bluuebunny/crossref_metadata_2025 huggingface dataset:
Proprioceptive feedback determines visuomotor gain inDrosophila
Authors: Bartussek Jan , Lehmann Fritz-Olaf
Published: January 2016

Multisensory integration is a prerequisite for effective locomotor control in most animals. Especially, the impressive aerial performance of insects relies on rapid and precise integration of multiple sensory modalities that provide feedback on different time scales. In flies, continuous visual signalling from the compound eyes is fused with phasic proprioceptive feedback to ensure precise neural activation of wing steering muscles (WSM) within narrow temporal phase bands of the stroke cycle. This phase-locked activation relies on mechanoreceptors distributed over wings and gyroscopic halteres. Here we investigate visual steering performance of tethered flying fruit flies with reduced haltere and wing feedback signalling. Using a flight simulator, we evaluated visual object fixation behaviour, optomotor altitude control and saccadic escape reflexes. The behavioural assays show an antagonistic effect of wing and haltere signalling on visuomotor gain during flight. Compared with controls, suppression of haltere feedback attenuates while suppression of wing feedback enhances the animal’s wing steering range. Our results suggest that the generation of motor commands owing to visual perception is dynamically controlled by proprioception. We outline a potential physiological mechanism based on the biomechanical properties of WSM and sensory integration processes at the level of motoneurons. Collectively, the findings contribute to our general understanding how moving animals integrate sensory information with dynamically changing temporal structure.
Spinel–rock salt transformation in LiCoMnO

4−
δ
Authors: Reeves-McLaren Nik , Sharp Joanne , Beltrán-Mir Héctor , Rainforth W. Mark , West Anthony R.
Published: January 2016

The transformation on heating LiCoMnO
4
, with a spinel structure, to LiCoMnO
3
, with a cation-disordered rock salt structure, accompanied by loss of 25% of the oxygen, has been followed using a combination of diffraction, microscopy and spectroscopy techniques. The transformation does not proceed by a topotactic mechanism, even though the spinel and rock salt phases have a similar, cubic close-packed oxygen sublattice. Instead, the transformation passes through two stages involving, first, precipitation of Li
2
MnO
3
, leaving behind a Li-deficient, Co-rich non-stoichiometric spinel and, second, rehomogenization of the two-phase assemblage, accompanied by additional oxygen loss, to give the homogeneous rock salt final product; a combination of electron energy loss spectroscopy and X-ray absorption near edge structure analyses showed oxidation states of Co
2+
and Mn
3+
in LiCoMnO
3
. Subsolidus phase diagram determination of the Li
2
O-CoO

x

-MnO

y

system has established the compositional extent of spinel solid solutions at approximately 500°C.
Geometric methods for optimal sensor design
Authors: Belabbas M.-A.
Published: January 2016

The Kalman–Bucy filter is the optimal estimator of the state of a linear dynamical system from sensor measurements. Because its performance is limited by the sensors to which it is paired, it is natural to seek optimal sensors. The resulting optimization problem is however non-convex. Therefore, many ad hoc methods have been used over the years to design sensors in fields ranging from engineering to biology to economics. We show in this paper how to obtain optimal sensors for the Kalman filter. Precisely, we provide a structural equation that characterizes optimal sensors. We furthermore provide a gradient algorithm and prove its convergence to the optimal sensor. This optimal sensor yields the lowest possible estimation error for measurements with a fixed signal-to-noise ratio. The results of the paper are proved by reducing the optimal sensor problem to an optimization problem on a Grassmannian manifold and proving that the function to be minimized is a Morse function with a unique minimum. The results presented here also apply to the dual problem of optimal actuator design.
Tuned resonant mass or inerter-based absorbers: unified calibration with quasi-dynamic flexibility and inertia correction
Authors: Krenk Steen , Høgsberg Jan
Published: January 2016

A common format is developed for a mass and an inerter-based resonant vibration absorber device, operating on the absolute motion and the relative motion at the location of the device, respectively. When using a resonant absorber a specific mode is targeted, but in the calibration of the device it may be important to include the effect of other non-resonant modes. The classic concept of a quasi-static correction term is here generalized to a quasi-dynamic correction with a background inertia term as well as a flexibility term. An explicit design procedure is developed, in which the background effects are included via a flexibility and an inertia coefficient, accounting for the effect of the non-resonant modes. The design procedure starts from a selected level of dynamic amplification and then determines the device parameters for an equivalent dynamic system, in which the background flexibility and inertia effects are introduced subsequently. The inclusion of background effect of the non-resonant modes leads to larger mass, stiffness and damping parameter of the device. Examples illustrate the relation between resonant absorbers based on a tuned mass or a tuned inerter element, and demonstrate the ability to attain balanced calibration of resonant absorbers also for higher modes.
Colony pace: a life-history trait affecting social insect epidemiology
Authors: Buechel Séverine Denise , Schmid-Hempel Paul
Published: January 2016

