bluuebunny/crossref_metadata_2025 huggingface dataset:
Lancet: genome-wide somatic variant calling using localized colored DeBruijn graphs
Authors: Narzisi Giuseppe , Corvelo André , Arora Kanika , Bergmann Ewa A. , Shah Minita , Musunuri Rajeeva , Emde Anne-Katrin , Robine Nicolas , Vacic Vladimir , Zody Michael C.
Published: October 2017

Reliable detection of somatic variations is of critical importance in cancer research. Lancet is an accurate and sensitive somatic variant caller which detects SNVs and indels by jointly analyzing reads from tumor and matched normal samples using colored DeBruijn graphs. Extensive experimental comparison on synthetic and real whole-genome sequencing datasets demonstrates that Lancet has better accuracy, especially for indel detection, than widely used somatic callers, such as MuTect, MuTect2, LoFreq, Strelka, and Strelka2. Lancet features a reliable variant scoring system which is essential for variant prioritization and detects low frequency mutations without sacrificing the sensitivity to call longer insertions and deletions empowered by the local assembly engine. In addition to genome-wide analysis, Lancet allows inspection of somatic variants in graph space, which augments the traditional read alignment visualization to help confirm a variant of interest. Lancet is available as an open-source program athttps://github.com/nygenome/lancet.
Nucleation of Multiple Buckled Structures in Intertwined DNA Double Helices
Authors: Brahmachari Sumitabha , Gunn Kathryn H. , Giuntoli Rebecca D. , Mondragón Alfonso , Marko John F.
Published: October 2017

We study the statistical-mechanical properties of intertwined double-helical DNAs (DNA braids). In magnetic tweezers experiments we find that torsionally-stressed stretched braids supercoil via an abrupt buckling transition, which is associated with nucleation of a braid end loop, and that the buckled braid is characterized by proliferation of multiple domains. Differences between the mechanics of DNA braids and supercoiled single DNAs can be understood as an effect of increased bulkiness in the structure of the former. The experimental results are in accord with the predictions of a previously-described statistical-mechanical model.
Effects of anthropogenic wildfire in low-elevation Pacific island vegetation communities in French Polynesia
Authors: Newman Erica A. , Winkler Carlea A. , Hembry David H.
Published: October 2017

Anthropogenic (or human-caused) wildfire is an increasingly important driver of ecological change on Pacific islands including southeastern Polynesia, but fire ecology studies are almost completely absent for this region. Where observations do exist, they mostly represent descriptions of fire effects on plant communities before the introduction of invasive species in the modern era. Understanding the effects of wildfire in southeastern Polynesian island vegetation communities can elucidate which species may become problematic invasives with continued wildfire activity. We investigate the effects of wildfire on vegetation in three low-elevation sites (45-379 m) on the island of Mo’orea in the Society Islands, French Polynesia, which are already heavily impacted by past human land use and invasive exotic plants, but retain some native flora. In six study areas (3 burned and 3 unburned comparisons), we placed 30 transects across sites and collected species and abundance information at 390 points. We analyzed each local community of plants in three categories: natives, those introduced by Polynesians before European contact (1767 C.E.), and those introduced since European contact. Burned areas had the same or lower mean species richness than paired comparison sites. Although wildfire did not affect the proportions of native and introduced species, it may increase the abundance of introduced species on some sites. Non-metric multidimensional scaling indicates that (not recently modified) comparison plant communities are more distinct from one another than are those on burned sites. We discuss conservation concerns for particular native plants absent from burned sites, as well as invasive species (includingLantana camaraandParaserianthes falcataria) that may be promoted by fire in the Pacific.
Transcriptomic characterization of MRI contrast with focus on the T1-w/T2-w ratio in the cerebral cortex
Authors: Ritchie Jacob , Pantazatos Spiro , French Leon
Published: October 2017

Magnetic resonance (MR) images of the brain are of immense clinical and research utility. At the atomic and subatomic levels, the sources of MR signals are well understood. However, at the macromolecular scale, we lack a comprehensive understanding of what determines MR signal contrast. To address this gap, we used genome-wide measurements to correlate gene expression with MR signal intensity across the cortex in the Allen Human Brain Atlas. We focused on the ratio of T1-weighted and T2-weighted intensities (T1-w/T2-w) which is considered to be a useful proxy for myelin content. Positive correlations between myelin-associated genes and the ratio supported its use as a myelin marker. However, stronger correlations were observed for neurofilaments, and genes linked to the production of formaldehyde (which cross-links protein to create larger molecules). There was also an association with protein mass, with genes coding for heavier proteins expressed in regions with high T1-w/T2-w values. Oligodendrocyte gene markers were strongly correlated but this was not driven by myelin-associated genes, suggesting this signal is from non-myelinating satellite oligodendrocytes. We find the strongest support for the previous finding of high aerobic glycolysis in regions with low T1-w/T2-w ratio. Specifically, many mitochondrial genes were negatively correlated with T1-w/T2-w ratio. Genes up-regulated by pH in the brain were also highly correlated with the ratio, suggesting the pH gradient in mitochondria may explain the aerobic glycolysis association. Expression of protease subunit genes was also inversely associated with the ratio, in agreement with the protein mass correlation. While we corroborate associations with myelin and synaptic plasticity, differences in the T1-w/T2-w ratio appear to be more attributable to molecule size, satellite oligodendrocyte proportion, mitochondrial number, alkalinity, and axon caliber. Using disease-associated gene lists, we observed an enrichment of negative T1-w/T2-w ratio correlations with human immunodeficiency virus (HIV) associated genes. Expanding our analysis to the whole brain results in strong positive T1-w/T2-w associations for immune system, inflammatory disease, and microglial genes. In contrast, neuron markers and synaptic plasticity genes are negatively enriched. Lastly, our results vary little when our analysis is performed on T1-w or inverted T2-w intensities alone, possibly because the noise reduction properties of the ratio are not needed for postmortem brain scans. These results provide a molecular characterization of MR contrast that will aid interpretation of future MR studies of the brain.
Brief targeted memory reactivation during the awake state enhances memory stability and benefits the weakest memories
Authors: Tambini Arielle , Berners-Lee Alice , Davachi Lila
Published: October 2017

