bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybridization and diversification are positively correlated across vascular plant families
Authors: Mitchell Nora , Whitney Kenneth D.
Published: August 2019

Hybridization has experimental and observational ties to evolutionary processes and outcomes such as adaptation, speciation, and radiation. Although it has been hypothesized that hybridization and diversification are correlated, this idea remains largely untested empirically. Here, we use a hybridization database on 195 plant families, life history information, and a time-calibrated family-level phylogeny to test for phylogenetically-corrected associations between hybridization and diversification rates, while also taking into account life-history traits that may be correlated with both processes. We show that diversification and hybridization are positively correlated using three different methods to estimate diversification rates and two different metrics of hybridization. Moreover, the relationship remains detectable when incorporating the correlations between diversification and two other life history characteristics, perenniality and woodiness. We further provide potential mechanisms for this association under three different scenarios: hybridization may drive diversification, diversification may drive hybridization, or both hybridization and diversification may jointly be driven by other factors. We suggest future studies to disentangle the causal structure.
Age-related decline in metabolite heavy isotope content in rodent organs
Authors: Li Xiyan , Snyder Michael P.
Published: August 2019

Heavy isotopes are discriminated by biological systems due to kinetic isotopic effects at the biochemical/metabolic levels. How these heavy isotopes are enriched or depleted over a long term is unclear, but artificial manipulation of heavy isotope content in various organisms has produced significant impacts on biological functions, suggesting the origin may arise with intrinsic mechanisms for a functional outcome. Our previous study has revealed an age-associated decline in metabolite heavy isotope content (HIC) in the budding yeast, which could be reversed in part by supplementing heavy water, and consequently, also increased yeast lifespans. In the current study, we report a similar age-dependent decline in HIC from three types of mouse tissues: brain, heart, and skeletal muscles. Furthermore, individual tissues exhibited different patterns of HIC change over age, which appeared to match their development and maturation timelines. These results have demonstrated that age-dependent decline in HIC also exists in mammals, which is likely a traceable feature of development and perhaps aging. Thus, we believe that reversing the decline in HIC could have the potential to extend the healthspan of humans.
Global Genetic Cartography of Urban Metagenomes and Anti-Microbial Resistance
Authors: Danko David , Bezdan Daniela , Afshinnekoo Ebrahim , Ahsanuddin Sofia , Bhattacharya Chandrima , Butler Daniel J , Chng Kern Rei , Donnellan Daisy , Hecht Jochen , Jackson Katelyn , Kuchin Katerina , Karasikov Mikhail , Lyons Abigail , Mak Lauren , Meleshko Dmitry , Mustafa Harun , Mutai Beth , Neches Russell Y , Ng Amanda , Nikolayeva Olga , Nikolayeva Tatyana , Png Eileen , Ryon Krista , Sanchez Jorge L , Shaaban Heba , Sierra Maria A , Thomas Dominique , Young Ben , Abudayyeh Omar O. , Alicea Josue , Bhattacharyya Malay , Blekhman Ran , Castro-Nallar Eduardo , Cañas Ana M , Chatziefthimiou Aspassia D , Crawford Robert W , De Filippis Francesca , Deng Youping , Desnues Christelle , Dias-Neto Emmanuel , Dybwad Marius , Elhaik Eran , Ercolini Danilo , Frolova Alina , Gankin Dennis , Gootenberg Jonathan S. , Graf Alexandra B , Green David C , Hajirasouliha Iman , Hernandez Mark , Iraola Gregorio , Jang Soojin , Kahles Andre , Kelly Frank J , Knights Kaymisha , Kyrpides Nikos C , Łabaj Paweł P , Lee Patrick K H , Leung Marcus H Y , Ljungdahl Per , Mason-Buck Gabriella , McGrath Ken , Meydan Cem , Mongodin Emmanuel F , Moraes Milton Ozorio , Nagarajan Niranjan , Nieto-Caballero Marina , Noushmehr Houtan , Oliveira Manuela , Ossowski Stephan , Osuolale Olayinka O , Özcan Orhan , Paez-Espino David , Rascovan Nicolas , Richard Hugues , Rätsch Gunnar , Schriml Lynn M , Semmler Torsten , Sezerman Osman U , Shi Leming , Shi Tieliu , Song Le Huu , Suzuki Haruo , Court Denise Syndercombe , Tighe Scott W , Tong Xinzhao , Udekwu Klas I , Ugalde Juan A , Valentine Brandon , Vassilev Dimitar I , Vayndorf Elena , Velavan Thirumalaisamy P , Wu Jun , Zambrano María M , Zhu Jifeng , Zhu Sibo , Mason Christopher E ,   The International MetaSUB Consortium
Published: August 2019

We have created a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities across 3 years. This is the first systematic, worldwide study cataloging the urban microbial ecosystem. We identify taxonomically-defined microorganisms collected across three years. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics AMR markers, and novel genetic elements, including 10,928 viral, 1302 bacteria, and 2 archaea novel species. We identify 4,424 species of urban microorganisms and a consistent “core” of 31 species found in nearly all samples that is largely distinct from any human commensal microbiome. Profiles of AMR genes show geographic variation in type and density. Together, these results constitute a high-resolution, global metagenomic atlas, which enables the discovery of new genetic components, highlights potential forensic applications, and provides an essential first draft of the global AMR burden of the world’s cities.
On the distribution of tract lengths during adaptive introgression
Authors: Shchur Vladimir , Svedberg Jesper , Medina Paloma , Corbett-Detig Russ , Nielsen RASMUS
Published: August 2019

