bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical long-slit spectroscopy in the cluster Abell S0805
Authors: da Rocha-Poppe P C , Fernandes-Martin V A , Faúndez-Abans M , de Oliveira-Abans M , Silva G A , Freitas-Lemes P , Lima-Dias C
Published: July 2019

This contribution aims to study the nature (kinematic, nuclear activity, and stellar population) of a sample of 10 galaxies in the poor cluster Abell S0805. As no detailed optical spectroscopy for some members has been published yet, the selected sample makes this study ideal for investigating the properties of the following objects: ESO 104- G(002, 006, 007, 008, 009, 010, 013), Fairall 0187, and PGC (062384, 062391). Our main results were obtained after subtraction of the underlying stellar population with the spectral synthesis code starlight. The residual spectra reveal seven galaxies with only absorption lines [ESO 104- G(002, 007, 008, 009), Fairall 0187 and PGC (062384, 062391)], and three galaxies with emission lines [ESO 104- G(006, 010, 013)]. According to the boundaries in the diagnostic diagrams, the intensities of H α and the low-ionization lines ([N ii] λ6584 Å and [S ii] λλ6716,6731 Å) suggest the following results: (i) the brightest cluster galaxy (ESO 104- G006, an elliptical cD galaxy) shows low-ionization nuclear emission-line region (LINER)-like excitation, quite common in ‘cool core clusters’; (ii) the ESO 104- G010 (‘X-Galaxy’ or ‘Crystal Frog’) shows an excess of the nitrogen emission-line [N ii] λ6584 Å not yet reported. We also suggest this object as a LINER; (iii) the spiral ESO 104- G013 is a star-forming galaxy with typical emission lines. No obvious signs of interaction were observed in this study. The heliocentric velocities agree within 1σ with the most recent values. The stellar population, rotation curves, and velocity dispersions are also discussed for the first time for some objects.
Symptom clusters in newly diagnosed glioma patients: which symptom clusters are independently associated with functioning and global health status?
Authors: Coomans Marijke B , Dirven Linda , Aaronson Neil K , Baumert Brigitta G , Van Den Bent Martin , Bottomley Andrew , Brandes Alba A , Chinot Olivier , Coens Corneel , Gorlia Thierry , Herrlinger Ulrich , Keime-Guibert Florence , Malmström Annika , Martinelli Francesca , Stupp Roger , Talacchi Andrea , Weller Michael , Wick Wolfgang , Reijneveld Jaap C , Taphoorn Martin J B
Published: July 2019

Background

Symptom management in glioma patients remains challenging, as patients suffer from various concurrently occurring symptoms. This study aimed to identify symptom clusters and examine the association between these symptom clusters and patients’ functioning.

Methods

Data of the CODAGLIO project was used, including individual patient data from previously published international randomized controlled trials (RCTs) in glioma patients. Symptom prevalence and level of functioning were assessed with European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C30 and QLQ-BN20 self-report questionnaires. Associations between symptoms were examined with Spearman correlation coefficients and partial correlation networks. Hierarchical cluster analyses were performed to identify symptom clusters. Multivariable regression analyses were performed to determine independent associations between the symptom clusters and functioning, adjusted for possible confounders.

Results

Included in the analysis were 4307 newly diagnosed glioma patients from 11 RCTs who completed the EORTC questionnaires before randomization. Many patients (44%) suffered from 5–10 symptoms simultaneously. Four symptom clusters were identified: a motor cluster, a fatigue cluster, a pain cluster, and a gastrointestinal/seizures/bladder control cluster. Having symptoms in the motor cluster was associated with decreased (≥10 points difference) physical, role, and social functioning (betas ranged from −11.3 to −15.9, all P < 0.001), independent of other factors. Similarly, having symptoms in the fatigue cluster was found to negatively influence role functioning (beta of −12.3, P < 0.001), independent of other factors.

Conclusions

Two symptom clusters, the fatigue and motor cluster, were frequently affected in glioma patients and were found to independently have a negative association with certain aspects of patients’ functioning as measured with a self-report questionnaire.
Non-Normative Logical Pluralism and the Revenge of the Normativity Objection
Authors: Stei Erik
Published: July 2019

Logical pluralism is the view that there is more than one correct logic. Most logical pluralists think that logic is normative in the sense that you make a mistake if you accept the premisses of a valid argument but reject its conclusion. Some authors have argued that this combination is self-undermining: Suppose that $\mathcal {L}_{1}$ and $\mathcal {L}_{2}$ are correct logics that coincide except for the argument from Γ to ϕ, which is valid in $\mathcal {L}_{1}$ but invalid in $\mathcal {L}_{2}$. If you accept all sentences in Γ, then, by normativity, you make a mistake if you reject ϕ. In order to avoid mistakes, you should accept ϕ or suspend judgment about ϕ. Both options are problematic for pluralism. Can pluralists avoid this worry by rejecting the normativity of logic? I argue that they cannot. All else being equal, the argument goes through even if logic is not normative.
Predicting Residual Function in Hemodialysis and Hemodiafiltration – A Population Kinetic, Decision Analytic Approach
Authors: Achakzai Mohammad I , Argyropoulos Christos , Roumelioti Maria-Eleni
Published: July 2019

