bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrinsic spin of elastic waves
Authors: Long Yang , Ren Jie , Chen Hong
Published: September 2018

Significance

Spin unveils the fundamental geometrical and topological properties of waves. Massive studies have shown that the circularly polarized transverse wave can carry nontrivial spin density and thus possess quantum spin Hall effect. However, the spin nature of the longitudinal wave still lacks research. Here, based on the elastic wave platform, we show that the longitudinal wave can carry unique spin angular momentum due to its special spin–orbit coupling, and, importantly, the mixed longitudinal–transverse waves will induce an unusual spin form: hybrid spin. These spins in an elastic wave will be responsible for several spin-related phenomena beyond a pure transverse wave. Our work can advance physical understanding about spin properties of elastic waves.
From Newton to Navier–Stokes, or how to connect fluid mechanics equations from microscopic to macroscopic scales
Authors: Gallagher Isabelle
Published: September 2018

In this survey we present an overview of some mathematical results concerning the passage from the microscopic description of fluids via Newton’s laws to the macroscopic description via the Navier–Stokes equations.
The Role of Figurative Complexity in the Comprehension and Appreciation of Advertisements
Authors: Pérez-Sobrino Paula , Littlemore Jeannette , Houghton David
Published: September 2018

To date, research in advertising has focussed almost exclusively on metaphor, with linguists and marketing scholars paying very little attention to alternative types of figurative expression. Beyond the finding that metaphor leads to an increased appreciation of advertisements, there has been surprisingly little research into how consumer response is affected by metonymy, or by metaphor–metonymy interactions. In this article, we present findings from a study that investigated the depth to which participants (n = 90) from a range of cultural and linguistic backgrounds (the UK, Spain, and China) were found to process 30 real-world adverts featuring creative metaphor and metonymy in multimodal format. We focus on the cross-cultural variation in terms of time taken to process, appreciation and perceived effectiveness of adverts, and on individual differences explained by different levels of need for cognition. We found significant variation in the understanding of advertisements containing metaphor, metonymy, and combinations of the two, between subjects and across nationalities in terms of (i) processing time, (ii) overall appeal, and (iii) the way in which participants interpreted the advertisements.
Parkour LIMS: high-quality sample preparation in next generation sequencing
Authors: Anatskiy E , Ryan D P , Grüning B A , Arrigoni L , Manke T , Bönisch U
Published: September 2018

Motivation

This paper presents Parkour, a software package for sample processing and quality management of next generation sequencing data and samples.

Results

Starting with user requests, Parkour allows tracking and assessing samples based on predefined quality criteria through different stages of the sample preparation workflow. Ideally suited for academic core laboratories, the software aims to maximize efficiency and reduce turnaround time by intelligent sample grouping and a clear assignment of staff to work units. Tools for automated invoicing, interactive statistics on facility usage and simple report generation minimize administrative tasks. Provided as a web application, Parkour is a convenient tool for both deep sequencing service users and laboratory personal. A set of web APIs allow coordinated information sharing with local and remote bioinformaticians. The flexible structure allows workflow customization and simple addition of new features as well as the expansion to other domains.

Availability and implementation

The code and documentation are available at https://github.com/maxplanck-ie/parkour.

Supplementary information

Supplementary data are available at Bioinformatics online.
Exploring sequence-based features for the improved prediction of DNA N4-methylcytosine sites in multiple species
Authors: Wei Leyi , Luan Shasha , Nagai Luis Augusto Eijy , Su Ran , Zou Quan
Published: September 2018

Motivation

As one of important epigenetic modifications, DNA N4-methylcytosine (4mC) is recently shown to play crucial roles in restriction–modification systems. For better understanding of their functional mechanisms, it is fundamentally important to identify 4mC modification. Machine learning methods have recently emerged as an effective and efficient approach for the high-throughput identification of 4mC sites, although high predictive error rates are still challenging for existing methods. Therefore, it is highly desirable to develop a computational method to more accurately identify m4C sites.

Results

In this study, we propose a machine learning based predictor, namely 4mcPred-SVM, for the genome-wide detection of DNA 4mC sites. In this predictor, we present a new feature representation algorithm that sufficiently exploits sequence-based information. To improve the feature representation ability, we use a two-step feature optimization strategy, thereby obtaining the most representative features. Using the resulting features and Support Vector Machine (SVM), we adaptively train the optimal models for different species. Comparative results on benchmark datasets from six species indicate that our predictor is able to achieve generally better performance in predicting 4mC sites as compared to the state-of-the-art predictors. Importantly, the sequence-based features can reliably and robust predict 4mC sites, facilitating the discovery of potentially important sequence characteristics for the prediction of 4mC sites.

Availability and implementation

The user-friendly webserver that implements the proposed 4mcPred-SVM is well established, and is freely accessible at http://server.malab.cn/4mcPred-SVM.