Admixture is increasingly being recognized as an important factor in evolutionary genetics. The distribution of genomic admixture tracts, and the resulting effects on admixture linkage disequilibrium, can be used to date the timing of admixture between species or populations. However, the theory used for such prediction assumes selective neutrality despite the fact that many famous examples of admixture involve natural selection acting for or against admixture. In this paper, we investigate the effects of positive selection on the distribution of tract lengths. We develop a theoretical framework that relies on approximating the trajectory of the selected allele using a logistic function. By numerically calculating the expected allele trajectory, we also show that the approach can be extended to cases where the logistic approximation is poor due to the effects of genetic drift. Using simulations, we show that the model is highly accurate under most scenarios. We use the model to show that positive selection on average will tend to increase the admixture tract length. However, perhaps counter-intuitively, conditional on the allele frequency at the time of sampling, positive selection will actually produce shorter expected tract lengths. We discuss the consequences of our results in interpreting the timing of the introgression of EPAS1 from Denisovans into the ancestors of Tibetans.
spectrum_utils: A Python package for mass spectrometry data processing and visualization
Authors: Bittremieux Wout
Published: August 2019

Given the wide diversity in applications of biological mass spectrometry, custom data analyses are often needed to fully interpret the results of an experiment. Such bioinformatics scripts necessarily include similar basic functionality to read mass spectral data from standard file formats, process it, and visualize it. Rather than having to reimplement this functionality, to facilitate this task,spectrum_utilsis a Python package for mass spectrometry data processing and visualization. Its high-level functionality enables developers to quickly prototype ideas for computational mass spectrometry projects in only a few lines of code. Notably, the data processing functionality is highly optimized for computational efficiency to be able to deal with the large volumes of data that are generated during mass spectrometry experiments. The visualization functionality makes it possible to easily produce publication-quality figures as well as interactive spectrum plots for inclusion on web pages.spectrum_utilsis available for Python 3.6+, includes extensive online documentation and examples, and can be easily installed using conda. It is freely available as open source under the Apache 2.0 license athttps://github.com/bittremieux/spectrum_utils.
TVA-based modeling of short-term memory capacity, speed of processing and perceptual threshold in chronic stroke patients: Case-control differences, reliability, and sensitivity to cognitive training
Authors: Richard Geneviève , Petersen Anders , Ulrichsen Kristine M. , Kolskår Knut , Alnæs Dag , Sanders Anne-Marthe , Dørum Erlend S. , Ihle-Hansen Hege , Nordvik Jan Egil , Westlye Lars T.
Published: August 2019

Attentional deficits following stroke are common and pervasive, and are important predictors for functional recovery. Attentional functions comprise a set of specific cognitive processes allowing to attend, filter and select among a continuous stream of stimuli. These mechanisms are fundamental for more complex cognitive functions such as learning, planning and cognitive control, all crucial for daily functioning, including social interactions. The distributed functional neuroanatomy of these processes is a likely explanation for the high prevalence of attentional impairments following stroke, and underscores the importance of a clinical implementation of computational approaches allowing for sensitive and specific modeling of attentional sub-processes. The Theory of Visual Attention (TVA) offers a theoretical, computational, neuronal and practical framework to assess the efficiency of visual selection performance and parallel processing of multiple objects. Here, using a whole-report experimental paradigm in a cross-sectional case-control comparison and in six repeated assessments over the course of a three-week intensive computerized cognitive training (CCT) intervention in chronic stroke patients (> 6 months since hospital admission, NIHSS < 7 at hospital discharge), we assessed the sensitivity and reliability of TVA parameters reflecting short-term memory capacity (K), processing speed (C) and perceptual threshold (t0). Cross-sectional group comparisons documented lower short-term memory capacity, slower processing speed and higher perceptual threshold in patients compared to age-matched healthy controls. Further, longitudinal analyses revealed high reliability of the TVA parameters in stroke patients, and higher processing speed at baseline was associated with larger cognitive benefits of the CCT. The results support the feasibility, reliability and sensitivity of TVA-based assessment of attentional functions in chronic stroke patients.
The evolution of paternal care: a role for microbes?
Authors: Gurevich Yael , Lewin-Epstein Ohad , Hadany Lilach
Published: August 2019

Paternal care is an evolutionary mystery. Despite extensive research, both theoretical and experimental, the reasons for its ubiquity remain unclear. Common explanations include kin selection and limited accuracy in parentage assessment. However, these explanations do not cover the breadth of circumstances in which paternal care has been observed, particularly in cases of uncertain paternity. Here we propose that microbes may play a key role in the evolution of paternal care among their hosts. Using computational models, we demonstrate that microbes associated with increased paternal care could be favoured by natural selection. We find that microbe-induced paternal care could evolve under wider conditions than suggested by genetic models. Moreover, we show that microbe-induced paternal care is more likely to evolve when considering paternal care interactions that increase microbial transmission, such as feeding and grooming. Our results imply that factors affecting the composition of host microbiome may also alter paternal behaviour.
Genome-wide analysis of polymorphisms identified domestication-associated polymorphism desert carrying important rice grain size/weight QTL
Authors: Kumar Angad , Daware Anurag , Kumar Arvind , Kumar Vinay , Krishnan S Gopala , Mondal Subhasish , Patra Bhaskar Chandra , Singh Ashok. K. , Tyagi Akhilesh K. , Parida Swarup K. , Thakur Jitendra K.
Published: August 2019

