bluuebunny/crossref_metadata_2025 huggingface dataset:
The purging of deleterious mutations in simple and complex mating environments
Authors: Colpitts Julie , Williscroft Darla , Sekhon Harmandeep Singh , Rundle Howard D.
Published: October 2017

There is a general expectation that sexual selection should align with natural selection to aid the purging of deleterious mutations, yet experiments comparing purging under monogamy versus polygamy have provided mixed results. Recent studies suggest that this may be because the simplified mating environments used in these studies reduce the benefit of sexual selection through males and hamper natural selection through females by increasing costs associated with sexual conflict. To test the effect of the physical mating environment on purging, we use experimental evolution inDrosophila melanogasterto track the frequency of four separate deleterious mutations in replicate populations that experience polygamy under either a simple or structurally complex mating arena while controlling for arena size. Consistent with past results suggesting a greater net benefit of polygamy in a complex environment, two of the mutations were purged significantly faster in this environment. The other two mutations showed no significant difference between environments.
Suction effects in cratered surfaces
Authors: Qiao Shutao , Wang Liu , Jeong Hyoyoung , Rodin Gregory J. , Lu Nanshu
Published: October 2017

It has been shown experimentally that cratered surfaces may have better adhesion properties than flat ones. However, the suction effect produced by the craters, which may be chiefly responsible for the improved adhesion, has not been properly modelled. This paper combines experimental, numerical simulation and analytical approaches towards developing a framework for quantifying the suction effect produced by isolated craters and cratered surfaces. The modelling approach emphasizes the essential role of large elastic deformation, while the airflow dynamics, microscopic mechanisms, like surface tension and air permeation, and rate-dependence are neglected. This approach is validated using experimental data for isolated hemi-spherical craters. The modelling approach is further applied to spherical cap (not necessarily hemi-spherical) craters with the objective of identifying optimal geometric and material properties, as well as the minimum preload necessary for attaining the maximum suction force. It is determined that stiff polymers with deep craters are capable of producing large suction forces. For soft materials, central to biomedical applications, large suction forces can be attained by reinforcing deep craters with thin stiff layers. Parametric optimization studies of reinforced craters reveal that some of them perform beyond common expectations. However, those high-performance reinforced craters are prone to surface instabilities, and therefore the practical use of such craters may be problematic.
Network-based approaches to quantify multicellular development
Authors: Jackson Matthew D. B. , Duran-Nebreda Salva , Bassel George W.
Published: October 2017

Multicellularity and cellular cooperation confer novel functions on organs following a structure–function relationship. How regulated cell migration, division and differentiation events generate cellular arrangements has been investigated, providing insight into the regulation of genetically encoded patterning processes. Much less is known about the higher-order properties of cellular organization within organs, and how their functional coordination through global spatial relations shape and constrain organ function. Key questions to be addressed include: why are cells organized in the way they are? What is the significance of the patterns of cellular organization selected for by evolution? What other configurations are possible? These may be addressed through a combination of global cellular interaction mapping and network science to uncover the relationship between organ structure and function. Using this approach, global cellular organization can be discretized and analysed, providing a quantitative framework to explore developmental processes. Each of the local and global properties of integrated multicellular systems can be analysed and compared across different tissues and models in discrete terms. Advances in high-resolution microscopy and image analysis continue to make cellular interaction mapping possible in an increasing variety of biological systems and tissues, broadening the further potential application of this approach. Understanding the higher-order properties of complex cellular assemblies provides the opportunity to explore the evolution and constraints of cell organization, establishing structure–function relationships that can guide future organ design.
Dual role of the chromatin-binding factor PHF13 in the pre- and post-integration phases of HIV-1 replication
Authors: Hofmann Stephan , Dehn Sandra , Businger Ramona , Bolduan Sebastian , Schneider Martha , Debyser Zeger , Brack-Werner Ruth , Schindler Michael
Published: October 2017

Viruses interact with multiple host cell factors. Some of these are required to promote viral propagation, others have roles in inhibiting infection. Here, we delineate the function of the cellular factor PHF13 (or SPOC1), a putative HIV-1 restriction factor. Early in the HIV-1 replication cycle PHF13 increased the number of integrated proviral copies and the number of infected cells. However, after HIV-1 integration, high levels of PHF13 suppressed viral gene expression. The antiviral activity of PHF13 is counteracted by the viral accessory protein Vpr, which mediates PHF13 degradation. Altogether, the transcriptional master regulator and chromatin binding protein PHF13 does not have purely repressive effects on HIV-1 replication, but also promotes viral integration. By the functional characterization of the dual role of PHF13 during the HIV-1 replication cycle, we reveal a surprising and intricate mechanism through which HIV-1 might regulate the switch from integration to viral gene expression. Furthermore, we identify PHF13 as a cellular target specifically degraded by HIV-1 Vpr.
Assessment of dynamic material properties of intact rocks using seismic wave attenuation: an experimental study
Authors: Wanniarachchi W. A. M. , Ranjith P. G. , Perera M. S. A. , Rathnaweera T. D. , Lyu Q. , Mahanta B.
Published: October 2017