Among colonies of social insects, the worker turnover rate (colony ‘pace’) typically shows considerable variation. This has epidemiological consequences for parasites, because in ‘fast-paced’ colonies, with short-lived workers, the time of parasite residence in a given host will be reduced, and further transmission may thus get less likely. Here, we test this idea and ask whether pace is a life-history strategy against infectious parasites. We infected bumblebees (Bombus terrestris) with the infectious gut parasiteCrithidia bombi, and experimentally manipulated birth and death rates to mimic slow and fast pace. We found that fewer workers and, importantly, fewer last-generation workers that are responsible for rearing sexuals were infected in colonies with faster pace. This translates into increased fitness in fast-paced colonies, as daughter queens exposed to fewer infected workers in the nest are less likely to become infected themselves, and have a higher chance of founding their own colonies in the next year. High worker turnover rate can thus act as a strategy of defence against a spreading infection in social insect colonies.
Moa diet fits the bill: virtual reconstruction incorporating mummified remains and prediction of biomechanical performance in avian giants
Authors: Attard Marie R. G. , Wilson Laura A. B. , Worthy Trevor H. , Scofield Paul , Johnston Peter , Parr William C. H. , Wroe Stephen
Published: January 2016

The moa (Dinornithiformes) are large to gigantic extinct terrestrial birds of New Zealand. Knowledge about niche partitioning, feeding mode and preference among moa species is limited, hampering palaeoecological reconstruction and evaluation of the impacts of their extinction on remnant native biota, or the viability of exotic species as proposed ecological ‘surrogates'. Here we apply three-dimensional finite-element analysis to compare the biomechanical performance of skulls from five of the six moa genera, and two extant ratites, to predict the range of moa feeding behaviours relative to each other and to living relatives. Mechanical performance during biting was compared using simulations of the birds clipping twigs based on muscle reconstruction of mummified moa remains. Other simulated food acquisition strategies included lateral shaking, pullback and dorsoventral movement of the skull. We found evidence for limited overlap in biomechanical performance between the extant emu (Dromaius novaehollandiae) and extinct upland moa (Megalapteryx didinus) based on similarities in mandibular stress distribution in two loading cases, but overall our findings suggest that moa species exploited their habitats in different ways, relative to both each other and extant ratites. The broad range of feeding strategies used by moa, as inferred from interspecific differences in biomechanical performance of the skull, provides insight into mechanisms that facilitated high diversities of these avian herbivores in prehistoric New Zealand.
Evolutionary origins of germline segregation in Metazoa: evidence for a germ stem cell lineage in the coralOrbicella faveolata(Cnidaria, Anthozoa)
Authors: Barfield Sarah , Aglyamova Galina V. , Matz Mikhail V.
Published: January 2016

The ability to segregate a committed germ stem cell (GSC) lineage distinct from somatic cell lineages is a characteristic of bilaterian Metazoans. However, the occurrence of GSC lineage specification in basally branching Metazoan phyla, such as Cnidaria, is uncertain. Without an independently segregated GSC lineage, germ cells and their precursors must be specified throughout adulthood from continuously dividing somatic stem cells, generating the risk of propagating somatic mutations within the individual and its gametes. To address the potential for existence of a GSC lineage in Anthozoa, the sister-group to all remaining Cnidaria, we identified moderate- to high-frequency somatic mutations and their potential for gametic transfer in the long-lived coralOrbicella faveolata(Anthozoa, Cnidaria) using a 2b-RAD sequencing approach. Our results demonstrate that somatic mutations can drift to high frequencies (up to 50%) and can also generate substantial intracolonial genetic diversity. However, these somatic mutations are not transferable to gametes, signifying the potential for an independently segregated GSC lineage inO. faveolata.In conjunction with previous research on germ cell development in other basally branching Metazoan species, our results suggest that the GSC system may be a Eumetazoan characteristic that evolved in association with the emergence of greater complexity in animal body plan organization and greater specificity of stem cell functions.
Heritable variation in heat shock gene expression: a potential mechanism for adaptation to thermal stress in embryos of sea turtles
Authors: Tedeschi J. N. , Kennington W. J. , Tomkins J. L. , Berry O. , Whiting S. , Meekan M. G. , Mitchell N. J.
Published: January 2016

The capacity of species to respond adaptively to warming temperatures will be key to their survival in the Anthropocene. The embryos of egg-laying species such as sea turtles have limited behavioural means for avoiding high nest temperatures, and responses at the physiological level may be critical to coping with predicted global temperature increases. Using the loggerhead sea turtle (
Caretta caretta
) as a model, we used quantitative PCR to characterise variation in the expression response of heat-shock genes (
hsp60, hsp70
and
hsp90;
molecular chaperones involved in cellular stress response) to an acute non-lethal heat shock. We show significant variation in gene expression at the clutch and population levels for some, but not all
hsp
genes. Using pedigree information, we estimated heritabilities of the expression response of
hsp
genes to heat shock and demonstrated both maternal and additive genetic effects. This is the first evidence that the heat-shock response is heritable in sea turtles and operates at the embryonic stage in any reptile. The presence of heritable variation in the expression of key thermotolerance genes is necessary for sea turtles to adapt at a molecular level to warming incubation environments.
Fitness costs of worker specialization for ant societies
Authors: Jongepier Evelien , Foitzik Susanne
Published: January 2016