Rice grain size and weight are major determinant of grain quality and yield and so have been under rigorous selection since domestication. However, genetic basis for contrasting grain size/weight trait among indian germplasm, and their association with domestication shaped evolutionary region is not studied before. To identify genetic basis of grain size/weight two long (LGG) and two short grain genotypes (SGG) were resequenced. LGG (LGR and Pusa Basmati 1121) differentiated from SGG (Sonasal and Bindli) by 504439 SNPs and 78166 InDels. TheLRKgene cluster was significantly affected and a truncation mutation in the LRK8 kinase domain was uniquely associated with LGG. Phylogeny with 3000 diverse rice accessions revealed four sequenced genotypes belonged tojaponicagroup and were at the edge of clades indicating source of genetic diversity available in Asian rice population. Five SNPs significantly were associated with grain size/weight and top three SNPs were validated in RIL mapping populations, suggesting this study as a valuable resource for high-throughput genotyping. A contiguous ∼6 Mb polymorphism desert region carrying a major grain weight QTL was identified on chromosome 5 in four sequenced genotypes. Further, among 3000, this region was identified as evolutionary important site with significant positive selection, elevated LD, and multiple selection sweeps, stabilising many domestication-related traits including grain size/weight. Theausgroup genotype retained more allelic variations in the desert region thanjaponicaandindica, and likely to be one of the differentiation point forausgroup. We suggest this desert region as an important evolutionary node that can be selected in breeding programs for improvement of grain yield and quality. All data and analysis can be accessed from RiceSzWtBase database.

Significance statement

Being an important trait, rice grain size/weight has been under rigorous selection since domestication. However, a link between this trait and domestication is not so directly established. In addition to characterization of novel grain size/weight-associated SNPs, in this study, ∼ 6 Mb polymorphism desert region harboring major grain weight QTL was identified on chromosome 5, which turned out to be an evolutionary important site with multiple selection sweeps and introgression events, significantly correlated with domestication-related traits.
Overtone focusing in biphonic Tuvan throat singing
Authors: Bergevin Christopher , Narayan Chandan , Williams Joy , Mhatre Natasha , Steeves Jennifer , Story Brad
Published: August 2019

Khoomei is a unique singing style originating from the Central Asian republic of Tuva. Singers produce two pitches simultaneously: a booming low-frequency rumble alongside a hovering high-pitched whistle-like tone. The biomechanics of this biphonation are not well-understood. Here, we use sound analysis, dynamic magnetic resonance imaging, and vocal tract modeling to demonstrate how biphonation is achieved by modulating vocal tract morphology. Tuvan singers show remarkable control in shaping their vocal tract to narrowly focus the harmonics (or overtones) emanating from their vocal cords. The biphonic sound is a combination of the fundamental pitch and a focused filter state, which is at the higher pitch (1-2 kHz) and formed by merging two formants, thereby greatly enhancing sound-production in a very narrow frequency range. Most importantly, we demonstrate that this biphonation is a phenomenon arising from linear filtering rather than a nonlinear source.
Widespread arginine phosphorylation in human cells - a novel protein PTM revealed by mass spectrometry
Authors: Fu Songsen , Fu Chuan , Zhou Quan , Lin Rongcan , Ouyang Han , Wang Minning , Sun Ying , Liu Yan , Zhao Yufen
Published: August 2019

Arginine phosphorylation (pArg) is recently discovered as a ubiquitous protein N- phosphorylation in bacteria. However, its prevalence and roles in mammalian cells remain largely unknown due to the lack of established workflow and the inherent lability of the phosphoramidate (P-N) bond. Emerging evidence suggests that N-phosphorylation may extensively exist in eukaryotes and play crucial roles. We report an experimental phosphoproteomic workflow, which for the first time allowed to reveal the widespread occurrence of pArg in human cells by mass spectrometry. By virtue of this approach, we identified 152 high-confidence pArg sit]es derived from 118 proteins. Remarkably, the discovered phosphorylation motif and gene ontology of pArg hint a possible cellular function of arginine phosphorylation by regulating the favorability of propeptide convertase substrate. The generated extensive data set should enable a better understanding of the biological functions of eukaryotic pArg in the future.