Reactivation of representations corresponding to recent experience is thought to be a critical mechanism supporting long-term memory stabilization. Targeted memory reactivation, or the re-exposure of recently learned cues, seeks to induce reactivation and has been shown to benefit later memory when it takes place during sleep. However, despite recent evidence for endogenous reactivation during post-encoding awake periods, less work has addressed whether awake targeted memory reactivation modulates memory. Here, we found that brief (50ms) visual stimulus re-exposure during a repetitive foil task enhanced the stability of cued versus uncued associations in memory. The extent of external or task-oriented attention prior to re-exposure was inversely related to cueing benefits, suggesting that an internally-orientated state may be most permissible to reactivation. Critically, cueing-related memory benefits were greatest in participants without explicit recognition of cued items and remained reliable when only considering associations not recognized as cued, suggesting that explicit cue-triggered retrieval processes did not drive cueing benefits. Cueing benefits were strongest for items and participants with the poorest initial learning. These findings expand our knowledge of the conditions under which targeted memory reactivation can benefit memory, and in doing so, support the notion that reactivation during awake time periods improves memory stabilization.
A combinatorial approach for the synthesis of multi-phosphorylated peptides: new tool for studying phosphorylation patterns in proteins
Authors: Samarasimhareddy Mamidi , Mayer Daniel , Metanis Norman , Veprintsev Dmitry , Hurevich Mattan , Friedler Assaf
Published: October 2017

Phosphorylation of proteins at multiple sites creates different phosphorylation patterns that are essential for their biological activity. For example, such patterns contribute to the redirection of signalling to alternative pathways. Multi-phosphorylated peptides are excellent tools to systematically study the impact of unique phosphorylation patterns on signalling, but their synthesis is extremely difficult. Here we present an efficient and general method for the synthesis of multi-phosphorylated peptides, using a combination of different tailor-made coupling conditions. The method was demonstrated for the synthesis of a library of Rhodopsin C terminal peptides with distinct phosphorylation patterns containing up to seven phosphorylated Ser (pSer) and Thr (pThr) residues in close proximity to one another. Our method can be used to synthesize peptides incorporating multiple phosphorylated amino acids at high efficiency. It does not require any special expertise and can be performed in any standard peptide laboratory. This approach opens the way for quantitative mechanistic studies of phosphorylation patterns and their biological roles.
Multiscale simulation of peripheral neural signaling
Authors: Lubba CH , Guen Y Le , Jarvis S , Jones NS , Cork SC , Eftekhar A , Schultz SR
Published: October 2017

Bioelectronic Medicines that modulate the activity patterns on peripheral nerves have promise as a new way of treating diverse medical conditions from epilepsy to rheumatism. Progress in the field builds upon time consuming and expensive experiments in living organisms to evaluate spontaneous activity patterns, stimulation efficiency, and organ responses. To reduce experimentation load and allow for a faster, more detailed analysis of both recording from and stimulation of peripheral nerves, adaptable computational models incorporating insights won in experiments will be of great help. We present a peripheral nerve simulator that combines biophysical axon models and numerically solved and idealized extracellular space models in one environment. Two different scales of abstraction were merged. On the one hand we modeled the extracellular space in a finite element solver as a three dimensional resistive continuum governed by the electro-quasistatic approximation of the Maxwell equations. Potential distributions were precomputed for different media (homogeneous, nerve in saline, nerve in cuff). Axons, on the other hand, were modeled at a higher level of abstraction as one dimensional chains of compartments; each consisting of lumped linear elements and, for some, channels with non-linear dynamics. Unmyelinated fibres were based on the Hodgkin-Huxley model; for myelinated fibers, we instead adapted the model proposed by McIntyre et al. in 2002 to smaller diameters. To obtain realistic axon shapes, an iterative algorithm positioned fibers along the nerve with variable tortuosity, with tortuosity values fit to imaged trajectories. We validated our model with data from the stimulated rat vagus nerve. Simulation results predicted that tortuosity leads to differentiation in recorded signal shapes, with unmyelinated axons being the most affected. Tortuosity was further shown to increase the stimulation threshold. The model we developed can easily be adapted to different nerves, and may be of use for Bioelectronic Medicine research in the future.
High-throughput cancer hypothesis testing with an integrated PhysiCell-EMEWS workflow
Authors: Ozik Jonathan , Collier Nicholson , Wozniak Justin M. , Macal Charles , Cockrell Chase , Friedman Samuel H. , Ghaffarizadeh Ahmadreza , Heiland Randy , An Gary , Macklin Paul
Published: October 2017

