bluuebunny/crossref_metadata_2025 huggingface dataset:
Within and Between-person Correlates of the Temporal Dynamics of Resting EEG Microstates
Authors: Zanesco Anthony P. , King Brandon G. , Skwara Alea C. , Saron Clifford D.
Published: September 2019

Microstates reflect transient brain states resulting from the activity of synchronously active brain networks that predominate in the broadband EEG time series. Despite increasing interest in understanding how the functional organization of the brain varies across individuals, or the extent to which its spatiotemporal dynamics are state dependent, comparatively little research has examined within and between-person correlates of microstate temporal parameters in healthy populations. In the present study, neuroelectric activity recorded during eyes-closed rest and during simple visual fixation was segmented into a time series of transient microstate intervals. It was found that five data-driven microstate configurations explained the preponderance of topographic variance in the EEG time series of the 374 recordings (from 187 participants) included in the study. We observed that the temporal dynamics of microstates varied within individuals to a greater degree than they differed between persons, with within-person factors explaining a large portion of the variance in mean microstate duration and occurrence rate. Nevertheless, several individual differences were found to predict the temporal dynamics of microstates. Of these, age and gender were the most reliable. These findings suggest that not only do the rich temporal dynamics of whole-brain neuronal networks vary considerably within-individuals, but that microstates appear to differentiate persons based on trait individual differences. The current findings suggest that rather than focusing exclusively on between-person differences in microstates as measures of brain function, researchers should turn their attention towards understanding the factors contributing to within-person variation.
Episodic memory retrieval success is associated with rapid replay of episode content
Authors: Wimmer G. Elliott , Liu Yunzhe , Vehar Neža , Behrens Timothy E.J. , Dolan Raymond J.
Published: September 2019

Memory for everyday experience shapes our representation of the structure of the world, while retrieval of these experiences is fundamental for informing our future decisions. The fine-grained neurophysiological mechanisms that support such retrieval are largely unknown. We studied participants who first experienced, without repetition, unique multi-component episodes. One day later, they engaged in cued retrieval of these episodes whilst undergoing magnetoencephalography (MEG). By decoding individual episode elements, we found that trial-by-trial successful retrieval was supported by sequential replay of episode elements, with a temporal compression factor greater than 60. The direction of replay supporting this retrieval, either backward or forward, depended on whether a participant’s goal was to retrieve elements of an episode that followed or preceded a retrieval cue, respectively. This sequential replay was weaker in very high performing participants, where instead we found evidence for simultaneous clustered reactivation. Our results demonstrate that memory-mediated decisions are supported by a rapid replay mechanism that can flexibly shift in direction in response to task requirements.

One Sentence Summary

Recall of extended episodes of experience is supported by compressed replay of memory elements that flexibly changes direction depending on task temporal orientation.
Surveying the sweetpotato rhizosphere, endophyte, and surrounding soil microbiomes at two North Carolina farms reveals underpinnings of sweetpotato microbiome community assembly
Authors: Pepe-Ranney C , Keyser C , Trimble J , Bissinger B
Published: September 2019

Farmers grow sweetpotatoes worldwide and some sub-Saharan African and Asian diets include sweetpotato as a staple, yet the sweetpotato microbiome is conspicuously less studied relative to crops such as maize, soybean, and wheat. Studying sweetpotato microbiome ecology may reveal paths to engineer the microbiome to improve sweetpotato yield, and/or combat sweetpotato pests and diseases. We sampled sweetpotatoes and surrounding soil from two North Carolina farms. We took samples from sweetpotato fields under two different land management regimes, conventional and organic, and collected two sweetpotato cultivars, ‘Beauregard’ and ‘Covington’. By comparing SSU rRNA gene amplicon sequence profiles from sweetpotato storage root skin, rhizosphere, and surrounding soil we found the skin microbiome possessed the least composition heterogeneity among samples and lowest alpha-diversity and was significantly nested by the rhizosphere in amplicon sequence variant (ASV) membership. Many ASVs were specific to a single field and/or only found in either the skin, rhizosphere, or surrounding soil. Notably, sweetpotato skin enriched forPlanctomycetaceaein relative abundance at both farms. This study elucidates underpinnings of sweetpotato microbiome community assembly, quantifies microbiome composition variance within a single farm, and reveals microorganisms associated with sweetpotato skin that belong to common but uncultured soil phylotypes.
Intrinsic base substitution patterns in diverse species reveal links to cancer and metabolism
Authors: Gelova Suzana P. , Doherty Kassidy N. , Alasmar Salma , Chan Kin
Published: September 2019

Analyses of large-scale sequencing data reveal that mutagenic processes create distinctive patterns of base substitutions, called mutational signatures. Here, we analyzed substitution patterns from seven model species and single nucleotide polymorphisms (SNPs) in 42 species, totalling >1.9 billion variants. We found that the base substitution patterns for many species most closely match mutational signature 5 in cancers. Signature 5 is also ubiquitous in cancers and normal human cells, suggesting similar patterns of mutation across species are likely due to conserved biochemistry. Finally, we present evidence from yeast that sugar metabolism is directly linked to this form of DNA damage. We propose that conserved metabolic processes in cells are coupled to continuous generation of mutations, which are acted upon by genetic selection to drive the evolution of species, and cancers.