In this study, we introduce a novel framework for the estimation of residual renal function (RRF), based on the population compartmental kinetic behavior of Beta 2 Microglobulin (B2M) and its dialytic removal. Using this model, we simulated a large cohort of patients with various levels of RRF receiving either conventional high-flux hemodialysis or on-line hemodiafiltration. These simulations were used to estimate a novel population kinetic (PK) equation for RRF (PK-RRF) that was validated in an external public dataset of real patients. We assessed the performance of the resulting equation(s) against their ability to estimate urea clearance using cross-validation. Our equations derived entirely from computer simulations and advanced statistical modeling, and had extremely high discrimination (AUC 0.888 – 0.909) when applied to a human dataset of measurements of RRF. A clearance-based equation that utilized pre and post dialysis B2M measurements, patient weight, treatment duration and ultrafiltration had higher discrimination than an equation previously derived in humans. Furthermore, the derived equations appeared to have higher clinical usefulness as assessed by Decision Curve Analysis, potentially supporting decisions that for individualizing dialysis frequency in patients with preserved RRF.
Quantifying the RNA cap epitranscriptome reveals novel caps in cellular and viral RNA
Authors: Wang Jin , Chew Bing Liang Alvin , Lai Yong , Dong Hongping , Xu Luang , Balamkundu Seetharamsingh , Cai Weiling Maggie , Cui Liang , Liu Chuan Fa , Fu Xin-Yuan , Lin Zhenguo , Shi Pei-Yong , Lu Timothy K. , Luo Dahai , Jaffrey Samie R. , Dedon Peter C.
Published: July 2019

Chemical modification of transcripts with 5’ caps occurs in all organisms. Here we report a systems-level mass spectrometry-based technique, CapQuant, for quantitative analysis of the cap epitranscriptome in any organism. The method was piloted with 21 canonical caps – m7GpppN, m7GpppNm, GpppN, GpppNm, and m2,2,7GpppG – and 5 “metabolite” caps – NAD, FAD, UDP-Glc, UDP-GlcNAc, and dpCoA. Applying CapQuant to RNA from purified dengue virus,Escherichia coli, yeast, mice, and humans, we discovered four new cap structures in humans and mice (FAD, UDP-Glc, UDP-GlcNAc, and m7Gpppm6A), cell- and tissue-specific variations in cap methylation, and surprisingly high proportions of caps lacking 2’-O-methylation, such as m7Gpppm6A in mammals and m7GpppA in dengue virus, and we did not detect cap m1A/m1Am in humans. CapQuant accurately captured the preference for purine nucleotides at eukaryotic transcription start sites and the correlation between metabolite levels and metabolite caps. The mystery around cap m1A/m1Am analysis remains unresolved.
Single Photon, Time-Gated, Phasor-based Fluorescence Lifetime Imaging Through Highly Scattering Medium
Authors: Ankri Rinat , Basu Arkaprabha , Ulku Arin Can , Bruschini Claudio , Charbon Edoardo , Weiss Shimon , Michalet Xavier
Published: June 2019

Fluorescence lifetime imaging (FLI) is a powerful tool forin vitroand non-invasivein vivobiomolecular and cellular investigations. Fluorescence lifetime is an intrinsic characteristic of any fluorescent dye which, to some extent, does not depend on excitation intensity and signal level. However, when usedin vivowith visible wavelength emitting fluorophores, FLI is complicated by (i) light scattering as well as absorption by tissues, which significantly reduces fluorescence intensity, (ii) tissue autofluorescence (AF), which decreases the signal to noise ratio and (iii) broadening of the decay signal, which can result in incorrect lifetime estimation. Here, we report the use of a large-frame time-gated single-photon avalanche diode (SPAD) imager,SwissSPAD2, with a very short acquisition time (in the milliseconds range) and a wide-field microscopy format. We use the phasor approach to convert each pixel’s data into its local lifetime. The phasor transformation provides a simple and fast visual method for lifetime imaging and is particularly suitable forin vivoFLI which suffers from deformation of the fluorescence decay, and makes lifetime extraction by standard fitting challenging. We show, for single dyes, that the phasor cloud distribution (of pixels) increases with decay broadening due to scattering and decreasing fluorescence intensity. Yet, as long as the fluorescence signal is higher than the tissue-like phantom AF, a distinct lifetime can still be clearly identified with an appropriate background correction. Lastly, we demonstrate the detection of few hundred thousand A459 cells expressing the fluorescent protein mCyRFP1 through highly scattering phantom layers, despite significant scattering and the presence of the phantom AF.
Aging is associated with a systemic length-driven transcriptome imbalance
Authors: Stoeger Thomas , Grant Rogan A. , McQuattie-Pimentel Alexandra C. , Anekalla Kishore , Liu Sophia S. , Tejedor-Navarro Heliodoro , Singer Benjamin D. , Abdala-Valencia Hiam , Schwake Michael , Tetreault Marie-Pier , Perlman Harris , Balch William E , Chandel Navdeep , Ridge Karen , Sznajder Jacob I. , Morimoto Richard I. , Misharin Alexander V. , Budinger G.R. Scott , Amaral Luis A. Nunes
Published: July 2019