The mechanical properties of any substance are essential facts to understand its behaviour and make the maximum use of the particular substance. Rocks are indeed an important substance, as they are of significant use in the energy industry, specifically for fossil fuels and geothermal energy. Attenuation of seismic waves is a non-destructive technique to investigate mechanical properties of reservoir rocks under different conditions. The attenuation characteristics of five different rock types, siltstone, shale, Australian sandstone, Indian sandstone and granite, were investigated in the laboratory using ultrasonic and acoustic emission instruments in a frequency range of 0.1–1 MHz. The pulse transmission technique and spectral ratios were used to calculate the attenuation coefficient (α) and quality factor (Q) values for the five selected rock types for both primary (P) and secondary (S) waves, relative to the reference steel sample. For all the rock types, the attenuation coefficient was linearly proportional to the frequency of both thePandSwaves. Interestingly, the attenuation coefficient of granite is more than 22% higher than that of siltstone, sandstone and shale for bothPandSwaves. ThePandSwave velocities were calculated based on their recorded travel time, and these velocities were then used to calculate the dynamic mechanical properties including elastic modulus (E), bulk modulus (K), shear modulus (µ) and Poisson's ratio (ν). ThePandSwave velocities for the selected rock types varied in the ranges of 2.43–4.61 km s−1and 1.43–2.41 km h−1, respectively. Furthermore, it was observed that thePwave velocity was always greater than theSwave velocity, and this confirmed the first arrival ofPwaves to the sensor. According to the experimental results, the dynamicEvalue is generally higher than the staticEvalue obtained by unconfined compressive strength tests.
Indentation of a floating elastic sheet: geometry versus applied tension
Authors: Box Finn , Vella Dominic , Style Robert W. , Neufeld Jerome A.
Published: October 2017

The localized loading of an elastic sheet floating on a liquid bath occurs at scales from a frog sitting on a lily pad to a volcano supported by the Earth’s tectonic plates. The load is supported by a combination of the stresses within the sheet (which may include applied tensions from, for example, surface tension) and the hydrostatic pressure in the liquid. At the same time, the sheet deforms, and may wrinkle, because of the load. We study this problem in terms of the (relatively weak) applied tension and the indentation depth. For small indentation depths, we find that the force–indentation curve is linear with a stiffness that we characterize in terms of the applied tension and bending stiffness of the sheet. At larger indentations, the force–indentation curve becomes nonlinear and the sheet is subject to a wrinkling instability. We study this wrinkling instability close to the buckling threshold and calculate both the number of wrinkles at onset and the indentation depth at onset, comparing our theoretical results with experiments. Finally, we contrast our results with those previously reported for very thin, highly bendable membranes.
Twistor theory at fifty: from contour integrals to twistor strings
Authors: Atiyah Michael , Dunajski Maciej , Mason Lionel J.
Published: October 2017

We review aspects of twistor theory, its aims and achievements spanning the last five decades. In the twistor approach, space–time is secondary with events being derived objects that correspond to compact holomorphic curves in a complex threefold—the twistor space. After giving an elementary construction of this space, we demonstrate how solutions to linear and nonlinear equations of mathematical physics—anti-self-duality equations on Yang–Mills or conformal curvature—can be encoded into twistor cohomology. These twistor correspondences yield explicit examples of Yang–Mills and gravitational instantons, which we review. They also underlie the twistor approach to integrability: the solitonic systems arise as symmetry reductions of anti-self-dual (ASD) Yang–Mills equations, and Einstein–Weyl dispersionless systems are reductions of ASD conformal equations. We then review the holomorphic string theories in twistor and ambitwistor spaces, and explain how these theories give rise to remarkable new formulae for the computation of quantum scattering amplitudes. Finally, we discuss the Newtonian limit of twistor theory and its possible role in Penrose’s proposal for a role of gravity in quantum collapse of a wave function.
Evolutionary contribution to coexistence of competitors in microbial food webs
Authors: Hiltunen Teppo , Kaitala Veijo , Laakso Jouni , Becks Lutz
Published: October 2017

The theory of species coexistence is a key concept in ecology that has received much attention. The role of rapid evolution for determining species coexistence is still poorly understood although evolutionary change on ecological time-scales has the potential to change almost any ecological process. The influence of evolution on coexistence can be especially pronounced in microbial communities where organisms often have large population sizes and short generation times. Previous work on coexistence has assumed that traits involved in resource use and species interactions are constant or change very slowly in terms of ecological time-scales. However, recent work suggests that these traits can evolve rapidly. Nevertheless, the importance of rapid evolution to coexistence has not been tested experimentally. Here, we show how rapid evolution alters the frequency of two bacterial competitors over time when grown together with specialist consumers (bacteriophages), a generalist consumer (protozoan) and all in combination. We find that consumers facilitate coexistence in a manner consistent with classic ecological theory. However, through disentangling the relative contributions of ecology (changes in consumer abundance) and evolution (changes in traits mediating species interactions) on the frequency of the two competitors over time, we find differences between the consumer types and combinations. Overall, our results indicate that the influence of evolution on species coexistence strongly depends on the traits and species interactions considered.
Bluetongue virus spread in Europe is a consequence of climatic, landscape and vertebrate host factors as revealed by phylogeographic inference
Authors: Jacquot Maude , Nomikou Kyriaki , Palmarini Massimo , Mertens Peter , Biek Roman
Published: October 2017