One Sentence Summary

Energy metabolism produces DNA damage leading to similar patterns of base substitutions in many species and in human cancers.
Metabolic insight into bacterial community assembly across ecosystem boundaries
Authors: Wisnoski Nathan I. , Muscarella Mario E. , Larsen Megan L. , Peralta Ariane L. , Lennon Jay T.
Published: September 2019

The movement of organisms across habitat boundaries has important consequences for populations, communities, and ecosystems. However, because most species are not well adapted to all habitat types, dispersal into suboptimal habitats could induce physiological changes associated with persistence strategies that influence community assembly. For example, high rates of cross-boundary dispersal are thought to maintain sink populations of terrestrial bacteria in aquatic habitats, but these bacteria may also persist by lowering their metabolic activity, introducing metabolic heterogeneity that buffers the population against niche selection. To differentiate between these assembly processes, we analyzed bacterial composition along a hydrological flow path from terrestrial soils through an aquatic reservoir by sequencing the active and total (active + inactive) portions of the community. When metabolic heterogeneity was ignored, our data were consistent with views that cross-boundary dispersal is important for structuring aquatic bacterial communities. In contrast, we found evidence for strong niche selection when metabolic heterogeneity was explicitly considered, suggesting that, relative to persistence strategies, dispersal may have a weaker effect on aquatic community assembly than previously thought. By accounting for metabolic heterogeneity in complex communities, our findings clarify the roles of local- and regional-scale assembly processes in terrestrial-aquatic meta-ecosystems.
Neuromodulation of pelvic nerve during early phase of spinal cord injury in rats using implantable prototype devices - a preliminary study
Authors: Peh Wendy Yen Xian , Alam Monzurul , Ahmed Rakib Uddin , Lee Sanghoon , Ong Li Jing , Lu Shuhao , Mogan Roshini , Gammad Gil Gerald Lasam , Ng Kian Ann , Rusly Astrid , Nag Sudip , Zheng Yong-Ping , Yen Shih-Cheng
Published: September 2019

Objectives

The bladder becomes retentive during the early phase of spinal cord injury, and requires proper bladder management to prevent damage to the lower urinary tract and kidney. We investigated the effects of on-demand pelvic nerve stimulation on the areflexive bladder during the earliest phase of complete spinal cord injury in rats and the use of pelvic nerve signals as a proxy to estimate intravesical pressure for closed-loop applications.

Materials and Methods

In order to stimulate the pelvic nerves in female Sprague-Dawley rats with complete spinal cord transection (T7 level), a flexible electrode was implanted unilaterally on pelvic nerve, and electrical stimulation was provided by a custom-built nerve stimulator. Stimulation-evoked voiding was monitored in the awake state while size, capacity and spontaneous contractions of the bladder were analysed under anaesthesia. Separately, recordings of the pelvic nerve signals, external urethral sphincter activity and intravesical pressure were performed in animals with intact and transected spinal cord under anaesthesia.

Results

Successful pelvic nerve stimulation enabled more frequent voiding, reduced overdistension of bladder, and preserved non-voiding spontaneous bladder contractions. Typical bladder management protocol for SCI rats (manual expression every 8 – 12 hours) resulted in more severe bladder overdistention. Signal processing of the recorded extraneural pelvic nerve signals successfully reconstructed changes in intravesical pressure, demonstrating their use in estimating the fullness and contractions of the bladder.

Conclusions

The preliminary results suggest that pelvic nerve stimulators can serve as an alternative method for frequent emptying of the areflexive bladder. Simultaneous recording of the same pelvic nerve will be useful for development of a closed-loop neuroprosthesis.
How to choose sets of ancestry informative markers: A supervised feature selection approach
Authors: Pfaffelhuber Peter , Grundner-Culemann Franziska , Lipphardt Veronika , Baumdicker Franz
Published: September 2019

Inference of the Biogeographical Ancestry (BGA) of a person or trace relies on three ingredients: (1) A reference database of DNA samples including BGA information; (2) a statistical clustering method; (3) a set of loci which segregate dependent on geographical location, i.e. a set of so-called Ancestry Informative Markers (AIMs). We used the theory of feature selection from statistical learning in order to obtain AIM-sets for BGA inference. Using simulations, we show that this learning procedure works in various cases, and outperforms ad hoc methods, based on statistics likeFSTor informativeness for the choice of AIMs. Applying our method to data from the 1000 genomes project (excluding Admixed Americans) we identified an AIMset of 17 SNPs, which partly overlaps with existing ones. For continental BGA, the AIMset outperforms existing AIMsets on the 1000 genomes dataset, and gives a vanishing misclassification error.
Over eight hundred cannabis strains characterized by the relationship between their psychoactive effects, perceptual profiles, and chemical compositions
Authors: de la Fuente Alethia , Zamberlan Federico , Ferrán Andrés Sánchez , Carrillo Facundo , Tagliazucchi Enzo , Pallavicini Carla
Published: September 2019

Background

Commercially available cannabis strains have multiplied in recent years as a consequence of regional changes in legislation for medicinal and recreational use. Lack of a standardized system to label plants and seeds hinders the consistent identification of particular strains with their elicited psychoactive effects. The objective of this work was to leverage information extracted from large databases to improve the identification and characterization of cannabis strains.

