bluuebunny/crossref_metadata_2025 huggingface dataset:
Mice modulate ultrasonic calling bouts according to sociosexual context
Authors: Matsumoto Yui K. , Okanoya Kazuo
Published: June 2018

Mice produce various sounds within the ultrasonic range in social contexts. Although these sounds are often used as an index of sociability in biomedical research, their biological significance remains poorly understood. We previously showed that mice repeatedly produced calls in a sequence (i.e. calling bout), which can vary in their structure, such as Simple, Complex or Harmonics. In this study, we investigated the use of the three types of calling bouts in different sociosexual interactions, including both same- and opposite-sex contexts. In same-sex contexts, males typically produced a Simple calling bout, whereas females mostly produced a Complex one. By contrast, in the opposite-sex context, they produced all the three types of calling bouts, but the use of each calling type varied according to the progress and mode of sociosexual interaction (e.g. Harmonic calling bout was specifically produced during reproductive behaviour). These results indicate that mice change the structure of calling bout according to sociosexual contexts, suggesting the presence of multiple functional signals in their ultrasonic communication.
Missing the point: re-evaluating the earliest lithic technology in the Middle Orinoco
Authors: Riris Philip , Oliver José Ramón , Mendieta Natalia Lozada
Published: June 2018

The Culebra site, located in close proximity to the Atures Rapids, is one of the very few open-air occupations in the entire Orinoco valley that is thought to date to the early Holocene. Following renewed excavations in this location, we characterize the stone technology in unprecedented detail and perform both quantitative and qualitative analyses of the assemblage deposited in the first cultural layers. Additionally, we directly date the sediment forming the depositional context of the assemblage using stratigraphically stable components of soil organic matter. Coupled with our stratigraphic and paedological data, the deposit is, contrary to established estimates, shown to date to the late Holocene, well after the appearance of ceramics in the region. The toolkit identified through the lithic analysis, therefore, does not reflect an Archaic hunter–gatherer adaptation as previously assumed. Our findings are placed in the context of previous research in the Orinoco and lowland South America more broadly. More work is needed to understand the changing role of different stone tool reduction sequences with reference to adaptational strategies and bioclimatic variability.
Water-limited vegetated ecosystems driven by stochastic rainfall: feedbacks and bimodality
Authors: Schaffer Benjamin E. , Rodriguez-Iturbe Ignacio
Published: June 2018

In arid or semi-arid ecosystems, water availability is one of the primary controls on vegetation growth. When subsurface water resources are unavailable, the vegetation growth is dictated by the rainfall, and the random nature of the rainfall arrivals and quantities induces a probability distribution of soil moisture and vegetation biomass via the coupled dynamic equations of biomass balance and water balance. We have previously obtained an exact solution for these distributions under certain conditions, and shown that the mapping of rainfall variability to observed biomass variability can be successfully applied to a field site. Here, we expand upon our earlier theoretical work to show how the dynamics can give rise to more complicated, bimodal (and multimodal) structures in the biomass distribution when positive feedbacks between growth and water availability are included. We also derive some new analytical results for the crossing properties of this system, which enable us to determine on what time scale the effects of these feedbacks will be felt, and, relatedly, how long the system will take to cross between different modes.
Nematic liquid crystals on curved surfaces: a thin film limit
Authors: Nitschke Ingo , Nestler Michael , Praetorius Simon , Löwen Hartmut , Voigt Axel
Published: June 2018

We consider a thin film limit of a Landau–de Gennes Q-tensor model. In the limiting process, we observe a continuous transition where the normal and tangential parts of the Q-tensor decouple and various intrinsic and extrinsic contributions emerge. The main properties of the thin film model, like uniaxiality and parameter phase space, are preserved in the limiting process. For the derived surface Landau–de Gennes model, we consider an
L
2
-gradient flow. The resulting tensor-valued surface partial differential equation is numerically solved to demonstrate realizations of the tight coupling of elastic and bulk free energy with geometric properties.
Composite wave models for elastic plates
Authors: Erbaş Barış , Kaplunov Julius , Nolde Evgeniya , Palsü Melike
Published: June 2018

The long-term challenge of formulating an asymptotically motivated wave theory for elastic plates is addressed. Composite two-dimensional models merging the leading or higher-order parabolic equations for plate bending and the hyperbolic equation for the Rayleigh surface wave are constructed. Analysis of numerical examples shows that the proposed approach is robust not only at low- and high-frequency limits but also over the intermediate frequency range.
Higher flight activity in the offspring of migrants compared to residents in a migratory insect
Authors: Dällenbach Laura J. , Glauser Alexandra , Lim Ka S. , Chapman Jason W. , Menz Myles H. M.
Published: June 2018

