bluuebunny/crossref_metadata_2025 huggingface dataset:
The FHA domain determinesDrosophilaChk2/Mnk localization to key mitotic structures and is essential for early embryonic DNA damage responses
Authors: Takada Saeko , Collins Eric R. , Kurahashi Kayo
Published: March 2015

DNA damage responses, including mitotic centrosome inactivation, cell-cycle delay in mitosis, and nuclear dropping from embryo cortex, maintain genome integrity in syncytial Drosophila embryos. A conserved signaling kinase, Chk2, known as Mnk/Loki, is essential for the responses. Here we demonstrate that functional EGFP-Mnk expressed from a transgene localizes to the nucleus, centrosomes, interkinetochore/centromere region, midbody, and pseudocleavage furrows without DNA damage and in addition forms numerous foci/aggregates on mitotic chromosomes upon DNA damage. We expressed EGFP-tagged Mnk deletion or point mutation variants and investigated domain functions of Mnk in vivo. A triple mutation in the phosphopeptide-binding site of the forkhead-associated (FHA) domain disrupted normal Mnk localization except to the nucleus. The mutation also disrupted Mnk foci formation on chromosomes upon DNA damage. FHA mutations and deletion of the SQ/TQ-cluster domain (SCD) abolished Mnk transphosphorylations and autophosphorylations, indicative of kinase activation after DNA damage. A potent NLS was found at the C-terminus, which is required for normal Mnk function. We propose that the FHA domain in Mnk plays essential dual functions in mediating embryonic DNA damage responses by means of its phosphopeptide-binding ability: activating Mnk in the nucleus upon DNA damage and recruiting Mnk to multiple subcellular structures independently of DNA damage.
Prostaglandins regulate nuclear localization of Fascin and its function in nucleolar architecture
Authors: Groen Christopher M. , Jayo Asier , Parsons Maddy , Tootle Tina L.
Published: March 2015

Fascin, a highly conserved actin-bundling protein, localizes and functions at new cellular sites in both Drosophila and multiple mammalian cell types. During Drosophila follicle development, in addition to being cytoplasmic, Fascin is in the nuclei of the germline-derived nurse cells during stages 10B–12 (S10B–12) and at the nuclear periphery during stage 13 (S13). This localization is specific to Fascin, as other actin-binding proteins, Villin and Profilin, do not exhibit the same subcellular distribution. In addition, localization of fascin1 to the nucleus and nuclear periphery is observed in multiple mammalian cell types. Thus the regulation and function of Fascin at these new cellular locations is likely to be highly conserved. In Drosophila, loss of prostaglandin signaling causes a global reduction in nuclear Fascin and a failure to relocalize to the nuclear periphery. Alterations in nuclear Fascin levels result in defects in nucleolar morphology in both Drosophila follicles and cultured mammalian cells, suggesting that nuclear Fascin plays an important role in nucleolar architecture. Given the numerous roles of Fascin in development and disease, including cancer, our novel finding that Fascin has functions within the nucleus sheds new light on the potential roles of Fascin in these contexts.
Multisite phosphorylation of the NDC80 complex gradually tunes its microtubule-binding affinity
Authors: Zaytsev Anatoly V. , Mick Jeanne E. , Maslennikov Evgeny , Nikashin Boris , DeLuca Jennifer G. , Grishchuk Ekaterina L.
Published: March 2015

Microtubule (MT) attachment to kinetochores is vitally important for cell division, but how these interactions are controlled by phosphorylation is not well known. We used quantitative approaches in vitro combined with molecular dynamics simulations to examine phosphoregulation of the NDC80 complex, a core kinetochore component. We show that the outputs from multiple phosphorylation events on the unstructured tail of its Hec1 subunit are additively integrated to elicit gradual tuning of NDC80-MT binding both in vitro and in silico. Conformational plasticity of the Hec1 tail enables it to serve as a phosphorylation-controlled rheostat, providing a new paradigm for regulating the affinity of MT binders. We also show that cooperativity of NDC80 interactions is weak and is unaffected by NDC80 phosphorylation. This in vitro finding strongly supports our model that independent molecular binding events to MTs by individual NDC80 complexes, rather than their structured oligomers, regulate the dynamics and stability of kinetochore-MT attachments in dividing cells.
Preventing farnesylation of the dynein adaptor Spindly contributes to the mitotic defects caused by farnesyltransferase inhibitors
Authors: Holland Andrew J. , Reis Rita M. , Niessen Sherry , Pereira Cláudia , Andres Douglas A. , Spielmann H. Peter , Cleveland Don W. , Desai Arshad , Gassmann Reto
Published: March 2015