Methods

We analyzed a large publicly available dataset where users freely reported their experiences with cannabis strains, including different subjective effects and flavour associations. This analysis was complemented with information on the chemical composition of a subset of the strains. Both supervised and unsupervised machine learning algorithms were applied to classify strains based on self-reported and objective features.

Results

Metrics of strain similarity based on self-reported effect and flavour tags allowed machine learning classification into three major clusters corresponding toCannabis sativa,Cannabis indica, and hybrids. Synergy between terpene and cannabinoid content was suggested by significative correlations between psychoactive effect and flavour tags. The use of predefined tags was validated by applying semantic analysis tools to unstructured written reviews, also providing breed-specific topics consistent with their purported medicinal and subjective effects. While cannabinoid content was variable even within individual strains, terpene profiles matched the perceptual characterizations made by the users and could be used to predict associations between different psychoactive effects.

Conclusions

Our work represents the first data-driven synthesis of self-reported and chemical information in a large number of cannabis strains. Since terpene content is robustly inherited and less influenced by environmental factors, flavour perception could represent a reliable marker to predict the psychoactive effects of cannabis. Our novel methodology contributes to meet the demands for reliable strain classification and characterization in the context of an ever-growing market for medicinal and recreational cannabis.
MAP Kinase inhibition reshapes tumor microenvironment of mouse pancreatic cancer by depleting anti-inflammatory macrophages
Authors: Delfino Pietro , Neander Christian , Filippini Dea , D’Agosto Sabrina L. , Vicentini Caterina , Fiorini Elena , Lupo Francesca , Fiorini Claudia , Rusev Borislav , Temgue Tane Gael D. , De Sanctis Francesco , Simbolo Michele , Ugel Stefano , Bronte Vincenzo , Fassan Matteo , Lawlor Rita T. , Boschi Federico , Barbi Stefano , Scarpa Aldo , Cheung Phyllis F. , Siveke Jens T. , Corbo Vincenzo
Published: September 2019

The RAF/MEK/ERK (MAP Kinase) pathway is the index oncogenic signaling towards which many compounds have been developed and tested for the treatment of KRAS-driven cancers, including pancreatic ductal adenocarcinoma (PDA). Here, we explored the immunological changes induced by targeted MEK1/2 inhibition (MEKi) using trametinib in preclinical mouse models of PDA. We evaluated the dynamic changes in the immune contexture of mouse PDA upon MEKi using a multidimensional approach (mRNA analyses, flow cytometry, and immunophenotyping). Effect of MEKi on the viability and metabolism of macrophages was investigated in vitro. We showed that transcriptional signatures of MAP Kinase activation are enriched in aggressive human PDA subtype (squamous/basal-like/quasimesenchymal), while short term MEKi treatment in mouse PDA induced subtype switching. Integrative mRNA expression and immunophenotypic analyses showed that MEKi reshapes the immune landscape of PDA by depleting rather than reprogramming macrophages, while augmenting infiltration by neutrophils. Depletion of macrophages is observed early in the course of in vivo treatment and is at least partially due to their higher sensitivity to MEKi. Tumor-associated macrophages were consistently reported to interfere with gemcitabine uptake by PDA cells. Here, our in vivo studies show a superior antitumor activity upon combination of MEKi and gemcitabine using a sequential rather than simultaneous dosing protocol. Our results show that MEK inhibition induces a dramatic remodeling of the tumor microenvironment of mouse PDA through depletion of macrophages, which substantially improves the antitumor activity of gemcitabine.
Understanding the effect of temperature on Bluetongue disease risk in livestock
Authors: El Moustaid Fadoua , Thronton Zorian , Slamani Hani , Ryan Sadie J. , Johnson Leah R.
Published: September 2019

The transmission of vector-borne diseases is governed by complex factors including pathogen characteristics, vector-host interactions, and environmental conditions. Temperature is a major driver for many vector-borne diseases including Bluetongue viral (BTV) disease, a midge-borne febrile disease of ruminants, notably livestock, whose etiology ranges from mild or asymptomatic to rapidly fatal, thus threatening animal agriculture and the economy of affected countries. Using modeling tools, we seek to predict where transmission can occur based on suitable temperatures for BTV. We fit thermal performance curves to temperature sensitive midge life history traits, using a Bayesian approach. Then, we incorporated these into a new formula for the disease basic reproductive number,R0, to include trait responses, for two species of key midge vectors,Culicoides sonorensisandCulicoides variipennis. Our results show that outbreaks of BTV are more likely between 15°C and 33°C with predicted peak transmission at 26°C. The greatest uncertainty inR0is associated with the uncertainty in: mortality and fecundity of midges near optimal temperature for transmission; midges’ probability of becoming infectious post infection at the lower edge of the thermal range; and the biting rate together with vector competence at the higher edge of the thermal range. We compare ourR0to two otherR0formulations and show that incorporating thermal curves into all three leads to similar BTV risk predictions. To demonstrate the utility of this model approach, we created global suitability maps indicating the areas at high and long-term risk of BTV transmission, to assess risk, and anticipate potential locations of establishment.
Neural hierarchical models of ecological populations
Authors: Joseph Maxwell B.
Published: September 2019