Division of labour is of fundamental importance for the success of societies, yet little is known about how individual specialization affects the fitness of the group as a whole. While specialized workers may be more efficient in the tasks they perform than generalists, they may also lack the flexibility to respond to rapid shifts in task needs. Such rigidity could impose fitness costs when societies face dynamic and unpredictable events, such as an attack by socially parasitic slavemakers. Here, we experimentally assess the colony-level fitness consequences of behavioural specialization in
Temnothorax longispinosus
ants that are attacked by the slavemaker ant
T. americanus
. We manipulated the social organization of 102
T. longispinosus
colonies, based on the behavioural responses of all 3842 workers. We find that strict specialization is disadvantageous for a colony's annual reproduction and growth during slave raids. These fitness costs may favour generalist strategies in dynamic environments, as we also demonstrate that societies exposed to slavemakers in the field show a lower degree of specialization than those originating from slavemaker-free populations. Our findings provide an explanation for the ubiquity of generalists and highlight their importance for the flexibility and functional robustness of entire societies.
Diversity and evolution of the primate skin microbiome
Authors: Council Sarah E. , Savage Amy M. , Urban Julie M. , Ehlers Megan E. , Skene J. H. Pate , Platt Michael L. , Dunn Robert R. , Horvath Julie E.
Published: January 2016

Skin microbes play a role in human body odour, health and disease. Compared with gut microbes, we know little about the changes in the composition of skin microbes in response to evolutionary changes in hosts, or more recent behavioural and cultural changes in humans. No studies have used sequence-based approaches to consider the skin microbe communities of gorillas and chimpanzees, for example. Comparison of the microbial associates of non-human primates with those of humans offers unique insights into both the ancient and modern features of our skin-associated microbes. Here we describe the microbes found on the skin of humans, chimpanzees, gorillas, rhesus macaques and baboons. We focus on the bacterial and archaeal residents in the axilla using high-throughput sequencing of the 16S rRNA gene. We find that human skin microbial communities are unique relative to those of other primates, in terms of both their diversity and their composition. These differences appear to reflect both ancient shifts during millions of years of primate evolution and more recent changes due to modern hygiene.
Mammalian development does not recapitulate suspected key transformations in the evolutionary detachment of the mammalian middle ear
Authors: Ramírez-Chaves Héctor E. , Wroe Stephen W. , Selwood Lynne , Hinds Lyn A. , Leigh Chris , Koyabu Daisuke , Kardjilov Nikolay , Weisbecker Vera
Published: January 2016

The ectotympanic, malleus and incus of the developing mammalian middle ear (ME) are initially attached to the dentary via Meckel's cartilage, betraying their origins from the primary jaw joint of land vertebrates. This recapitulation has prompted mostly unquantified suggestions that several suspected—but similarly unquantified—key evolutionary transformations leading to the mammalian ME are recapitulated in development, through negative allometry and posterior/medial displacement of ME bones relative to the jaw joint. Here we show, using µCT reconstructions, that neither allometric nor topological change is quantifiable in the pre-detachment ME development of six marsupials and two monotremes. Also, differential ME positioning in the two monotreme species is not recapitulated. This challenges the developmental prerequisites of widely cited evolutionary scenarios of definitive mammalian middle ear (DMME) evolution, highlighting the requirement for further fossil evidence to test these hypotheses. Possible association between rear molar eruption, full ME ossification and ME detachment in marsupials suggests functional divergence between dentary and ME as a trigger for developmental, and possibly also evolutionary, ME detachment. The stable positioning of the dentary and ME supports suggestions that a ‘partial mammalian middle ear’ as found in many mammaliaforms—probably with a cartilaginous Meckel's cartilage—represents the only developmentally plausible evolutionary DMME precursor.
Presence of a loner strain maintains cooperation and diversity in well-mixed bacterial communities
Authors: Inglis R. F. , Biernaskie J. M. , Gardner A. , Kümmerli R.
Published: January 2016

Cooperation and diversity abound in nature despite cooperators risking exploitation from defectors and superior competitors displacing weaker ones. Understanding the persistence of cooperation and diversity is therefore a major problem for evolutionary ecology, especially in the context of well-mixed populations, where the potential for exploitation and displacement is greatest. Here, we demonstrate that a ‘loner effect’, described by economic game theorists, can maintain cooperation and diversity in real-world biological settings. We use mathematical models of public-good-producing bacteria to show that the presence of a loner strain, which produces an independent but relatively inefficient good, can lead to rock–paper–scissor dynamics, whereby cooperators outcompete loners, defectors outcompete cooperators and loners outcompete defectors. These model predictions are supported by our observations of evolutionary dynamics in well-mixed experimental communities of the bacteriumPseudomonas aeruginosa. We find that the coexistence of cooperators and defectors that produce and exploit, respectively, the iron-scavenging siderophore pyoverdine, is stabilized by the presence of loners with an independent iron-uptake mechanism. Our results establish the loner effect as a simple and general driver of cooperation and diversity in environments that would otherwise favour defection and the erosion of diversity.
Assessing Variations in Areal Organization for the Intrinsic Brain: From Fingerprints to Reliability
Authors: Xu Ting , Opitz Alexander , Craddock R. Cameron , Wright Margaret , Zuo Xi-Nian , Milham Michael P.
Published: January 2016