The clinical interest in farnesyltransferase inhibitors (FTIs) makes it important to understand how these compounds affect cellular processes involving farnesylated proteins. Mitotic abnormalities observed after treatment with FTIs have so far been attributed to defects in the farnesylation of the outer kinetochore proteins CENP-E and CENP-F, which are involved in chromosome congression and spindle assembly checkpoint signaling. Here we identify the cytoplasmic dynein adaptor Spindly as an additional component of the outer kinetochore that is modified by farnesyltransferase (FTase). We show that farnesylation of Spindly is essential for its localization, and thus for the proper localization of dynein and its cofactor dynactin, to prometaphase kinetochores and that Spindly kinetochore recruitment is more severely affected by FTase inhibition than kinetochore recruitment of CENP-E and CENP-F. Molecular replacement experiments show that both Spindly and CENP-E farnesylation are required for efficient chromosome congression. The identification of Spindly as a new mitotic substrate of FTase provides insight into the causes of the mitotic phenotypes observed with FTase inhibitors.
A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner
Authors: Umeda Kentaro , Iwasawa Nariaki , Negishi Manabu , Oinuma Izumi
Published: March 2015

Precise wiring patterns of axons are among the remarkable features of neuronal circuit formation, and establishment of the proper neuronal network requires control of outgrowth, branching, and guidance of axons. R-Ras is a Ras-family small GTPase that has essential roles in multiple phases of axonal development. We recently identified afadin, an F-actin–binding protein, as an effector of R-Ras mediating axon branching through F-actin reorganization. Afadin comprises two isoforms—l-afadin, having the F-actin–binding domain, and s-afadin, lacking the F-actin–binding domain. Compared with l-afadin, s-afadin, the short splicing variant of l-afadin, contains RA domains but lacks the F-actin–binding domain. Neurons express both isoforms; however, the function of s-afadin in brain remains unknown. Here we identify s-afadin as an endogenous inhibitor of cortical axon branching. In contrast to the abundant and constant expression of l-afadin throughout neuronal development, the expression of s-afadin is relatively low when cortical axons branch actively. Ectopic expression and knockdown of s-afadin suppress and promote branching, respectively. s-Afadin blocks the R-Ras–mediated membrane translocation of l-afadin and axon branching by inhibiting the binding of l-afadin to R-Ras. Thus s-afadin acts as a dominant-negative isoform in R-Ras-afadin–regulated axon branching.
A statistical physics perspective on alignment-independent protein sequence comparison
Authors: Chattopadhyay Amit K. , Nasiev Diar , Flower Darren R.
Published: March 2015

Motivation: Within bioinformatics, the textual alignment of amino acid sequences has long dominated the determination of similarity between proteins, with all that implies for shared structure, function and evolutionary descent. Despite the relative success of modern-day sequence alignment algorithms, so-called alignment-free approaches offer a complementary means of determining and expressing similarity, with potential benefits in certain key applications, such as regression analysis of protein structure-function studies, where alignment-base similarity has performed poorly.

Results: Here, we offer a fresh, statistical physics-based perspective focusing on the question of alignment-free comparison, in the process adapting results from ‘first passage probability distribution’ to summarize statistics of ensemble averaged amino acid propensity values. In this article, we introduce and elaborate this approach.

Contact: d.r.flower@aston.ac.uk
DISSCO: direct imputation of summary statistics allowing covariates
Authors: Xu Zheng , Duan Qing , Yan Song , Chen Wei , Li Mingyao , Lange Ethan , Li Yun
Published: March 2015

Background: Imputation of individual level genotypes at untyped markers using an external reference panel of genotyped or sequenced individuals has become standard practice in genetic association studies. Direct imputation of summary statistics can also be valuable, for example in meta-analyses where individual level genotype data are not available. Two methods (DIST and ImpG-Summary/LD), that assume a multivariate Gaussian distribution for the association summary statistics, have been proposed for imputing association summary statistics. However, both methods assume that the correlations between association summary statistics are the same as the correlations between the corresponding genotypes. This assumption can be violated in the presence of confounding covariates.

Methods: We analytically show that in the absence of covariates, correlation among association summary statistics is indeed the same as that among the corresponding genotypes, thus serving as a theoretical justification for the recently proposed methods. We continue to prove that in the presence of covariates, correlation among association summary statistics becomes the partial correlation of the corresponding genotypes controlling for covariates. We therefore develop direct imputation of summary statistics allowing covariates (DISSCO).

Results: We consider two real-life scenarios where the correlation and partial correlation likely make practical difference: (i) association studies in admixed populations; (ii) association studies in presence of other confounding covariate(s). Application of DISSCO to real datasets under both scenarios shows at least comparable, if not better, performance compared with existing correlation-based methods, particularly for lower frequency variants. For example, DISSCO can reduce the absolute deviation from the truth by 3.9–15.2% for variants with minor allele frequency <5%.

Availability and implementation:  http://www.unc.edu/∼yunmli/DISSCO.

Contact:  yunli@med.unc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
ASBench: benchmarking sets for allosteric discovery
Authors: Huang Wenkang , Wang Guanqiao , Shen Qiancheng , Liu Xinyi , Lu Shaoyong , Geng Lv , Huang Zhimin , Zhang Jian
Published: March 2015

Summary: Allostery allows for the fine-tuning of protein function. Targeting allosteric sites is gaining increasing recognition as a novel strategy in drug design. The key challenge in the discovery of allosteric sites has strongly motivated the development of computational methods and thus high-quality, publicly accessible standard data have become indispensable. Here, we report benchmarking data for experimentally determined allosteric sites through a complex process, including a ‘Core set’ with 235 unique allosteric sites and a ‘Core-Diversity set’ with 147 structurally diverse allosteric sites. These benchmarking sets can be exploited to develop efficient computational methods to predict unknown allosteric sites in proteins and reveal unique allosteric ligand–protein interactions to guide allosteric drug design.