Neural networks are increasingly being used in science to infer hidden dynamics of natural systems from noisy observations, a task typically handled by hierarchical models in ecology. This paper describes a class of hierarchical models parameterized by neural networks: neural hierarchical models. The derivation of such models analogizes the relationship between regression and neural networks. A case study is developed for a neural dynamic occupancy model of North American bird populations, trained on millions of detection/non-detection time series for hundreds of species, providing insights into colonization and extinction at a continental scale. Flexible models are increasingly needed that scale to large data and represent ecological processes. Neural hierarchical models satisfy this need, providing a bridge between deep learning and ecological modeling that combines the function representation power of neural networks with the inferential capacity of hierarchical models.
Subjective value, not a gridlike code, describes neural activity in ventromedial prefrontal cortex during value-based decision-making
Authors: Lee Sangil , Yu Linda Q. , Lerman Caryn , Kable Joseph W.
Published: September 2019

Across many studies, ventromedial prefrontal cortex (vmPFC) activity has been found to correlate with subjective value during value-based decision-making. Recently, however, vmPFC has also been shown to reflect a hexagonal gridlike code during navigation through physical and conceptual space. This raises the possibility that the subjective value correlates previously observed in vmPFC may have actually been a misconstrued gridlike signal. Here, we first show that, in theory, a hexagonal gridlike code of two-dimensional attribute space could mimic vmPFC activity previously attributed to subjective value. However, using fMRI data from a large number of subjects performing an intertemporal choice task, we show clear and unambiguous evidence that subjective value is a better description of vmPFC activity than a hexagonal gridlike code. In fact, we find no significant evidence at all for a hexagonal gridlike code in vmPFC activity during intertemporal choice. This result limits the generality of gridlike modulation as description of vmPFC activity. We suggest that vmPFC may flexibly switch representational schemes so as to encode the most relevant information for the current task.
Effects of feeding treatment on growth rate and performance of primiparous Holstein dairy heifers
Authors: Le Cozler Yannick , Jurquet Julien , Bedere Nicolas.
Published: September 2019

The objective of this study was to investigate effects of feeding-rearing programs that aim for first calving at 20-27 months (mo) of age on growth, reproduction and production performance of Holstein cows at nulliparous and primiparous stages. We hypothesised that, in a seasonal autumn-calving strategy, heifers born late in the season could catch up to the growth of heifers born earlier and be inseminated during the same period, at a body weight (BW) of at least 370 kg. This approach would result in first calving age at 21-22 mo of age without impairing their later performance. To test this hypothesis, we studied 217 heifers over 3 years. They were split into three treatment groups: control feeding (SD), an intensive-plane diet (ID1) from birth to 6 mo of age or an intensive-plane diet from birth to one year of age. Heifers in groups SD and ID1 were born from September until the end of November, while those in ID2 were born later. The present study showed that late-born heifers (ID2) could catch up with the growth of the others due to the feeding treatment, although they were still 42 kg lighter than the SD and ID1 heifers at first calving. No difference in reproductive performance was observed among groups. Once primiparous, the cows reared with the ID2 treatment tended to produce less milk than SD and ID1 cows (ca. 400 kg less on a 305 d basis throughout lactation), and no differences in milk composition, feed intake, body condition score or BW were observed among groups. Age at first service (AFS) was classified a posteriori into three classes: 12.5 (AFS12.5), 14.0 (AFS14.0) and 15.5 mo (AFS15.5) of age. Heifers in AFS12.5 grew faster than those in AFS14.0 and AFS15.5. Once primiparous, the AFS12.5 cows tended to produce less milk at peak than AFS14.0 and AFS15.5 cows (ca. 1.5 kg/d less) although no difference in total milk yield during lactation was observed. No differences in milk composition, feed intake, body condition score or BW were observed among groups. These results support the conclusion that the feeding treatment can enable late-born heifers to catch up to the growth of heifers born earlier in the season. This strategy results in an earlier first calving that does not impair their reproductive performance but does decrease milk yield slightly during first lactation. Future studies should investigate long-term effects of this strategy.
Platelet proteolytic machinery assessment in Alzheimer’s Diseases
Authors: Muriu Roy G. , Sage Jessica M. , Agbas Abdulbaki
Published: September 2019

Aim

Platelets provide substantial information about the proteolytic system profile in neurodegenerative diseases. Assessment of autophagy and proteasome target proteins in platelets may reflect tissue proteolytic machinery profile in central nervous system in Alzheimer’s diseases (AD). We aimed to demonstrate the optimum assay conditions and identify target proteins in platelet proteolytic machinery.

Methods

Platelet samples were obtained from clinically verified AD patients and age-matched non-demented control subjects that were recruited by University of Kansas Alzheimer’s disease Center.

Autophagosome participating proteins in platelets were identified by Western blotting analysis. Standard gel electrophoresis and electro transfer apparatus were used for protein transfer onto the membrane. Several antibodies were tested to identify the best working antibodies, and their concentrations were optimized. An ELISA kit was used for platelet proteasome protein determination. Infrared imaging technology was used for visualizing the proteins on the membrane.