Supplementary information

Supplementary data are available at Bioinformatics online.
Biomonitoring an albumin adduct of the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in humans
Authors: Bellamri Medjda , Wang Yi , Yonemori Kim , White Kami K , Wilkens Lynne R , Le Marchand Loïc , Turesky Robert J
Published: September 2018

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is formed in cooked meats and may be linked to dietary-associated colorectal, prostate and mammary cancers. Genotoxic N-oxidized metabolites of PhIP react with the Cys34 of albumin (Alb) to form a sulfinamide adduct, a biomarker of the biologically effective dose. We examined the kinetics of PhIP-Alb adduct formation in plasma of volunteers on a 4-week semicontrolled diet of cooked meat containing known quantities of PhIP. The adduct was below the limit of detection (LOD) (10 femtograms PhIP/mg Alb) in most subjects before the meat feeding but increased by up to 560-fold at week 4 in subjects who ate meat containing 8.0 to 11.7 μg of PhIP per 150–200 g serving. In contrast, the adduct remained below the LOD in subjects who ingested 1.2 or 3.0 μg PhIP per serving. Correlations were not seen between PhIP-Alb adduct levels and PhIP intake levels (P = 0.76), the amount of PhIP accrued in hair (P = 0.13), the amounts of N-oxidized urinary metabolites of PhIP (P = 0.66) or caffeine CYP1A2 activity (P = 0.55), a key enzyme involved in the bioactivation of PhIP. The half-life of the PhIP-Alb adduct was <2 weeks, signifying that the adduct was not stable. PhIP-Alb adduct formation is direct evidence of bioactivation of PhIP in vivo. However, the PhIP hair biomarker is a longer lived and more sensitive biomarker to assess exposure to this potential human carcinogen.
Chromosome-level genome assembly of the spotted sea bass, Lateolabrax maculatus
Authors: Shao Changwei , Li Chang , Wang Na , Qin Yating , Xu Wenteng , Liu Qun , Zhou Qian , Zhao Yong , Li Xihong , Liu Shanshan , Chen Xiaowu , Mahboob Shahid , Liu Xin , Chen Songlin
Published: September 2018

Background

The spotted sea bass (Lateolabrax maculatus) is a valuable commercial fish that is widely cultured in China. While analyses using molecular markers and population genetics have been conducted, genomic resources are lacking.

Findings

Here, we report a chromosome-scale assembly of the spotted sea bass genome by high-depth genome sequencing, assembly, and annotation. The genome scale was 0.67 Gb with contig and scaffold N50 length of 31 Kb and 1,040 Kb, respectively. Hi-C scaffolding of the genome resulted in 24 pseudochromosomes containing 77.68% of the total assembled sequences. A total of 132.38 Mb repeat sequences were detected, accounting for 20.73% of the assembled genome. A total of 22, 015 protein-coding genes were predicted, of which 96.52% were homologous to proteins in various databases. In addition, we constructed a phylogenetic tree using 1,586 single-copy gene families and identified 125 unique gene families in the spotted sea bass genome.

Conclusions

We assembled a spotted sea bass genome that will be a valuable genomic resource to understanding the biology of the spotted sea bass and will also lead to the development of molecular breeding techniques to generate spotted sea bass with better economic traits.
Single-cell RNA-seq reveals dynamic transcriptome profiling in human early neural differentiation
Authors: Shang Zhouchun , Chen Dongsheng , Wang Quanlei , Wang Shengpeng , Deng Qiuting , Wu Liang , Liu Chuanyu , Ding Xiangning , Wang Shiyou , Zhong Jixing , Zhang Doudou , Cai Xiaodong , Zhu Shida , Yang Huanming , Liu Longqi , Fink J Lynn , Chen Fang , Liu Xiaoqing , Gao Zhengliang , Xu Xun
Published: September 2018

Background

Investigating cell fate decision and subpopulation specification in the context of the neural lineage is fundamental to understanding neurogenesis and neurodegenerative diseases. The differentiation process of neural-tube-like rosettes in vitro is representative of neural tube structures, which are composed of radially organized, columnar epithelial cells and give rise to functional neural cells. However, the underlying regulatory network of cell fate commitment during early neural differentiation remains elusive.

Results

In this study, we investigated the genome-wide transcriptome profile of single cells from six consecutive reprogramming and neural differentiation time points and identified cellular subpopulations present at each differentiation stage. Based on the inferred reconstructed trajectory and the characteristics of subpopulations contributing the most toward commitment to the central nervous system lineage at each stage during differentiation, we identified putative novel transcription factors in regulating neural differentiation. In addition, we dissected the dynamics of chromatin accessibility at the neural differentiation stages and revealed active cis-regulatory elements for transcription factors known to have a key role in neural differentiation as well as for those that we suggest are also involved. Further, communication network analysis demonstrated that cellular interactions most frequently occurred in the embryoid body stage and that each cell subpopulation possessed a distinctive spectrum of ligands and receptors associated with neural differentiation that could reflect the identity of each subpopulation.