Migration has evolved among many animal taxa and migratory species are found across all major lineages. Insects are the most abundant and diverse terrestrial migrants, with trillions of animals migrating annually. Partial migration, where populations consist of resident and migratory individuals, is ubiquitous among many taxa. However, the underlying mechanisms are relatively poorly understood and may be driven by physiological, behavioural or genetic variation within populations. We investigated the differences in migratory tendency between migratory and resident phenotypes of the hoverfly,
Episyrphus balteatus
, using tethered flight mills. Further, to test whether migratory flight behaviour is heritable and to disentangle the effects of environment during development, we compared the flight behaviour of laboratory-reared offspring of migrating, overwintering and summer animals. Offspring of migrants initiated more flights than those of resident individuals. Interestingly, there were no differences among wild-caught phenotypes with regard to number of flights or total flight duration. Low activity in field-collected migrants might be explained by an energy-conserving state that migrants enter into when under laboratory conditions, or a lack of suitable environmental cues for triggering migration. Our results strongly suggest that flight behaviour is heritable and that genetic factors influence migratory tendency in
E. balteatus
. These findings support the growing evidence that genetic factors play a role in partial migration and warrant careful further investigation.
Naked chancelloriids from the lower Cambrian of China show evidence for sponge-type growth
Authors: Cong Pei-Yun , Harvey Thomas H. P. , Williams Mark , Siveter David J. , Siveter Derek J. , Gabbott Sarah E. , Li Yu-Jing , Wei Fan , Hou Xian-Guang
Published: June 2018

Chancelloriids are an extinct group of spiny Cambrian animals of uncertain phylogenetic position. Despite their sponge-like body plan, their spines are unlike modern sponge spicules, but share several features with the sclerites of certain Cambrian bilaterians, notably halkieriids. However, a proposed homology of these ‘coelosclerites' implies complex transitions in body plan evolution. A new species of chancelloriid,
Allonnia nuda
, from the lower Cambrian (Stage 3) Chengjiang Lagerstätte is distinguished by its large size and sparse spination, with modified apical sclerites surrounding an opening into the body cavity. The sclerite arrangement in
A. nuda
and certain other chancelloriids indicates that growth involved sclerite addition in a subapical region, thus maintaining distinct zones of body sclerites and apical sclerites. This pattern is not seen in halkieriids, but occurs in some modern calcarean sponges. With scleritome assembly consistent with a sponge affinity, and in the absence of cnidarian- or bilaterian-grade features, it is possible to interpret chancelloriids as sponges with an unusually robust outer epithelium, strict developmental control of body axis formation, distinctive spicule-like structures and, by implication, minute ostia too small to be resolved in fossils. In this light, chancelloriids may contribute to the emerging picture of high disparity among early sponges.
Ocean warming alters predicted microbiome functionality in a common sea urchin
Authors: Brothers Cecilia J. , Van Der Pol William J. , Morrow Casey D. , Hakim Joseph A. , Koo Hyunmin , McClintock James B.
Published: June 2018

The microbiome of sea urchins plays a role in maintaining digestive health and innate immunity. Here, we investigated the effects of long-term (90 day) exposure to elevated seawater temperatures on the microbiome of the common, subtropical sea urchin
Lytechinus variegatus
. The community composition and diversity of microbes varied according to the type of sample collected from the sea urchin (seawater, feed, intestines, coelomic fluid, digested pellet and faeces), with the lowest microbial diversity (predominately the order Campylobacterales) located in the intestinal tissue. Sea urchins exposed to near-future seawater temperatures maintained the community structure and diversity of microbes associated with their tissues. However, marginal, non-significant shifts in microbial community structure with elevated temperature resulted in significant changes in predicted metagenomic functions such as membrane transport and amino acid and carbohydrate metabolism. The predicted changes in key metabolic categories suggest that near-future climate-induced increases in seawater temperature could shift microbial community function and impact sea urchin digestive and immune physiology.
Adaptive developmental plasticity in rhesus macaques: the serotonin transporter gene interacts with maternal care to affect juvenile social behaviour
Authors: Madrid Jesus E. , Mandalaywala Tara M. , Coyne Sean P. , Ahloy-Dallaire Jamie , Garner Joseph P. , Barr Christina S. , Maestripieri Dario , Parker Karen J.
Published: June 2018

Research has increasingly highlighted the role that developmental plasticity—the ability of a particular genotype to produce variable phenotypes in response to different early environments—plays as an adaptive mechanism. One of the most widely studied genetic contributors to developmental plasticity in humans and rhesus macaques is a serotonin transporter gene-linked polymorphic region (5-HTTLPR), which determines transcriptional efficiency of the serotonin transporter gene
in vitro
and modifies the availability of synaptic serotonin in these species. A majority of studies to date have shown that carriers of a loss-of-function variant of the 5-HTTLPR, the short (s) allele, develop a stress-reactive phenotype in response to adverse early environments compared with long (l) allele homozygotes, leading to the prevalent conceptualization of the s-allele as a vulnerability allele. However, this framework fails to address the independent evolution of these loss-of-function mutations in both humans and macaques as well as the high population prevalence of s-alleles in both species. Here we show in free-ranging rhesus macaques that s-allele carriers benefit more from supportive early social environments than l-allele homozygotes, such that s-allele carriers which receive higher levels of maternal protection during infancy demonstrate greater social competence later in life. These findings provide, to our knowledge, the first empirical support for the assertion that the s-allele grants high undirected biological sensitivity to context in primates and suggest a mechanism through which the 5-HTTLPR s-allele is maintained in primate populations.
The evolution of juvenile susceptibility to infectious disease
Authors: Ashby Ben , Bruns Emily
Published: June 2018