Results

Autophagosome participating proteins showed elevated levels in AD patient platelet cytosol. Only LC3-I autophagosome protein levels were significantly elevated. The concentrations of platelet lysate proteasome were assessed. AD patient’s proteasome levels were elevated but they were statistically not important as compared to controls.

Conclusions

Platelets can be used for assessing whether proteolytic system is functional. Blood-based sampling from human donors is less-invasive and analyzing platelet proteolytic system profile may help to develop pharmaceutical intervention approaches for neurodegenerative diseases in general.
Novel model of distal myopathy caused by the myosin rod mutation R1500P disrupts acto-myosin binding
Authors: Wilson Genevieve C. K. , Buvoli Ada , Buvoli Massimo , Woulfe Kathleen C. , Walker Lori A. , Leinwand Leslie A.
Published: September 2019

Introduction

More than 400 mutations in β-myosin, a slow myosin motor, can cause both cardiac and skeletal myopathy in humans. A small subset of these mutations, mostly located in the myosin rod, leads to a progressive skeletal muscle disease known as Laing distal myopathy (MPD1). While this disease has previously been studied using a variety of systems, it has never been studied in the mammalian muscle environment. Here, we describe a mouse model for the MPD1-causing mutation R1500P to elucidate disease pathogenesis and to act as a future platform for testing therapeutic interventions.

Methods

Because mice have very few slow skeletal muscles compared to humans, we generated mice expressing the β-myosin R1500P mutation or WT β-myosin in fast skeletal muscle fibers and determined the structural and functional consequences of the R1500P mutation.

Results

The mutant R1500P myosin affects both muscle histological structure and function and the mice exhibit a number of the histological hallmarks that are often identified in patients with MPD1. Furthermore, R1500P mice show decreased muscle strength and endurance, as well as ultrastructural abnormalities in the SR & t-tubules. Somewhat surprisingly because of its location in the rod, the R1500P mutation weakens acto-myosin binding by affecting cross-bridge detachment rate.

Conclusions

While each group of MPD1-causing mutations most likely operates through distinct mechanisms, our model provides new insight into how a mutation in the rod domain impacts muscle structure and function and leads to disease.
Enhancing natural killer cell function with gp41-targeting bispecific antibodies to combat HIV infection
Authors: Ramadoss Nitya S. , Zhao Nancy Q. , Richardson Barbra A. , Grant Philip M. , Kim Peter S. , Blish Catherine A.
Published: September 2019

Objective(s)

To develop and evaluate the activity of bispecific antibodies (bsAbs) to enhance NK cell antibody-dependent cellular cytotoxicity (ADCC) against HIV-infected cells.

Design

These bsAbs are based on patient-derived antibodies targeting the conserved gp41 stump of HIV Env, and also incorporate a high affinity scFv targeting the activating receptor CD16 on NK cells. Overall, we expect the bsAbs to provide increased affinity and avidity over their corresponding monoclonal antibodies, allowing for improved ADCC activity against Env-expressing target cells.

Methods

bsAbs and their corresponding mAbs were expressed in 293T cells and purified. The binding of bsAbs and mAbs to their intended targets was determined using Bio-Layer Interferometry, as well as flow cytometry-based binding assays onin vitroinfected cells. The ability of these bsAbs to improve NK cell activity against HIV-infected cells was tested usingin vitroco-culture assays, using flow cytometry and calcein release to analyze NK cell degranulation and target cell killing, respectively.

Results

The bsAbs bound gp41 with similar affinity to their corresponding mAbs, and had increased affinity for CD16. The bsAbs also bound to primary CD4 T cells infectedin vitrowith two different strains of HIV. In addition, the bsAbs induce increased NK cell degranulation and killing of autologous HIV-infected CD4 T cells.

Conclusions

These bsAbs may provide a promising strategy to improve NK-mediated immune targeting of infected cells during HIV infection.
Widespread Receptor Driven Modulation in Peripheral Olfactory Coding
Authors: Xu Lu , Li Wenze , Voleti Venkatakaushik , Hillman Elizabeth M. C. , Firestein Stuart
Published: September 2019

We utilized swept confocally aligned planar excitation (SCAPE) microscopy to measure odor-driven activity simultaneously in many (>10,000) olfactory sensory neurons distributed over large areas of intact mouse olfactory epithelium. This approach allowed us to investigate the responses to mixtures or blends of odors and their components, a more realistic stimulus than monomolecular odors. In up to 38% of responding cells, responses to a mixture of odors were different - absent, smaller or larger - than what would be expected from the sum of the individual components. Further investigation revealed instances of both antagonism and allosteric enhancement in the primary olfactory sensory neurons. All 10 of the odor compounds tested were found to act as both agonists and antagonists at different receptors. We present a hypothetical scheme for how modulation at the peripheral receptors increases the capability of the olfactory system to recognize patterns of complex odor mixtures. The widespread modulation of primary sensory receptors argues against a simple combinatorial code and should motivate a search for alternative coding strategies.
Live-cell imaging of early events following pollen perception in self-incompatibleArabidopsis thaliana
Authors: Rozier Frédérique , Riglet Lucie , Kodera Chie , Bayle Vincent , Durand Eléonore , Schnabel Jonathan , Gaude Thierry , Fobis-Loisy Isabelle
Published: September 2019