Background

Cancer is a complex, multiscale dynamical system, with interactions between tumor cells and non-cancerous host systems. Therapies act on this combined cancer-host system, sometimes with unexpected results. Systematic investigation of mechanistic computational models can augment traditional laboratory and clinical studies, helping identify the factors driving a treatment’s success or failure. However, given the uncertainties regarding the underlying biology, these multiscale computational models can take many potential forms, in addition to encompassing high-dimensional parameter spaces. Therefore, the exploration of these models is computationally challenging. We propose that integrating two existing technologies—one to aid the construction of multiscale agent-based models, the other developed to enhance model exploration and optimization—can provide a computational means for high-throughput hypothesis testing, and eventually, optimization.

Results

In this paper, we introduce a high throughput computing (HTC) framework that integrates a mechanistic 3-D multicellular simulator (PhysiCell) with an extreme-scale model exploration platform (EMEWS) to investigate high-dimensional parameter spaces. We show early results in applying PhysiCell-EMEWS to 3-D cancer immunotherapy and show insights on therapeutic failure. We describe a generalized PhysiCell-EMEWS workflow for high-throughput cancer hypothesis testing, where hundreds or thousands of mechanistic simulations are compared against data-driven error metrics to perform hypothesis optimization.

Conclusions

While key notational and computational challenges remain, mechanistic agent-based models and high-throughput model exploration environments can be combined to systematically and rapidly explore key problems in cancer. These high-throughput computational experiments can improve our understanding of the underlying biology, drive future experiments, and ultimately inform clinical practice.
Quantifying male and female pheromone-based mate choice inCaenorhabditisnematodes using a novel microfluidic technique
Authors: Borne Flora , Kasimatis Katja R. , Phillips Patrick C.
Published: October 2017

Pheromone cues are an important component of intersexual communication, particularly in regards to mate choice.Caenorhabditisnematodes predominant rely on pheromone production for mate finding and mate choice. Here we describe a new microfluidic paradigm for studying mate choice in nematodes. Specifically, the Pheromone Arena allows for a constant flow of small molecule signals to be passed in real time from signaling worms to those making a choice without any physical contact. We validated this microfluidic paradigm by corroborating previous studies in showing that virginC. remaneiandC. elegansmales have a strong preference for virgin females over mated ones. Moreover, our results suggest that the strength of attraction is an additive effect of male receptivity and female signal production. We go on to explicitly examine female choice and find that females are more attracted to virgin males. However, a female’s mate choice is strongly dependent on her mating status.
Novel genes required for the fitness ofStreptococcus pyogenesin human saliva
Authors: Zhu Luchang , Charbonneau Amelia R. L. , Waller Andrew S. , Olsen Randall J. , Beres Stephen B. , Musser James M.
Published: October 2017

Streptococcus pyogenes(group AStreptococcus, or GAS) causes 600 million cases of pharyngitis each year. Despite this considerable disease burden, the molecular mechanisms used by GAS to infect, cause clinical pharyngitis, and persist in the human oropharynx are poorly understood. Saliva is ubiquitous in the human oropharynx and is the first material GAS encounters in the upper respiratory tract. Thus, a fuller understanding of how GAS survives and proliferates in saliva may provide valuable insights into the molecular mechanisms at work in the human oropharynx. We generated a highly saturated transposon insertion mutant library in serotype M1 strain MGAS2221, a strain genetically representative of a pandemic clone that arose in the 1980s and spread globally. The transposon mutant library was exposed to human saliva to screen for GAS genes required for wild-type fitness in this clinically relevant fluid. Using transposon-directed insertion site sequencing (TraDIS), we identified 92 genes required for GAS fitness in saliva. The more prevalent categories represented are genes involved in carbohydrate transport/metabolism, amino acid transport/metabolism, and inorganic ion transport/metabolism. Using six isogenic mutant strains, we confirmed that each of the mutants are significantly impaired for growth or persistence in human salivaex vivo. Mutants with an inactivatedspy0644(sptA) orspy0646(sptC) gene have especially severe persistence defects. This study is the first use of TraDIS to study bacterial fitness in human saliva. The new information we obtained is valuable for future translational maneuvers designed to prevent or treat human GAS infections.