Infection prior to reproduction usually carries greater fitness costs for hosts than infection later in life, suggesting selection should tend to favour juvenile resistance. Yet, juveniles are generally more susceptible than adults across a wide spectrum of host taxa. While physiological constraints and a lack of prior exposure can explain some of this pattern, studies in plants and insects suggest that hosts may trade off juvenile susceptibility against other life-history traits. However, it is unclear precisely how trade-offs shape the evolution of juvenile susceptibility. Here, we theoretically explore the evolution of juvenile susceptibility subject to trade-offs with maturation or reproduction, which could realistically occur due to resource allocation during development (e.g. prioritizing growth over immune defence). We show how host lifespan, the probability of maturation (i.e. of reaching the adult stage) and transmission mode affect the results. Our key finding is that elevated juvenile susceptibility is expected to evolve over a wide range of conditions, but should be lowest when hosts have moderate lifespans and an intermediate probability of reaching the adult stage. Our results elucidate how interactions between trade-offs and the epidemiological-demographic structure of the population can lead to the evolution of elevated juvenile susceptibility.
Cyclic dominance emerges from the evolution of two inter-linked cooperative behaviours in the social amoeba
Authors: Shibasaki Shota , Shimada Masakazu
Published: June 2018

Evolution of cooperation has been one of the most important problems in sociobiology, and many researchers have revealed mechanisms that can facilitate the evolution of cooperation. However, most studies deal only with one cooperative behaviour, even though some organisms perform two or more cooperative behaviours. The social amoebaDictyostelium discoideumperforms two cooperative behaviours in starvation: fruiting body formation and macrocyst formation. Here, we constructed a model that couples these two behaviours, and we found that the two behaviours are maintained because of the emergence of cyclic dominance, although cooperation cannot evolve if only either of the two behaviours is performed. The common chemoattractant cyclic adenosine 3′,5′-monophosphate (cAMP) is used in both fruiting body formation and macrocyst formation, providing a biological context for this coupling. Cyclic dominance emerges regardless of the existence of mating types or spatial structure in the model. In addition, cooperation can re-emerge in the population even after it goes extinct. These results indicate that the two cooperative behaviours of the social amoeba are maintained because of the common chemical signal that underlies both fruiting body formation and macrocyst formation. We demonstrate the importance of coupling multiple games when the underlying behaviours are associated with one another.
Phylogenomics resolves the deep phylogeny of seed plants and indicates partial convergent or homoplastic evolution between Gnetales and angiosperms
Authors: Ran Jin-Hua , Shen Ting-Ting , Wang Ming-Ming , Wang Xiao-Quan
Published: June 2018

After decades of molecular phylogenetic studies, the deep phylogeny of gymnosperms has not been resolved, and the phylogenetic placement of Gnetales remains one of the most controversial issues in seed plant evolution. To resolve the deep phylogeny of seed plants and to address the sources of phylogenetic conflict, we conducted a phylotranscriptomic study with a sampling of all 13 families of gymnosperms and main lineages of angiosperms. Multiple datasets containing up to 1 296 042 sites across 1308 loci were analysed, using concatenation and coalescence approaches. Our study generated a consistent and well-resolved phylogeny of seed plants, which places Gnetales as sister to Pinaceae and thus supports the Gnepine hypothesis. Cycads plus
Ginkgo
is sister to the remaining gymnosperms. We also found that Gnetales and angiosperms have similar molecular evolutionary rates, which are much higher than those of other gymnosperms. This implies that Gnetales and angiosperms might have experienced similar selective pressures in evolutionary histories. Convergent molecular evolution or homoplasy is partially responsible for the phylogenetic conflicts in seed plants. Our study provides a robustly reconstructed backbone phylogeny that is important for future molecular and morphological studies of seed plants, in particular gymnosperms, in the light of evolution.
S-CAP extends clinical-grade pathogenicity prediction to genetic variants that affect RNA splicing
Authors: Jagadeesh Karthik A. , Paggi Joseph M. , Ye James S. , Stenson Peter D. , Cooper David N. , Bernstein Jonathan A. , Bejerano Gill
Published: June 2018

There are over 15,000 known variants that cause human inherited disease by disrupting RNA splicing. While severalin silicomethods such as CADD, EIGEN and LINSIGHT are commonly used to predict the pathogenicity of noncoding variants, we introduce S-CAP, a tool developed specially for splicing which is better able to effectively distinguish pathogenic splicing-relevant variants from benign variants. S-CAP is a novel splicing pathogenicity predictor that reduces the number of splicing-relevant variants of uncertain significance in patient exomes by 41%, a nearly 3-fold improvement over existing noncoding pathogenicity measures while correctly classifying known pathogenic splicing-relevant variants with a clinical-grade 95% sensitivity.
Lineage segregation, pluripotency and X-chromosome inactivation in the pig pre-gastrulation embryo
Authors: Ramos-Ibeas Priscila , Sang Fei , Zhu Qifan , Tang Walfred W.C. , Withey Sarah , Klisch Doris , Loose Matt , Surani M. Azim , Alberio Ramiro
Published: June 2018