Conclusions

Our study provides a comprehensive and integrative study of the transcriptomics and epigenetics of human early neural differentiation, which paves the way for a deeper understanding of the regulatory mechanisms driving the differentiation of the neural lineage.
A nonsense mutation in myelin protein zero causes congenital hypomyelination neuropathy through altered P0 membrane targeting and gain of abnormal function
Authors: Fratta Pietro , Ornaghi Francesca , Dati Gabriele , Zambroni Desirée , Saveri Paola , Belin Sophie , D’Adamo Patrizia , Shy Michael , Quattrini Angelo , Laura Feltri M , Wrabetz Lawrence
Published: September 2018

Protein zero (P0) is the major structural protein in peripheral myelin, and mutations in the Myelin Protein Zero (Mpz) gene produce wide-ranging hereditary neuropathy phenotypes. To gain insight in the mechanisms underlying a particularly severe form, congenital hypomyelination (CH), we targeted mouse Mpz to encode P0Q215X, a nonsense mutation associated with the disease, that we show escapes nonsense mediated decay and is expressed in CH patient nerves. The knock-in mice express low levels of the resulting truncated protein, producing a milder phenotype when compared to patients, allowing to dissect the subtle pathogenic mechanisms occurring in otherwise very compromised peripheral myelin. We find that P0Q215X does not elicit an unfolded protein response, which is a key mechanism for other pathogenic MPZ mutations, but is instead in part aberrantly trafficked to non-myelin plasma membranes and induces defects in radial sorting of axons by Schwann cells. We show that the loss of the C-terminal Tyr-Ala-Met-Leu motif is responsible for P0 mislocalization, as its addition is able to restore correct P0Q215X trafficking in vitro. Lastly, we show that P0Q215X acts through dose-dependent gain of abnormal function, as wild-type P0 is unable to rescue the hypomyelination phenotype. Collectively, these data indicate that alterations at the premyelinating stage, linked to altered targeting of P0, may be responsible for CH, and that different types of gain of abnormal function produce the diverse neuropathy phenotypes associated with MPZ, supporting future allele-specific therapeutic silencing strategies.
A simple mathematical model to describe antibody-dependent enhancement in heterologous secondary infection in dengue
Authors: Cerón Gómez Miller , Yang Hyun Mo
Published: September 2018

We develop a mathematical model to describe the role of antibody-dependent enhancement (ADE) in heterologous secondary infections, assuming that antibodies specific to primary dengue virus (DENV) infection are being produced by immunological memory. The model has a virus-free equilibrium (VFE) and a unique virus-presence equilibrium (VPE). VFE is asymptotically stable when VPE is unstable; and unstable, otherwise. Additionally, there is an asymptotic attractor (not a fixed point) due to the fact that the model assumes unbounded increase in memory cells. In the analysis of the model, ADE must be accounted in the initial stage of infection (a window of time of few days), period of time elapsed from the heterologous infection until the immune system mounting an effective response against the secondary infection. We apply the results yielded by model to evaluate ADE phenomonon in heterologous DENV infection. We also associate the possible occurrence of severe dengue with huge viremia mediated by ADE phenomenon.
Canonical NF-κB signaling regulates satellite stem cell homeostasis and function during regenerative myogenesis
Authors: Straughn Alex R , Hindi Sajedah M , Xiong Guangyan , Kumar Ashok
Published: September 2018

Skeletal muscle regeneration in adults is attributed to the presence of satellite stem cells that proliferate, differentiate, and eventually fuse with injured myofibers. However, the signaling mechanisms that regulate satellite cell homeostasis and function remain less understood. While IKKβ-mediated canonical NF-κB signaling has been implicated in the regulation of myogenesis and skeletal muscle mass, its role in the regulation of satellite cell function during muscle regeneration has not been fully elucidated. Here, we report that canonical NF-κB signaling is induced in skeletal muscle upon injury. Satellite cell-specific inducible ablation of IKKβ attenuates skeletal muscle regeneration in adult mice. Targeted ablation of IKKβ also reduces the number of satellite cells in injured skeletal muscle of adult mice, potentially through inhibiting their proliferation and survival. We also demonstrate that the inhibition of specific components of the canonical NF-κB pathway causes precocious differentiation of cultured satellite cells both ex vivo and in vitro. Finally, our results highlight that the constitutive activation of canonical NF-κB signaling in satellite cells also attenuates skeletal muscle regeneration following injury in adult mice. Collectively, our study demonstrates that the proper regulation of canonical NF-κB signaling is important for the regeneration of adult skeletal muscle.
Equality, Liberty and the Limits of Person-centred Care’s Principle of Co-production
Authors: Badano Gabriele
Published: September 2018

The idea that healthcare should become more person-centred is extremely influential. By using recent English policy developments as a case study, this article aims to critically analyse an important element of person-centred care, namely, the belief that to treat patients as persons is to think that care should be ‘co-produced’ by formal healthcare providers and patients together with unpaid carers and voluntary organizations. I draw on insights from political philosophy to highlight overlooked tensions between co-production and values like equality and liberty. Regarding equality, I argue that co-production compounds both problems of gender inequality in the distribution of care labour and the challenges associated with securing equal access to care. Turning to liberty, I identify important commonalities between co-production and republicanism in political philosophy, given their shared insistence on common citizens’ civic virtue. Then, I use against co-production some liberal arguments against republicanism, to highlight a problem of over-demandingness. In bringing my argument to a close, however, I wish to caution against hastily rejecting co-production as a policy programme.
Stability for hyperplane complements of type B/C and statistics on squarefree polynomials over finite fields
Authors: Jiménez Rolland Rita , Wilson Jennifer C H
Published: September 2018