IMPORTANCE

The human bacterial pathogenStreptococcus pyogenes(group A streptococcus, GAS) causes more than 600 million cases of pharyngitis annually worldwide, 15 million of which occur in the United States. The human oropharynx is the primary anatomic site for GAS colonization and infection, and saliva is the first material encountered. Using a genome-wide transposon mutant screen, we identified 92 GAS genes required for wild-type fitness in human saliva. Many of the identified genes are involved in carbohydrate transport/metabolism, amino acid transport/metabolism, and inorganic ion transport/metabolism. The new information is potentially valuable for developing novel GAS therapeutics and vaccine research.
Higher physical fitness levels are associated with less language decline in healthy ageing
Authors: Segaert K. , Lucas S.J.E. , Burley C.V. , Segaert P. , Milner A. E. , Ryan M. , Wheeldon L.
Published: October 2017

Healthy ageing is associated with decline in cognitive abilities such as language. Aerobic fitness has been shown to ameliorate decline in some cognitive domains, but the potential benefits for language have not been examined. In a cross-sectional sample, we investigated the relationship between aerobic fitness and tip-of-the-tongue states. These are among the most frequent cognitive failures in healthy older adults and occur when a speaker knows a word but is unable to produce it. We found that healthy older adults indeed experience more tip-of-the-tongue states than young adults. Importantly, higher aerobic fitness levels decrease the probability of experiencing tip-of-the-tongue states in healthy older adults. Fitness-related differences in word finding abilities are observed over and above effects of age. This is the first demonstration of a link between aerobic fitness and language functioning in healthy older adults.
PeatlandAcidobacteriawith a dissimilatory sulfur metabolism
Authors: Hausmann Bela , Pelikan Claus , Herbold Craig W. , Köstlbacher Stephan , Albertsen Mads , Eichorst Stephanie A. , del Rio Tijana Glavina , Huemer Martin , Nielsen Per H. , Rattei Thomas , Stingl Ulrich , Tringe Susannah G. , Trojan Daniela , Wentrup Cecilia , Woebken Dagmar , Pester Michael , Loy Alexander
Published: October 2017

Sulfur-cycling microorganisms impact organic matter decomposition in wetlands and consequently greenhouse gas emissions from these globally relevant environments. However,their identities and physiological properties are largely unknown. By applying a functional metagenomics approach to an acidic peatland, we recovered draft genomes of seven novelAcidobacteriaspecies with the potential for dissimilatory sulfite (dsrAB,dsrC,dsrD,dsrN, dsrT, dsrMKJOP) or sulfate respiration (sat, aprBA, qmoABCplusdsrgenes). Surprisingly, the genomes also encodeddsrL, a unique gene of the sulfur oxidation pathway. Metatranscriptome analysis demonstrated expression of acidobacterial sulfur-metabolism genes in native peat soil and their upregulation in diverse anoxic microcosms. This indicated an active sulfate respiration pathway, which, however, could also operate in reverse for sulfur oxidation as recently shown for other microorganisms.Acidobacteriathat only harbored genes for sulfite reduction additionally encoded enzymes that liberate sulfite from organosulfonates, which suggested organic sulfur compounds as complementary energy sources. Further metabolic potentials included polysaccharide hydrolysis and sugar utilization, aerobic respiration, several fermentative capabilities, and hydrogen oxidation. Our findings extend both, the known physiological and genetic properties ofAcidobacteriaand the known taxonomic diversity of microorganisms with a DsrAB-based sulfur metabolism, and highlight new fundamental niches for facultative anaerobicAcidobacteriain wetlands based on exploitation of inorganic and organic sulfur molecules for energy conservation.
The genome sequence of the soft-rot fungusPenicillium purpurogenumreveals a high gene dosage for lignocellulolytic enzymes
Authors: Mardones Wladimir , Genova Alex Di , Cortés María Paz , Travisany Dante , Maass Alejandro , Eyzaguirre Jaime
Published: October 2017

The high lignocellulolytic activity displayed by the soft-rot fungusP. purpurogenumhas made it a target for the study of novel lignocellulolytic enzymes. We have obtained a reference genome of 36.2Mb of non-redundant sequence (11,057 protein-coding genes). The 49 largest scaffolds cover 90% of the assembly, and CEGMA analysis reveals that our assembly covers most if not all all protein-coding genes. RNASeq was performed and 93.1% of the reads aligned within the assembled genome. These data, plus the independent sequencing of a set of genes of lignocellulose-degrading enzymes, validate the quality of the genome sequence.P. purpurogenumshows a higher number of proteins with CAZy motifs, transcription factors and transporters as compared to other sequencedPenicillia. These results demonstrate the great potential for lignocellulolytic activity of this fungus and the possible use of its enzymes in related industrial applications.
Fibroblasts from metastatic sites induce broad-spectrum drug desensitization via modulation of mitochondrial priming
Authors: Landry Benjamin D. , Leete Thomas , Richards Ryan , Cruz-Gordillo Peter , Ren Gary , Schwartz Alyssa D. , Peyton Shelly R. , Lee Michael J.
Published: October 2017

Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor micro-environment. Using a large-scale co-culture assay optimized to measure drug-induced cell death, we identify tumor-stroma interactions that modulate drug sensitivity. Our data show that the chemo-insensitivity typically associated with aggressive subtypes of breast cancer is not cell intrinsic, but rather a product of tumor-fibroblast interactions. Additionally, we find that fibroblast cells influence tumor drug response in two distinct and divergent manners, which were predicable based on the anatomical origin from which the fibroblasts were harvested. These divergent phenotypes result from modulation of “mitochondrial priming” of tumor cells, caused by secretion of inflammatory cytokines, such as IL6 and IL8, from stromal cells.
Conditional Robust Calibration (CRC): a new computational Bayesian methodology for model parameters estimation and identifiability analysis
Authors: Bianconi Fortunato , Antonini Chiara , Tomassoni Lorenzo , Valigi Paolo
Published: October 2017

Computational modeling is a remarkable and common tool to quantitatively describe a biological process. However, most model parameters, such as kinetics parameters, initial conditions and scale factors, are usually unknown because they cannot be directly measured.

Therefore, key issues in Systems Biology are model calibration and identifiability analysis, i.e. estimate parameters from experimental data and assess how well those parameters are determined by the dimension and quality of the data.

Currently in the Systems Biology and Computational Biology communities, the existing methodologies for parameter estimation are divided in two classes: frequentist methods and Bayesian methods. The first ones are based on the optimization of a cost function while the second ones estimate the posterior distribution of model parameters through different sampling techniques.

In this work, we present an innovative Bayesian method, called Conditional Robust Calibration (CRC), for model calibration and identifiability analysis. The algorithm is an iterative procedure based on parameter space sampling and on the definition of multiple objective functions related to each output variables. The method estimates step by step the probability density function (pdf) of parameters conditioned to the experimental measures and it returns as output a subset in the parameter space that best reproduce the dataset.

We apply CRC to six Ordinary Differential Equations (ODE) models with different characteristics and complexity to test its performances compared with profile likelihood (PL) and Approximate Bayesian Computation Sequential Montecarlo (ABC-SMC) approaches. The datasets selected for calibration are time course measurements of different nature: noisy or noiseless, real or in silico.

Compared with PL, our approach finds a more robust solution because parameter identifiability is inferred by conditional pdfs of estimated parameters. Compared with ABC-SMC, we have found a more precise solution with a reduced computational cost.
Hierarchical Brain Network for Face and Voice Integration of Emotion Expression
Authors: Davies-Thompson Jodie , Elli Giulia V. , Rezk Mohamed , Benetti Stefania , Ackeren Markus van , Collignon Olivier
Published: October 2017

The brain has separate specialized computational units to process faces and voices located in occipital and temporal cortices. However, humans seamlessly integrate signals from the faces and voices of others for optimal social interaction. How are emotional expressions, when delivered by different sensory modalities (faces and voices), integrated in the brain? In this study, we characterized the brains’ response to faces, voices, and combined face-voice information (congruent, incongruent), which varied in expression (neutral, fearful). Using a whole-brain approach, we found that only the right posterior superior temporal sulcus (rpSTS) responded more to bimodal stimuli than to face or voice alone but only when the stimuli contained emotional expression. Face-and voice-selective regions of interest extracted from independent functional localizers, similarly revealed multisensory integration in the face-selective rpSTS only; further, this was the only face-selective region that also responded significantly to voices. Dynamic Causal Modeling revealed that the rpSTS receives unidirectional information from the face-selective fusiform face area (FFA), and voice-selective temporal voice area (TVA), with emotional expression affecting the connection strength. Our study promotes a hierarchical model of face and voice integration, with convergence in the rpSTS, and that such integration depends on the (emotional) salience of the stimuli.
A State Space Model of a Visuomotor Rotation Experiment
Authors: Broucke Mireille E.
Published: October 2017

We present a new linear time-invariant (LTI) state space model to explain adaptation in human motor control. We focus on a visuomotor rotation experiment in which a human subject must rapidly move a cursor on a horizontal screen through a target disk. The hand itself is occluded from view, while the cursor is rotated relative to the hand angle by an amount of r degrees. Our model is based on the application of well-known techniques from control theory, in particular regulator theory. The model is simple, yet it reveals a plausible architecture for the high level computations underlying human motor control, including a representation of the internal model. It is a two state LTI model, where each state has a physical interpretation
Hierarchical organization endows the kinase domain with regulatory plasticity
Authors: Creixell Pau , Pandey Jai P. , Palmeri Antonio , Santa-Olalla Marc C. , Ranganathan Rama , Pincus David , Yaffe Michael B.
Published: October 2017