Abstract Figure
A widely distributed metalloenzyme class enables gut microbial metabolism of host- and diet-derived catechols
Authors: Rekdal Vayu Maini , Bernardino Paola Nol , Luescher Michael U. , Kiamehr Sina , Turnbaugh Peter J. , Bess Elizabeth N. , Balskus Emily P.
Published: August 2019

Catechol dehydroxylation is a central chemical transformation in the gut microbial metabolism of plant- and host-derived small molecules. However, the molecular basis for this transformation and its distribution among gut microorganisms are poorly understood. Here, we characterize a molybdenum-dependent enzyme from the prevalent human gut bacteriumEggerthella lentathat specifically dehydroxylates catecholamine neurotransmitters available in the human gut. Our findings suggest that this activity enablesE. lentato use dopamine as an electron acceptor under anaerobic conditions. In addition to characterizing catecholamine dehydroxylation, we identify candidate molybdenum-dependent enzymes that dehydroxylate additional host-and plant-derived small molecules. These gut bacterial catechol dehydroxylases are specific in their substrate scope and transcriptional regulation and belong to a distinct group of largely uncharacterized molybdenum-dependent enzymes that likely mediate both primary and secondary metabolism in multiple environments. Finally, we observe catechol dehydroxylation in the gut microbiotas of diverse mammals, suggesting that this chemistry is present in habitats beyond the human gut. Altogether, our data reveal the molecular basis of catechol dehydroxylation among gut bacteria and suggest that the chemical strategies that mediate metabolism and interactions in the human gut are relevant to a broad range of species and habitats.
APOBEC3B-dependent kataegis and TREX1-driven chromothripsis in telomere crisis
Authors: Maciejowski John , Chatzipli Aikaterini , Dananberg Alexandra , de Lange Titia , Campbell Peter J.
Published: August 2019

Chromothripsis and kataegis are frequently observed in cancer and can arise from telomere crisis, a period of genome instability during tumorigenesis when depletion of the telomere reserve generates unstable dicentric chromosomes1–5. Here we report on the mechanism underlying chromothripsis and kataegis using an in vitro telomere crisis model. We show that the cytoplasmic exonuclease TREX1, which promotes the resolution of dicentric chromosomes4, plays a prominent role in chromothriptic fragmentation. In absence of TREX1, the genome alterations induced by telomere crisis primarily involve Breakage-Fusion-Bridge cycles and simple genome rearrangements rather than chromothripsis. Furthermore, we show that the kataegis observed at chromothriptic breakpoints is the consequence of cytosine deamination by APOBEC3B. In addition, APOBEC3B increased the frequency of chromothriptic fragmentation, possibly due to strand breakage after cytosine deamination. These data reveal that chromothripsis and kataegis arise from a combination of nucleolytic processing by TREX1 and cytosine editing by APOBEC3B.
The Integrator complex terminates promoter-proximal transcription at protein-coding genes
Authors: Elrod Nathan D. , Henriques Telmo , Huang Kai-Lieh , Tatomer Deirdre C. , Wilusz Jeremy E. , Wagner Eric J. , Adelman Karen
Published: August 2019

The transition of RNA polymerase II (Pol II) from initiation to productive elongation is a central, regulated step in metazoan gene expression. At many genes, Pol II pauses stably in early elongation, remaining engaged with the 25-60 nucleotide-long nascent RNA for many minutes while awaiting signals for release into the gene body. However, a number of genes display highly unstable promoter Pol II, suggesting that paused polymerase might dissociate from template DNA at these promoters and release a short, non-productive mRNA. Here, we report that paused Pol II can be actively destabilized by the Integrator complex. Specifically, Integrator utilizes its RNA endonuclease activity to cleave nascent RNA and drive termination of paused Pol II. These findings uncover a previously unappreciated mechanism of metazoan gene repression, akin to bacterial transcription attenuation, wherein promoter-proximal Pol II is prevented from entering productive elongation through factor-regulated termination.

Highlights

The Integrator complex inhibits transcription elongation at ∼15% of mRNA genes

Integrator targets promoter-proximally paused Pol II for termination

The RNA endonuclease of Integrator subunit 11 is critical for gene attenuation

Integrator-repressed genes are enriched in signaling and growth-responsive pathways
Seroprevalence and parasite rates ofPlasmodium malariaein a high malaria transmission setting of southern Nigeria
Authors: Oriero Eniyou C. , Olukosi Adeola Y. , Oduwole Olabisi A. , Djimde Abdoulaye , D’Alessandro Umberto , Meremikwu Martin M. , Amambua-Ngwa Alfred
Published: August 2019

WhilePlasmodium falciparumcontinues to be the main target for malaria elimination, otherPlasmodiumspecies persist in Africa. Their clinical diagnosis is uncommon while rapid diagnostic tests (RDTs), the most widely used malaria diagnostic tool, are only able to distinguish betweenP. falciparumand non-falciparum species, the latter as ‘pan-species’. Blood samples, both from clinical cases and communites, were collected in southern Nigeria (Lagos and Calabar) in 2017 (October-December) and 2018 (October–November), and analysed by several methods, namely microscopy, quantitative real-time PCR (qPCR), and peptide serology targeting candidate antigens (PmAMA1, PmLDH and PmCSP). The sensitivity of the diagnostic approaches for the dominantP. falciparumwere comparable, detecting approx. 80% infection, but not so for non-falciparum species – 3% and 10% infection forP. malariae; 0% and 3% infection forP. ovaleby microscopy and qPCR respectively, across communities.P. ovaleprevalence was less than 5%. Infection rates forP. malariaevaried between age groups, with the highest rates in individuals > 5 years.P. malariaespecific seroprevalence rates fluctuated in those < 10 years but generally reached the peak around 20 years of age for all peptides. The heterogeneity and rates of these non-falciparum species calls for increased specific diagnosis and targeting by elimination strategies.
SNAPPy: a snakemake pipeline for scalable HIV-1 subtyping by phylogenetic pairing
Authors: Araújo Pedro M.M. , Martins Joana S. , Osório Nuno S.
Published: August 2019