In this paper, we explore a relationship between the topology of the complex hyperplane complements ℳBCn(ℂ) in type B/C and the combinatorics of certain spaces of degree-n polynomials over a finite field Fq. This relationship is a consequence of the Grothendieck trace formula and work of Lehrer and Kim. We use it to prove a correspondence between a representation-theoretic convergence result on the cohomology algebras H*(ℳBCn(ℂ);ℂ), and an asymptotic stability result for certain polynomial statistics on monic squarefree polynomials over Fq with non-zero constant term. This result is the type B/C analogue of a theorem due to Church, Ellenberg, and Farb in type A, and we include a new proof of their theorem. To establish these convergence results, we realize the sequences of cohomology algebras of the hyperplane complements as FIW-algebras finitely generated inFIW-degree 2, and we investigate the asymptotic behaviour of general families of algebras with this structure. We prove a negative result implying that this structure alone is not sufficient to prove the necessary convergence conditions. Our proof of convergence for the cohomology algebras involves the combinatorics of their relators.
Parametrized monomial surfaces in 4-space
Authors: Rodrigues Hernandes M E , Ruas M A S
Published: September 2018

In this work, we classify parametrized monomial surfaces f:(ℂ2,0)→(ℂ4,0) that are A-finitely determined. We study invariants that can be obtained in terms of invariants of a parametrized curve.
On locally repeated values of arithmetic functions over Fq[T]
Authors: Rudnick Zeév , Peled Ron
Published: September 2018

The frequency of occurrence of ‘locally repeated’ values of arithmetic functions is a common theme in analytic number theory, for instance in the Erdős–Mirsky problem on coincidences of the divisor function at consecutive integers, the analogous problem for the Euler totient function and the quantitative conjectures of Erdős, Pomerance and Sarkőzy and of Graham, Holt and Pomerance on the frequency of occurrences. In this paper, we introduce the corresponding problems in the setting of polynomials over a finite field, and completely solve them in the large finite field limit.
Genetic Diversity ofPseudomonas syringaepv.actinidiaeStrains from Different Geographic Regions in China
Authors: He Rong , Liu Pu , Jia Bing , Xue Shizhou , Wang Xiaojie , Hu Jiayong , Al Shoffe Yosef , Gallipoli Lorenzo , Mazzaglia Angelo , Balestra Giorgio M. , Zhu Liwu
Published: September 2018

Pseudomonas syringae pv. actinidiae causes kiwifruit bacterial canker, with severe infection of the kiwifruit plant resulting in heavy economic losses. Little is known regarding the biodiversity and genetic variation of populations of P. syringae pv. actinidiae in China. A collection of 269 strains of P. syringae pv. actinidiae was identified from 300 isolates obtained from eight sampling sites in five provinces in China. The profiles of 50 strains of P. syringae pv. actinidiae and one strain of P. syringae pv. actinidifoliorum were characterized by Rep-, insertion sequences 50, and randomly amplified polymorphic DNA polymerase chain reaction (PCR). Discriminant analysis of principal coordinates, principal component analysis, and hierarchical cluster analysis were used to analyze the combined fingerprints of the different PCR assays. The results revealed that all isolates belonged to the Psa3 group, that strains of P. syringae pv. actinidiae from China have broad genetic variability that was related to source geographic region, and that Chinese strains can be readily differentiated from strains from France but are very similar to those from Italy. Multilocus sequence typing of 24 representative isolates using the concatenated sequences of five housekeeping genes (cts, gapA, gyrB, pfk, and rpoD) demonstrated that strain Jzhy2 from China formed an independent clade compared with the other biovars, which possessed the hopH1 effector gene but lacked the hopA1 effector gene. A constellation analysis based on the presence or absence of the four loci coding for phytotoxins and a cluster analysis based on the 11 effector genes showed that strains from China formed two distinct clades. All of the strains, including K3 isolated in 1997 from Jeju, Korea, lacked the cfl gene coding for coronatine. In contrast, the tox-argK gene cluster coding for phaseolotoxin was detected in K3 and in the biovar 1 strains (K3, Kw30, and Psa92), and produced a false-positive amplicon for the hopAM1-like gene in this study. To date, only one biovar (biovar 3) is represented by the strains of P. syringae pv. actinidiae from China, despite China being the center of origin for kiwifruit.
Nocturnal scent in a ‘bird-fig’: a cue to attract bats as additional dispersers?
Authors: Ripperger Simon P. , Rehse Saskia , Wacker Stefanie , Kalko Elisabeth K. V. , Schulz Stefan , Rodriguez-Herrera Bernal , Ayasse Manfred
Published: September 2018