Early events occurring at the surface of the female organ are critical for plant reproduction, especially in species with a dry stigma. Following landing on the stigmatic papilla cells, the pollen hydrates and germinates a tube, which penetrates the cell wall and grows towards the ovules to convey the male gametes to the embryo sac. In self-incompatible (SI) species within the Brassicaceae, these processes are blocked when the stigma encounters an incompatible pollen. Here, based on the generation of SI-Arabidopsis lines and by setting up a live imaging system, we showed that control of pollen hydration has a central role in pollen selectivity. The faster pollen pumps water from the papilla during an initial period of 10 minutes, the faster it germinates. Furthermore, we found that the SI barriers act to block the proper hydration of incompatible pollen and when hydration is promoted by high humidity, an additional control prevents pollen tube penetration into the stigmatic wall. In papilla cells, actin bundles focalize at the contact site with the compatible pollen but not with the incompatible one, raising the possibility that stigmatic cells react to the mechanical pressure applied by the invading growing tube.

Highlight

A live imaging system coupled with self-incompatible Arabidopsis lines highlight the role of stigmatic cells in controlling pollen hydration and in reacting to pollen tube intrusion by remodeling actin cytoskeleton.
A flexible anatomic set of mechanical models for the organ of Corti
Authors: Berger Jorge , Rubinstein Jacob
Published: September 2019

We build a flexible platform for the study of the mechanical performance of the organ of Corti (OoC) in the transduction of basilar membrane (BM) vibrations to motion of an inner hair cell bundle (IHB). In this platform, each anatomic component of the OoC is described by an equation of motion that can be followed in time. We propose an initial set of models that attempt to capture the nonlinearities of somatic and bundle motility, but can nevertheless be easily handled. The anatomic components that we consider are the outer hair cells (OHCs), the outer hair cell bundles, Deiters cells, Hensen cells, the IHB and various sections of the reticular lamina. We study endolymph fluid motion in the subtectorial gap and then the mutual interactions among the components of the OoC, including the pressure exerted by endolymph. Minute bending of the apical ends of the OHCs can have a significant impact on the passage of motion from the BM to the IHB, including possible critical oscillator behaviour, even without the assistance of tectorial motion, shearing, or bundle motility. Thus, the components of the OoC could cooperate to enhance frequency selectivity, amplitude compression and signal to noise ratio in the passage from the BM to the IHB. Our models also provide a mechanism that could contribute to appropriate amplification of the wave travelling along the cochlea.
Temperature–Energy-space Sampling Molecular Dynamics: Deterministic, Iteration-free, and Single-replica Method utilizing Continuous Temperature System
Authors: Fukuda Ikuo , Moritsugu Kei
Published: September 2019

We developed coupled Nosé–Hoover (NH) molecular dynamics equations of motion (EOM), wherein the heat-bath temperature for the physical system (PS) fluctuates according to an arbitrary predetermined weight. The coupled NH is defined by suitably jointing the NH EOM of the PS and the NH EOM of the temperature system (TS), where the inverse heat-bath temperature β is a dynamical variable. In this study, we define a method to determine the effective weight for enhanced sampling of the PS states. The method, based on ergodic theory, is reliable, and eliminates the need for time-consuming iterative procedures and resource-consuming replica systems. The resulting TS potential in a two dimensional (β, ϵ)-space forms a valley, and the potential minimum path forms a river flowing through the valley. β oscillates around the potential minima for each energy ϵ, and the motion of β derives a motion of ϵ and receives the ϵ’s feedback, which leads to a mutual boost effect. Thus, it also provides a specific dynamical mechanism to explain the features of enhanced sampling such that the temperature-space “random walk” enhances the energy-space “random walk.” Surprisingly, these mutual dynamics between β and ϵ naturally arise from the static probability theory formalism of double density dynamics that was previously developed, where the Liouville equation with an arbitrarily given probability density function is the fundamental polestar. Numerical examples using a model system and an explicitly solvated protein system verify the reliability, simplicity, and superiority of the method.
Measuring genome sizes using read-depth, k-mers, and flow cytometry: methodological comparisons in beetles (Coleoptera)
Authors: Pflug James M. , Holmes Valerie Renee , Burrus Crystal , Spencer Johnston J. , Maddison David R.
Published: September 2019