Aging manifests itself through a decline in organismal homeostasis and a multitude of cellular and physiological functions1. Efforts to identify a common basis for vertebrate aging face many challenges; for example, while there have been documented changes in the expression of many hundreds of mRNAs, the results across tissues and species have been inconsistent2. We therefore analyzed age-resolved transcriptomic data from 17 mouse organs and 51 human organs using unsupervised machine learning3–5 to identify the architectural and regulatory characteristics most informative on the differential expression of genes with age. We report a hitherto unknown phenomenon, a systemic age-dependent length-driven transcriptome imbalance that for older organisms disrupts the homeostatic balance between short and long transcript molecules for mice, rats, killifishes, and humans. We also demonstrate that in a mouse model of healthy aging, length-driven transcriptome imbalance correlates with changes in expression of splicing factor proline and glutamine rich (Sfpq), which regulates transcriptional elongation according to gene length6. Furthermore, we demonstrate that length-driven transcriptome imbalance can be triggered by environmental hazards and pathogens. Our findings reinforce the picture of aging as a systemic homeostasis breakdown and suggest a promising explanation for why diverse insults affect multiple age-dependent phenotypes in a similar manner.
miR-1/206 down-regulates splicing factor Srsf9 to promote myogenesis
Authors: Bjorkman Kristen K. , Buvoli Massimo , Pugach Emily K. , Polmear Michael M. , Leinwand Leslie A.
Published: July 2019

Background

Myogenesis is driven by specific changes in the transcriptome that occur during the different stages of muscle differentiation. In addition to controlled transcriptional transitions, several other post-transcriptional mechanisms direct muscle differentiation. Both alternative splicing and miRNA activity regulate gene expression and production of specialized protein isoforms. Importantly, disruption of either process often results in severe phenotypes as reported for several muscle diseases. Thus, broadening our understanding of the post-transcriptional pathways that operate in muscles will lay the foundation for future therapeutic interventions.

Methods

We employed bioinformatics analysis in concert with the well-established C2C12 cell system for predicting and validating novel miR-1 and miR-206 targets engaged in muscle differentiation. We used reporter gene assays to test direct miRNA targeting and studied C2C12 cells stably expressing one of the cDNA candidates fused to a heterologous, miRNA-resistant 3’ UTR. We monitored effects on differentiation by measuring fusion index, myotube area, and myogenic gene expression during time course differentiation experiments.

Results

Gene ontology analysis revealed a strongly enriched set of putative miR-1 and miR-206 targets associated with RNA metabolism. Notably, the expression levels of several candidates decreased during C2C12 differentiation. We discovered that the splicing factor Srsf9 is a direct target of both miRNAs during myogenesis. Persistent Srsf9 expression during differentiation impaired myotube formation and blunted induction of the early pro-differentiation factor myogenin as well as the late differentiation marker sarcomeric myosin, Myh8.

Conclusions

Our data uncover novel miR-1 and miR-206 cellular targets and establish a functional link between the splicing factor Srsf9 and myoblast differentiation. The finding that miRNA-mediated clearance of Srsf9 is a key myogenic event illustrates the coordinated and sophisticated interplay between the diverse components of the gene regulatory network.
A generalised approach to detect selected haplotype blocks in Evolve and Resequence experiments
Authors: Otte Kathrin A. , Schlötterer Christian
Published: July 2019

Shifting from the analysis of single nucleotide polymorphisms to the reconstruction of selected haplotypes greatly facilitates the interpretation of Evolve and Resequence (E&R) experiments. Merging highly correlated hitchhiker SNPs into haplotype blocks reduces thousands of candidates to few selected regions. Current methods of haplotype reconstruction from Pool-Seq data need a variety of data-specific parameters that are typically defined ad hoc and require haplotype sequences for validation. Here, we introduce haplovalidate, a tool which detects selected haplotypes in a broad range of Pool-seq time series data without the need of sequenced haplotypes. Haplovalidate makes data-driven choices of two key parameters for the clustering procedure, the minimum correlation between SNPs constituting a cluster and the window size. Applying haplovalidate to simulated and experimental E&R data reliably detects selected haplotype blocks with low false discovery rates – independent if few or many selection targets are included. Our analyses identified an important restriction of the haplotype block-based approach to describe the genomic architecture of adaptation. We detected a substantial fraction of haplotypes containing multiple selection targets. These blocks were considered as one region of selection and therefore led to under-estimation of the number of selection targets. We demonstrate that the separate analysis of earlier time points can significantly increase the separation of selection targets into individual haplotype blocks. We conclude that the analysis of selected haplotype blocks has a large potential for the characterisation of the adaptive architecture with E&R experiments.
Channeling macrophage polarization via selective translation inhibition by rocaglates increases macrophage resistance to Mycobacterium tuberculosis
Authors: Chatterjee Sujoy , Yabaji Shivraj M. , Bhattacharya Bidisha , Waligurski Emily , Vallavoju Nandini , Ray Somak , Brown Lauren E. , Beeler Aaron B. , Ivanov Alexander R. , Kobzik Lester , Porco John A. , Kramnik Igor
Published: July 2019

Macrophages contribute to host immunity and tissue homeostasis via alternative activation programs. M1-like macrophages control intracellular bacterial pathogens and tumor progression. In contrast, M2-like macrophages shape reparative microenvironments that can be conducive for pathogen survival or tumor growth. An imbalance of these macrophages phenotypes may perpetuate sites of chronic unresolved inflammation, such as infectious granulomas and solid tumors.