Availability and implementation: The benchmarking sets are freely available at http://mdl.shsmu.edu.cn/asbench.

Contact:  jian.zhang@sjtu.edu.cn

Supplementary information:  Supplementary data are available at Bioinformatics online
Computational modeling of the expansion of human cord blood CD133+ hematopoietic stem/progenitor cells with different cytokine combinations
Authors: Gullo Francesca , van der Garde Mark , Russo Giulia , Pennisi Marzio , Motta Santo , Pappalardo Francesco , Watt Suzanne
Published: March 2015

Motivation: Many important problems in cell biology require dense non-linear interactions between functional modules to be considered. The importance of computer simulation in understanding cellular processes is now widely accepted, and a variety of simulation algorithms useful for studying certain subsystems have been designed. Expansion of hematopoietic stem and progenitor cells (HSC/HPC) in ex vivo culture with cytokines and small molecules is a method to increase the restricted numbers of stem cells found in umbilical cord blood (CB), while also enhancing the content of early engrafting neutrophil and platelet precursors. The efficacy of the expanded product depends on the composition of the cocktail of cytokines and small molecules used for culture. Testing the influence of a cytokine or small molecule on the expansion of HSC/HPC is a laborious and expensive process. We therefore developed a computational model based on cellular signaling interactions that predict the influence of a cytokine on the survival, duplication and differentiation of the CD133+ HSC/HPC subset from human umbilical CB.

Results: We have used results from in vitro expansion cultures with different combinations of one or more cytokines to develop an ordinary differential equation model that includes the effect of cytokines on survival, duplication and differentiation of the CD133+ HSC/HPC. Comparing the results of in vitro and in silico experiments, we show that the model can predict the effect of a cytokine on the fold expansion and differentiation of CB CD133+ HSC/HPC after 8-day culture on a 3D scaffold.

Availability and implementation: The model is available visiting the following URL: http://www.francescopappalardo.net/Bioinformatics_CD133_Model.

Contact:  francesco.pappalardo@unict.it or suzanne.watt@nhsbt.nhs.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
New puerulus collector design suitable for fishery-dependent settlement monitoring
Authors: Ewing Graeme , Frusher Stewart
Published: March 2015

Fishery-independent diver-based puerulus settlement monitoring has been conducted for over two decades in sheltered inshore shallow sites on the Tasmanian coast and has been utilized in the development of a predictive capacity for the Tasmanian lobster fishery. However, the majority of catches in this fishery are sourced from deep (>50 m), remote, and highly exposed areas where it is impractical and expensive to conduct fishery-independent routine settlement monitoring. To determine if pueruli settle in deeper waters, we adapted a crevice puerulus collector to fit within a lobster trap frame specifically designed to be deployed and serviced by vessels typical of the Tasmanian lobster fleet. A 5-month trial yielded puerulus catches similar to those from inshore shallow sites including recording puerulus from waters more than 100 m depth. The collector design was reported by fishers to be safe and convenient to service in regions exposed to strong westerly winds and swell more than 7 m. This collector will allow a cost-effective fishery-dependent approach to puerulus settlement monitoring utilizing commercial fishers for field operations and researchers for administration, sorting, and analysis.
Effects of baited crab pots on cultivated mussel (Mytilus edulis) survival rates
Authors: Calderwood Julia , O'Connor Nessa E. , Roberts Dai
Published: March 2015

The shore crab, Carcinus maenas, is recognized as a voracious predator of blue mussels, Mytilus edulis, having the potential to greatly reduce stocks in the benthic cultivation industry. As a consequence, baited crab pots are often deployed on and around cultivated benthic mussel beds to trap and remove crabs, in an attempt to reduce predatory pressure. Little is known about how C. maenas behaves around crab pots, but for many other crustacean fisheries, the trapping efficiency of pots is often low. Crabs may be attracted towards but not enter pots, instead feeding on cultivated mussels outside pots on the surrounding substratum. We tested whether the rate of loss of mussels attached to plates differed in areas next to baited pots compared with unbaited pots and to areas without any pots, at two sea loughs (60 km apart) in Northern Ireland. In Strangford Lough, more mussels were lost from plates next to baited pots than the other treatments. In Carlingford Lough, however, we found no difference in the number of mussels lost from plates in any treatment. This difference could be attributed to the different assemblages of mobile benthic predators at the two loughs. The presence of the starfish Asterias rubens, which was absent from experimental sites in Carlingford Lough, was thought to be responsible for increased predation rates near baited pots in Strangford. It is, therefore, important to consider local predator communities when deploying crab pots as a predator mitigation technique to ensure predation rates are in fact reduced and not enhanced. This study is of relevance not only to attempts to limit predation on commercial stocks of benthic cultivated mussels but also in situations where baited traps are deployed close to species vulnerable to mobile benthic predators.
Physiological constrains on Sverdrup's Critical-Depth-Hypothesis: the influences of dark respiration and sinking
Authors: Lindemann Christian , Backhaus Jan O. , St John Michael A.
Published: March 2015