Measuring genome size across different species can yield important insights into evolution of the genome and allow for more informed decisions when designing next-generation genomic sequencing projects. New techniques for estimating genome size using shallow genomic sequence data have emerged which have the potential to augment our knowledge of genome sizes, yet these methods have only been used in a limited number of empirical studies. In this project, we compare estimation methods using next-generation sequencing (k-mer methods and average read depth of single-copy genes) to measurements from flow cytometry, the gold standard for genome size measures, using ground beetles (Carabidae) and other members of the beetle suborder Adephaga as our test system. We also present a new protocol for using read-depth of single-copy genes to estimate genome size. Additionally, we report flow cytometry measurements for five previously unmeasured carabid species, as well as 21 new draft genomes and six new draft transcriptomes across eight species of adephagan beetles. No single sequence-based method performed well on all species, and all tended to underestimate the genome sizes, although only slightly in most samples. For one species,Bembidion haplogonum, most sequence-based methods yielded estimates half the size suggested by flow cytometry. This discrepancy for k-mer methods can be explained by a large number of repetitive sequences, but we have no explanation for why read-depth methods yielded results that were also strikingly low.
In vitro comparison of the internal ribosomal entry site activity from rodent hepacivirus and pegivirus
Authors: Sims Stuart , Michaelsen Kevin , Burkhard Sara , Fraefel Cornel
Published: September 2019

The 5’ untranslated region (5’ UTR) of rodent hepacivirus (RHV) and pegivirus (RPgV) contain sequence homology to the HCV type IV internal ribosome entry sites (IRES). Utilizing a monocistronic expression vector with an RNA polymerase I promoter to drive transcription we show cell-specific IRES translation and regions within the IRES required for full functionality. Focusing on RHV we further pseudotyped lentivirus with RHV and showed cell surface expression of the envelope proteins and transduction of murine hepatocytes.
A multi-view model for relative and absolute microbial abundances
Authors: Williamson Brian D. , Hughes James P. , Willis Amy D.
Published: September 2019

The absolute abundance of bacterial taxa in human host-associated environments play a critical role in reproductive and gastrointestinal health. However, obtaining the absolute abundance of many bacterial species is typically prohibitively expensive. In contrast, relative abundance data for many species is comparatively cheap and easy to collect (e.g., with universal primers for the 16S rRNA gene). In this paper, we propose a method to jointly model relative abundance data for many taxa and absolute abundance data for a subset of taxa. Our method provides point and interval estimates for the absolute abundance of all taxa. Crucially, our proposal accounts for differences in the efficiency of taxon detection in the relative and absolute abundance data. We show that modeling taxon-specific efficiencies substantially reduces the estimation error for absolute abundance, and controls the coverage of interval estimators. We demonstrate the performance of our proposed method via a simulation study, a sensitivity study where we jackknife the taxa with observed absolute abundances, and a study of women with bacterial vaginosis.
IRG1 controls host responses to restrict Mycobacterium tuberculosis infection
Authors: Machelart Arnaud , Belhaouane Imène , Deboosere Nathalie , Poncin Isabelle , Saint-André Jean-Paul , Pauwels Anne-Marie , Song Ok-Ryul , Jouny Samuel , Rouanet Carine , Poncet Anaïs , Marion Sabrina , Laine William , Kluza Jérôme , Muraille Eric , Beyaert Rudi , Majlessi Laleh , Canaan Stéphane , Brodin Priscille , Hoffmann Eik
Published: September 2019

Mycobacterium tuberculosis (Mtb), the pathogen causing human tuberculosis, has evolved multiple strategies to successfully prevent clearance by immune cells and to establish dissemination and long-term survival in the host. The modulation of host immunity to maximize pathogen elimination while minimizing inflammation-mediated tissue damage may provide another tool to fight drug-resistant Mtb strains. Metabolic reprogramming of phagocytes can dramatically influence the intracellular colonization by Mtb and the key players involved in this process remain a matter of debate. Here, we demonstrate that aconitate decarboxylase 1 (Acod1; also known as immune-responsive gene 1, IRG1), which converts cis-aconitate into the metabolite itaconate, is a major player in controlling the acute phase of Mtb infection. Exposure of IRG1-deficient mice to a virulent Mtb strain (H37Rv) was lethal, while M. bovis BCG and the H37Ra attenuated Mtb strain induced neither lethality nor severe lung immunopathology. Lungs of IRG1-deficient mice infected by Mtb H37Rv displayed large areas of necrotizing granulomatous inflammation and neutrophil infiltration, accompanied by reduced levels of B and T lymphocytes and increased levels of alveolar and interstitial macrophage populations, compared to their wild type counterparts. Next, we show that IRG1, beyond its recruitment to Mtb-containing vacuoles, restricts Mtb replication and lipid droplets accumulation in phagocytes, hallmarks of a tight interplay between the bacillus and the host. Altogether, IRG1 confines the host response to create a favourable phagocytic environment for Mtb controlled intracellular replication.
Rapid and independent evolution of ancestral and novel defenses in a genus of toxic plants (Erysimum, Brassicaceae)
Authors: Züst Tobias , Strickler Susan R. , Powell Adrian F. , Mabry Makenzie E. , An Hong , Mirzaei Mahdieh , York Thomas , Holland Cynthia K. , Kumar Pavan , Erb Matthias , Petschenka Georg , Goméz José María , Perfectti Francisco , Müller Caroline , Pires J. Chris , Mueller Lukas A. , Jander Georg
Published: September 2019