High-resolution molecular programs delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis of human embryos is limited to pre-implantation stages, since early post-implantation embryos are inaccessible. Notwithstanding, we previously suggested conserved principles of pig and human early development. For further insight on pluripotent states and lineage delineation, we analysed pig embryos at single cell resolution. Here we show progressive segregation of inner cell mass and trophectoderm in early blastocysts, and then of epiblast and hypoblast in late blastocysts. We detected distinct pluripotent states, first as a short ‘naïve’ state followed by a protracted primed state. Dosage compensation with respect to the X-chromosome in females is attained via X-inactivation in late epiblasts. Detailed human-pig comparison is a basis towards comprehending early human development and a foundation for further studies of human pluripotent stem cell differentiation in pig interspecies chimeras.
Applying biophysical models to understand the role of white matter in cognitive development
Authors: Huber Elizabeth , Henriques Rafael Neto , Owen Julia P. , Rokem Ariel , Yeatman Jason D.
Published: June 2018

Diffusion MRI (dMRI) holds great promise for illuminating the biological changes that underpin cognitive development. The diffusion of water molecules probes the cellular structure of brain tissue, and biophysical modeling of the diffusion signal can be used to make inferences about specific tissue properties that vary over development or predict cognitive performance. However, applying these models to study development requires that the parameters can be reliably estimated given the constraints of data collection with children. Here we collect repeated scans using a multi-shell diffusion MRI protocol in a group of children (ages 7-12) and use two popular biophysical models to characterize axonal properties. We first assess the scan-rescan reliability of model parameters and show that axon water faction can be reliably estimated from a relatively fast acquisition, without applying spatial smoothing or de-noising. We then investigate developmental changes in the white matter, and individual differences in white matter that correlate with reading skill. Specifically, we test the hypothesis that previously reported correlations between reading skill and diffusion anisotropy in the corpus callosum reflect increased axon density in poor readers. Both models support this interpretation, highlighting the utility of biophysical models for testing specific hypotheses about cognitive development.
Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix
Authors: Scholz Nicole , Ehmann Nadine , Sachidanandan Divya , Imig Cordelia , Cooper Benjamin H. , Jahn Olaf , Reim Kerstin , Brose Nils , Pauli Martin , Heckmann Manfred , Stigloher Christian , Langenhan Tobias , Kittel Robert J.
Published: June 2018

Information processing by the nervous system depends on the release of neurotransmitter from synaptic vesicles (SVs) at the presynaptic active zone. Molecular components of the cytomatrix at the active zone (CAZ) regulate the final stages of the SV cycle preceding exocytosis and thereby shape the efficacy and plasticity of synaptic transmission. Part of this regulation is reflected by a physical association of SVs with filamentous CAZ structures. However, our understanding of the protein interactions underlying SV tethering by the CAZ is far from complete. The very C-terminal region of Bruchpilot (Brp), a key component of theDrosophilaCAZ, participates in SV tethering. Yet so far, no vesicular or cytoplasmic molecules have been reported to engage in an interaction with Brp’s C-terminus. Here, we carried out an in vivo screen for molecules that link the Brp C-terminus to SVs. This strategy identified the conserved SNARE (solubleN-ethylmaleimide-sensitive factor (NSF) attachment protein receptor) regulator Complexin (Cpx) as a vesicular interaction partner of Brp. We show that Brp and Cpx interact genetically and functionally. Interfering with Cpx targeting to SVs mirrored distinctive features of a C-terminal Brp truncation: impaired SV recruitment to the CAZ and enhanced short-term synaptic depression. Extending the study beyondDrosophilasynapses, we interrogated active zones of mouse rod bipolar cells. Here, too, we collected evidence for an evolutionarily conserved role of Cpx upstream of SNARE complex assembly where it participates in SV tethering to the CAZ.
Reannotation of eight Drosophila genomes
Authors: Yang Haiwang , Jaime Maria , Polihronakis Maxi , Kanegawa Kelvin , Markow Therese , Kaneshiro Kenneth , Oliver Brian
Published: June 2018

The sequenced genomes in the Drosophila phylogeny is a central resource for comparative work supporting the understanding of the Drosophila melanogaster non-mammalian model system. These have also facilitated studying the selected and random differences that distinguish the thousands of extant species of Drosophila. However, full utility has been hampered by uneven genome annotation. We have generated a large expression profile dataset for nine species of Drosophila and trained a transcriptome assembly approach on Drosophila melanogaster to develop a pipeline that best matched the extensively curated annotation. We then applied this to the other species to add tens of thousands of new gene models per species. We also developed new orthologs to facilitate cross-species comparisons. We validated the new annotation of the distantly related Drosophila grimshawi with an extensive collection of newly sequenced cDNAs. This reannoation will facilitate understanding both the core commonalities and the species differences in this important group of model organisms.
A fast and cost-effective microsampling protocol incorporating reduced animal usage for time-series transcriptomics in rodent malaria parasites
Authors: Ramaprasad Abhinay , Subudhi Amit Kumar , Culleton Richard , Pain Arnab
Published: June 2018