The functional diversity of kinases enables specificity in cellular signal transduction. Yet general rules for how the kinase domain allows the more than 500 members of the human kinome to receive specific regulatory inputs and convey information to appropriate substrates – all while using the common signaling currency of phosphorylation – remain enigmatic. Here, using co-evolution analysis and quantitative live-cell assays, we reveal a deep hierarchical organization of the kinase domain that facilitates the orthogonal evolution of regulatory inputs and substrate outputs while maintaining catalytic function. Three quasi-independent functional units in the kinase domain (known as protein sectors) encode for catalysis, substrate specificity and regulation, and these distinct subdomains are differentially exploited by somatic cancer mutations and harnessed by allosteric inhibitors. We propose that this functional architecture endows the kinase domain with inherent regulatory plasticity.
Mechanics and buckling of biopolymeric shells and cell nuclei
Authors: Banigan Edward J. , Stephens Andrew D. , Marko John F.
Published: October 2017

We study a Brownian dynamics simulation model of a biopolymeric shell deformed by axial forces exerted at opposing poles. The model exhibits two distinct linear force-extension regimes, with the response to small tensions governed by linear elasticity and the response to large tensions governed by an effective spring constant that scales with radius asR−0.25. When extended beyond the initial linear elastic regime, the shell undergoes a hysteretic, temperature-dependent buckling transition. We experimentally observe this buckling transition by stretching and imaging the lamina of isolated cell nuclei. Furthermore, the interior contents of the shell can alter mechanical response and buckling, which we show by simulating a model for the nucleus that quantitatively agrees with our micromanipulation experiments stretching individual nuclei.
Genome-wide homology analysis reveals new insights into the origin of the wheat B genome
Authors: Zhang Wei , Zhang Mingyi , Zhu Xianwen , Cao Yaping , Sun Qing , Ma Guojia , Chao Shiaoman , Yan Changhui , Xu Steven S. , Cai Xiwen
Published: October 2017

Wheat is a typical allopolyploid with three homoeologous subgenomes (A, B, and D). The ancestors of the subgenomes A and D had been identified, but not for the subgenome B. The goatgrassAegilops speltoides(genome SS) has been controversially considered a candidate for the ancestor of the wheat B genome. However, the relationship of theAe. speltoidesS genome with the wheat B genome remains largely obscure, which has puzzled the wheat research community for nearly a century. In the present study, the genome-wide homology analysis identified perceptible homology between wheat chromosome 1B andAe. speltoideschromosome 1S, but not between other chromosomes in the B and S genomes. AnAe. speltoides-originated segment spanning a genomic region of approximately 10.46 Mb was identified on the long arm of wheat chromosome 1B (1BL). TheAe. speltoides-originated segment on 1BL was found to co-evolve with the rest of the B genome in wheat species. Thereby, we conclude thatAe. speltoideshad been involved in the origin of the wheat B genome, but should not be considered an exclusive ancestor of this genome. The wheat B genome might have a polyphyletic origin with multiple ancestors involved, includingAe. speltoides. These novel findings provide significant insights into the origin and evolution of the wheat B genome, and will facilitate polyploid genome studies in wheat and other plants as well.
Reprogramming Mouse Fibroblasts with piggyBac Transposons
Authors: Behringer Richard , Gertsenstein Marina , Nagy Kristina Vintersten , Nagy Andras
Published: October 2017

In 2006, Shinya Yamanaka and his student Kazutoshi Takahashi showed that the expression of only four specific genes is sufficient to reprogram fully differentiated somatic cells into pluripotent stem cells. These cells, termed induced pluripotent stem (iPS) cells, share many of their characteristics with embryonic stem (ES) cells. In this protocol, we describe one of the simplest ways of generating iPS cells from mouse fibroblasts. It combines an efficient transposon-mediated transfection and the tetracycline-inducible system to control the expression of the Yamanaka reprogramming factors.
Isolation of High-Molecular-Weight DNA from Mammalian Blood Using Proteinase K and Phenol
Authors: Green Michael R. , Sambrook Joseph
Published: October 2017

This procedure is the method of choice for purification of genomic DNA from mammalian blood when large amounts of DNA are required, for example, for Southern blotting. The usual yield of DNA from buffy coat lymphocytes isolated from 20 mL of normal blood is ∼250 µg.
Rescue Strategy for Nonviable Hybridomas: Amplifying Heavy- and Light-Chain Sequences from Genomic DNA by Polymerase Chain Reaction
Authors: Dasch James R. , Dasch Amy L.
Published: October 2017

Many hybridoma researchers have lost an important hybridoma because of instability, mechanical breakdown of a freezer, or contamination. In many cases, however, it is possible to retrieve the heavy- and light-chain sequences from those hybridomas. Although most cloning methods associated with isolation of VH or VL gene sequences require the isolation of intact, nondegraded mRNA, alternative approaches based on genomic DNA have been reported. With genomic DNA, the DNA sample can remain relatively intact in cases in which the mRNA has been degraded. If intact DNA can be obtained from a nonviable hybridoma, the method described here can be used to recover the heavy- and light-chain sequences. The method uses PCR based on a combination of primers in the 5′ untranslated region of VH and VL and in the JH and JL segments. Although a relatively large number of primers are required for this method, the ability to obtain a full-length V gene without having intact mRNA could be of general interest for rescuing lost hybridomas.
Assay for β-Galactosidase in Extracts of Mammalian Cells
Authors: Uchil Pradeep D. , Nagarajan Arvindhan , Kumar Priti
Published: October 2017