The plant genus Ficus is a keystone resource in tropical ecoystems. One of the unique features of figs is the diversity of fruit traits, which in many cases match their various dispersers, the so-called fruit syndromes. The classic example of this is the strong phenotypic differences found between figs with bat and bird dispersers (color, size, and presentation). The ‘bird-fig’ Ficus colubrinae represents an exception to this trend since it attracts the small frugivorous bat species Ectophylla alba at night, but during the day attracts bird visitors. Here we investigate the mechanism by which this ‘bird-fig’ attracts bats despite its fruit traits, which should appeal solely to birds. We performed feeding experiments with Ectophylla alba to assess the role of fruit scent in the detection of ripe fruits. Ectophylla alba was capable of finding ripe figs by scent alone under exclusion of other sensory cues. This suggests that scent is the main foraging cue for Ectophylla alba. Analyses of odor bouquets from the bat- and bird-dispersal phases (i.e. day and night) differed significantly in their composition of volatiles. The combination of these two findings raises the question whether E. alba and F. colubrinae resemble a co-adaptation that enables a phenotypically classic ‘bird-fig’ to attract bat dispersers by an olfactory signal at night thus maximizing dispersal.
Deciphering defective subventricular adult neurogenesis in cyclin D2-deficient mice
Authors: Płatek Rafał , Kaczmarek Leszek , Czupryn Artur
Published: September 2018

Adult neurogenesis occurring in the brain of adult mammals is considered to have potential therapeutical applications. New neurons are produced constitutively from postnatal neural stem cells/precursors residing in two neurogenic regions: the subventricular zone (SVZ) of the lateral ventricles and the subgranular layer in the dentate gyrus of the hippocampus. Newly-generated neuroblasts from the SVZ migrate long distance towards the olfactory bulb and repopulate different subtypes of inhibitory interneurons modulating the olfactory processing. It was reported that cyclin D2 knockout mice (cD2-KO) present reduced generation of new hippocampal neurons, however proliferation deficiency and mechanisms responsible for dysregulation of subventricular precursors, derived progenitors, and olfactory interneurons need to be detaily investigated. In this report, proliferative activity of different subpopulations of SVZ neural precursors, cell migration, and differentiation in cD2-KO mice was characterized. For that goal, EdU, a thymidine analogue, proliferation mapping combined with multi-epitope immunohisto-chemical detection of endogenous stage-specific cell markers was carried out. Severely reduced number of newly-generated cells in the subventricular niche was demonstrated that was not accompanied by increased level of apoptotic death. Surprisingly, the number of B1 quiescent precursor subpopulation was not affected, whereas the number of B1 type active primary precursors, intermediate/transiently-amplifying progenitors (C type cells), and neuroblasts (A type cells) were reduced. The analyses suggest that cycline D2 might be critical for transition of B1 precursor quiescent cells into B1 active cells. We also demonstrate that the subpopulation of calbindin interneurons is reduced in the olfactory bulb. Deciphering processes underlying a potential modulation of intensity of adult neurogenesis at the cellular levels could lead to replacement therapies after injury, stroke, or neurodegenerative disease in the central nervous system.
Mutual transcriptional repression betweenGli3andHox13genes determines the anterior-posterior asymmetry of the autopod
Authors: Bastida Ma Félix , Pérez-Gómez Rocío , Trofka Anna , Sheth Rushikesh , Stadler H. Scott , Mackem Susan , Ros Marian A.
Published: September 2018

In the present study we have investigated the molecular causes of the absence of digit 1 in theHoxa13mutant and why the absence of Hoxa13 protein, whose expression spans the entire autopod, specifically impacts the anterior-most digit. We show that in the absence ofHoxa13, the expression ofHoxd13does not extend into the anterior mesoderm consequently leaving the presumptive territory of digit1 devoid of distalHoxexpression and providing an explanation for the agenesis of digit 1. We provide compelling evidence that the lack ofHoxd13transcription in the anterior mesoderm is due to increased Gli3R activity, in turn resulting from the loss of transcriptional repression exerted by Hoxa13 onGli3. Our results are compatible with a mutual transcriptional repression betweenGli3andHox13genes that determines the anterior-posterior asymmetry of the autopod.
Apical caspase reporters uncover unknown stages of apoptosis and enable ready visualization of undead cells
Authors: Baena-Lopez Luis Alberto , Arthurton Lewis , Bischoff Marcus , Vincent Jean-Paul , Alexandre Cyrille , McGregor Reuben
Published: September 2018

The caspase-mediated regulation of many cellular processes, including apoptosis, justifies the substantial interest in understanding all of the biological features of these enzymes. To complement functional assays, it is critical to identify caspase-activating cells in live tissues. Our work describes new caspase-reporters that, for the first time, provide direct information concerning the initial steps of the caspase activation cascade in Drosophila tissues. One of our caspase-sensors has capitalized on the rapid subcellular localization change of a fluorescent marker to uncover novel cellular apoptotic events. These refer to the actin-mediated positioning of the nucleus before cell delamination. The other construct has benefited from a caspase-induced nuclear translocation of a QF transcription factor. This feature enables the genetic manipulation of caspase-activating cells, whilst showing the spatio-temporal patterns of apical caspase activation. Collectively, our sensors offer new experimental opportunities that are already illuminating unknown aspects of caspase-dependent processes in apoptotic and non-apoptotic cellular scenarios.