The transcriptional regulation occurring in malaria parasites during the clinically important life stages within host erythrocytes can be studied in vivo with rodent malaria parasites propagated in mice. Time-series transcriptome profiling commonly involves the euthanasia of groups of mice at specific time points followed by the extraction of parasite RNA from whole blood samples. Current methodologies for parasite RNA extraction involve several steps and when multiple time points are profiled, these protocols are laborious, time consuming, and require the euthanisation of large cohorts of mice. We designed a simplified protocol for parasite RNA extraction from blood volumes as low as 20 microliters (microsamples), serially bled from mice via tail snips and directly lysed with TRIzol reagent. Gene expression data derived from microsampling using RNA-seq were closely matched to those derived from larger volumes of leucocyte-depleted and saponin-treated blood obtained from euthanized mice and also tightly correlated between biological replicates. Transcriptome profiling of microsamples taken at different time points during the intra-erythrocytic developmental cycle of the rodent malaria parasite Plasmodium vinckei revealed the transcriptional cascade commonly observed in malaria parasites. Microsampling is a quick, robust and cost-efficient approach to sample collection for in vivo time-series transcriptomic studies in rodent malaria parasites.
Identification of different putative outer membrane electron conduits necessary for Fe(III) citrate, Fe(III)-oxide, Mn(IV)-oxide, or electrode reduction by
Geobacter sulfurreducens
.
Authors: Jiménez Otero Fernanda , Chan Chi Ho , Bond Daniel R
Published: June 2018

At least five gene clusters in the
Geobacter sulfurreducens
genome encode putative ‘electron conduits’ implicated in electron transfer across the outer membrane, each containing a periplasmic multiheme
c
-type cytochrome, integral outer membrane anchor, and outer membrane redox lipoprotein(s). Markerless single gene cluster deletions and all possible multiple deletion combinations were constructed and grown with soluble Fe(III) citrate, Fe(III)- and Mn(IV)-oxides, and graphite electrodes poised at +0.24 V and -0.1 V vs. SHE. Different gene clusters were necessary for reduction of each electron acceptor. During metal oxide reduction, deletion of the previously described
omcBC
cluster caused defects, but deletion of additional components in an Δ
omcBC
background, such as
extEFG
, were needed to produce defects greater than 50% compared to wild type. Deletion of all five gene clusters abolished all metal reduction. During electrode reduction, only the Δ
extABCD
mutant had a severe growth defect at both redox potentials, while this mutation did not affect Fe(III)-oxide, Mn(IV)-oxide, or Fe(III) citrate reduction. Some mutants containing only one cluster were able to reduce particular terminal electron acceptors better than wild type, suggesting routes for improvement by targeting specific electron transfer pathways. Transcriptomic comparisons between fumarate and electrode-based growth showed all of these
ext
clusters to be constitutive, and transcriptional analysis of the triple-deletion strain containing only
extABCD
detected no significant changes in expression of known redox proteins or pili components. These genetic experiments reveal new outer membrane conduit complexes necessary for growth of
G. sulfurreducens
, depending on the available extracellular electron acceptor.
DiverseEscherichia colilineages, from domestic animals and humans in a household, carry colistin resistance genemcr-1in Ecuador
Authors: Loayza María Fernanda , Salinas Liseth , Villavicencio Fernando , Rafael Tamayo , Salas Stephanie , Villacís José , Satan Carolina , Ushiña Liliana , Rivera Ruth , Muñoz Olga , Zurita Jeannete , Nathalie Tijet , Melano Roberto , Reyes Jorge , Trueba Gabriel
Published: June 2018

The aim of this study was to investigate the presence ofEscherichia colicarryingmcr-1gene in domestic animals close to a child who suffered a peritoneal infection by amcr-1positiveE. coli. Rectal or cloacal swabs and fecal samples from domestic animals were plated on selective media to isolate colistin-resistantE. coliand isolates were submitted to detection ofmcr-1gene, pulsed field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), replicon typing and S1-PFGE. Fourmcr-1positiveE. coliisolates (from chicken, turkey and dog) were recovered. No shared PFGE pattern or MLST sequence type were observed among isolates. A 60Kb IncI1γmcr-1-carrying plasmid was detected in all isolates. Our results suggest thatmcr-1gene was horizontally disseminated amongst different lineages ofE. colifrom domestic animals in the child’s household.

Importance

Horizontally transferable colistin resistance (mcr-1 gene) is thought to have originated in domestic animals and transferred to humans through meat and dairy products. In the present report we show evidence that themcr-1 gene could be transferred to differentE. colistrains colonizing different hosts (humans and pets) in the same household.
The transferable resistome of produce
Authors: Blau Khald , Bettermann Antje , Jechalke Sven , Fornefeld Eva , Vanrobaeys Yann , Stalder Thibault , Top Eva , Smalla Kornelia
Published: June 2018