Resting state fMRI (R-fMRI) is a powerful in-vivo tool for examining the functional architecture of the human brain. Recent studies have demonstrated the ability to characterize transitions between functionally distinct cortical areas through the mapping of gradients in intrinsic functional connectivity (iFC) profiles. To date, this novel approach has primarily been applied to iFC profiles averaged across groups of individuals, or in one case, a single individual scanned multiple times. Here, we used a publically available R-fMRI dataset, in which 30 healthy participants were scanned 10 times (10 minutes per session), to investigate differences in full-brain transition profiles (i.e., gradient maps, edge maps) across individuals, and their reliability. 10-minute R-fMRI scans were sufficient to achieve high accuracies in efforts to “fingerprint” individuals based upon full-brain transition profiles. Regarding testretest reliability, the image-wise intraclass correlation coefficient (ICC) was moderate, and vertex-level ICC varied depending on region; larger durations of data yielded higher reliability scores universally. Initial application of gradient-based methodologies to a recently published dataset obtained from twins suggested inter-individual variation in areal profiles might have genetic and familial origins. Overall, these results illustrate the utility of gradient-based iFC approaches for studying inter-individual variation in brain function.
Engineered acetoacetate-inducible whole-cell biosensors based on the AtoSC two-component system
Authors: Rutter Jack W. , Dekker Linda , Fedorec Alex J. H. , Gonzales David T. , Wen Ke Yan , Tanner Lewis E. S. , Donovan Emma , Ozdemir Tanel , Thomas Geraint , Barnes Chris P.
Published: January 2016

Whole-cell biosensors hold potential in a variety of industrial, medical and environmental applications. These biosensors can be constructed through the repurposing of bacterial sensing mechanisms, including the common two-component system. Here we report on the construction of a range of novel biosensors that are sensitive to acetoacetate, a molecule that plays a number of roles in human health and biology. These biosensors are based on the AtoSC two-component system. An ODE model to describe the action of the AtoSC two-component system was developed and sensitivity analysis of this model used to help inform biosensor design. The final collection of biosensors constructed displayed a range of switching behaviours, at physiologically relevant acetoacetate concentrations and can operate in severalEscherichia colihost strains. It is envisaged that these biosensor strains will offer an alternative to currently available commercial strip tests and, in future, may be adopted for more complexin vivoor industrial monitoring applications.
Identification of the ventral occipital visual field maps in the human brain
Authors: Winawer Jonathan , Witthoft Nathan
Published: January 2016

The location and topography of the first three visual field maps in the human brain, V1-V3, are well agreed upon and routinely measured across most laboratories. The position of 4thvisual field map, ‘hV4’, is identified with less consistency in the neuroimaging literature. Using magnetic resonance imaging (MRI) data, we describe landmarks to help identify the position and borders of hV4. The data consist of anatomical images, visualized as cortical meshes to highlight the sulcal and gyral patterns, and functional data obtained from retinotopic mapping experiments, visualized as eccentricity and angle maps on the cortical surface.

Several features of the functional and anatomical data can be found across nearly all subjects and are helpful for identifying the location and extent of the hV4 map. The medial border of hV4 is shared with the posterior, ventral portion of V3, and is marked by a retinotopic representation of the upper vertical meridian. The anterior border of hV4 is shared with the VO-1 map, and falls on a retinotopic representation of the peripheral visual field, usually coincident with the posterior transverse collateral sulcus. The ventro-lateral edge of the map typically falls on the inferior occipital gyrus, where functional MRI artifacts often obscure the retinotopic data. Finally, we demonstrate the continuity of retinotopic parameters between hV4 and its neighbors; hV4 and V3v contain iso-eccentricity lines in register, whereas hV4 and VO-1 contain iso-polar angle lines in register.

Together, the multiple constraints allow for a consistent identification of the hV4 map across most human subjects.
Comparative evaluation of the genomes of common bacterial members of theDrosophilaintestinal community
Authors: Petkau Kristina , Fast David , Duggal Aashna , Foley Edan
Published: January 2016

Drosophila melanogasteris an excellent model to explore the molecular exchanges that occur between an animal intestine and their microbial passengers. For example, groundbreaking studies in flies uncovered a sophisticated web of host responses to intestinal bacteria. The outcomes of these responses define critical events in the host, such as the establishment of immune responses, access to nutrients, and the rate of larval development. Despite our steady march towards illuminating the host machinery that responds to bacterial presence in the gut, we know remarkably little about the microbial products that influence bacterial association with a fly host. To address this deficiency, we sequenced and characterized the genomes of three commonDrosophila-associated microbes:Lactobacillus plantarum, Lactobacillus brevisandAcetobacter pasteurianus. In each case, we compared the genomes ofDrosophila-associated strains to the genomes of strains isolated from alternative sources. This approach allowed us to identify molecular functions common toDrosophila-associated microbes, and, in the case ofA. pasteurianus, to identify genes that are essential for association with the host. Of note, many of the gene products unique to fly-associated strains have established roles in the stabilization of host-microbe interactions. We believe that these data provide a valuable starting point for a more thorough examination of the microbial perspective on host-microbe relationships.
Reverse signaling by Semaphorin-6A regulates cellular aggregation and neuronal morphology
Authors: Perez-Branguli Francesc , Zagar Yvrick , Shanley Daniel K. , Graef Isabella A. , Chédotal Alain , Mitchell Kevin J.
Published: January 2016

