driving data. The aim is to comprehensively figure out different types of features in LC maneuvers and select the most contributive features over various LC scenarios.
Suction and injection effect on flow between two plates with reference to Casson fluid model
Authors: V.S. Sampath Kumar , Pai N.P.
Published: December 2018

Purpose

The purpose of this paper is to study the effect of injection and suction on velocity profile, skin friction and pressure distribution of a Casson fluid flow between two parallel infinite rectangular plates approaching or receding from each other with suction or injection at the porous plates.

Design/methodology/approach

The governing Navier–Stokes equations are reduced to the fourth-order non-linear ordinary differential equation through the similarity transformations. The approximated analytic solution based on the Homotopy perturbation method is given and also compared with the classical finite difference method.

Findings

From this study, the authors observed that the skin friction is less in non-Newtonian fluids compared to Newtonian fluids. The use of non-Newtonian fluids reduces the pressure in all the cases compared to Newtonian and hence load-carrying capacity will be more. As γ value increases velocity, skin friction and pressure decreases. When γ is fixed, it is observed that skin friction and pressure is minimum for A=0.5 and maximum when A=−0.5. The result of this study also shows that the effect of suction on the velocity profiles, pressure and skin friction is opposite to the effect of injection.

Originality/value

The present work analyzes the characteristic of non-Newtonian fluid having practical and industrial applications.
Dating past colonization events to project future species distributions
Authors: Singer Alexander , Bradter Ute , Fabritius Henna , Snäll Tord
Published: December 2018

Knowledge on the colonization process is important to understand and project future species distributions. The classic method to quantify colonization rates is time‐consuming, as it requires recording infrequent colonization events during extensive, repeated surveys.

We present the novel “dating‐based approach” that requires one complete survey of species occurrence and estimates of subpopulation ages to back‐date colonization events. These data allow statistical reconstruction of a virtual, repeated survey to estimate colonization rates in response to environmental covariates or connectivity.

With only 30% of survey effort, the dating‐based approach provided similar estimates of rate and distance of dispersal of a metapopulation of the epiphytic moss Neckera pennata as the classic approach relying on long‐term surveys. Projections of the number of colonization events during the next 100 years differed by only 2.3% (95%‐credible interval: [−1.9%; 7.1%]) between methods.

The dating‐based approach is applicable across spatial scales and promises enhanced species distribution models with urgently needed quantitative dispersal information.