We have found that plant-derived and synthetic rocaglates sensitize macrophages to low concentrations of the M1-inducing cytokine IFN-gamma and inhibit their responsiveness to IL-4, a prototypical activator of the M2-like phenotype. Treatement of primary macrophages with rocaglates increased their resilience to oxidative stress, stimulated autophagy and killing of intracellular mycobacteria. Thus, rocaglates represent a novel class of immunomodulators that can direct macrophage polarization towards the M1-like phenotype in complex microenvironments associated with hypofunction of type 1 and/or hyperactivation of type 2 immunity, e.g. chronic bacterial infections, allergies and, possibly, certain tumors.
Genetic immunodeficiency and autoimmune disease reveal distinct roles of Hem1 in the WAVE2 and mTORC2 complexes
Authors: Comrie William A. , Poli M. Cecilia , Cook Sarah A. , Similuk Morgan , Oler Andrew J. , Faruqi Aiman J. , Kuhns Douglas B. , Yang Sheng , Carisey Alexandre F. , Fournier Benjamin , Anderson D. Eric , Price Susan , Chahla Wadih Abou , Vargas-Hernandez Alexander , Forbes Lisa R. , Mace Emily M. , Cao Tram N. , Coban-Akdemir Zeynep H. , Jhangiani Shalini N. , Muzny Donna M. , Gibbs Richard A. , Lupski James R. , Orange Jordan S. , Cuvelier Geoffrey D.E. , Hassani Moza Al , Kaabi Nawal AL , Yafei Zain Al , Jyonouchi Soma , Raje Nikita , Caldwell Jason W. , Huang Yanping , Burkhardt Janis K. , Latour Sylvain , Chen Baoyu , ElGhazali Gehad , Rao V. Koneti , Chinn Ivan K. , Lenardo Michael J.
Published: July 2019

Immunodeficiency often coincides with immune hyperresponsiveness such as autoimmunity, lymphoproliferation, or atopy, but the molecular basis of this paradox is typically unknown. We describe four families with immunodeficiency coupled with atopy, lymphoproliferation, cytokine overproduction, hemophagocytic lymphohistocytosis, and autoimmunity. We discovered loss-of-function variants in the gene NCKAP1L, encoding the hematopoietic-specific Hem1 protein. Three mutations cause Hem1 protein and WAVE regulatory complex (WRC) loss, thereby disrupting actin polymerization, synapse formation, and immune cell migration. Another mutant, M371V encodes a stable Hem1 protein but abrogates binding of the Arf1 GTPase and identifies Arf1 as a critical Hem1 regulator. All mutations reduce the cortical actin barrier to cytokine release explaining immune hyperresponsiveness. Finally, Hem1 loss blocked mTORC2-dependent AKT phosphorylation, T cell proliferation, and effector cytokine production during T cell activation. Thus, our data show that Hem1 independently governs two key regulatory complexes, the WRC and mTORC2, and how Hem1 loss causes a combined immunodeficiency and immune hyperresponsiveness disease.

One sentence summary

Hem1 loss of function mutations cause a congenital immunodysregulatory disease and reveal its role regulating WAVE2 and mTORC2 signaling.
In vitro ribosome synthesis and evolution through ribosome display
Authors: Hammerling Michael J. , Fritz Brian R. , Yoesep Danielle J. , Kim Do Soon , Carlson Erik D. , Jewett Michael C.
Published: July 2019

Directed evolution of the ribosome for expanded substrate incorporation and novel functions is challenging because the requirement of cell viability limits the mutations that can be made. However, our recent development of an integrated strategy for the in vitro synthesis and assembly of translationally competent ribosomes (iSAT) enables the rapid generation of large libraries of ribosome variants in a cell-free environment. Here we combine the iSAT system with ribosome display to develop a fully in vitro methodology for ribosome synthesis and evolution (called RISE). We validate this method by selecting highly active genotypes which are resistant to the antibiotic clindamycin from a library of ribosome variants. We further demonstrate the prevalence of positive epistasis in successful genotypes, highlighting the importance of such interactions in selecting for new function. We anticipate that RISE will facilitate understanding of molecular translation and enable selection of ribosomes with altered properties.
A systems genomics approach to uncover patient-specific pathogenic pathways and proteins in a complex disease
Authors: Brooks Johanne , Modos Dezso , Sudhakar Padhmanand , Fazekas David , Zoufir Azedine , Kapuy Orsolya , Szalay-Beko Mate , Madgwick Matthew , Verstockt Bram , Hall Lindsay , Watson Alastair , Tremelling Mark , Parkes Miles , Vermeire Severine , Bender Andreas , Carding Simon R. , Korcsmaros Tamas
Published: July 2019

We describe a novel precision medicine workflow, the integrated single nucleotide polymorphism network platform (iSNP), designed to identify the exact mechanisms of how SNPs affect cellular regulatory networks, and how SNP co-occurrences contribute to disease pathogenesis in ulcerative colitis (UC). Using SNP profiles of 377 UC patients, we mapped the regulatory effects of the SNPs to a human signalling network containing protein-protein, miRNA-mRNA and transcription factor binding interactions. Unsupervised clustering algorithms grouped these patient-specific networks into four distinct clusters based on two large disease hubs, NFKB1 and PKCB. Pathway analysis identified the epigenetic modification as common and the T-cell specific responses as differing signalling pathways in the clusters. By integrating individual transcriptomes in active and quiescent disease setting to the patient networks, we validated the impact of non-coding SNPs. The iSNP approach identified regulatory effects of disease-associated non-coding SNPs, and identified how pathogenesis pathways are activated via different genetic modifications.
Free-energy-based framework for early forecasting of stem cell differentiation
Authors: Suresh H. , Shishvan S.S. , Vigliotti A. , Deshpande V.S.
Published: July 2019