The transmembrane semaphorin, Sema6A, has important roles in axon guidance, cell migration and neuronal connectivity in multiple regions of the nervous system, mediated by context-dependent interactions with plexin receptors, PlxnA2 and PlxnA4. Here, we demonstrate that Sema6A can also signal cell-autonomously, in two modes, constitutively, or in response to higher-order clustering mediated by either PlxnA2-binding or chemically induced multimerisation. Sema6A activation stimulates recruitment of Abl to the cytoplasmic domain of Sema6A and phosphorylation of this cytoplasmic tyrosine kinase, as well as phosphorylation of additional cytoskeletal regulators. Sema6A reverse signaling affects the surface area and cellular complexity of non-neuronal cells and aggregation and neurite formation of primary neuronsin vitro. Sema6A also interacts with PlxnA2 incis, which reduces binding by PlxnA2 of Sema6Ain transbut not vice versa. These experiments reveal the complex nature of Sema6A biochemical functions and the molecular logic of the context-dependent interactions between Sema6A and PlxnA2.
Canvas: versatile and scalable detection of copy number variants
Authors: Roller Eric , Ivakhno Sergii , Lee Steve , Royce Thomas , Tanner Stephen
Published: January 2016

Motivation: Increased throughput and diverse experimental designs of large-scale sequencing studies necessi-tate versatile, scalable and robust variant calling tools. In particular, identification of copy number changes re-mains a challenging task due to their complexity, susceptibility to sequencing biases, variation in coverage data and dependence on genome-wide sample properties, such as tumor polyploidy or polyclonality in cancer samples.

Results: We have developed a new tool, Canvas, for identification of copy number changes from diverse se-quencing experiments including whole-genome matched tumor-normal and single-sample normal re-sequencing, as well as whole-exome matched and unmatched tumor-normal studies. In addition to variant calling, Canvas infers genome-wide parameters such as cancer ploidy, purity and heterogeneity. It provides fast and simple to execute workflows that can scale to thousands of samples and can be easily incorporated into existing variant calling pipelines.

Availability: Canvas is distributed under an open source license and can be downloaded fromhttps://github.com/Illumina/canvas.

Contact:eroller@illumina.com

Supplementary information: Supplementary data are available atBioinformaticsonline.
Local opposite orientation preferences in V1: fMRI sensitivity to fine-grained pattern information
Authors: Alink Arjen , Walther Alexander , Krugliak Alexandra , Kriegeskorte Nikolaus
Published: January 2016

The orientation of a visual grating can be decoded from human primary visual cortex (V1) using functional magnetic resonance imaging (fMRI) at conventional resolutions (2-3 mm voxel width, 3T scanner). It is unclear to what extent this information originates from different spatial scales of neuronal selectivity, ranging from orientation columns to global areal maps. According to the global-areal-map account, fMRI orientation decoding relies exclusively on fMRI voxels in V1 exhibiting a radial or vertical preference. Here we show, by contrast, that 2-mm isotropic voxels in a small patch of V1 within a quarterfield representation exhibit reliable opposite selectivities. Sets of voxels with opposite selectivities are locally intermingled and each set can support orientation decoding. This indicates that global areal maps cannot fully account for orientation information in fMRI and demonstrates that fMRI also reflects fine-grained patterns of neuronal selectivity.

Significance statement

Conventional (3T)functional magnetic resonance imaging (fMRI) allows one measure brain activity at a spatial resolution of 2-3 mm. Brain response patterns in the primary visual cortex (V1) measured with fMRI have been shown to contain robust information about the orientation of visual grating stimuli. However, it is unclear whether this information arises only from global-areal patterns or also from more fine-grained patterns. Here we show that opposite orientation preferences are present and replicable within small V1 patches. This finding demonstrates that fine-grained fMRI patterns contribute to the orientation information present in fMRI data.
Identification and characterization of long non-coding RNAs as targets of mammary tumor cell proliferation and migration
Authors: Diermeier Sarah D. , Chang Kung-Chi , Freier Susan M. , Song Junyan , Krasnitz Alexander , Rigo Frank , Bennett C. Frank , Spector David
Published: January 2016