Human immunodeficiency virus 1 (HIV-1) genome sequencing is routinely done for drug resistance monitoring in hospitals worldwide. Subtyping these extensive datasets of HIV-1 sequences is a critical first step in molecular epidemiology and surveillance studies. The clinical relevance of HIV-1 subtypes is increasingly recognized. Several studies suggest subtype-related differences in disease progression, transmission route efficiency, immune evasion, and even therapeutic outcomes. HIV-1 subtyping is mainly done using web servers. These tools have limitations in scalability and potential noncompliance with data protection legislation. Thus, the aim of this work was to develop an efficient method for local and high-throughput HIV-1 subtyping. We designed SNAPPy: a snakemake pipeline for scalable HIV-1 subtyping by phylogenetic pairing. It contains several tasks of phylogenetic inference and BLAST queries, which can be executed sequentially or in parallel, taking advantage of multiple-core processing units. Although it was built for subtyping, SNAPPy is also useful to perform extensive HIV-1 alignments. This tool facilitates large-scale sequence-based HIV-1 research by providing a local, resource efficient and scalable alternative for HIV-1 subtyping. It is capable of analysing full-length genomes or partial HIV-1 genomic regions (GAG, POL, ENV) and recognizes more than 90 circulating recombinant forms. SNAPPy is freely available at:https://github.com/PMMAraujo/snappy.
Axon-like protrusions promote small cell lung cancer migration and metastasis
Authors: Yang Dian , Qu Fangfei , Cai Hongchen , Chuang Chen-Hua , Lim Jing Shan , Jahchan Nadine , Grüner Barbara M. , Kong Christina , Oudin Madeleine J. , Winslow Monte M. , Sage Julien
Published: August 2019

Metastasis is the main cause of death in cancer patients but remains a poorly understood process. Small cell lung cancer (SCLC) is one of the most lethal and most metastatic types of human cancer. SCLC cells normally express neuroendocrine and neuronal gene programs but accumulating evidence indicates that these cancer cells become relatively more neuronal and less neuroendocrine as they gain the ability to metastasize. Here we show that mouse and human SCLC cells in culture andin vivocan grow cellular protrusions that resemble axons. The formation of these protrusions is controlled by multiple neuronal factors implicated in axonogenesis, axon guidance, and neuroblast migration. Disruption of these axon-like protrusions impairs cell migration in culture and inhibits metastatic abilityin vivo. The co-option of developmental neuronal programs is a novel molecular and cellular mechanism that contributes to the high metastatic ability of SCLC.
Bayesian inference of reassortment networks reveals fitness benefits of reassortment in human influenza viruses
Authors: Müller Nicola F. , Stolz Ugnė , Dudas Gytis , Stadler Tanja , Vaughan Timothy G.
Published: August 2019

Reassortment is an important source of genetic diversity in segmented viruses and is the main source of novel pathogenic influenza viruses. Despite this, studying the reassortment process has been constrained by the lack of a coherent, model-based inference framework. We here introduce a novel coalescent based model that allows us to explicitly model the joint coalescent and reassortment process. In order to perform inference under this model, we present an efficient Markov chain Monte Carlo algorithm to sample rooted networks and the embedding of phylogenetic trees within networks. Together, these provide the means to jointly infer coalescent and reassortment rates with the reassortment network and the embedding of segments in that network from full genome sequence data. Studying reassortment patterns of different human influenza datasets, we find large differences in reassortment rates across different human influenza viruses. Additionally, we find that reassortment events predominantly occur on selectively fitter parts of reassortment networks showing that on a population level, reassortment positively contributes to the fitness of human influenza viruses.
Altered visual population receptive fields in human albinism
Authors: Alvarez Ivan , Smittenaar Rebecca , Handley Sian E. , Liasis Alki , Sereno Martin I. , Schwarzkopf D. Samuel , Clark Chris A.
Published: August 2019

1

Albinism is a congenital disorder where misrouting of the optic nerves at the chiasm gives rise to abnormal visual field representations in occipital cortex. In typical human development, the left occipital cortex receives retinal input predominantly from the right visual field, and vice-versa. In albinism, there is a more complete decussation of optic nerve fibers at the chiasm, resulting in partial representation of the temporal hemiretina (ipsilateral visual field) in the contralateral hemisphere. In this study, we characterize the receptive field properties for these abnormal representations by conducting detailed fMRI population receptive field mapping in a rare subset of participants with albinism and no ocular nystagmus. We find a nasal bias for receptive field positions in the abnormal temporal hemiretina representation. In addition, by modelling responses to bilateral visual field stimulation in the overlap zone, we found evidence in favor of discrete unilateral receptive fields, suggesting a conservative pattern of spatial selectivity in the presence of abnormal retinal input.