Discussions on the controls initiating the onset of the phytoplankton spring bloom in particular in the North Atlantic have since Sverdrup been dominated by the role of physical and biological drivers. Undoubtedly, these drivers play an important role in phytoplankton dynamics and thus the onset of the spring bloom. However, they neglect the cells ability to modify vital rates in response to changes in the external environment. In this study, we use a non-hydrostatic convection model coupled to an Individual-Based-Model to simulate changes phytoplankton cells during the transition from winter conditions as driven by convective mixing, and the onset of thermal stratification resulting in the spring bloom. The comparison between a simulation using a standard fixed rate approach in line with the original Sverdrup hypothesis and a simulation parameterized to include variable respiration and sinking rates showed that the latter approach was able to capture the observed phytoplankton concentration during deep convective mixing, the timing and magnitude of the spring bloom as well as simulating realistic physiological rates. In contrast, the model employing fixed rate parameterizations could only replicate field observations when employing unrealistic parameter values. These results highlight the necessity to consider not only the physical and biological external controls determining phytoplankton dynamics but also the cells ability to modify critical physiological rates in response to external constraints. Understanding these adaptive qualities will be of increasing importance in the future as species assemblages and physical controls change with changing climate.
The timing, duration, and management of symptoms of children with an
incurable brain tumor: a retrospective study of the palliative phase
Authors: Jagt- van Kampen Charissa T. , van de Wetering Marianne D. , Schouten–van Meeteren Antoinette Y.N.
Published: March 2015

Background

A brain tumor is diagnosed in 25% of pediatric oncology patients and carries a 30% mortality rate. To increase proactive support of children with a progressive brain tumor, we obtained information on timing, duration, and management of symptoms in the palliative trajectory.

Methods

A retrospective review of medical charts of patients treated at a children's university hospital, who were dying from a brain tumor between May 2007 and September 2012.

Results

Thirty-four children were included. After 0–2480 days (median, 168 days) from initial diagnosis, incurable disease was evident, with death occurring after 1–603 days (median, 80 days). Palliative cancer-directed therapy was given to 23 (68%) patients. Early presenting symptoms were altered mobility, speech disorders, and loss of sight or hearing. The symptoms with the shortest duration were somnolence, dysphagia, and dyspnea. The most frequent symptoms were pain (91%), poor mobility (74%), and somnolence (71%). Pain necessitated a short period of intravenous treatment with morphine in 38% of patients, for a median 4 days, and sedation in 15%, for a median 2.5 days. Do-not-resuscitate agreements were discussed with all parents at 0–576 days before death (median, 50 days) and were agreed upon by 33 (97%) parents. Twenty-seven (79%) patients died at home, and one died in a hospice. Six (18%) patients were admitted for intravenous anticonvulsants, pain medication, and sedation until death.

Conclusions

This study reports specific information on the timing of occurrence and duration of symptoms. This information will provide support for pediatric oncologists in preparing parents and primary health care professionals and anticipating symptom management and timely end-of-life decision-making in the palliative care phase for children with a brain tumor.
Society for Neuro-Oncology 2014 annual meeting updates on central nervous system metastases
Authors: Lukas Rimas V. , Mehta Minesh P. , Lesniak Maciej S.
Published: March 2015

Introduction

The 19th Annual Meeting of the Society for Neuro-Oncology (SNO) took place in November of 2014. The focus of many abstracts, as well as the Education Day, was on recent advances in the study of central nervous system (CNS) metastases.

Tumor Biology

Key studies evaluating the factors in tumors and their microenvironment associated with the development and growth of brain metastases are reviewed.

Prognostication

Studies investigating the factors that independently influence survival in participants with brain metastases are presented.

Response Assessment

The Response Assessment for Neuro-Oncology criteria for brain metastases (RANO-BM) and the Neurological Assessment in Neuro-Oncology (NANO) criteria, which were both presented, are recapped.

Radiotherapy

Studies are reviewed evaluating factors that influence survival outcomes in participants with brain metastases who were treated with radiotherapy. Studies investigating the potential risk of radiation necrosis with the combination of radiotherapy and immunotherapies are presented.

Systemic Therapies

Brain metastases-focused subset analyses from the ASCEND-1 trial for ALK-translocated non–small cell lung cancer are presented. Preclinical and clinical work on solid tumor leptomeningeal carcinomatosis is also covered.

Sequelae of Central Nervous System Metastases and Their Treatments

An overview is provided of treatment- related toxicities as well as important concepts that may influence strategies to protect against these toxicities.