Recent genome-wide studies revealed that as much as 80% of the human genome can be transcribed whereas only 2% of this RNA is translated into proteins. Non-coding transcripts can be subdivided into several groups, with long non-coding RNAs (lncRNAs) representing the largest and most diverse class. With breast cancer being the most frequent malignancy in women worldwide, we set out to investigate the potential of lncRNAs as novel therapeutic targets. By performing RNA-Seq on tumor sections and mammary organoids from MMTV-PyMT and MMTV-Neu-NDL mice, modeling the luminal B and HER2/neu-amplified subtypes of human breast cancer respectively, we generated a comprehensive catalog of differentially expressed lncRNAs. We identified several hundred potentially oncogenic lncRNAs that were over-expressed in a subtype-specific manner as well as numerous lncRNAs up-regulated in both models. Among these lncRNA we defined a subset of 30 previously uncharacterized lncRNAs as Mammary Tumor Associated RNAs (MaTARs) and we identified human orthologs. We functionally validated the role of these MaTARs by antisense oligonucleotide (ASO) mediated knockdown in primary mammary tumor cells and 3Dex vivoorganoids. Upon independent knockdown of 15 MaTARs, we observed significantly reduced cell proliferation, invasion and/or collective cell migration in a cancer-specific context. Thus, MaTARs are likely key drivers of mammary tumor progression and/or metastasis and represent promising new therapeutic targets.
Evaluation of TagSeq, a reliable low-cost alternative for RNAseq
Authors: Lohman Brian K , Weber Jesse N , Bolnick Daniel I
Published: January 2016

RNAseq is a relatively new tool for ecological genetics that offers researchers insight into changes in gene expression in response to a myriad of natural or experimental conditions. However, standard RNAseq methods (e.g., Illumina TruSeq®or NEBNext®) can be cost prohibitive, especially when study designs require large sample sizes. Consequently, RNAseq is often underused as a method, or is applied to small sample sizes that confer poor statistical power. Low cost RNAseq methods could therefore enable far greater and more powerful applications of transcriptomics in ecological genetics and beyond. Standard mRNAseq is costly partly because one sequences portions of the full length of all transcripts. Such whole-mRNA data is redundant for estimates of relative gene expression. TagSeq is an alternative method that focuses sequencing effort on mRNAs 3-prime end, thereby reducing the necessary sequencing depth per sample, and thus cost. Here we present a revised TagSeq protocol, and compare its performance against NEBNext®, the gold-standard whole mRNAseq method. We built both TagSeq and NEBNext®libraries from the same biological samples, each spiked with control RNAs. We found that TagSeq measured the control RNA distribution more accurately than NEBNext®, for a fraction of the cost per sample (∽10%). The higher accuracy of TagSeq was particularly apparent for transcripts of moderate to low abundance. Technical replicates of TagSeq libraries are highly correlated, and were correlated with NEBNext®results. Overall, we show that our modified TagSeq protocol is an efficient alternative to traditional whole mRNAseq, offering researchers comparable data at greatly reduced cost.
Cell Assembly Dynamics of Sparsely-connected Inhibitory Networks: a Simple Model for the Collective Activity of Striatal Projection Neurons
Authors: Angulo-Garcia David , Berke Joshua D. , Torcini Alessandro
Published: January 2016

Striatal projection neurons form a sparsely-connected inhibitory network, and this arrangement may be essential for the appropriate temporal organization of behavior. Here we show that a simplified, sparse inhibitory network of Leaky-Integrate-and-Fire neurons can reproduce some key features of striatal population activity, as observed in brain slices. In particular we develop a new metric to determine the conditions under which sparse inhibitory networks form anti-correlated cell assemblies with time-varying activity of individual cells. We find that under these conditions the network displays an input-specific sequence of cell assembly switching, that effectively discriminates similar inputs. Our results support the proposal that GABAergic connections between striatal projection neurons allow stimulus-selective, temporally-extended sequential activation of cell assemblies. Furthermore, we help to show how altered intrastriatal GABAergic signaling may produce aberrant network-level information processing in disorders such as Parkinson’s and Huntington’s diseases.

Author Summary

Neuronal networks that are loosely coupled by inhibitory connections can exhibit potentially useful properties. These include the ability to produce slowly-changing activity patterns, that could be important for organizing actions and thoughts over time. The striatum is a major brain structure that is critical for appropriately timing behavior to receive rewards. Striatal projection neurons have loose inhibitory interconnections, and here we show that even a highly simplified model of this striatal network is capable of producing slowly-changing activity sequences. We examine some key parameters important for producing these dynamics, and help explain how changes in striatal connectivity may contribute to serious human disorders including Parkinson’s and Huntington’s diseases.
Assembly of ZnIIand CdIIcoordination polymers based on a flexible multicarboxylate ligand and nitrogen-containing auxiliary ligands through a mixed-ligand synthetic strategy: syntheses, structures and fluorescence properties
Authors: Lu Ji-Tao , Meng Dan-Dan , Meng Qing-Guo
Published: January 2016