Spatio-temporal patterns of the spread of infectious diseases are commonly driven by environmental and ecological factors. This is particularly true for vector-borne diseases because vector populations can be strongly affected by host distribution as well as by climatic and landscape variables. Here, we aim to identify environmental drivers for bluetongue virus (BTV), the causative agent of a major vector-borne disease of ruminants that has emerged multiple times in Europe in recent decades. In order to determine the importance of climatic, landscape and host-related factors affecting BTV diffusion across Europe, we fitted different phylogeographic models to a dataset of 113 time-stamped and geo-referenced BTV genomes, representing multiple strains and serotypes. Diffusion models using continuous space revealed that terrestrial habitat below 300 m altitude, wind direction and higher livestock densities were associated with faster BTV movement. Results of discrete phylogeographic analysis involving generalized linear models broadly supported these findings, but varied considerably with the level of spatial partitioning. Contrary to common perception, we found no evidence for average temperature having a positive effect on BTV diffusion, though both methodological and biological reasons could be responsible for this result. Our study provides important insights into the drivers of BTV transmission at the landscape scale that could inform predictive models of viral spread and have implications for designing control strategies.
Bayesian and likelihood phylogenetic reconstructions of morphological traits are not discordant when taking uncertainty into consideration: a comment on Puttick
et

al
.
Authors: Brown Joseph W. , Parins-Fukuchi Caroline , Stull Gregory W. , Vargas Oscar M. , Smith Stephen A.
Published: October 2017

Puttick
et al.
(2017
Proc. R. Soc. B
284
, 20162290 (
doi:10.1098/rspb.2016.2290
)) performed a simulation study to compare accuracy among methods of inferring phylogeny from discrete morphological characters. They report that a Bayesian implementation of the Mk model (Lewis 2001
Syst. Biol.
50
, 913–925 (
doi:10.1080/106351501753462876
)) was most accurate (but with low resolution), while a maximum-likelihood (ML) implementation of the same model was least accurate. They conclude by strongly advocating that Bayesian implementations of the Mk model should be the default method of analysis for such data. While we appreciate the authors' attempt to investigate the accuracy of alternative methods of analysis, their conclusion is based on an inappropriate comparison of the ML point estimate, which does not consider confidence, with the Bayesian consensus, which incorporates estimation credibility into the summary tree. Using simulation, we demonstrate that ML and Bayesian estimates are concordant when confidence and credibility are comparably reflected in summary trees, a result expected from statistical theory. We therefore disagree with the conclusions of Puttick
et al.
and consider their prescription of any default method to be poorly founded. Instead, we recommend caution and thoughtful consideration of the model or method being applied to a morphological dataset.
Punctuated invasion of water, ice, snow and terrestrial ecozones by segmented worms (Oligochaeta: Enchytraeidae:Mesenchytraeus)
Authors: Lang Shirley A. , Saglam Naim , Kawash Joseph , Shain Daniel H.
Published: October 2017

Segmented worms (Annelida) are among the most successful animal inhabitants of extreme environments worldwide. An unusual group of enchytraeid oligochaetes of genusMesenchytraeusare abundant in the Pacific northwestern region of North America and occupy geographically proximal ecozones ranging from low elevation rainforests and waterways to high altitude glaciers. Along this altitudinal transect,Mesenchytraeusrepresentatives from disparate habitat types were collected and subjected to deep mitochondrial and nuclear phylogenetic analyses. Our data identify significant topological discordance among gene trees, and near equivalent interspecific divergence levels indicative of a rapid radiation event. Collectively, our results identify aMesenchytraeus‘explosion’ coincident with mountain building in the Pacific northwestern region that gave rise to closely related aquatic, ice, snow and terrestrial worms.
A human model for primate personality
Authors: Weiss Alexander
Published: October 2017

In this article, I review the literature to determine how successful the latent trait theory model of personality from differential psychology has been for studying personality in non-human primates. The evidence for the success of this model is quite good, and offers insights and directions for personality research in primates and other animals. This, I conclude, stems from (i) the human trait model's simplicity, and (ii) the fact that the human differential model of personality developed in the face of harsh criticism, which led researchers to test and refine their models.
Combined effects of night warming and light pollution on predator–prey interactions
Authors: Miller Colleen R. , Barton Brandon T. , Zhu Likai , Radeloff Volker C. , Oliver Kerry M. , Harmon Jason P. , Ives Anthony R.
Published: October 2017