Produce is increasingly recognized as a reservoir of human pathogens and transferable antibiotic resistance genes. This study aimed to explore methods to characterize the transferable resistome of bacteria associated with produce. Mixed salad, arugula, and cilantro purchased from supermarkets were analyzed by means of cultivation- and DNA-based methods. Before and after a nonselective enrichment step, tetracycline (tet) resistantEscherichia coliwere isolated and plasmids conferring tet resistance were captured by exogenous plasmid isolation. Tet resistantE. coliisolates, transconjugants and total community (TC)-DNA from the microbial fraction detached from leaves or after enrichment were analyzed for the presence of resistance genes, class 1 integrons and various plasmids by real-time PCR and PCR-Southern blot hybridization. Real-time PCR primers were developed for IncI and IncF plasmids. Tet resistantE. coliisolated from arugula and cilantro carried IncF, IncI1, IncN, IncH11, IncU and IncX1 plasmids. Three isolates from cilantro were positive for IncN plasmids andblaCTX-M-1. From mixed salad and cilantro, IncF, Inc11, and IncP-1β plasmids were captured exogenously. Importantly, whereas direct detection of IncI and IncF plasmids in TC-DNA failed, these plasmids became detectable in DNA extracted from enrichment cultures. This confirms that cultivation-independent DNA-based methods are not always sufficiently sensitive to detect the transferable resistome in the rare microbiome. In summary, this study showed that an impressive diversity of self-transmissible multiple resistance plasmids was detected in bacteria associated with produce that is consumed raw, and exogenous capturing intoE. colisuggests that they could transfer to gut bacteria as well.
Staged developmental mapping and X chromosome transcriptional dynamics during mouse spermatogenesis
Authors: Ernst Christina , Eling Nils , Martinez-Jimenez Celia P , Marioni John C , Odom Duncan T
Published: June 2018

Understanding male fertility requires an in-depth characterisation of spermatogenesis, the developmental process by which male gametes are generated. Spermatogenesis occurs continuously throughout a male’s reproductive window and involves a complex sequence of developmental steps, both of which make this process difficult to decipher at the molecular level. To overcome this, we transcriptionally profiled single cells from multiple distinct stages during the first wave of spermatogenesis, where the most mature germ cell type is known. This naturally enriches for spermatogonia and somatic cell types present at very low frequencies in adult testes. Our atlas, available as a shiny app (https://marionilab.cruk.cam.ac.uk/SpermatoShiny), allowed us to reconstruct the three main processes of spermatogenesis: spermatogonial differentiation, meiosis, and spermiogenesis. Additionally, we profiled the chromatin changes associated with meiotic silencing of the X chromosome, revealing a set of genes specifically and strongly repressed by H3K9me3 in the spermatocyte stage, but which escape post-meiotic silencing in spermatids.
Trade-offs in provisioning and stability of multiple ecosystem services in agroecosystems
Authors: Montoya Daniel , Haegeman Bart , Gaba Sabrina , Mazancourt Claire de , Bretagnolle Vincent , Loreau Michel
Published: June 2018

Changes in land use generate trade-offs in the delivery of ecosystem services in agricultural landscapes. However, we know little about how the stability of ecosystem services responds to landscape composition, and what ecological mechanisms underlie these trade-offs. Here, we develop a model to investigate the dynamics of three ecosystem services in intensively-managed agroecosystems, i.e. pollination-independent crop yield, crop pollination, and biodiversity. Our model reveals trade-offs and synergies imposed by landscape composition that affect not only the magnitude but also the stability of ecosystem service delivery. Trade-offs involving crop pollination are strongly affected by the degree to which crops depend on pollination and by their relative requirement for pollinator densities. We show conditions for crop production to increase with biodiversity and decreasing crop area, reconciling farmers’ profitability and biodiversity conservation. Our results further suggest that, for pollination-dependent crops, management strategies that focus on maximising yield will often overlook its stability. Given that agriculture has become more pollination-dependent over time, it is essential to understand the mechanisms driving these trade-offs to ensure food security.
A framework for offline evaluation and optimization of real-time algorithms for use in neurofeedback, demonstrated on an instantaneous proxy for correlations
Authors: Ramot Michal , Gonzalez-Castillo Javier
Published: June 2018

Interest in real-time fMRI neurofeedback has grown exponentially over the past few years, both for use as a basic science research tool, and as part of the search for novel clinical interventions for neurological and psychiatric illnesses. In order to expand the range of questions which can be addressed with this tool however, new neurofeedback methods must be developed, going beyond feedback of activations in a single region. These new methods, several of which have already been proposed, are by their nature complex, involving many possible parameters. Here we suggest a framework for evaluating and optimizing algorithms for use in a real-time setting, before beginning the neurofeedback experiment, by offline simulations of algorithm output using a previously collected dataset. We demonstrate the application of this framework on the instantaneous proxy for correlations which we developed for training connectivity between different network nodes, identify the optimal parameters for use with this algorithm, and compare it to more traditional correlation methods. We also examine the effects of advanced imaging techniques, such as multi-echo acquisition, and the integration of these into the realtime processing stream.
A mechanism for synaptic copy between neural circuits
Authors: Shao Yuxiu , Wang Binxu , Sornborger Andrew T. , Tao Louis
Published: June 2018