The structures of coordination polymers are strongly influenced by the organic ligands and metal ions used for their construction, so it is important to choose suitable ligands and metal ions and appropriate synthetic processes. Two noveld10coordination polymers, namely poly[[diaquabis(2,2′-bipyridine)[μ4-4,4′-(1,4-phenylenedioxy)bis(benzene-1,2-dicarboxylato)]dizinc(II)] dihydrate], {[Zn2(C22H10O10)(C10H8N2)2(H2O)2]·2H2O}n, (1), and poly[[diaquabis(1,10-phenanthroline)[μ4-4,4′-(1,4-phenylenedioxy)bis(benzene-1,2-dicarboxylato)]dicadmium(II)] dimethylformamide disolvate], {[Cd2(C22H10O10)(C12H8N2)2(H2O)2]·2C3H7NO}n, (2), have been synthesized from 4,4′-(1,4-phenylenedioxy)bis(benzene-1,2-dicarboxylic acid) (H4L) and two different N-containing auxiliary ligands through a mixed-ligand synthetic strategy under a solvothermal environment. The structures were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, elemental analysis and IR spectroscopy. Compounds (1) and (2) both present one-dimensional chain structures and two-dimensional supramolecular layer structures constructed by weak hydrogen bonds. It is interesting to note that the carboxylate ligands reveal stabletransconfigurations in both compounds. The fluorescence properties of (1) and (2) in the solid state were also investigated.
Nobiletin: a citrus flavonoid displaying potent physiological activity
Authors: Noguchi Shuji , Atsumi Haruka , Iwao Yasunori , Kan Toshiyuki , Itai Shigeru
Published: January 2016

Nobiletin [systematic name: 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-4H-chromen-4-one; C21H22O8] is a flavonoid found in citrus peels, and has been reported to show a wide range of physiological properties, including anti-inflammatory, anticancer and antidementia activities. We have solved the crystal structure of nobiletin, which revealed that the chromene and arene rings of its flavone moiety, as well as the two methoxy groups bound to its arene ring, were coplanar. In contrast, the C atoms of the four methoxy groups bound to the chromene ring are out of the plane, making the molecule conformationally chiral. A comparison of the crystal structures of nobiletin revealed that it could adopt a variety of different conformations through rotation of the covalent bond between the chromene and arene rings, and the orientations of methoxy groups bound to the chromene ring.
From backyard to commercial hog production
Authors: Huang Weiming , Qiao Fangbin , Liu Huaiju , Jia Xiangping , Lohmar Bryan
Published: January 2016

Purpose

– The purpose of this paper is to analyze the impact of structural changes in hog production manure management practices.

Design/methodology/approach

– The data used in this study are obtained from a large-scale nationwide hog producers’ survey in rural China conducted by the Center for Chinese Agricultural Policy, Chinese Academy of Sciences, in 2010. A descriptive analysis between hog manure management and its main determinants was conducted. Based on the collected data, an econometric model on the determinants of hog manure management was constructed and used for analysis.

Findings

– The results of this study suggest that the scale of hog production has an important impact on the pattern of hog manure management. Moreover, the results from descriptive statistics and multivariate estimation suggest that smaller hog producers are more likely to apply hog manure to their own lands, while larger hog producers are more likely to sell the manure or find other ways to dispose of it.

Originality/value

– This study contributes to the existing literature by examining the impact of structural changes in hog production on hog manure management and the environment.
Trans-disciplinary community groups: an initiative for improving healthcare
Authors: Sideras James Demetri
Published: January 2016

Purpose

– In the context of budget constraints and the current quality crisis facing UK healthcare, the purpose of this paper is to examine the use of trans-disciplinary community groups (TCG) – an innovative and inexpensive initiative for improving patient care.

Design/methodology/approach

– Using an action research study, TCG was implemented within a private healthcare firm for vulnerable adults. Qualitative data were gathered over 12 months from 33 participants using depth interviews and focus groups.

Findings

– TCG led to improved patient activities and increased patient decision-making and confidence in self-advocacy. Key prerequisites were top management commitment, democratic leadership and employee empowerment. However, staff nurses resisted TCG because they were inclined to using managerial control and their own independent clinical judgements.

Research limitations/implications

– Whilst the findings from this study should not be generalized across all healthcare sectors, its results could be replicated in contexts where there is wide commitment to TCG and where managers adopt a democratic style of leadership. Researchers could take this study further by exploring the applicability of TCG in public healthcare organizations or other multi-disciplinary service contexts.

Practical implications

– The findings of this research paper provide policy makers and healthcare managers with practical insights on TCG and the factors that are likely to obstruct and facilitate its implementation.

Originality/value

– Adopting TCG could enable healthcare managers to ameliorate their services with little or no extra cost, which is especially important in a budget constraint context and the current quality crisis facing UK healthcare.
Factors influencing change in clinical practice
Authors: Rajasekhar Praveen T , Rees Colin J , Nixon Catherine , East James E , Brown Sally
Published: January 2016

Purpose

– The quality improvement in colonoscopy study was a region wide service improvement study to improve adenoma detection rate at colonoscopy by implementing evidence into routine colonoscopy practice. Implementing evidence into clinical practice can be challenging. The purpose of this paper is to perform a qualitative interview study to evaluate factors that influenced implementation within the study.

Design/methodology/approach

– Semi-structured interviews were conducted with staff in endoscopy units taking part in the quality improvement in colonoscopy study, after study completion. Units and interviewees were purposefully sampled to ensure a range of experiences was represented. Interviews were conducted with 11 participants.