Interactions between multiple anthropogenic environmental changes can drive non-additive effects in ecological systems, and the non-additive effects can in turn be amplified or dampened by spatial covariation among environmental changes. We investigated the combined effects of night-time warming and light pollution on pea aphids and two predatory ladybeetle species. As expected, neither night-time warming nor light pollution changed the suppression of aphids by the ladybeetle species that forages effectively in darkness. However, for the more-visual predator, warming and light had non-additive effects in which together they caused much lower aphid abundances. These results are particularly relevant for agriculture near urban areas that experience both light pollution and warming from urban heat islands. Because warming and light pollution can have non-additive effects, predicting their possible combined consequences over broad spatial scales requires knowing how they co-occur. We found that night-time temperature change since 1949 covaried positively with light pollution, which has the potential to increase their non-additive effects on pea aphid control by 70% in US alfalfa. Our results highlight the importance of non-additive effects of multiple environmental factors on species and food webs, especially when these factors co-occur.
Men's preferences for women's body odours are not associated with human leucocyte antigen
Authors: Probst Fabian , Fischbacher Urs , Lobmaier Janek S. , Wirthmüller Urs , Knoch Daria
Published: October 2017

Body odours reportedly portray information about an individual's genotype at the major histocompatibility complex (MHC, called human leucocyte antigen, HLA, in humans). While there is strong experimental support for MHC-associated mating behaviour in animals, the situation in humans is more complex. A lot of effort has been spent on testing HLA-associated odour preferences of women. To date, only very few studies have looked at HLA-linked olfactory preferences in men and these studies have revealed inconsistent results. Here, we investigate men's HLA-associated preferences for women's body odours. Importantly, and in contrast to previous studies, these odours were gathered at peak fertility (i.e. just before ovulation) when any HLA-associated odour preferences should be strongest. We scrutinized whether men's preference for women's body odours is influenced by (i) the number of shared HLA alleles between men and women, (ii) HLA heterozygosity, and (iii) the frequency of rare HLA alleles. We found that men could readily differentiate between odours they found attractive and odours they found less attractive, but that these preferences were not associated with HLA. Specifically, men did not prefer odours from women who are HLA dissimilar, HLA heterozygous, or who have rare HLA alleles. Together, these findings suggest that HLA has no effect on men's odour preferences.
Riboglow: a multicolor riboswitch-based platform for live cell imaging of mRNA and small non-coding RNA in mammalian cells
Authors: Braselmann Esther , Wierzba Aleksandra J. , Polaski Jacob T. , Chromiński Mikołaj , Holmes Zachariah E. , Hung Sheng-Ting , Batan Dilara , Wheeler Joshua R. , Parker Roy , Jimenez Ralph , Gryko Dorota , Batey Robert T. , Palmer Amy E.
Published: October 2017

RNAs directly regulate a vast array of critical cellular processes, emphasizing the need for robust approaches to fluorescently tag and track RNAs in living cells. Here, we develop an RNA imaging platform using the cobalamin riboswitch as an RNA tag and a series of probes containing cobalamin as a fluorescence quencher. This highly modular ‘Riboglow’ platform leverages different color fluorescent dyes, linkers and riboswitch RNA tags to elicit fluorescent turn-on upon binding RNA. We demonstrate the ability of two different Riboglow probes to track mRNA and small non-coding U RNA in live mammalian cells. A direct side-by-side comparison revealed that Riboglow outperformed the dye binding aptamer Broccoli and performed on par with the current gold standard RNA imaging system, the MS2-fluorescent protein system, while featuring a much smaller RNA tag. Together, the versatility of the Riboglow platform and ability to track diverse RNAs suggest broad applicability for a variety of imaging approaches.

Graphical abstract
Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites
Authors: Meerstein-Kessel Lisette , van der Lee Robin , Stone Will , Lanke Kjerstin , Baker David A , Alano Pietro , Silvestrini Francesco , Janse Chris J , Khan Shahid M , van de Vegte-Bolmer Marga , Graumans Wouter , Siebelink-Stoter Rianne , Kooij Taco WA , Marti Matthias , Drakeley Chris , Campo Joseph J. , van Dam Teunis JP , Sauerwein Robert , Bousema Teun , Huynen Martijn A
Published: October 2017

Plasmodiumgametocytes are the sexual forms of the malaria parasite essential for transmission to mosquitoes. To better understand how gametocytes differ from asexual blood-stage parasites, we performed a systematic analysis of available ‘omics data forP. falciparumand otherPlasmodiumspecies. 18 transcriptomic and proteomic data sets were evaluated for the presence of curated “gold standards” of 41 gametocyte-specific versus 46 non-gametocyte genes and integrated using Bayesian probabilities, resulting in gametocyte-specificity scores for allP. falciparumgenes.