The brain has a central, short-term learning module, the hippocampus, which transfers what it has learned to long-term memory in cortex during non-REM sleep. The putative mechanism responsible for this type of memory consolidation invokes hierarchically nested hippocampal ripples (100-250 Hz), thalamo-cortical spindles (7-15 Hz), and cortical slow oscillations (< 1 Hz) to enable transfer. Suppression of, for instance, thalamic spindles has been shown to impair hippocampus-dependent memory consolidation. Cortical oscillations are central to information transfer in neural systems. Significant evidence supports the idea that coincident spike input can allow the neural threshold to be overcome, and spikes to be propagated downstream in a circuit. Thus, an observation of oscillations in neural circuits would be an indication that repeated synchronous spiking is enabling information transfer. However, for memory transfer, in which synaptic weights must be being transferred from one neural circuit (region) to another, what is the mechanism? Here, we present a synaptic transfer mechanism whose structure provides some understanding of the phenomena that have been implicated in memory transfer, including the nested oscillations at various frequencies. The circuit is based on the principle of pulse-gated, graded information transfer between neural populations.

PACS numbers: 87.18.Sn,87.19.lj,87.19.lm,87.19.lq
Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat
Authors: Mont Carme , Pilego Polinka Hernandez , Cañete Toni , Oliveras Ignasi , Río-Álamos Cristóbal , Blázquez Gloria , López-Aumatell Regina , Martínez-Membrives Esther , Tobeña Adolf , Flint Jonathan , Fernández-Teruel Alberto , Mott Richard
Published: June 2018

We develop theory, based on earlier work, to partition heritability into a component due to a combination of parent of origin, maternal, paternal and shared environment, and another component that estimates classical additive genetic variance. We then investigate the effects on heritability of the parental origin of alleles in outbred heterogeneous stock rats across 199 complex traits. Parent-of-origin-like heritability was on average 2.7-fold larger than classical additive heritability. Among the phenotypes with the most enhanced parent-of-origin heritability were 10 coping style behaviors, with average 3.2-fold heritability enrichment. To confirm these findings on coping behaviour, and to eliminate the possibility that the parent of origin effects are due to confounding with shared environment, we performed a reciprocal F1 cross between the behaviourally divergent RHA and RLA rat strains. We observed parent-of-origin effects on F1 rat anxiety/coping-related behavior in the Elevated Zero Maze test. Our results are the first to assess genetic parent-of-origin effects in rats, and confirm earlier findings in mice that such effects influence mammalian coping and impulsive behavior.
Exploration of miRNA-mediated fertility regulation network of cytoplasmic male sterility during flower bud development in soybean
Authors: Xianlong Ding , Hao Zhang , Hui Ruan , Yanwei Li , Linfeng Chen , Tanliu Wang , Ling Jin , Xiaoqiang Li , Shouping Yang , Junyi Gai
Published: June 2018

Cytoplasmic male sterility (CMS) plays an important role in the production of soybean hybrid seeds. MicroRNAs (miRNAs) are a class of non-coding endogenous ~21 nt small RNAs that play crucial roles in flower and pollen development by targeting genes in plants. Here, two small RNA libraries and two degradome libraries were constructed from the flower buds of the soybean CMS line NJCMS1A and its restorer (Rf) line NJCMS1C. Following high-throughput sequencing, 558 known miRNAs, 103 novel miRNAs on the other arm of known pre-miRNAs, 10 novel miRNAs, and a number of base-edited miRNAs were identified. Among the identified miRNAs, 76 differentially expressed miRNAs were discovered with greater than two-fold changes between NJCMS1A and NJCMS1C. By degradome analysis, a total of 466 distinct transcripts targeted by 200 miRNAs and 122 distinct transcripts targeted by 307 base-edited miRNAs were detected. Further integrated analysis of transcriptome and small RNA found some miRNAs and their targets’ expression patterns showing a negative correlation, such as miR156b-GmSPL and miR4413b-GmPPR. Previous reports showed that these targets might be related to flower bud development, suggesting that miRNAs might act as regulators of soybean CMS fertility. These findings may provide a better understanding of the miRNA-mediated regulatory networks in CMS mechanisms of soybean.
Directional selection rather than functional constraints can shape the G matrix in rapidly adapting asexuals
Authors: Gomez Kevin , Bertram Jason , Masel Joanna
Published: June 2018

Genetic covariances represent a combination of pleiotropy and linkage disequilibrium, shaped by the population’s history. Observed genetic covariance is most often interpreted in pleiotropic terms. In particular, functional constraints restricting which phenotypes are physically possible can lead to a stableGmatrix with high genetic variance in fitness-associated traits and high pleiotropic negative covariance along the phenotypic curve of constraint. In contrast, population genetic models of relative fitness assume endless adaptation without constraint, through a series of selective sweeps that are well described by recent traveling wave models. We describe the implications of such population genetic models for theGmatrix when pleiotropy is excluded by design, such that all covariance comes from linkage disequilibrium. TheGmatrix is far less stable than has previously been found, fluctuating over the timescale of selective sweeps. However, its orientation is relatively stable, corresponding to high genetic variance in fitness-associated traits and strong negative covariance - the same pattern often interpreted in terms of pleiotropic constraints but caused instead by linkage disequilibrium. We find that different mechanisms drive the instabilities along versus perpendicular to the fitness gradient. The origin of linkage disequilibrium is not drift, but small amounts of linkage disequilibrium are instead introduced by mutation and then amplified during competing selective sweeps. This illustrates the need to integrate a broader range of population genetic phenomena into quantitative genetics.
Functional Analysis of TM6 MADS-box gene in the Octoploid Strawberry by CRISPR/Cas9 directed mutagenesis
Authors: Martín-Pizarro Carmen , Triviño Juan Carlos , Posé David
Published: June 2018