Conclusions

Key concepts regarding tumor biology, prognostication, response assessment, therapeutic management, and sequelae of treatment for CNS metastases are summarized. Advances in our understanding of the basic and clinical science of CNS metastases have the potential to improve outcomes for patients.
Preventives Versus Treatments *
Authors: Kremer Michael , Snyder Christopher M.
Published: March 2015

Preventives are sold ex ante, before disease status is realized, while treatments are sold ex post. Even if the mean of the ex ante distribution of consumer values is the same as that ex post, the shape of the distributions may differ, generating a difference between the surplus each product can extract. If, for example, consumers differ only in ex ante disease risk, then a monopolist would have more difficulty extracting surplus with a preventive than with a treatment because treatment consumers, having contracted the disease, no longer differ in disease risk. We show that the ratio of preventive to treatment producer surplus can be arbitrarily small, in particular when the distribution of consumer values has a Zipf shape and the disease is rare. The firm’s bias toward treatments can be reversed, for example, if the source of private information is disease severity learned ex post. The difference between the producer surplus earned from the products can result in distorted R&D incentives; the deadweight loss from this distortion can be as large as the entire producer-surplus difference. Calibrations for HIV and heart attacks based on risk factors in the U.S. population suggest that the distribution of disease risk is sufficiently Zipf-similar to generate substantial differences between producer surplus from preventives and treatments. Empirically, we find that proxies for the Zipf-similarity of the disease-risk distribution are associated a significantly lower likelihood of vaccine development but not drug development.
Mammalian synthetic biology: emerging medical applications
Authors: Kis Zoltán , Pereira Hugo Sant'Ana , Homma Takayuki , Pedrigi Ryan M. , Krams Rob
Published: March 2015

In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes.
Multicomponent model of deformation and detachment of a biofilm under fluid flow
Authors: Tierra Giordano , Pavissich Juan P. , Nerenberg Robert , Xu Zhiliang , Alber Mark S.
Published: March 2015

A novel biofilm model is described which systemically couples bacteria, extracellular polymeric substances (EPS) and solvent phases in biofilm. This enables the study of contributions of rheology of individual phases to deformation of biofilm in response to fluid flow as well as interactions between different phases. The model, which is based on first and second laws of thermodynamics, is derived using an energetic variational approach and phase-field method. Phase-field coupling is used to model structural changes of a biofilm. A newly developed unconditionally energy-stable numerical splitting scheme is implemented for computing the numerical solution of the model efficiently. Model simulations predict biofilm cohesive failure for the flow velocity between

and

m s
−1
which is consistent with experiments. Simulations predict biofilm deformation resulting in the formation of streamers for EPS exhibiting a viscous-dominated mechanical response and the viscosity of EPS being less than

. Higher EPS viscosity provides biofilm with greater resistance to deformation and to removal by the flow. Moreover, simulations show that higher EPS elasticity yields the formation of streamers with complex geometries that are more prone to detachment. These model predictions are shown to be in qualitative agreement with experimental observations.
Social deprivation affects cooperative predator inspection in a cichlid fish
Authors: Hesse Saskia , Anaya-Rojas Jaime M. , Frommen Joachim G. , Thünken Timo
Published: March 2015

The social environment individuals are exposed to during ontogeny shapes social skills and social competence in group-living animals. Consequently, social deprivation has serious effects on behaviour and development in animals but little is known about its impact on cooperation. In this study, we examined the effect of social environment on cooperative predator inspection. Predator inspection behaviour is a complex behaviour, which is present in a variety of shoaling fish species. Often, two fish leave the safety of the group and inspect a potentially dangerous predator in order to gather information about the current predation risk. As predator inspection is highly risky, it is prone to conflicts and cheating. However, cooperation among individuals may reduce the individual predation risk. We investigated this complex social behaviour in juveniles of the cichlid fishPelvicachromis taeniatusthat were reared in two different social environments throughout development. Fish reared in a group inspected more often than isolation-reared fish and were more likely to cooperate, i.e. they conducted conjoint inspection of a predator. By contrast, isolation-reared fish were more likely to perform a single inspection without a companion. These results suggest an impairment of cooperative behaviour in isolation-reared fish most probably due to lack of social experience and resulting in lowered social skills needed in coordinated behaviour.
Taking a closer look: disentangling effects of functional diversity on ecosystem functions with a trait-based model across hierarchy and time
Authors: Holzwarth Frédéric , Rüger Nadja , Wirth Christian
Published: March 2015

Biodiversity and ecosystem functioning (BEF) research has progressed from the detection of relationships to elucidating their drivers and underlying mechanisms. In this context, replacing taxonomic predictors by trait-based measures of functional composition (FC)—bridging functions of species and of ecosystems—is a widely used approach. The inherent challenge of trait-based approaches is the multi-faceted, dynamic and hierarchical nature of trait influence: (i) traits may act via different facets of their distribution in a community, (ii) their influence may change over time and (iii) traits may influence processes at different levels of the natural hierarchy of organization. Here, we made use of the forest ecosystem model ‘LPJ-GUESS’ parametrized with empirical trait data, which creates output of individual performance, community assembly, stand-level states and processes. To address the three challenges, we resolved the dynamics of the top-level ecosystem function ‘annual biomass change’ hierarchically into its various component processes (growth, leaf and root turnover, recruitment and mortality) and states (stand structures, water stress) and traced the influence of different facets of FC along this hierarchy in a path analysis. We found an independent influence of functional richness, dissimilarity and identity on ecosystem states and processes and hence biomass change. Biodiversity effects were only positive during early succession and later turned negative. Unexpectedly, resource acquisition (growth, recruitment) and conservation (mortality, turnover) played an equally important role throughout the succession. These results add to a mechanistic understanding of biodiversity effects and place a caveat on simplistic approaches omitting hierarchical levels when analysing BEF relationships. They support the view that BEF relationships experience dramatic shifts over successional time that should be acknowledged in mechanistic theories.
Data-driven prognosis: a multi-physics approach verified via balloon burst experiment
Authors: Chandra Abhijit , Kar Oliva
Published: March 2015