Summary statement

We describe a novel set of caspase sensors that directly detect early caspase activation. The exclusive features of our reporters uncovered unknown stages of apoptosis and properties of caspase-activating cells.
Parcellation of motor sequence representations in the human neocortex
Authors: Yokoi Atsushi , Diedrichsen Jörn
Published: September 2018

While previous studies have revealed an extended network of cortical regions associated with motor sequence production, the specific role of each of these areas is still elusive. To address this issue, we designed a novel behavioural paradigm that allowed us to experimentally manipulate the structure of motor sequences representations in individual participants. We then conducted fMRI while participants executed 8 trained sequences to examine how this structure is reflected in the associated activity patterns. Both model-based and model-free approaches revealed a clear distinction between primary and non-primary motor cortices in their representational contents, with M1 specifically representing individual finger movements, and premotor and parietal cortices showing a mixture of chunk, sequence and finger transition representations. Using model-free representational parcellation, we could divide these non-primary motor cortices into separate clusters, each with a unique representation along the stimulus-to-action gradient. These results provide new insights into how human neocortex organizes movement sequences.
Separate lanes for math and reading in the white matter highways of the human brain
Authors: Grotheer Mareike , Zhen Zonglei , Lerma-Usabiaga Garikoitz , Grill-Spector Kalanit
Published: September 2018

Math and reading involve distributed brain networks and have both shared (e.g. encoding of visual stimuli) and dissociated (e.g. quantity processing) cognitive components. To date, it is unknown what are shared vs. dissociated gray and white matter substrates of the math and reading networks. Here we address this question using an innovative, multimodal approach applying functional MRI, diffusion MRI, and quantitative MRI to define these networks and evaluate the structural properties of their fascicles. Results reveal that i) there are distinct gray matter regions which are preferentially engaged in either math or reading and ii) the superior longitudinal (SLF) and arcuate (AF) fascicles are shared across math and reading networks. Strikingly, within these fascicles, reading- and math-related tracts are segregated into parallel sub-bundles and show structural differences related to myelination. These novel findings open a new avenue of research that examines the contribution of sub-bundles within fascicles to specific behaviors.
Optimization of Dose Schedules for Chemotherapy of Early Colon Cancer Determined by High Performance Computer Simulations
Authors: Cockrell Chase , Axelrod David E.
Published: September 2018

Cancer chemotherapy dose schedules are conventionally applied intermittently, with dose duration of the order of hours, intervals between doses of days or weeks, and cycles repeated for weeks. The large number of possible combinations of values of duration, interval, and lethality has been an impediment to empirically determine the optimal set of treatment conditions. The purpose of this project was to determine the set of parameters for duration, interval, and lethality that would be most effective for treating early colon cancer. An agent-based computer model that simulated cell proliferation kinetics in normal human colon crypts was calibrated with measurements of human biopsy specimens. Mutant cells were simulated as proliferating and forming an adenoma, or dying if treated with cytotoxic chemotherapy. Using a high performance computer, a total of 28,800 different parameter sets of duration, interval, and lethality were simulated. The effect of each parameter set on the stability of colon crypts, the time to cure a crypt of mutant cells, and the accumulated dose was determined. Of the 28,800 parameter sets, 434 parameter sets were effective in curing the crypts of mutant cells before they could form an adenoma and allowed the crypt normal cell dynamics to recover to pretreatment levels. A group of 14 similar parameter sets produced a minimal time to cure mutant cells. A different group of 9 similar parameter sets produced the least accumulated dose. These parameter sets may be considered as candidate dose schedules to guide clinical trials for early colon cancer.
A GABAergic Maf-expressing interneuron subset regulates the speed of locomotion inDrosophila
Authors: Babski H , Surel C , Yoshikawa S , Valmier J , Thomas J.B , Carroll P , Garcès A
Published: September 2018

Interneurons (INs) coordinate motoneurons activity to generate adequate patterns of muscle contractions, providing animals with the ability to adjust their body posture and to move over a range of speeds. In theDrosophilalarvae several IN subtypes have been morphologically described and their function well documented. However, the general lack of molecular characterization of those INs prevents the identification of evolutionary counterparts in other model animals, limiting our understanding of widespread principles ruling neuronal circuits organization and functioning. Here we characterize a highly restricted neuronal subset expressing the Maf transcription factor Traffic Jam (TJ). We found that TJ+neurons are highly diverse and their activation using intersectional genetics disrupted larval body posture and locomotion speed. We also showed that a small subset of TJ+GABAergic INs, singled out by the unique expression ofPer,Fkh,GrainandHlh3b, a molecular signature reminiscent to V2bINs in vertebrate, impacted the larvae crawling speed.
Tpr regulates the total number of nuclear pore complexes per cell nucleus
Authors: McCloskey Asako , Ibarra Arkaitz , Hetzer Martin W.
Published: September 2018