Highlights

We characterized population receptive fields in albinotic participants with no ocular nystagmus

Confirmed overlapping representations of left and right visual fields in cortex

Detected nasal bias in receptive field location for temporal hemiretina representation

Evidence in favor of discrete unilateral receptive fields and against double coding
Biological Pathways and Gene Networks Link Inflammation and Vascular Remodeling to Both Heart Failure with Preserved and Reduced Ejection Fraction in Women across Ethnicities
Authors: Liu Qing , Chan Kei Hang K. , Morrison Alan R. , McGarvey Stephen T. , Luo Xi , Wilson James G. , Correa Adolfo , Reiner Alexander P. , Li Jie , Liu Simin , Wu Wen-Chih
Published: August 2019

Introduction

Heart failure (HF) is understudied among women; especially, genomic evidence implicating shared or unique mechanisms of HF with respect to reduced or preserved ejection fraction (HFrEF, HFpEF) is lacking across ethnic populations of women. Prior genome-wide association studies (GWAS) have identified approximately 30 suggestive genetic variants for HF, although none have been specifically linked to HFrEF or HFpEF.

Objectives

We aimed to define, replicate, and annotate genetic variants to HFrEF, HFpEF, or both, as well as to investigate potential biological mechanisms underlying HFrEF and HFpEF among African American (AA) and European American (EA) women in three well-characterized, high-quality prospective cohorts, the Women’s Health Initiative (WHI) study, the Jackson Heart Study (JHS), and the Framingham Heart Study (FHS).

Methods

GWAS analysis on HFrEF and HFpEF were first performed among 7,982 AA and 4,133 EA in the WHI, followed by pathway analysis employing two independent methodological platforms (GSA-SNP and Mergeomics) curating KEGG, Reactome, and BioCarta pathway databases. GWAS signals and biological pathways identified using the WHI were replicated in the JHS and FHS. For all replicated pathways, we performed cross-phenotype and cross-ethnicity validation analyses to examine shared pathways between HFrEF and HFpEF, and phenotype-specific pathways, across ethnicities. We further prioritized key driver genes for HF according to specific pathways identified.

Results

We validated one previously reported genetic locus and identified six new ones, among which one locus was allocated to HFrEF and five to HFpEF. Additionally, we defined five biological pathways shared between HFrEF and HFpEF and discovered six HFpEF-specific pathways. These pathways overlapped in two main domains for molecular signaling: 1) inflammation and 2) vascular remodeling (including angiogenesis and vascular patterning), involving key driver genes from collagen and HLA gene families.

Conclusions

Our network analysis of three large prospective cohorts of women in the United States defined several novel loci for HF and its subtypes. In particular, several key driver genes reinforce the mechanistic role of inflammation and vascular remodeling in the development of HF, especially HFpEF. Given that therapeutic strategies developed for left ventricular dysfunction have had limited success for HFpEF, several new targets and pathways identified and validated in this study should be further assessed in risk stratification as well as the design of potential new HF interventions.
Cyclin B1 scaffolds MAD1 at the corona to activate the spindle assembly checkpoint
Authors: Allan Lindsey A , Reis Magda , Liu Yahui , Huis in ’t Veld Pim , Kops Geert JPL , Musacchio Andrea , Saurin Adrian T
Published: August 2019

The Cyclin B:CDK1 kinase complex is the master regulator of mitosis that phosphorylates hundreds of proteins to coordinate mitotic progression. We show here that, in addition to these kinase functions, Cyclin B also scaffolds a localised signalling pathway to help preserve genome stability. Cyclin B1 localises to an expanded region of the outer kinetochore, known as the corona, where it scaffolds the spindle assembly checkpoint (SAC) machinery by binding directly to MAD1. In vitro reconstitutions map the key binding interface to a few acidic residues in the N-terminus of MAD1, and point mutations in this region remove corona MAD1 and weaken the SAC. Therefore, Cyclin B1 is the long-sought-after scaffold that links MAD1 to the corona and this specific pool of MAD1 is needed to generate a robust SAC response. Robustness, in this context, arises because Cyclin B1-MAD1 localisation becomes MPS1-independent after the corona has been established. We demonstrate that this allows corona-MAD1 to persist at kinetochores when MPS1 activity falls, ensuring that it can still be phosphorylated on a key C-terminal catalytic site by MPS1. Therefore, this study explains how corona MAD1 generates a robust SAC signal and why stripping of this pool by dynein is essential for SAC silencing. It also reveals that the key mitotic kinase, Cyclin B1-Cdk1, scaffolds the pathway that inhibits its own degradation.
Resilience to multiple stressors in an aquatic plant and its microbiome
Authors: O’Brien Anna M. , Yu Zhu Hao , Luo Dian-ya , Laurich Jason , Passeport Elodie , Frederickson Megan
Published: August 2019

Premise

Environments are changing rapidly, and outcomes of species interactions, especially mutualisms, are notoriously dependent on the environment. A growing number of studies have investigated responses of mutualisms to anthropogenic changes, yet most studies have focused on nutrient pollution or climate change, and tested single stressors. Relatively little is known about impacts of simultaneous chemical contaminants, which may differ fundamentally from nutrient or climate stressors, and are especially widespread in aquatic habitats.