A multi-physics formulation for data-driven prognosis (DDP) is developed. Unlike traditional predictive strategies that require controlled offline measurements or ‘training’ for determination of constitutive parameters to derive the transitional statistics, the proposed DDP algorithm relies solely on
in situ
measurements. It uses a deterministic mechanics framework, but the stochastic nature of the solution arises naturally from the underlying assumptions regarding the order of the conservation potential as well as the number of dimensions involved. The proposed DDP scheme is capable of predicting onset of instabilities. Because the need for offline testing (or training) is obviated, it can be easily implemented for systems where such
a priori
testing is difficult or even impossible to conduct. The prognosis capability is demonstrated here via a balloon burst experiment where the instability is predicted using only online visual observations. The DDP scheme never failed to predict the incipient failure, and no false-positives were issued. The DDP algorithm is applicable to other types of datasets. Time horizons of DDP predictions can be adjusted by using memory over different time windows. Thus, a big dataset can be parsed in time to make a range of predictions over varying time horizons.
Interconnections between various analytic approaches applicable to third-order nonlinear differential equations
Authors: Mohanasubha R. , Chandrasekar V. K. , Senthilvelan M. , Lakshmanan M.
Published: March 2015

We unearth the interconnection between various analytical methods which are widely used in the current literature to identify integrable nonlinear dynamical systems described by third-order nonlinear ODEs. We establish an important interconnection between the extended Prelle–Singer procedure and λ-symmetries approach applicable to third-order ODEs to bring out the various linkages associated with these different techniques. By establishing this interconnection we demonstrate that given any one of the quantities as a starting point in the family consisting of Jacobi last multipliers, Darboux polynomials, Lie point symmetries, adjoint-symmetries, λ-symmetries, integrating factors and null forms one can derive the rest of the quantities in this family in a straightforward and unambiguous manner. We also illustrate our findings with three specific examples.
Lactobacillus mixtipabuli sp. nov. isolated from total mixed ration silage
Authors: Tohno Masanori , Kitahara Maki , Irisawa Tomohiro , Ohmori Hideyuki , Masuda Takaharu , Ohkuma Moriya , Tajima Kiyoshi
Published: March 2015

Using a polyphasic taxonomic approach, we investigated three bacterial strains – IWT30T, IWT8 and IWT75 – isolated from total mixed ration silage prepared in Hachimantai, Iwate, Japan. The isolates comprised Gram-stain positive, non-motile, non-spore-forming, catalase-negative, rod-shaped bacteria. Good growth occurred at 15–45 °C and at pH 4.0–7.5. Their major cellular fatty acids were C18:1ω9c and C19:1 cyclo 9,10.The G+C content of genomic DNA of strain IWT30T was 44.6 mol%. Comparative 16S rRNA gene sequence analysis showed that these novel strains belonged to the genus Lactobacillus. These strains shared 100 % 16S rRNA gene sequence similarity and were most closely related to the type strains of Lactobacillus silagei, Lactobacillus odoratitofui, Lactobacillus similis, Lactobacillus collinoides, Lactobacillus paracollinoides and Lactobacillus kimchicus, with sequence similarity values of 99.5, 98.8, 98.7, 97.8, 97.8 and 96.8 %, respectively. The level of DNA–DNA relatedness between these strains and their closest phylogenetic neighbours was less than 30 %. On the basis of additional phylogenetic analysis of pheS and rpoA gene sequences and phenotypic and chemotaxonomic characteristics, we conclude that these three strains represent a novel species of the genus Lactobacillus, for which we propose the name Lactobacillus mixtipabuli sp. nov. The type strain is IWT30T ( = JCM 19805T = DSM 28580T).
Sphingobium phenoxybenzoativorans sp. nov., a 2-phenoxybenzoic-acid-degrading bacterium
Authors: Cai Shu , Shi Chao , Zhao Jia-Dong , Cao Qin , He Jian , Chen Li-Wei
Published: March 2015