The total number of nuclear pore complexes (NPCs) per nucleus varies greatly between different cell types and is known to change during cell differentiation and cell transformation. However, the underlying mechanisms that control how many nuclear transport channels are assembled into a given nuclear envelope remain unclear. Here, we report that depletion of the NPC basket protein Tpr, but not Nup153, dramatically increases the total NPC number in various cell types. This negative regulation of Tpr occurs via a phosphorylation cascade of extracellular signal-regulated kinase (ERK), the central kinase of the mitogen-activated protein kinase (MAPK) pathway. Tpr serves as a scaffold for ERK to phosphorylate the nucleoporin (Nup) Nup153, which is critical for early stages of NPC biogenesis. Our results reveal a critical role of the Nup Tpr in coordinating signal transduction pathways during cell proliferation and the dynamic organization of the nucleus.
The Complete Sequence of the Zebrafish (Danio rerio) Mitochondrial Genome and Evolutionary Patterns in Vertebrate Mitochondrial DNA
Authors: Broughton Richard E. , Milam Jami E. , Roe Bruce A.
Published: September 2018

We describe the complete sequence of the 16,596-nucleotide mitochondrial genome of the zebrafish (Danio rerio); contained are 13 protein genes, 22 tRNAs, 2 rRNAs, and a noncoding control region. Codon usage in protein genes is generally biased toward the available tRNA species but also reflects strand-specific nucleotide frequencies. For 19 of the 20 amino acids, the most frequently used codon ends in either A or C, with A preferred over C for fourfold degenerate codons (the lone exception was AUG: methionine). We show that rates of sequence evolution vary nearly as much within vertebrate classes as between them, yet nucleotide and amino acid composition show directional evolutionary trends, including marked differences between mammals and all other taxa. Birds showed similar compositional characteristics to the other nonmammalian taxa, indicating that the evolutionary trend in mammals is not solely due to metabolic rate and thermoregulatory factors. Complete mitochondrial genomes provide a large character base for phylogenetic analysis and may provide for robust estimates of phylogeny. Phylogenetic analysis of zebrafish and 35 other taxa based on all protein-coding genes produced trees largely, but not completely, consistent with conventional views of vertebrate evolution. It appears that even with such a large number of nucleotide characters (11,592), limited taxon sampling can lead to problems associated with extensive evolution on long phyletic branches.
Identification and Classification of Differentially Expressed Genes in Renal Cell Carcinoma by Expression Profiling on a Global Human 31,500-Element cDNA Array
Authors: Boer Judith M. , Huber Wolfgang K. , Sültmann Holger , Wilmer Friederike , von Heydebreck Anja , Haas Stefan , Korn Bernhard , Gunawan Bastian , Vente Andreas , Füzesi Laszlo , Vingron Martin , Poustka Annemarie
Published: September 2018

We investigated the changes in gene expression accompanying the development and progression of kidney cancer by use of 31,500-element complementary DNA arrays. We measured expression profiles for paired neoplastic and noncancerous renal epithelium samples from 37 individuals. Using an experimental design optimized for factoring out technological and biological noise, and an adapted statistical test, we found 1738 differentially expressed cDNAs with an expected number of six false positives. Functional annotation of these genes provided views of the changes in the activities of specific biological pathways in renal cancer. Cell adhesion, signal transduction, and nucleotide metabolism were among the biological processes with a large proportion of genes overexpressed in renal cell carcinoma. Down-regulated pathways in the kidney tumor cells included small molecule transport, ion homeostasis, and oxygen and radical metabolism. Our expression profiling data uncovered gene expression changes shared with other epithelial tumors, as well as a unique signature for renal cell carcinoma.

[Expression data for the differentially expressed cDNAs are available as a Web supplement athttp://www.dkfz-heidelberg.de/abt0840/whuber/rcc. The array data have been submitted to the GEO data repository under accession no. GSE3.]
Sequence, Regulation, and Evolution of the Maize 22-kD α Zein Gene Family
Authors: Song Rentao , Llaca Victor , Linton Eric , Messing Joachim
Published: September 2018

We have isolated and sequenced all 23 members of the 22-kD α zein (z1C) gene family of maize. This is one of the largest plant gene families that has been sequenced from a single genetic background and includes the largest contiguous genomic DNA from maize with 346,292 bp to date. Twenty-two of the z1C members are found in a roughly tandem array on chromosome 4S forming a dense gene cluster 168,489-bp long. The twenty-third copy of the gene family is also located on chromosome 4S at a site ∼20 cM closer to the centromere and appears to be the wild-type allele of the floury-2(fl2) mutation. On the basis of an analysis of maize cDNA databases, only seven of these genes appear to be expressed including the fl2 allele. The expressed genes in the cluster are interspersed with nonexpressed genes. Interestingly, some of the expressed genes differ in their transcriptional regulation. Gene amplification appears to be in blocks of genes explaining the rapid and compact expansion of the cluster during the evolution of maize.