To illustrate the utility of the gametocyte score, we explored newly predicted gametocyte-specific genes as potential biomarkers of gametocyte carriage and exposure. We analyzed the humoral immune response in field samples against 30 novel gametocyte-specific antigens and found five antigens to be differentially recognized by gametocyte carriers as compared to malaria-infected individuals without detectable gametocytes. We also validated the gametocyte-specificity of 15 identified gametocyte transcripts on culture material and samples from naturally infected individuals, resulting in eight transcripts that were >1000-fold higher expressed in gametocytes compared to asexual parasites and whose transcript abundance allowed gametocyte detection in naturally infected individuals. Our integrated genome-wide gametocyte-specificity scores provide a comprehensive resource to identify targets and monitorP. falciparumgametocytemia.
WDR11-mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome
Authors: Kim Yeon-Joo , Osborn Daniel P.S. , Lee Ji-Young , Araki Masatake , Araki Kimi , Mohun Timothy , Känsäkoski Johanna , Brandstack Nina , Kim Hyun-Taek , Miralles Francesc , Kim Cheol-Hee , Brown Nigel A. , Kim Hyung-Goo , Martinez-Barbera Juan Pedro , Ataliotis Paris , Raivio Taneli , Layman Lawrence C. , Kim Soo-Hyun
Published: October 2017

WDR11 has been implicated in congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS), human developmental genetic disorders defined by delayed puberty and infertility. However, WDR11’s role in development is poorly understood. Here we report that WDR11 modulates the Hedgehog (Hh) signalling pathway and is essential for ciliogenesis. Disruption of WDR11 expression in mouse and zebrafish results in phenotypic characteristics associated with defective Hh signalling, accompanied by dysgenesis of ciliated tissues.Wdr11null mice also exhibit early onset obesity. We found that WDR11 shuttles from the cilium to the nucleus in response to Hh signalling. WDR11 was also observed to regulate the proteolytic processing of GLI3 and cooperate with EMX1 transcription factor to induce the expression of downstream Hh pathway genes and gonadotrophin releasing hormone production. The CHH/KS-associated human mutations result in loss-of-function of WDR11. Treatment with the Hh agonist purmorphamine partially rescued the WDR11-haploinsufficiency phenotypes. Our study reveals a novel class of ciliopathy caused by WDR11 mutations and suggests that CHH/KS may be a part of the human ciliopathy spectrum.
The centrosomin CM2 domain is a multi-functional binding domain with distinct cell cycle roles
Authors: Citron Y. Rose , Fagerstrom Carey J. , Keszthelyi Bettina , Huang Bo , Rusan Nasser M , Kelly Mark J S , Agard David A.
Published: October 2017

The centrosome serves as the main microtubule-organizing center in metazoan cells, yet despite its functional importance, little is known mechanistically about the structure and organizational principles that dictate protein organization in the centrosome. In particular, the protein-protein interactions that allow for the massive structural transition between the tightly organized interphase centrosome and the highly expanded matrix-like arrangement of the mitotic centrosome have been largely uncharacterized. Among the proteins that undergo a major transition is theDrosophila melanogasterprotein centrosomin that contains a conserved carboxyl terminus motif, CM2. Recent crystal structures have shown this motif to be dimeric and capable of forming an intramolecular interaction with a central region of centrosomin. Here we use a combination of in-cell microscopy andin vitrooligomer assessment to show that dimerization is not necessary for CM2 recruitment to the centrosome and that CM2 alone undergoes a significant cell cycle dependent rearrangement. We use NMR binding assays to confirm this intramolecular interaction and show that residues involved in solution interactions are consistent with the published crystal structure and identify L1137 as critical for binding. Additionally, we show for the first time anin vitrointeraction of CM2 with theDrosophilapericentrin-like-protein that exploits the same set of residues as the intramolecular interaction. Furthermore, NMR experiments reveal a calcium sensitive interaction between CM2 and calmodulin. Although unexpected because of sequence divergence, this suggests that centrosomin-mediated assemblies, like the mammalian pericentrin, may be calcium regulated. From these results we suggest a model where during interphase CM2 interacts with pericentrin-like-protein to form a layer of centrosomin around the centriole wall and that at the onset of mitosis this population acts as a nucleation site of intramolecular centrosomin interactions that support the expansion into the metaphase matrix.
How epigenome drives chromatin folding and dynamics, insights from efficient coarse-grained models of chromosomes
Authors: Ghosh Surya K. , Jost Daniel
Published: October 2017

The 3D organization of chromosome is crucial for regulating gene expression and cell function. Many experimental and polymer modeling efforts are dedicated to deciphering the mechanistic principles behind chromosome folding. Chromosomes are long and densely packed - topologically constrained - polymers. The main challenge is therefore to develop adequate models and simulation methods to investigate properly the multi spatio-temporal scales of such macromolecules. Here, we discussed a generic strategy to develop efficient coarse-grained models for self-avoiding polymers on a lattice. Accounting accurately for the polymer entanglement length and the volumic density, we show that our simulation scheme not only captures the steady-state structural and dynamical properties of the system but also tracks the same dynamics at different coarse-graining. This strategy allows a strong power-law gain in numerical efficiency and offers a systematic way to define reliable coarse-grained null models for chromosomes and to go beyond the current limitations by studying long chromosomes during an extended time period with good statistics. We use our formalism to investigate in details the time evolution of the 3D organization of chromosome 3R (20 Mbp) in drosophila during one cell cycle (20 hours). We show that a combination of our coarse-graining strategy with a one-parameter block copolymer model integrating epigenomic-driven interactions quantitatively reproduce experimental data at the chromosome-scale and predict that chromatin motion is very dynamic during the cell cycle.
Error-prone bypass of DNA lesions during lagging strand replication is a common source of germline and cancer mutations
Authors: Seplyarskiy Vladimir B. , Akkuratov Evgeny E. , Akkuratova Natalia V. , Andrianova Maria A. , Nikolaev Sergey I. , Bazykin Georgii A. , Adameyko Igor , Sunyaev Shamil R.
Published: October 2017