Commitment of stem cells to different lineages is inherently stochastic but regulated by a range of environmental bio/chemo/mechanical cues. Here we develop an integrated stochastic modelling framework for predicting the differentiation of hMSCs in response to a range of environmental cues including sizes of adhesive islands, stiffness of substrates and treatment with ROCK inhibitors in both growth and mixed media. The statistical framework analyses the fluctuations of cell morphologies over around a 24-hour period after seeding the cells in the specific environment and uses the distribution of their cytoskeletal free-energy to forecast the lineage the hMSCs will commit to. The cytoskeletal free-energy which succinctly parameterises the biochemical state of the cell is shown to capture hMSC commitment over a range of environments while simple morphological factors such as cell shape, tractions on their own are unable to correlate with lineages hMSCs adopt.
High density of white-faced capuchins (Cebus capucinus) and habitat quality in the Taboga Forest of Costa Rica
Authors: Johnson Elizabeth Tinsley , Benítez Marcela E. , Fuentes Alexander , McLean Celia R. , Norford Ariek B. , Ordoñez Juan Carlos , Beehner Jacinta C. , Bergman Thore J.
Published: July 2019

Across the globe, primate species and habitats are threatened by human activity. This is especially true for species found in tropical dry forests, which are widely distributed and comprise diverse habitats that remain largely unprotected. Evidence suggests that some primate species endemic to tropical dry forests may be more sensitive to anthropogenic disturbance than others, but our ability to predict primate abundance in the face of disturbance also depends on the specific variables for each site. Here, we consider the factors that explain the high density of white-faced capuchins (Cebus capucinus) found in the Taboga Forest, Costa Rica, a relatively small fragment of tropical dry forest surrounded by agricultural fields. Our analyses suggest that, for capuchins (and potentially for mantled howler monkeys,Alouatta palliata), the size and disturbance of a forest fragment may matter less than the composition and availability of key resources, like above-ground water. Group sightings for both species were higher near permanent water sources, but group sightings did not vary between edge and interior forest. These findings help explain why some primate species can flourish even alongside anthropogenic disturbance and thus carry important implications for conservation efforts. Smaller forest fragments, like Taboga, may be able to support high densities of some species because they provide a mosaic of habitats and key resources that buffer adverse ecological conditions. Future studies will assess the extent to which primates in the Taboga Forest rely on the canals versus the river and will consider how the high density of capuchins in Taboga influences ranging patterns, home range overlap, and the frequency and intensity of intergroup encounters.

RESEARCH HIGHLIGHTS

Here we introduce a new white-faced capuchin study site in the Taboga Forest, Costa Rica, a fragmented tropical dry forest.

Forest fragments like Taboga may support high primate densities because they provide a mosaic of habitats and key resources.
Voxel-to-voxel predictive models reveal unexpected structure in unexplained variance
Authors: Mell Maggie Mae , St-Yves Ghislain , Naselaris Thomas
Published: July 2019

Encoding models based on deep convolutional neural networks (DCNN) more accurately predict BOLD responses to natural scenes in the visual system than any other currently available model. However, DCNN-based encoding models fail to predict a significant amount of variance in the activity of most voxels in all visual areas. This failure could reflect limitations in the data (e.g., a noise ceiling), or could reflect limitations of the DCNN as a model of computation in the brain. Understanding the source and structure of the unexplained variance could therefore provide helpful clues for improving models of brain computation. Here, we characterize the structure of the variance that DCNN-based encoding models cannot explain. Using a publicly available dataset of BOLD responses to natural scenes, we determined if the source of unexplained variance was shared across voxels, individual brains, retinotopic locations, and hierarchically distant visual brain areas. We answered these questions using voxel-to-voxel (vox2vox) models that predict activity in a target voxel given activity in a population of source voxels. We found that simple linear vox2vox models increased within-subject prediction accuracy over DCNN-based models for any pair of source/target visual areas, clearly demonstrating that the source of unexplained variance is widely shared within and across visual brain areas. However, vox2vox models were not more accurate than DCNN-based models when source and target voxels came from separate brains, demonstrating that the source of unexplained variance was not shared across brains. Furthermore, the weights of these vox2vox models permitted explicit readout of the receptive field location of target voxels, demonstrating that the source of unexplained variance induces correlations primarily between the activities of voxels with overlapping receptive fields. Finally, we found that vox2vox model prediction accuracy was heavily dependent upon the signed hierarchical distance between the source and target voxels: for feed-forward models (source area lower in the visual hierarchy than target area) prediction accuracy decreased with hierarchical distance between source and target. It did not decrease for feedback models. In contrast, the same analysis applied across layers of a DCNN did not reveal this feed-forward/feedback asymmetry. Given these results, we argue that the structured variance unexplained by DCNN-based encoding models is unlikely to be entirely caused by spatially correlated noise or eye movements; rather, our results point to a need for brain models that include endogenous dynamics and a pattern of connectivity that is not strictly feed-forward.
Multiplicative modulations in hue-selective cells enhance unique hue representation
Authors: Mehrani Paria , Mouraviev Andrei , Tsotsos John K.
Published: July 2019