[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF090447,AF031569, and AF090446]
A Short Pseudoautosomal Region in Laboratory Mice
Authors: Perry Jo , Palmer Steve , Gabriel Anastasia , Ashworth Alan
Published: September 2018

The pseudoautosomal region (PAR) of mammalian sex chromosomes is a small region of sequence identity that is the site of an obligatory pairing and recombination event between the X and Y chromosomes during male meiosis. During female meiosis, X chromosomes can pair and recombine along their entire length; recombination in the PAR is therefore ∼10× greater in male meiosis compared with female meiosis. A consequence of the presence of the PAR in two copies in males and females is that genes in the region escape the process of X-inactivation. Although the structure and gene content of the human PAR at Xq/Yq is well understood, the mouse PAR, which appears to be of independent evolutionary origin, is poorly characterized. Here we describe a yeast artificial chromosome (YAC) contig covering the distal part of the mouse X chromosome, which we have used to define the pseudoautosomal boundary, that is, the point of divergence of X-specific and X-Y–identical sequences. In addition, we have investigated the size of the mouse PAR by integrating a unique restriction endonuclease recognition site just proximal to the pseudoautosomal boundary by homologous recombination. Restriction digestion of this modified DNA and pulsed field gel electrophoresis reveal that the PAR in these cells is ∼700 kb. Thus, the mouse PAR, although small in size, has retained essential sex chromosome pairing functions despite its rapid rate of evolution.
Transcriptional fates of human-specific segmental duplications in brain
Authors: Dougherty Max L. , Underwood Jason G. , Nelson Bradley J. , Tseng Elizabeth , Munson Katherine M. , Penn Osnat , Nowakowski Tomasz J. , Pollen Alex A. , Eichler Evan E.
Published: September 2018

Despite the importance of duplicate genes for evolutionary adaptation, accurate gene annotation is often incomplete, incorrect, or lacking in regions of segmental duplication. We developed an approach combining long-read sequencing and hybridization capture to yield full-length transcript information and confidently distinguish between nearly identical genes/paralogs. We used biotinylated probes to enrich for full-length cDNA from duplicated regions, which were then amplified, size-fractionated, and sequenced using single-molecule, long-read sequencing technology, permitting us to distinguish between highly identical genes by virtue of multiple paralogous sequence variants. We examined 19 gene families as expressed in developing and adult human brain, selected for their high sequence identity (average >99%) and overlap with human-specific segmental duplications (SDs). We characterized the transcriptional differences between related paralogs to better understand the birth–death process of duplicate genes and particularly how the process leads to gene innovation. In 48% of the cases, we find that the expressed duplicates have changed substantially from their ancestral models due to novel sites of transcription initiation, splicing, and polyadenylation, as well as fusion transcripts that connect duplication-derived exons with neighboring genes. We detect unannotated open reading frames in genes currently annotated as pseudogenes, while relegating other duplicates to nonfunctional status. Our method significantly improves gene annotation, specifically defining full-length transcripts, isoforms, and open reading frames for new genes in highly identical SDs. The approach will be more broadly applicable to genes in structurally complex regions of other genomes where the duplication process creates novel genes important for adaptive traits.
Crystal structure determination of rac-11′-(1-acetyl-1H-indazol-3-yl)-11′,11a′-dihydro-10′H,17′H-spiro[indene-2,18′-[5a,16b]methanotriindeno[1,2-b:1′,2′-d:2′′,1′′-g]oxocine]-1,3,10′,12′,17′(10a′H)-pentaone acetonitrile 1.5-solvate
Authors: Baranov Mark , Vainer Radion , Sigalov Mark V.
Published: September 2018

The title compound, C46H26N2O7·1.5CH3CN, is the aldol condensation product of bindone with indazole-3-carbaldehyde followed by double intermolecular cyclization. The asymmetric unit, which has monoclinic P21/c symmetry, contains two independent molecules of the title compound and three acetonitrile molecules. The title molecule comprises a central eight-membered ring, which contains an enol–ester, from which five arms extend. The arms exhibit intermolecular interactions within the crystal lattice between molecules of the title compound and with co-crystallized solvent molecules (acetonitrile).
Sites of translation in digital reporting
Authors: Locke Joanne , Rowbottom Nick , Troshani Indrit
Published: September 2018

Purpose

The purpose of this paper is to analyse the process by which “analogue” corporate reports produced under a “paper paradigm” are translated into a machine language as required by digital reporting. The paper uses Austin and Searle’s linguistic speech act theory to examine how digitally translating reporting information into atomised data affects the infrastructure and practice of accounting.

Design/methodology/approach

Extensive interview and observation evidence focussed on the IFRS Foundation’s digital reporting project is analysed. An interpretive approach is informed by the concepts of L compatibility, illocution and perlocutionary acts which are drawn from speech act theory.

Findings

Two key sites of translation are identified. The first site concerns the translation of accounting standards, principles and practices into taxonomies for digital tagging. Controversies arise over the definition of accounting concepts in a site populated by accounting and IT-orientated experts. The second site of translation is in the routine production and dissemination of digital reports which impacts the L compatibility between preparers and users.

Originality/value

The paper highlights a previously unexplored field of translation in accounting and contributes a unique perspective that demonstrates that machine translation is no longer marginalised but is the “primary” text with effects on the infrastructure and practice of accounting. It extends speech act theory by applying it to the digital domain and in the context of translation between languages.