Spontaneously occurring mutations are of great relevance in diverse fields including biochemistry, oncology, evolutionary biology, and human genetics. Studies in experimental systems have identified a multitude of mutational mechanisms including DNA replication infidelity as well as many forms of DNA damage followed by inefficient repair or replicative bypass. However, the relative contributions of these mechanisms to human germline mutations remain completely unknown. Here, based on the mutational asymmetry with respect to the direction of replication and transcription, we suggest that error-prone damage bypass on the lagging strand plays a major role in human mutagenesis. Asymmetry with respect to transcription is believed to be mediated by the action of transcription-coupled DNA repair (TC-NER). TC-NER selectively repairs DNA lesions on the transcribed strand; as a result, lesions on the non-transcribed strand are preferentially converted into mutations. In human polymorphism we detect a striking similarity between transcriptional asymmetry and asymmetry with respect to replication fork direction. This parallels the observation that damage-induced mutations in human cancers accumulate asymmetrically with respect to the direction of replication, suggesting that DNA lesions are asymmetrically resolved during replication. Re-analysis of XR-seq data, Damage-seq data and cancers with defective NER corroborate the preferential error-prone bypass of DNA lesions on the lagging strand. We experimentally demonstrate that replication delay greatly attenuates the mutagenic effect of UV-irradiation, in line with the key role of replication in conversion of DNA damage to mutations. We conservatively estimate that at least 10% of human germline mutations arise due to DNA damage rather than replication infidelity. The number of these damage-induced mutations is expected to scale with the number of replications and, consequently, paternal age.
Decoupled Maternal and Zygotic Genetic Effects Shape the Evolution of Development
Authors: Zakas Christina , Deutscher Jennifer M. , Kay Alex D. , Rockman Matthew V.
Published: October 2017

Many animals develop indirectly via a larval stage that is morphologically and ecologically distinct from its adult form. Hundreds of lineages across animal phylogeny have secondarily lost larval forms, instead producing offspring that directly develop into adult form without a distinct larval ecological niche1–7. Indirect development in the sea is typically planktotrophic: females produce large numbers of small offspring that require exogenous planktonic food to develop before metamorphosing into benthic juveniles. Direct development is typically lecithotrophic: females produce a smaller number of larger eggs, each developing into a juvenile without the need for larval feeding, provisioned by yolk. Evolutionary theory suggests that these alternative developmental strategies represent stable alternative fitness peaks, while intermediate states are disfavored4,8–11. Transitions from planktotrophy to lecithotrophy thus require crossing a fitness valley and represent radical and coordinated transformations of life-history, fecundity, ecology, dispersal, and development7,12–16. Here we dissect this transition inStreblospio benedicti, the sole genetically tractable species that harbors both states as heritable variation17–19. We identify large-effect loci that act maternally to influence larval size and independent, unlinked large-effect loci that act zygotically to affect discrete aspects of larval morphology. Because lecithotrophs and planktotrophs differ in both size and morphology, the genetic basis of larval form exhibits strong maternal-by-zygotic epistasis for fitness20. The fitness of zygotic alleles depends on their maternal background, creating a positive frequency-dependence that may homogenize local populations. Developmental and population genetics interact to shape larval evolution.
Alzheimer’s Genetic Risk Score linked to Incident Mild Behavioral Impairment
Authors: Andrews Shea J. , Ismail Zahinoor , Anstey Kaarin J. , Mortby Moyra
Published: October 2017