Phytochemical diversity is thought to result from coevolutionary cycles as specialization in herbivores imposes diversifying selection on plant chemical defenses. Plants in the speciose genusErysimum(Brassicaceae) produce both ancestral glucosinolates and evolutionarily novel cardenolides as defenses. Here we test macroevolutionary hypotheses on co-expression, co-regulation, and diversification of these potentially redundant defenses across this genus. We sequenced and assembled the genome ofE. cheiranthoidesand foliar transcriptomes of 47 additionalErysimumspecies to construct a highly resolved phylogeny, revealing that cardenolide diversity increased rapidly rather than gradually over evolutionary time. Concentrations, inducibility, and diversity of the two defenses varied independently among species, with no evidence for trade-offs. Closely related species shared similar cardenolide traits, but not glucosinolate traits, likely as a result of specific selective pressures acting on distinct molecular diversification mechanisms. Ancestral and novel chemical defenses inErysimumthus appear to provide complementary rather than redundant functions.
Regulatory non-coding small RNAs are diverse and abundant in an extremophilic microbial community
Authors: Gelsinger Diego R. , Uritskiy Gherman , Reddy Rahul , Munn Adam , Farney Katie , DiRuggiero Jocelyne
Published: September 2019

Regulatory small RNAs (sRNAs) represent a major class of regulatory molecules that play large-scale and essential roles in many cellular processes across all domains of life. Microbial sRNAs have been primarily investigated in a few model organisms and little is known about the dynamics of sRNA synthesis in natural environments, and the roles of these short transcripts at the community level. Analyzing the metatranscriptome of a model extremophilic community inhabiting halite nodules (salt rocks) from the Atacama Desert with SnapT – a new sRNA annotation pipeline – we discovered hundreds of intergenic (itsRNAs) and antisense (asRNAs) sRNAs. The halite sRNAs were taxonomically diverse with the majority expressed by members of the Halobacteria. We found asRNAs with expression levels negatively correlated with that of their putative overlapping target, suggesting a potential gene regulatory mechanism. A number of itsRNAs were conserved and significantly differentially expressed (FDR<5%) between 2 sampling time points allowing for stable secondary structure modeling and target prediction. This work demonstrates that metatranscriptomic field experiments link environmental variation with changes in RNA pools and have the potential to provide new insights into environmental sensing and responses in natural microbial communities through non-coding RNA mediated gene regulation.
Dopamine in the songbird auditory cortex shapes auditory preference
Authors: Barr Helena J. , Wall Erin M. , Woolley Sarah C.
Published: September 2019

In vocal communication, vocal signals can provide listeners with information and also elicit motivated responses. Auditory cortical and mesolimbic reward circuits are often considered to have distinct roles in these processes, with auditory cortical circuits responsible for detecting and discriminating sounds and mesolimbic circuits ascribing salience and modulating preference for those sounds. Here, we investigated whether dopamine within auditory cortical circuits themselves can shape the incentive salience of a vocal signal. Using female zebra finches, who show natural preferences for vocal signals produced by males (‘songs’), we found that pairing passive song playback with pharmacological manipulations of dopamine in the secondary auditory cortex drives changes to song preferences. Plasticity of song preferences by dopamine lasted for at least one week and was not influenced by norepinephrine manipulations. These data suggest that dopamine acting directly in sensory processing areas can shape the incentive salience of communication signals.
The consequences of mixed-species malaria parasite co-infections in mice and mosquitoes for disease severity, parasite fitness, and transmission success
Authors: Tang Jianxia , Templeton Thomas J. , Cao Jun , Culleton Richard
Published: September 2019

The distributions of human malaria parasite species overlap in most malarious regions of the world, and co-infections involving two or more malaria parasite species are common. Little is known about the consequences of interactions between species during co-infection for disease severity and parasite transmission success. Anti-malarial interventions can have disproportionate effects on malaria parasite species, and may locally differentially reduce the number of species in circulation. Thus, it is important to have a clearer understanding of how the interactions between species affect disease and transmission dynamics. Controlled competition experiments using human malaria parasites are impossible, and thus we assessed the consequences of mixed-species infections on parasite fitness, disease severity, and transmission success using the rodent malaria parasite species Plasmodium chabaudi, P. yoelii yoelii, and P. vinckei lentum. We compared the fitness of individual species within single species and co-infections in mice. We also assessed the disease severity of single versus mixed infections in mice by measuring mortality rates, anaemia, and weight loss. Finally, we compared the transmission success of parasites in single or mixed species infections by quantifying oocyst development in Anopheles stephensi mosquitoes. We found that co-infections of P. yoelii with either P. vinckei or P. chabaudi led to a dramatic increase in infection virulence, with 100% mortality observed in mixed species infections, compared to no mortality for P. yoelii and P. vinckei single infections, and 40% mortality for P. chabaudi single infections. The increased mortality in the mixed infections was associated with an inability to clear parasitaemia, with the non-P. yoelii parasite species persisting at higher parasite densities than in single infections. P. yoelii growth was suppressed in all mixed infections compared to single infections. Transmissibility of P. vinckei and P. chabaudi to mosquitoes was also reduced in the presence of P. yoelii in co-infections compared to single infections. The increased virulence of co-infections containing P. yoelii (reticulocyte restricted) and P. chabaudi or P. vinckei (predominantly normocyte restricted) may be due to parasite cell tropism and/or immune modulation of the host. We explain the reduction in transmission success of species in co-infections in terms of inter-species gamete incompatibility.