A Gram-stain-negative, aerobic, yellow-pigmented, rod-shaped bacterium, designated strain SC_3T, was isolated from pesticide-contaminated soil sediment. The strain was able to mineralize 2-phenoxybenzoic acid. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain SC_3T formed a monophyletic lineage in the genus Sphingobium, and showed highest similarity to the type strains of Sphingobium abikonense (97.0 %), followed by Sphingobium lactosutens (96.8 %) and Sphingobium cloacae (96.7 %). The DNA–DNA relatedness between strain SC_3T and its closest phylogenetic neighbours was lower than 70 %. The major fatty acids (>5 % of the total) were summed feature 8 (comprising C18:1ω7c/C18:1ω6c), summed feature 3 (comprising C16:1ω7c/C16:1ω6c), C14:0 2-OH, C16:0 and C17:1ω6c. The predominant quinone was ubiquinone Q-10, and the major polyamine was spermidine. The polar lipid profile contained diphosphatidylglycerol (DPG), sphingoglycolipid (SGL), phosphatidylethanolamine (PDME), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylmonomethylethanolamine (PMME), an unknown aminolipid (AL), two unknown lipids (L1, L2) and several unknown phospholipids (PL1–6). The genomic DNA G+C content of strain SC_3T was 62.9 mol%. On the basis of phenotypic, chemotaxonomic, phylogenetic and genotypic data, strain SC_3T represents a novel species of the genus Sphingobium, for which the name Sphingobium phenoxybenzoativorans sp. nov. is proposed. The type strain is SC_3T ( = CCTCC AB 2014349T = KACC 42448T).
Methanobacterium aggregans sp. nov., a hydrogenotrophic methanogenic archaeon isolated from an anaerobic digester
Authors: Kern Tobias , Linge Mary , Rother Michael
Published: March 2015

A novel, strictly anaerobic, hydrogenotrophic methanogen, strain E09F.3T, was isolated from a commercial biogas plant in Germany. Cells of E09F.3Twere Gram-stain-negative, non-motile, slightly curved rods, long chains of which formed large aggregates consisting of intertwined bundles of chains. Cells utilized H2+CO2and, to a lesser extent, formate as substrates for growth and methanogenesis. The optimal growth temperature was around 40 °C; maximum growth rate was obtained at pH around 7.0 with approximately 6.8 mM NaCl. The DNA G+C content of strain E09F.3Twas 39.1 mol%. Phylogenetic analyses based on 16S rRNA andmcrAgene sequences placed strain E09F.3Twithin the genusMethanobacterium. On the basis of 16S rRNA gene sequence similarity, strain E09F.3Twas closely related toMethanobacterium congolenseCTbut morphological, physiological and genomic characteristics indicated that strain E09F.3Trepresents a novel species. The nameMethanobacterium aggreganssp. nov. is proposed for this novel species, with strain E09F.3T( = DSM 29428T = JCM 30569T) as the type strain.
Threshold trait architecture of Hsp90-buffered variation
Authors: Carey Charles C. , Gorman Kristen , Howsmon Becky , Aragaki Aaron K. , Kooperberg Charles , Rutherford Suzannah
Published: March 2015

Common genetic variants buffered by Hsp90 are candidates for human diseases of signaling such as cancer. Like cancer, morphological abnormalities buffered by Hsp90 are discrete threshold traits with a continuous underlying basis of liability determining their probability of occurrence. QTL and deletion maps for one of the most frequent Hsp90-dependent abnormalities in Drosophila, deformed eye (dfe), were replicated across three genetically related artificial selection lines using strategies dependent on proximity to thedfethreshold and the direction of genetic and environmental effects. Up to 17dfeloci (QTL) linked by 7 interactions were detected based on the ability of small recombinant regions of an unaffected and completely homozygous control genotype to dominantly suppress or enhancedfepenetrance at its threshold in groups of isogenic recombinant flies, and over 20 deletions increaseddfepenetrance from a low expected value in one or more line, identifying a complex network of genes responsible for thedfephenotype. Replicated comparisons of these whole-genome mapping approaches identified several QTL regions narrowly defined by deletions and 4 candidate genes, with additional uncorrelated QTL and deletions highlighting differences between the approaches and the need for caution in attributing the effect of deletions directly to QTL genes.
Adaptation, Clonal Interference, and Frequency-Dependent Interactions in a Long-Term Evolution Experiment withEscherichia coli
Authors: Maddamsetti Rohan , Lenski Richard E. , Barrick Jeffrey E.
Published: March 2015

Twelve replicate populations ofEscherichia colihave been evolving in the laboratory for more than 25 years and 60,000 generations. We analyzed bacteria from whole-population samples frozen every 500 generations through 20,000 generations for one well-studied population, called Ara-1. By tracking 42 known mutations in these samples, we reconstructed the history of this population’s genotypic evolution over this period. The evolutionary dynamics of Ara-1 show strong evidence of selective sweeps as well as clonal interference between competing lineages bearing different beneficial mutations. In some cases, sets of several mutations approached fixation simultaneously, often conveying no information about their order of origination; we present several possible explanations for the existence of these mutational cohorts. Against a backdrop of rapid selective sweeps both earlier and later, we found that two clades coexisted for over 6000 generations before one drove the other extinct. In that time, at least nine mutations arose in the clade that prevailed. We found evidence that the clades evolved a frequency-dependent interaction, which prevented the competitive exclusion of either clade, but which eventually collapsed as beneficial mutations accumulated in the clade that prevailed. Clonal interference and frequency dependence can occur even in the simplest microbial populations. Furthermore, frequency dependence may generate dynamics that extend the period of coexistence that would otherwise be sustained by clonal interference alone.
Interventional Nerve Visualization via the Intrinsic Anisotropic Optical Properties of the Nerves
Authors: Chin Kenneth W.T.K. , Meijerink Andries , Chin Patrick T.K.
Published: March 2015