This protocol contains a method for the detection of β-galactosidase expressed from reporter vectors that have been transfected into mammalian cells. The assay is both simple and rapid and can be performed using a visible light spectrophotometer.
Live Cell Imaging in Fission Yeast
Authors: Mulvihill Daniel P.
Published: October 2017

Live cell imaging complements the array of biochemical and molecular genetic approaches to provide a comprehensive insight into functional dependencies and molecular interactions in fission yeast. Fluorescent proteins and vital dyes reveal dynamic changes in the spatial distribution of organelles and the proteome and how each alters in response to changes in environmental and genetic composition. This introduction discusses key issues and basic image analysis for live cell imaging of fission yeast.
Crystal structure of poly[diaquabis(μ5-benzene-1,3-dicarboxylato)(N,N-dimethylformamide)cadmium(II)disodium(I)]
Authors: Sangsawang Matimon , Chainok Kittipong , Wannarit Nanthawat
Published: October 2017

The title compound, [CdNa2(C8H4O4)2(C3H7NO)(H2O)2]nor [CdNa2(1,3-bdc)2(DMF)(H2O)2]n, is a new CdII–NaIheterobimetallic coordination polymer. The asymmetric unit consists of one CdIIatom, two NaIatoms, two 1,3-bdc ligands, two coordinated water molecules and one coordinated DMF molecule. The CdIIatom exhibits a seven-coordinate geometry, while the NaIatoms can be considered to be pentacoordinate. The metal ions and their symmetry-related equivalents are connectedviachelating–bridging carboxylate groups of the 1,3-bdc ligands to generate a three-dimensional framework. In the crystal, there are classical O—H...O hydrogen bonds involving the coordinated water molecules and the 1,3-bdc carboxylate groups and π–π stacking between the benzene rings of the 1,3-bdc ligands present within the frameworks.
Clustering, innovation and hotel competitiveness: evidence from the Colombia destination
Authors: Rodríguez-Victoria Orietha Eva , Puig Francisco , González-Loureiro Miguel
Published: October 2017

Purpose

This paper aims to explore the relationship between clustering and hotel competitiveness in emerging economy destinations by analyzing potential mediation of the management innovations implemented.

Design/methodology/approach

This empirical study is based on hotel-level information from a survey including 131 hotels in 2014. Colombia was chosen as a representative of Colombia, Indonesia, Vietnam, Egypt, Turkey and South Africa (CIVETS) emerging destinations. The relationships were analyzed by structural modeling and partial least squares.

Findings

Clustering has a positive direct impact on hotel competitiveness and innovation, and there is a positive effect of innovation on competitiveness. Therefore, the link between clustering and competitiveness is partially mediated through implementation of management innovations.

Practical implications

Hotels should actively participate in agglomerated destinations and build relationships with established firms by clustering. Interaction with related firms and implementation of management innovations will lead to increased levels of economic competitiveness. Public policymakers should foster collaborative strategic networking in the hospitality industry of emerging economy destinations.

Originality/value

This paper focused on separating the direct and indirect effects of clustering on hotel competitiveness. Implementation of management innovations was considered as an outcome derived from clustering in emerging tourist destinations, using the example of Colombia. Clustering stimulates and eases management innovations within the location, and that combination reinforces the role that cooperating while competing plays in hotel competitiveness for destinations with lagging innovation.
Perfectionism in occupational science students: occupational therapy implications
Authors: Wagner Mary Elizabeth , Causey-Upton Renee
Published: October 2017

Purpose

The purpose of this study is to categorize perfectionism and determine how perfectionism impacts the occupations and perceived health of students in a Bachelor of Science in Occupational Science program.

Design/methodology/approach

A descriptive study with a survey component was conducted. Participants were categorized as perfectionists or non-perfectionists using the Almost Perfect Scale-Revised (APS-R). Time logs were collected to compare categories of time-use between groups over a one-week period. An online survey was conducted with a sub-sample of the perfectionists.

Findings

More students were categorized as perfectionists (N = 41) than non-perfectionists (N = 3). Both groups spent similar amounts of time engaged in productive, pleasurable and restorative occupations. Some perfectionists reported that perfectionism supported health, but others reported negative impacts on well-being.

Research limitations/implications

This study included a small sample size limited to one Occupational Science program in the USA.

Originality/value

Results demonstrated positive and negative health impacts because of perfectionism. The majority of participants were identified as perfectionists; rigorous academic programs may attract students with perfectionistic qualities. Findings are relevant for Occupational Therapy, as these students will become future occupational therapists after completing a Master’s program in Occupational Therapy and may be susceptible to negative outcomes associated with perfectionism such as workaholism and poor health.
Experiences of men with psychosis participating in a community-based football programme
Authors: Moloney Laura , Rohde Daniela
Published: October 2017

Purpose

Physical activity is associated with both physical and mental health benefits for people with psychosis. However, mental health services have been criticised for failing to adequately promote physical activities. Occupational Therapy, with its focus on meaningful everyday occupations, is well placed to incorporate physical activity interventions. The purpose of this study was to explore the experiences of men with psychosis participating in an Irish community-based football programme.