The B-class of MADS-box transcription factors has been studied in many plant species, but remain functionally uncharacterized in theRosaceaefamily. APETALA3 (AP3), a member of this class, controls the identity of petals and stamens inArabidopsis thaliana. In this work, we identified two members of the AP3 lineage in the cultivated strawberry (Fragaria×ananassa):FaAP3andFaTM6. Interestingly,FaTM6, and notFaAP3, shows an expression pattern equivalent to that ofAP3inArabidopsis. Genome editing using Cluster Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system is becoming a robust tool for targeted and stable mutagenesis of DNA. However, whether it can be efficiently used in an octoploid species such asF. ×ananassais not known. Here we report for the first time the application of CRISPR/Cas9 inF. ×ananassato characterize the function of FaTM6 in flower development. An exhaustive analysis by high-throughput sequencing of theFaTM6locus spanning the target sites showed a high efficiency genome editing already in the T0 generation. The phenotypic characterization of the mutant lines indicates that FaTM6 plays a key role in petal and especially in anther development in strawberry. in an octoploid species such asF. ×ananassa, and offer new opportunities for engineering strawberry to improve traits of interest in breeding programs.
Time preferences are reliable across time-horizons and verbal vs. experiential tasks
Authors: Lukinova Evgeniya , Wang Yuyue , Lehrer Steven F. , Erlich Jeffrey C.
Published: June 2018

Individual differences in delay-discounting correlate with important real world outcomes, e.g. education, income, drug use, & criminality. As such, delay-discounting has been extensively studied by economists, psychologists and neuroscientists to reveal its behavioral and biological mechanisms in both human and non-human animal models. However, two major methodological differences hinder comparing results across species. Human studies present long time-horizon options verbally, whereas animal studies employ experiential cues and short delays. To bridge these divides, we developed a novel language-free experiential task inspired by animal decision-making studies. We find that subjects’ time-preferences are reliable across both verbal/experiential differences and also second/day differences. When we examined whether discount factors shifted or scaled across the tasks, we found a surprisingly strong effect of temporal context. Taken together, this indicates that subjects have a stable, but context-dependent, time-preference that can be reliably assessed using different methods; thereby, providing a foundation to bridge studies of time-preferences across species.
An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics
Authors: Angelidis Ilias , Simon Lukas M. , Fernandez Isis E. , Strunz Maximilian , Mayr Christoph H. , Greiffo Flavia R. , Tsitsiridis George , Graf Elisabeth , Strom Tim-Matthias , Eickelberg Oliver , Mann Matthias , Theis Fabian J. , Schiller Herbert B.
Published: June 2018

Aging promotes lung function decline and susceptibility to chronic lung diseases, which are the third leading cause of death worldwide. We used single cell transcriptomics and mass spectrometry to quantify changes in cellular activity states of 30 cell types and the tissue proteome from lungs of young and old mice. Aging led to increased transcriptional noise, indicating deregulated epigenetic control. We observed highly distinct effects of aging on cell type level, uncovering increased cholesterol biosynthesis in type-2 pneumocytes and lipofibroblasts as a novel hallmark of lung aging. Proteomic profiling revealed extracellular matrix remodeling in old mice, including increased collagen IV and XVI and decreased Fraser syndrome complex proteins and Collagen XIV. Computational integration of the aging proteome and single cell transcriptomes predicted the cellular source of regulated proteins and created a first unbiased reference of the aging lung. The lung aging atlas can be accessed via an interactive user-friendly webtool at: https://theislab.github.io/LungAgingAtlas
Stable networks of water-mediated interactions are conserved in activation of diverse GPCRs
Authors: Venkatakrishnan A. J. , Ma Anthony K. , Fonseca Rasmus , Latorraca Naomi R. , Kelly Brendan , Betz Robin M. , Asawa Chaitanya , Kobilka Brian K. , Ron O. Dror
Published: June 2018

G protein-coupled receptors (GPCRs) have evolved to recognize incredibly diverse extracellular ligands while sharing a common architecture and structurally conserved intracellular signaling partners. It remains unclear how binding of diverse ligands brings about GPCR activation, the common structural change that enables intracellular signaling. Here, we identify highly conserved networks of water-mediated interactions that play a central role in activation. Using atomic-level simulations of diverse GPCRs, we show that most of the water molecules in GPCR crystal structures are highly mobile. Several water molecules near the G protein-coupling interface, however, are stable. These water molecules form two kinds of polar networks that are conserved across diverse GPCRs: (i) a network that is maintained across the inactive and the active states and (ii) a network that rearranges upon activation. Comparative analysis of GPCR crystal structures independently confirms the striking conservation of water-mediated interaction networks. These conserved water-mediated interactions near the G protein-coupling region, along with diverse water-mediated interactions with extracellular ligands, have direct implications for structure-based drug design and GPCR engineering.