We present an optical concept to visualize nerves during surgical interventions. The concept relies on the anisotropic optical properties of the nerves which allows for specific switching of the optical reflection by the nervous-tissue. Using a low magnification polarized imaging system we are able to visualize the on and off switching of the optical reflection of the nervous-tissue, enabling a non-invasive nerve specific real-time nerve visualization during surgery.
Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing
Authors: Garelli Andres , Heredia Fabiana , Casimiro Andreia P. , Macedo Andre , Nunes Catarina , Garcez Marcia , Mantas Dias Angela R. , Volonte Yanel A. , Koyama Takashi , Gontijo Alisson M.
Published: March 2015

How different organs in the body sense growth perturbations in distant tissues to coordinate their size during development is poorly understood. Here, we mutated an invertebrate orphan relaxin receptor, theDrosophila Lgr3, and found body asymmetries similar to those found in insulin/relaxin-like peptide 8 (dilp8) mutants, which fail to coordinate growth with developmental timing. Indeed, mutation or RNAi againstLgr3suppresses the delay in pupariation induced by imaginal disc growth perturbation or ectopic Dilp8 expression. By fluorescently-tagging the endogenous Lgr3 protein and performing CNS-specific RNAi, we find that Lgr3 is expressed and required in a novel subset of CNS neurons to transmit the peripheral tissue stress signal, Dilp8, to the neuroendocrine centers controlling developmental timing. Our work sheds new light on the function and evolution of relaxin receptors and reveals a novel neuroendocrine circuit responsive to growth aberrations.
Parental Age Affects Somatic Mutation Rates in the Progeny of Flowering Plants
Authors: Singh Amit Kumar , Bashir Tufail , Sailer Christian , Gurumoorthy Viswanathan , Ramakrishnan Anantha Maharasi , Dhanapal Shanmuhapreya , Grossniklaus Ueli , Baskar Ramamurthy
Published: March 2015

In humans, it is well known that the parental reproductive age has a strong influence on mutations transmitted to their progeny. Meiotic nondisjunction is known to increase in older mothers, and base substitutions tend to go up with paternal reproductive age. Hence, it is clear that the germinal mutation rates are a function of both maternal and paternal ages in humans. In contrast, it is unknown whether the parental reproductive age has an effect on somatic mutation rates in the progeny, because these are rare and difficult to detect. To address this question, we took advantage of the plant model system Arabidopsis (Arabidopsis thaliana), where mutation detector lines allow for an easy quantitation of somatic mutations, to test the effect of parental age on somatic mutation rates in the progeny. Although we found no significant effect of parental age on base substitutions, we found that frameshift mutations and transposition events increased in the progeny of older parents, an effect that is stronger through the maternal line. In contrast, intrachromosomal recombination events in the progeny decrease with the age of the parents in a parent-of-origin-dependent manner. Our results clearly show that parental reproductive age affects somatic mutation rates in the progeny and, thus, that some form of age-dependent information, which affects the frequency of double-strand breaks and possibly other processes involved in maintaining genome integrity, is transmitted through the gametes.
Integrating BIM and augmented reality for interactive architectural visualisation
Authors: Wang Jun , Wang Xiangyu , Shou Wenchi , Xu Bo
Published: March 2015

Purpose

– The purpose of this research is to investigate a new approach with its supporting building information modelling (BIM) + augmented reality (AR) tool to enhance architectural visualisation in building life cycle. Traditional approaches to visualise architectural design concentrate on static pictures or three-dimensional (3D) scale models which cause problems, such as expensive design evolution, lack of stakeholders’ communication and limited reusability. The 3D animated fly-throughs still occur on a computer screen in two-dimensions and seem cold and mechanical, unless done with advanced production software.

Design/methodology/approach

– The method of this research included case study and interview. It was, first, stated, from the building process perspective, how the BIM + AR for Architectural Visualisation System (BAAVS) was realised by integrating two types of visualisation techniques: BIM and AR, and four stages of building life cycle. Then the paper demonstrated four case studies to validate the BAAVS. Finally, four interviews were made with each case manager and team members to collect feedback on utilising BAAVS technology. Questions were asked in the areas of benefits, drawbacks and technical limitations with respect to BAAVS.

Findings

– Feedback from the stakeholders involved in the four cases indicated that BAAVS was useful and efficient to visualise architectural design and communicate with each other.

Originality/value

– This paper demonstrates BAAVS that integrated BIM and AR into architectural visualisation. The system supports an innovative performance that allows: designers to put virtual building scheme in physical environment; owners to gain an immersive and interactive experience; and property sellers to communicate with customers efficiently.