Design/methodology/approach

Six men with psychosis participated in qualitative interviews. The interviews were audio-recorded and transcribed verbatim. Interview data were analysed thematically.

Findings

Participants identified many benefits of engaging in the programme. Football became a valued part of weekly routines and fostered re-engagement with previously valued roles. Participants identified improvements in social confidence and motor and process skills, as well as a positive impact on their mental and physical health.

Originality/value

This study highlights the value and meaning of participation in football for men with psychosis, as well as demonstrating the longer-term feasibility of football as a therapeutic medium in Occupational Therapy mental health service provision. Findings could help to promote the routine use of sports interventions to mental health services.
Occupational Therapy embraces the National #Littlethings mental health and wellbeing campaign in Offaly via an Operation Transformation Programme
Authors: Deegan Deirdre , McKiver Eileen
Published: October 2017

Purpose

In early 2015, an Occupational Therapy led Operation Transformation healthy eating and exercise programme produced results suggestive of the value and need to promote and integrate physical activity interventions into mental health services.

Design/methodology/approach

In all, 41 clients with various mental illness diagnoses participated in the eight-week Operation Transformation programme. The outcome measures involved weekly weigh-ins and an end of programme evaluation form.

Findings

The quantifiable benefits – a total weight loss of nine stone ten and a half pounds – were mirrored in equally impressive qualitative impacts. Participants’ feedback via anonymous evaluation forms, echoed the findings of the articles appraised in the literature, including improvements in mood and energy levels, better sleep and increased motivation.

Practical implications

The organisers will benefit from lessons learned in this first experience, including overcoming logistical and organisational difficulties experienced in enabling clients’ full participation.

Originality/value

The evidence base points to the successful benefits of physical activity in promoting positive mental health. Occupational Therapists have a unique opportunity to drive forward the message of promoting physical activity via meaningful occupations.
A spatial analysis of suicide rates in Tennessee
Authors: Difurio Ferdinand Gabriel , Lewis Willis
Published: October 2017

Purpose

Suicide rates at the county level may be influenced by various macro-level factors emanating from surrounding communities. The purpose of this paper is to measure the extent of geographic spillover effects from socioeconomic factors on suicide rates.

Design/methodology/approach

Using county level, panel data over the years 2002-2007, a spatial dependence function is applied to measure how socioeconomic factors within surrounding counties may influence suicide rates in neighboring, adjacent counties in the state of TN.

Findings

A negative correlation is identified between divorce and suicide rates within each county, which seems to contradict traditional beliefs that these variables move together. Also contrary to expectations, unemployment and suicide are not significantly related within counties. When the analysis measures the spillover effects of surrounding communities, county-level variables such as income, crime, and church density are significant. And although the signs on income and crime are consistent with past findings, church density counters research expectations.

Practical implications

These results suggest that certain socioeconomic factors influence suicide in surrounding communities, while others do not. Incorporating spatial analysis into future research on suicide and mental health may assist practitioners with suicide prevention. Appropriate prevention policies should be designed and implemented at the local or regional level. Regional differences make broad policies based on national data inappropriate for local areas that differ from national norms.

Originality/value

Studies on the external links to suicide and suicide rates have made significant contributions to raise the understanding about mental health issues. Very few, however, have directly employed research methods to capture spillover effects when the study encompasses spatial elements.
Beyond the equal-weight framework of the Social Progress Index
Authors: Jitmaneeroj Boonlert
Published: October 2017

Purpose

Although the Social Progress Index offers a thorough overview of the top-ranked countries with a highly developed social performance, it assigns the same weight to all component scores, implying that each component has identical and independent contribution to the SPI. By removing these flawed assumptions, the purpose of this paper is to examine the causal relationships among component scores and identify the critical components for reform priorities.

Design/methodology/approach

The authors propose an alternative approach to exploring the causal relationships and prioritizing the underlying components of the SPI. The four-step methodology comprises cluster analysis, data mining, partial least square path modeling, and importance-performance matrix analysis.

Findings

The authors find evidence of causal interrelations between the 12 components of the SPI. To accelerate social progress, the authors suggest that policy makers should allocate resources in order of priority to personal freedom and choice, personal rights, access to advanced education, water and sanitation, access to information and communications, tolerance and inclusion, personal safety, shelter, ecosystem sustainability, nutrition and basic medical care, health and wellness, and, finally, access to basic knowledge.

Practical implications

Policy makers in government, business, and civil society should become aware of causal relationships among the 12 components of the SPI and select an appropriate methodology to prioritize areas where social improvement is most needed.

Originality/value

Allowing for unequal weighting and causal relationships between component scores of the SPI, the authors’ methodology is the first attempt to offer a concrete way to identify which areas of social progress should constitute priorities for policy reforms.