There is still much to understand about the color processing mechanisms in the brain and the transformation from cone-opponent representations to perceptual hues. Moreover, it is unclear which areas(s) in the brain represent unique hues. We propose a hierarchical model inspired by the neuronal mechanisms in the brain for local hue representation, which reveals the contributions of each visual cortical area in hue representation. Local hue encoding is achieved through incrementally increasing processing nonlinearities beginning with cone input. Besides employing nonlinear rectifications, we propose multiplicative modulations as a form of nonlinearity. Our simulation results indicate that multiplicative modulations have significant contributions in encoding of hues along intermediate directions in the MacLeod-Boynton diagram and that model V4 neurons have the capacity to encode unique hues. Additionally, responses of our model neurons resemble those of biological color cells, suggesting that our model provides a novel formulation of the brain’s color processing pathway.
Potential impacts of insect-induced harvests in the mixed forests of New England
Authors: MacLean Meghan Graham , Holt Jonathan , Borsuk Mark , Markowski-Lindsay Marla , Butler Brett J. , Kittredge David B. , Duveneck Matthew J. , Laflower Danelle , Orwig David A. , Foster David R. , Thompson Jonathan R.
Published: July 2019

Forest insects and pathogens (FIPs) have significant impacts on U.S. forests, each year affecting an area nearly three times the area of wildfires and timber harvesting combined. We surveyed family forest owners (FFOs) in the northeastern U.S. and 84% of respondents indicated they would harvest in at least one of the presented FIP infestation scenarios. This harvest response represents a potentially significant shift in the timing, extent, and species selection of harvesting in the Northeast. Here we used the landowner survey, regional forest inventory data, and characteristics of the emerald ash borer (EAB, Agrilus planipennis) invasion to examine the potential for a rapidly spreading FIP to alter harvest regimes and affect regional forest conditions. Twenty-five percent of the FFO parcels in the Connecticut River Watershed in New England are likely to be harvested in response to EAB within 10 years. This prediction represents an increase in harvest frequencies, from 2.9%/yr (historically) to 3.7%/yr, on FFO woodlands. At typical harvest intensities, this would result in 13% of the total aboveground biomass removed through these harvests, with 81% of that biomass from species other than ash, creating a forest disturbance that is over twice the magnitude of the disturbance from EAB alone.
Transmembrane 163 (TMEM163) protein effluxes zinc
Authors: Sanchez Vanessa B. , Ali Saima , Escobar Adrian , Cuajungco Math P.
Published: July 2019

Recent investigations of rodent Tmem163 suggest that it binds to and transports zinc as a dimer, and that alanine mutagenesis of its two species-conserved aspartate (D123A/D127A) residues proposed to bind zinc perturbs protein function. Direct corroboration, however, is lacking whether it is an influx or efflux transporter in cells. We hypothesized that human TMEM163 is a zinc effluxer based on its predicted protein characteristics. We used cultured human cell lines that either stably or transiently expressed TMEM163, and pre-loaded the cells with zinc to determine transport activity. We found that TMEM163-expressing cells exhibited significant reduction of intracellular zinc levels as evidenced by two zinc-specific fluorescent dyes and radionuclide zinc-65. The specificity of the fluorescence signal was confirmed upon treatment with TPEN, a high-affinity zinc chelator. Multiple sequence alignment and phylogenetic analyses showed that TMEM163 is related to distinct members of the cation diffusion facilitator (CDF) protein family. To further characterize the efflux function of TMEM163, we substituted alanine in two homologous aspartate residues (D124A/D128A) and performed site-directed mutagenesis of several conserved amino acid residues identified as non-synonymous single nucleotide polymorphism (S61R, S95C, S193P, and E286K). We found a significant reduction of zinc efflux upon cellular expression of D124A/D128A or E286K protein variant when compared with wild-type, suggesting that these particular amino acids are important for normal protein function. Taken together, our findings demonstrate that TMEM163 effluxes zinc and should now be designated ZNT11, as a new member of the mammalian CDF family of zinc efflux transporters.
siland: an R package for estimating the spatial influence of landscape
Authors: Carpentier Florence , Martin Olivier
Published: July 2019

Context

The spatial distributions of species and populations are both influenced by local variables and by characteristics of surrounding landscapes. Understanding how landscape features spatially structure the frequency of a trait in a population, the abundance of a species or the species’ richness remains difficult specially because the spatial scale effects of the landscape variables are often unknown.

Objectives

Here, we present “siland”, an R package for analyzing the effect of landscape features on georeferenced point observations (described in a Geographic Information System shapefile format).

Methods & Results

“siland” simultaneously estimates the spatial scales and intensities of landscape variable effects. It does not require any information about the scale of effect. Two methods are available: one is based on focal sample site (Bsiland method, b for buffer) and one is distance weighted using Spatial Influence Function (Fsiland method, f for function). ‘siland’ allows for effects tests, effects maps and models comparison.