Findings

– Key themes influencing uptake of the quality improvement in colonoscopy evidence bundle included time, study promotion, training, engagement, positive outcomes and modifications. Areas within themes were increased awareness of quality in colonoscopy (QIC), emphasis on withdrawal time and empowerment of endoscopy nurses to encourage the use of quality measures were positive outcomes of the study. The simple, visible study posters were reported as useful in aiding study promotion. Feedback sessions improved engagement. Challenges included difficulty arranging set-up meetings and engaging certain speciality groups.

Originality/value

– This evaluation suggests that methods to implement evidence into clinical practice should include identification and empowerment of team members who can positively influence engagement, simple, visible reminders and feedback. Emphasis on timing of meetings and strategies to engage speciality groups should also be given consideration. Qualitative evaluations can provide important insights into why quality improvement initiatives are successful or not, across different sites.
Information-theoretic approach to quantifying currency risk
Authors: Fiedor Paweł , Hołda Artur
Published: January 2016

Purpose

– This paper aims to present a framework enriching currency risk analyses based on information theory.

Design/methodology/approach

– Information-theoretic measures of predictability (entropy rate) and co-dependence (mutual information) are used to enhance existing methods of analysing and measuring currency risk.

Findings

– The currency exchange rates have varying degrees of predictability, which should be accounted for in currency risk analyses. In case of baskets of currencies, a network approach rooted in portfolio theory may be useful.

Research limitations/implications

– The currency exchange rate time series must be discretised for the information-theoretic analysis (although the results are robust). An agent-based simulation may be a necessary further study to show what the impact of accounting for predictability in managing currency risk is.

Practical implications

– Practical analyses measuring currency risk should take predictability of currency rate changes into account wherever the currency exposure is actively managed.

Originality/value

– The paper introduces predictability into measuring currency risk, which has previously been ignored, despite the nature of the risk being inherently tied to uncertainty of the currency rate changes. The paper also introduces a portfolio theory-based approach to quantifying currency risk, which accounts for non-linear co-dependence in the currency markets.
The impact of auditing strategies on insurers’ profitability
Authors: Müller Katja , Schmeiser Hato , Wagner Joël
Published: January 2016

Purpose

– The purpose of this paper paper is to study effective measures in dealing with the phenomenon of insurance claims’ fraud. In fact, fraud is one of the major industry concerns. It occurs in all classes of insurance and accounts for a substantial portion of indemnity payments each year.

Design/methodology/approach

– This paper develops a model framework based on a costly state verification setting in which – while policyholders observe the amount of loss privately – the insurance company can decide to audit incoming claims at some cost. The aim is to derive optimal auditing strategies from the insurance company’s perspective while maintaining contract attractiveness to policyholders willing to adhere to the insurance relationship. The possibility for each stakeholder to adapt its behavioral strategy over the course of several periods is taken into account. Using a numerical approach based on Monte Carlo simulations, the impact of different parameterizations on the optimal auditing range by means of a sensitivity analysis is illustrated and analyzed.

Findings

– The central outcome of the model is an auditing range which selects those claims which should be subject to verification.

Practical implications

– This paper comes to the conclusion that, given some constant cost per audit, it is optimal to verify the accuracy of claims from the mid-value segment. Furthermore, it can be shown that while the option to adapt one’s strategy might be favorable from the insurance company perspective, it has a negative impact on the policyholders’ position. This disproves the common belief that adapting the defrauding strategy with the help of signals from service providers would be advantageous.

Originality/value

– This paper extends the stand of literature on costly state verification and gives indications for optimal auditing strategies in industry practice.
Does risk affect capital structure adjustments?
Authors: Rashid Abdul
Published: January 2016

Purpose

– This paper aims to theorize that if risk affects costs and benefits of capital structure adjustments, then it should affect the speed at which firms adjust their leverage toward the target. To investigate this hypothesis, the author empirically examines the role of firm-specific and macroeconomic risk on firms’ capital structure adjustments.

Design/methodology/approach

– The author augments the standard reduced-form partial adjustment model of capital structure by incorporating firm-specific and macroeconomic risk. The two-step robust system-generalized method of moments (GMM) estimator is used to estimate the proposed model for a large panel of UK manufacturing firms. An unbalanced annual panel data set covering the period from 1981 to 2009 is utilized for empirical analysis.

Findings

– The estimated adjustment speeds indicate that both firm-specific risk and macroeconomic risk significantly affect the speed at which firms adjust their capital structure toward the target. In particular, the author shows that firms adjust their leverage faster toward the target when firm-specific risk is relatively low. This is perhaps because firms face lower costs of adjustment when both firm-specific and macroeconomic risks are low. Overall, the paper provides evidence that different levels and different types of risk exert asymmetric effects on capital structure adjustments.

Practical implications

– The results presented in this paper suggest that managers have to carefully consider both the overall state of the economy and the solvency of their own business activities when making their financing decisions. The results also help in explaining why firms time equity and debt markets.

Originality/value

– The paper significantly adds to our understanding of asymmetries in adjustment speed across firms and over times. The paper can also be useful to understand why firms would not aggressively act to offset the effects of changes in the market value of equity or gains and losses in earnings.