Methods

We investigated the impacts of two common contaminants on interactions between the common duckweed Lemna minor and its microbiome. Sodium chloride (salt) and benzotriazole (a corrosion inhibitor) negatively affect aquatic organisms individually, yet commonly co-occur in runoff to duckweed-inhabited sites. We tested three L. minor genotypes with and without the culturable portion of their microbiome across field realistic gradients of salt (3 levels) and benzotriazole (4 levels) in a fully factorial experiment (72 treatments), and measured plant and microbial growth.

Key Results

We found that stressors had conditional effects. Salt decreased both plant and microbial growth, but decreased plant survival more as benzotriazole concentrations increased. In contrast, benzotriazole did not affect microbial abundance, and benefited plants when salt and microbes were absent, perhaps due to the biotrans-formation we observed without salt. Microbes did not ameliorate duckweed stressors, as microbial inoculation increased plant growth, but not at high salt concentrations.

Conclusions

Our results suggest that multistressor effects matter when predicting responses of mutualisms to global change, but that mutualisms may not buffer organisms from stressors.
Protein yield is tunable by synonymous codon changes of translation initiation sites
Authors: Bhandari Bikash K. , Lim Chun Shen , Remus Daniela M. , Chen Augustine , van Dolleweerd Craig , Gardner Paul P.
Published: August 2019

Recombinant protein production is a key process in generating proteins of interest in the pharmaceutical industry and biomedical research. However, about 50% of recombinant proteins fail to be expressed in a variety of host cells. To address this problem, we modified up to the first nine codons of messenger RNAs with synonymous substitutions and showed that protein levels can be tuned. These modifications alter the ‘accessibility’ of translation initiation sites. We also reveal the dynamics between accessibility, gene expression, and turnovers using a coarse-grained simulation.
Unraveling the genetic structure of the coconut scale insect pest (Aspidiotus rigidusReyne) outbreak populations in the Philippines
Authors: Serrana Joeselle M. , Ishitani Naoto , Carvajal Thaddeus M. , Almarinez Billy Joel M. , Barrion Alberto T. , Amalin Divina M. , Watanabe Kozo
Published: August 2019

The Philippines suffered from a devastating outbreak of the coconut scale insect pest,Aspidiotus rigidusReyne inflicting significant economic losses to the country’s coconut industry. Despite the massive outbreak, little is known about the population and dispersal history of this invasive pest in the Philippines. Here, we examined the genetic diversity, structure and demographic history ofA. rigidussampled from localities with reported outbreaks from 2014 to 2017. We analyzed the genetic structure of sevenA. rigidusoutbreak populations using mitochondrialCOIand nuclearEF-1α markers. Both markers and all methods of population genetic structure analyses indicate clear differentiation among theA. rigiduspopulations separating the northern (i.e., Luzon provinces) from the southern (i.e., Basilan and Zamboanga Peninsula) regions of the Philippines. Very low or no genetic differentiation was observed within and amongst the populations per geographic region indicating two unrelated outbreak events of the pest originating from two genetically uniform populations isolated in each respective region. Historical data supports the resurgence of an establishedA. rigiduspopulation in the south which could have been driven by sudden climatic changes or human-induced habitat imbalance. Given no historical information, we disregard the possible resurgence from the northern population and infer that the outbreak could have resulted from a recent introduction of a non-nativeA. rigidusin the region. Our study provides valuable information on the genetic differentiation of the twoA. rigidusgroups that would be useful for developing and implementing biological control strategies against this pest in the Philippines.
Polygenic and clinical risk scores and their impact on age at onset of cardiometabolic diseases and common cancers
Authors: Mars Nina J. , Koskela Jukka T. , Ripatti Pietari , Kiiskinen Tuomo T.J. , Havulinna Aki S. , Lindbohm Joni V. , Ahola-Olli Ari , Kurki Mitja , Karjalainen Juha , Palta Priit ,   FinnGen, Neale Benjamin M. , Daly Mark , Salomaa Veikko , Palotie Aarno , Widén Elisabeth , Ripatti Samuli
Published: August 2019

Background

Polygenic risk scores (PRS) have shown promise in predicting susceptibility to common diseases. However, the extent to which PRS and clinical risk factors act jointly and identify high-risk individuals for early onset of disease is unknown.

Methods

We used large-scale biobank data (the FinnGen study; n=135,300), with up to 46 years of prospective follow-up, and the FINRISK study with standardized clinical risk factor measurements to build genome-wide PRSs with >6M variants for coronary heart disease (CHD), type 2 diabetes (T2D), atrial fibrillation (AF), and breast and prostate cancer. We evaluated their associations with first disease events, age at disease onset, and impact together with routinely used clinical risk scores for predicting future disease.

Results

Compared to the 20-80thpercentiles, a PRS in the top 2.5% translated into hazard ratios (HRs) for incident disease ranging from 2.03 to 4.28 (p-values 1.96×10−59to <1.00×10−100) and the bottom 2.5% into HRs ranging from 0.20 to 0.61. The estimated difference in age at disease onset between top and bottom 2.5% of PRSs was 6 to 13 years. Among early-onset cases, 21.3-32.9% had a PRS in the highest decile and in CHD and AF.