Conclusions

Adaptable and user-friendly, the “siland” package is a very practical tool to perform landscape analysis.
consensusDE: an R package for assessing consensus of multiple RNA-seq algorithms with RUV correction
Authors: Waardenberg Ashley J. , Field Matt A.
Published: July 2019

Extensive evaluation of RNA-seq methods have demonstrated that no single algorithm consistently outperforms all others. Removal of unwanted variation (RUV) has also been proposed as a method for stabilizing differential expression (DE) results. Despite this, it remains a challenge to run multiple RNA-seq algorithms to identify significant differences common to multiple algorithms, whilst also integrating and assessing the impact of RUV into all algorithms. consensusDE was developed to automate the process of identifying significant DE by combining the results from multiple algorithms with minimal user input and with the option to automatically integrate RUV. consensusDE only requires a table describing the sample groups, a directory containing BAM files or preprocessed count tables and an optional transcript database for annotation. It supports merging of technical replicates, paired analyses and outputs a compendium of plots to guide the user in subsequent analyses. Herein, we also assess the ability of RUV to improve DE stability when combined with multiple algorithms through application to real and simulated data. We find that, although RUV demonstrated improved FDR in a setting of low replication, the effect was algorithm specific and diminished with increased replication, reinforcing increased replication for recovery of true DE genes. We finish by offering some rules and considerations for the application of RUV in a consensus-based setting.

consensusDE is freely available, implemented in R and available as a Bioconductor package, under the GPL-3 license, along with a comprehensive vignette describing functionality: http://bioconductor.org/packages/consensusDE/
Cross-species Functional Alignment Reveals Evolutionary Hierarchy Within the Connectome
Authors: Xu Ting , Nenning Karl-Heinz , Schwartz Ernst , Hong Seok-Jun , Vogelstein Joshua T. , Fair Damien A. , Schroeder Charles E. , Margulies Daniel S. , Smallwood Jonny , Milham Michael P. , Langs Georg
Published: July 2019

Evolution provides an important window into how cortical organization shapes function and vice versa. The complex mosaic of changes in brain morphology and functional organization that have shaped the mammalian cortex during evolution, complicates attempts to chart cortical differences across species. It limits our ability to fully appreciate how evolution has shaped our brain, especially in systems associated with unique human cognitive capabilities that lack anatomical homologues in other species. Here, we demonstrate a function-based method for cross-species cortical alignment that leverages recent advances in understanding cortical organization and that enables the quantification of homologous regions across species, even when their location is decoupled from anatomical landmarks. Critically, our method establishes that cross-species similarity in cortical organization decreases with geodesic distance from unimodal systems, and culminates in the most pronounced changes in posterior regions of the default network (angular gyrus, posterior cingulate and middle temporal cortices). Our findings suggest that the establishment of the default network, as the apex of a cognitive hierarchy, as is seen in humans, is a relatively recent evolutionary adaptation. They also highlight functional changes in regions such as the posterior cingulate cortex and angular gyrus as key influences on uniquely human features of cognition.
Individual variation of the masticatory system dominates 3D skull shape in the herbivory-adapted marsupial wombats
Authors: Weisbecker Vera , Guillerme Thomas , Speck Cruise , Sherratt Emma , Abraha Hyab Mehari , Sharp Alana C. , Terhune Claire E. , Collins Simon , Johnston Steve , Panagiotopoulou Olga
Published: July 2019

Background

Within-species skull shape variation of marsupial mammals is widely considered low and strongly size-dependent (allometric), possibly due to developmental constraints arising from the altricial birth of marsupials. However, species whose skulls are impacted by strong muscular stresses – particularly those produced through mastication of tough food items – may not display such intrinsic patterns very clearly because of the known plastic response of bone to muscle activity of the individual. In such cases, shape variation should not be dominated by allometry; ordination of shape in a geometric morphometric context through principal component analysis (PCA) should reveal main variation in areas under masticatory stress (incisor region/zygomatic arches/mandibular ramus); but this main variation should emerge from high individual variability and thus have low eigenvalues.

Results

We assessed the evidence for high individual variation through 3D geometric morphometric shape analysis of crania and mandibles of thre species of grazing-specialized wombats, whose diet of tough grasses puts considerable strain on their masticatory system. As expected, we found little allometry and low Principal Component 1 (PC1) eigenvalues within crania and mandibles of all three species. Also as expected, the main variation was in the muzzle, zygomatic arches, and masticatory muscle attachments of the mandibular ramus. We then implemented a new test to ask if the landmark variation reflected on PC1 was reflected in individuals with opposite PC1 scores and with opposite shapes in Procrustes space. This showed that correspondence between individual and ordinated shape variation was limited, indicating high levels of individual variability in the masticatory apparatus.

Discussion

Our results are inconsistent with hypotheses that skull shape variation within marsupial species reflects a constraint pattern. Rather, they support suggestions that individual plasticity can be an important determinant of within-species shape variation in marsupials (and possibly other mammals) with high masticatory stresses, making it difficult to understand the degree to which intrinsic constraint act on shape variation at the within-species level. We conclude that studies that link micro- and macroevolutionary patterns of shape variation might benefit from a focus on species with low-impact mastication, such as carnivorous or frugivorous species.
Emergence of the Ug99 lineage of the wheat stem rust pathogen through somatic hybridisation
Authors: Li Feng , Upadhyaya Narayana M. , Sperschneider Jana , Matny Oadi , Nguyen-Phuc Hoa , Mago Rohit , Raley Castle , Miller Marisa E. , Silverstein Kevin A.T. , Henningsen Eva , Hirsch Cory D. , Visser Botma , Pretorius Zacharias A. , Steffenson Brian J. , Schwessinger Benjamin , Dodds Peter N. , Figueroa Melania
Published: July 2019