Mild Behavioral Impairment (MBI) describes the emergence of later-life Neuropsychiatric Symptoms (NPS) as an at-risk state for cognitive decline and dementia and as a potential manifestation of prodromal dementia. How NPS mechanistically link to the development of Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) is not fully understood. Potential mechanisms include either shared risk factors that are related to both NPS and cognitive impairment, or AD pathology promoting NPS. This is the first study to examine whether AD genetic loci, individually and as a genetic risk score, are a shared risk factor with MBI. 1377 older adults (aged 72-79; 738 males; 763 normal cognition) from the PATH Through Life project. MBI was assessed in accordance with Criterion 1 of the ISTAART-AA diagnostic criteria using the Neuropsychiatric Inventory. 25 LOAD risk loci were genotyped and a weighted genetic risk score (GRS) was constructed. Binomial logistic regression adjusting for age, gender, and education examined the association between LOAD GRS and MBI domains. An increase in the LOAD GRS and APOE*ε4 were associated with higher likelihood of Affective Dysregulation;MS4A4A-rs4938933*C andMS4A6A-rs610932*G were associated with a reduced likelihood of Affective Dysregulation;ZCWPW1-rs1476679*C was associated with a reduced likelihood of Social Inappropriateness and Abnormal Perception;BIN1-rs744373*G andEPHA1-rs11767557*C were associated with higher likelihood of Abnormal Perception;NME8-rs2718058*G was associated with a reduced likelihood Decreased Motivation. These findings suggest a common genetic etiology between MBI and traditionally recognized memory problems observed in AD and improve our understanding of the pathophysiological features underlying MBI.
Heartfelt Face Perception via the Interoceptive Pathway – an MEG study
Authors: Kim Jaejoong , Park Hyeong-Dong , Kim Ko Woon , Shin Dong Woo , Lim Sanghyun , Kwon Hyukchan , Kim Min-Young , Kim Kiwoong , Jeong Bumseok
Published: October 2017

The somatic marker hypothesis proposes that the cortical representation of visceral signals is a crucial component of emotion processing. No previous study has investigated the causal relationships among brain regions that process visceral information during emotional perception. In this magnetoencephalography study of 32 healthy subjects, heartbeat-evoked potentials (HEPs), which reflect the cortical processing of heartbeats, were modulated by the perception of a sad face. The modulation effect was localized to the prefrontal cortices, the globus pallidus, and an interoceptive network including the right anterior insula (RAI) and anterior cingulate cortex (RACC). Importantly, our Granger causality analysis provides the first evidence for increased causal flow of heartbeat information from the RAI to the RACC during sad face perception. Moreover, this HEP modulation effect was neither an artefact nor an effect of visual-evoked potentials. These findings provide important progress in the understanding of brain-body interactions during emotion processing.
Time-Consistent Reconciliation Maps and Forbidden Time Travel
Authors: Nøjgaard Nikolai , Geiß Manuela , Stadler Peter F. , Merkle Daniel , Wieseke Nicolas , Hellmuth Marc
Published: October 2017

Background

In the absence of horizontal gene transfer it is possible to reconstruct the history of gene families from empirically determined orthology relations, which are equivalent toevent-labeledgene trees. Knowledge of the event labels considerably simplifies the problem of reconciling a gene treeTwith a species treesS, relative to the reconciliation problem without prior knowledge of the event types. It is well-known that optimal reconciliations in the unlabeled case may violate time-consistency and thus are not biologically feasible. Here we investigate the mathematical structure of the event labeled reconciliation problem with horizontal transfer.

Results

We investigate the issue of time-consistency for the event-labeled version of the reconciliation problem, provide a convenient axiomatic framework, and derive a complete characterization of time-consistent reconciliations. This characterization depends on certain weak conditions on the event-labeled gene trees that reflect conditions under which evolutionary events are observable at least in principle. We give an 𝒪(|V(T)|log(|V(S)|))-time algorithm to decide whether a time-consistent reconciliation map exists. It does not require the construction of explicit timing maps, but relies entirely on the comparably easy task of checking whether a small auxiliary graph is acyclic. The algorithms are implemented in C++ using the boost graph library and are freely available athttps://github.com/Nojgaard/tc-recon.

Significance

The combinatorial characterization of time consistency and thus biologically feasible reconciliation is an important step towards the inference of gene family histories with horizontal transfer from orthology data, i.e., without presupposed gene and species trees. The fast algorithm to decide time consistency is useful in a broader context because it constitutes an attractive component for all tools that address tree reconciliation problems.
Open Source LED controller for circadian experiments
Authors: Ogueta Maite , Rodriguez Luis Garcia
Published: October 2017

Controlling the light conditions when performing a circadian experiment is a key factor. In this article a simple, affordable and open source LED controller is presented. Using commercial available solutions like and Arduino [1] and LED stripes the cost is dramatically reduced.
Improved orientation sampling for indexing diffraction patterns of polycrystalline materials
Authors: Larsen Peter Mahler , Schmidt Søren
Published: October 2017

Orientation mapping is a widely used technique for revealing the microstructure of a polycrystalline sample. The crystalline orientation at each point in the sample is determined by analysis of the diffraction pattern, a process known as pattern indexing. A recent development in pattern indexing is the use of a brute-force approach, whereby diffraction patterns are simulated for a large number of crystalline orientations and compared against the experimentally observed diffraction pattern in order to determine the most likely orientation. Whilst this method can robustly identify orientations in the presence of noise, it has very high computational requirements. In this article, the computational burden is reduced by developing a method for nearly optimal sampling of orientations. By using the quaternion representation of orientations, it is shown that the optimal sampling problem is equivalent to that of optimally distributing points on a four-dimensional sphere. In doing so, the number of orientation samples needed to achieve a desired indexing accuracy is significantly reduced. Orientation sets at a range of sizes are generated in this way for all Laue groups and are made available online for easy use.
Melting and freezing temperatures of confined Bi nanoparticles over a wide size range
Authors: Degenhardt Hermann Franz , Kellermann Guinther , Craievich Aldo Felix
Published: October 2017