Conclusions

The properties of PRS were similar in all five diseases. PRS identified a considerable proportion early-onset cases, and for all ages the performance of PRS was comparable to established clinical risk scores. These findings warrant further clinical studies on application of polygenic risk information for stratified screening or for guiding lifestyle and preventive medical interventions.
Uncoating of COPII from ER exit site membranes precedes cargo accumulation and membrane fission
Authors: Shomron Olga , Nevo-Yassaf Inbar , Aviad Tamar , Yaffe Yakey , Zahavi Eitan Erez , Dukhovny Anna , Perlson Eran , Brodsky Ilya , Yeheskel Adva , Pasmanik-Chor Metsada , Mironov Anna , Beznoussenko Galina V. , Mironov Alexander A. , Sklan Ella H. , Patterson George H. , Yonemura Yoji , Kaether Christoph , Hirschberg Koret
Published: August 2019

COPII and COPI are considered to be analogous sets of vesicle coat protein heterocomplexes. Coupled to cargo selection, they mediate the formation of membrane vesicles translocating in opposite directions to differ rent destinations within the secretory pathway. Here, live cell and electron microscopy provided evidence for a different localization and mode of function of the COPII coat during protein export from the endoplasmic reticulum (ER). Pharmaceutical and genetic perturbations of ER-Golgi transport were used to demonstrate that COPII is recruited to membranes defining the boundary of ER-ER Exit Sites (ERES) where it facilitates selective cargo concentration. Uncoating of COPII membranes precedes cargo accumulation and fission of Golgi-bound carriers. Moreover, we report what may be direct transfer of cargo to the Golgi apparatus from Golgi-associated BFA sensitive ERESs. Finally, in ldlF cells the stably expressed functional ε-COPI-EYFP labeled both ERESs and anterograde carriers. These findings change our understanding of the role of coat proteins in ER to Golgi transport.
Genomic assessment of local adaptation in dwarf birch to inform assisted gene flow
Authors: Borrell James S. , Zohren Jasmin , Nichols Richard A. , Buggs Richard J. A.
Published: August 2019

When populations of a rare species are small, isolated and declining under climate change, some populations may become locally maladapted. Detecting this maladaptation may allow effective rapid conservation interventions, even if based on incomplete knowledge. Population maladaptation may be estimated by finding genome-environment associations (GEA) between allele frequencies and environmental variables across a local species range, and identifying populations whose allele frequencies do not fit with these trends. We can then design assisted gene flow strategies for maladapted populations, to adjust their allele frequencies, entailing lower levels of intervention than with undirected conservation action. Here, we investigate this strategy in Scottish populations of the montane plant dwarf birch (Betula nana). In genome-wide single nucleotide polymorphism (SNP) data we found 267 significant associations between SNP loci and environmental variables. We ranked populations by maladaptation estimated using allele frequency deviation from the general trends at these loci; this gave a different prioritization for conservation action than the Shapely Index, which seeks to preserve rare neutral variation. Populations estimated to be maladapted in their allele frequencies at loci associated with annual mean temperature were found to have reduced catkin production. Using an environmental niche modelling (ENM) approach, we found annual mean temperature (35%), and mean diurnal range (15%), to be important predictors of the dwarf birch distribution. Intriguingly, there was a significant correlation between the number of loci associated with each environmental variable in the GEA, and the importance of that variable in the ENM. Together, these results suggest that the same environmental variables determine both adaptive genetic variation and species range in Scottish dwarf birch. We suggest an assisted gene flow strategy that aims to maximize the local adaptation of dwarf birch populations under climate change by matching allele frequencies to current and future environments.
Spatial and temporal variation in small mammal abundance and diversity under protection, pastoralism and agriculture in the Serengeti Ecosystem, Tanzania
Authors: Shilereyo Monica T. , Magige Flora J. , Ogutu Joseph O. , Røskaft Eivin
Published: August 2019

Land use is an important factor influencing animal abundance, species richness and diversity in both protected and human-dominated landscapes. Increase in human population and activities intensify changes in habitat structure and hence abundance, species richness and diversity. We investigated the influences of land use and seasonality on small mammal abundance, species richness and diversity in 10 habitat types distributed over protected, agricultural and pastoral landscapes in the Serengeti ecosystem in Tanzania. We used live traps (n= 141) and capture-recapture methods in each of 10 fixed plots distributed across three landscapes for a total of 28,200 trap nights of effort. Trapping was carried out in the wet and dry seasons for two consecutive years (April 2017 to October 2018). Small mammal abundance was higher in the pastoral than in the protected and in the agricultural landscape. Abundance was higher in the dry than the wet season across all the three landscapes. Species richness and diversity were higher in the protected, middling in the agricultural and lowest in the pastoral landscape. The high abundance in the pastoral landscape was due to the numerical dominance of two species, namely A.niloticusin the shrubland andM. natalensisin the cropland habitat, resulting in low species richness and diversity. Abundance was more evenly distributed across all habitats in the protected area due to less disturbance. The low abundance in the agricultural landscape, likely reflects disturbance from cultivation. High species richness and diversity in the protected area indicate high habitat heterogeneity while high species diversity in the agricultural landscape was likely due to high food availability during and soon after harvests. These findings emphasize the importance of protection in maintaining habitat heterogeneity for wildlife. They also reaffirm the need for buffer zones around protected areas to cushion them from intensifying human activities.