Parasexuality contributes to diversity and adaptive evolution of haploid (monokaryotic) fungi. However non-sexual genetic exchange mechanisms are not defined in dikaryotic fungi (containing two distinct haploid nuclei). Newly emerged strains of the wheat stem rust pathogen, Puccinia graminis f. sp. tritici (Pgt), such as Ug99, are a major threat to global food security. Here we show that Ug99 arose by somatic hybridisation and nuclear exchange between dikaryons. Fully haplotype-resolved genome assembly and DNA proximity analysis revealed that Ug99 shares one haploid nucleus genotype with a much older African lineage of Pgt, with no recombination or reassortment. Generation of genetic variation by nuclear exchange may favour the evolution of dikaryotism by providing an advantage over diploidy.
Diversity and some bioactivities of soil actinomycetes from southwestern China
Authors: Jiang Yi , Li Guiding , Li Qinyuan , Zhang Kun , Jiang Longqian , Chen Xiu , Jiang Chenglin
Published: July 2019

With the natural medicine exploring, the actinomycetes (actinobacteria) have gotten more and more recognition. 815 soil samples were collected from six areas in the southwestern China. 7063 purified strains of actinomycetes were isolated from these samples by using four media. The 16S rRNA gene sequences of 1998 selected strains of the 7063 were determined, and the phylogenetic analysis was carried out. The diversity of actinomycetes is analyzed. Total 33 genera of actinomycetes as the purified cultivation were identified from these soil samples. 14, 13, 5, 9 and 26 genera of actinobacteria were identified from E, A, B, D, C and F area respectively, and the communities of actinomycetes are very different from each other. The diversity of Xishuangbanna (F area) is the richest, and 26 genera were isolated. That of Emei and Qingcheng Mountain (C area) is monotone, and only five genera were isolated. 158 of 1998 strains (7.9 %) are possible new species. Antimicrobial activities of 1070 selected strains against 11 bacteria and fungi were tested using agar well diffusion method, and biosynthetic genes of type I and II polyketide synthases (PKS I, PKS II), nonribosomal peptide synthase (NRPS) and polygene cytochrome P450 hydroxylase (CYP) of 1036 selected strains were detected by PCR. High rate of antimicrobial activity and the four antibiotic biosynthetic genes existed in these actinomycetes. Results of this study indicates that firstly more unknown actinomycetes can be obtained from soil samples, specially primeval tropical forests. Second, isolation methods for actinomycetes must be continually improved and improved.

Importance

First, discarding repeat of a mass of known microbes and compounds is very difficult. Second, pharmaceuticals development can still not overtake the increase of resistance of pathogens to antibiotics, and new diseases continuously and fleetly occur. Soil actinomycetes of these regions are researched few by microbiologist yet. In order to get much more unknown actinomycetes for discovery of new bioactive metabolites, the actinomycetes of forest soil in southwestern China were isolated and identified. Anti-microbial activities and synthetic gene clusters’ of four kinds of antibiotics of some selected strains were detected.
Late Upper Palaeolithic hunter-gatherers in the Central Mediterranean: new archaeological and genetic data from the Late Epigravettian burial Oriente C (Favignana, Sicily)
Authors: Catalano Giulio , Lo Vetro Domenico , Fabbri Pier Francesco , Mallick Swapan , Reich David , Rohland Nadin , Sineo Luca , Mathieson Iain , Martini Fabio
Published: July 2019

Grotta d’Oriente, a small coastal cave located on the island of Favignana (Sicily, Italy) is a key site for the study of the early human colonization of Sicily. The individual known as Oriente C was found in the lower portion of an anthropogenic deposit containing typical local Late Upper Palaeolithic (Late Epigravettian) stone assemblages. Two radiocarbon dates on charcoal from the deposit containing the burial are consistent with the archaeological context and refer Oriente C to a period spanning about 14,200-13,800 cal. BP. Anatomical features are close to those of Late Upper Palaeolithic populations of the Mediterranean and show strong affinity with Palaeolithic individuals of San Teodoro. Here we present new ancient DNA data from Oriente C. Our results, confirming previous genetic analysis, suggest a substantial genetic homogeneity among Late Epigravettian hunter-gatherer populations of Central Mediterranean, presumably as a consequence of continuous gene flow among different groups, or a range expansion following the Last Glacial Maximum (LGM).
Theory of antiparallel microtubule overlap stabilization by motors and diffusible crosslinkers
Authors: Lera-Ramirez Manuel , Nédélec François J.
Published: July 2019

Antiparallel microtubule bundles are essential structural elements of many cytoskeletal structures, for instance the mitotic spindle. In such bundles, neighbouring microtubules are bonded by specialised crosslinkers of the Ase1/PRC1/MAP65 family that can diffuse longitudinally along microtubules. Similarly, some kinesin motors implicated in bundle formation have a diffusible tail allowing them to slide passively along microtubules. We develop here a theory of two microtubules connected by motors and diffusible connectors, in different configurations that can be realized experimentally. In all cases, the microtubule sliding speed derived analytically is validated by stochastic simulations and used to discuss recent experimental results, such as force generation by kinesin-14, and overlap stabilization by Ase1. Some systems can produce steady overlaps that are determined by the density of crosslinkers on the microtubule lattice. This property naturally leads to robust coordination between sliding and growth in dynamic bundles of microtubules, an essential property in mitosis.