The size dependences of the melting and freezing temperatures, T
m and T
f, respectively, of spherical Bi nanoparticles embedded in a sodium borate glass were determined by applying a new experimental procedure based on the combined and simultaneous use of small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS). This experimental procedure is particularly useful for materials in which a widely polydisperse set of nanoparticles are embedded. The results provide additional and stronger evidence supporting the main previous conclusions: (i) the melting and freezing temperatures both decrease linearly for increasing reciprocal radius (1/R); and (ii) the effect of undercooling is suppressed for Bi nanoparticles with radii smaller than a critical value equal to 1.8 nm. These results confirm a previously proposed low-resolution structural model for Bi nanocrystals below their melting temperature and with radius R > 1.8 nm, which consists of a crystalline core surrounded by a disordered shell. In the present work, a number of samples with different and partially overlapping radius distributions were studied, allowing the determination of T
m(R) and T
f(R) functions over a wide range of radii (1 < R < 11 nm). Comparison of the experimentally determined T
m(R) and T
f(R) functions corresponding to different samples indicates good reproducibility of the experimental results. This allowed the verification of the robustness of the experimental procedure based on in situ combined use of SAXS and WAXS for determination of the radius dependence of the melting and freezing temperatures of spherical nanoparticles in dilute solution.
Advancing reverse Monte Carlo structure refinements to the nanoscale
Authors: Eremenko M. , Krayzman V. , Gagin A. , Levin I.
Published: October 2017

Over the past decade, the RMCProfile software package has evolved into a powerful computational framework for atomistic structural refinements using a reverse Monte Carlo (RMC) algorithm and multiple types of experimental data. However, realizing the full potential of this method, which can provide a consistent description of atomic arrangements over several length scales, requires a computational speed much higher than that permitted by the current software. This problem has been addressed via substantial optimization and development of RMCProfile, including the introduction of the new parallel-chains RMC algorithm. The computing speed of this software has been increased by nearly two orders of magnitude, as demonstrated using the refinements of a simulated structure with two distinct correlation lengths for the atomic displacements. The new developments provide a path for achieving even faster performance as more advanced computing hardware becomes available. This version of RMCProfile permits refinements of atomic configurations of the order of 500 000 atoms (compared to the current limit of 20 000), which sample interatomic distances up to 10 nm (versus 3 nm currently). Accurate, computationally efficient corrections of the calculated X-ray and neutron total scattering data have been developed to account for the effects of instrumental resolution. These corrections are applied in both reciprocal and real spaces, thereby enabling RMC fitting of an atomic pair distribution function, which is obtained as the Fourier transform of the total-scattering intensity, over the entire nanoscale distance range accessible experimentally.
Information retrieval of a disaster event from cross-platform social media
Authors: Shen Shi , Murzintcev Nikita , Song Changqing , Cheng Changxiu
Published: October 2017

Purpose

The purpose of this study is to propose a method to retrieve data on an event based on a preliminary collection of event-specific hashtags.

Design/methodology/approach

Extra knowledge, or a list of events with recorded features that can be used to characterize an event and separate it from other simultaneously occurring social phenomena, is employed. The first step involves the estimation and use of the impact area to retrieve messages from Twitter. This is followed by an extraction of hashtags from these messages. After that, the noisy hashtags would be filtered out by some heuristic rules. Finally, hashtags are used to collect relevant messages from not only Twitter but also other social media platforms.

Findings

The proposed method has high selectivity and is able to collect distinct sets of hashtags even for similar simultaneous events. In addition, spatial and temporal features are sufficient to improve collecting information of disaster events.

Originality/value

This work discusses a method of information retrieval of an event from cross-platform social media. The proposed method can be applied to other studies of geographically related events.
The impacts of knowledge sharing-based value co-creation on user continuance in online communities
Authors: Chen Chen , Du Rong , Li Jin , Fan Weiguo
Published: October 2017

Purpose

Though online communities offer unprecedented opportunities to involve people in knowledge sharing, the reasons why users would like to participate in those activities in online communities have still been under-explored. In this research, the authors aim to use the value co-creation theory to build and test a continuance usage model, which focuses more on experiential values resulted from the knowledge sharing behavior.

Design/methodology/approach

An integrative research model is built to investigate how knowledge sharing behavior affects users’ co-creation value and then drives their continuance usage in online communities. Online survey data collected from 239 Sina Microblog users in China are utilized to validate the proposed model and hypotheses.

Findings

Empirical results indicate that the knowledge sharing behavior helps improve users’ co-creation value, including customer learning value, social integrative value and hedonic value. This co-creation value can subsequently affect users’ future participation intention in online communities.

Originality/value

This paper seeks to fill the research gap by examining customers’ motivations or perceptions underlying their knowledge sharing behavior at the usage-stage, instead of the pre-usage stage mainly concentrated on by previous studies. The managerial implications can be utilized for policy making to encourage customers’ participation and operate a better online community.