bluuebunny/crossref_metadata_2025 huggingface dataset:
LOTUS: a Single- and Multitask Machine Learning Algorithm for the Prediction of Cancer Driver Genes
Authors: Collier Olivier , Stoven Véronique , Vert Jean-Philippe
Published: August 2018

Cancer driver genes, i.e., oncogenes and tumor suppressor genes, are involved in the acquisition of important functions in tumors, providing a selective growth advantage, allowing uncontrolled proliferation and avoiding apoptosis. It is therefore important to identify these driver genes, both for the fundamental understanding of cancer and to help finding new therapeutic targets. Although the most frequently mutated driver genes have been identified, it is believed that many more remain to be discovered, particularly for driver genes specific to some cancer types.

In this paper we propose a new computational method called LOTUS to predict new driver genes. LOTUS is a machine-learning based approach which allows to integrate various types of data in a versatile manner, including informations about gene mutations and protein-protein interactions. In addition, LOTUS can predict cancer driver genes in a pan-cancer setting as well as for specific cancer types, using a multitask learning strategy to share information across cancer types.

We empirically show that LOTUS outperforms three other state-of-the-art driver gene prediction methods, both in terms of intrinsic consistency and prediction accuracy, and provide predictions of new cancer genes across many cancer types.

Author summary

Cancer development is driven by mutations and dysfunction of important, so-called cancer driver genes, that could be targeted by targeted therapies. While a number of such cancer genes have already been identified, it is believed that many more remain to be discovered. To help prioritize experimental investigations of candidate genes, several computational methods have been proposed to rank promising candidates based on their mutations in large cohorts of cancer cases, or on their interactions with known driver genes in biological networks. We propose LOTUS, a new computational approach to identify genes with high oncogenic potential. LOTUS implements a machine learning approach to learn an oncogenic potential score from known driver genes, and brings two novelties compared to existing methods. First, it allows to easily combine heterogeneous informations into the scoring function, which we illustrate by learning a scoring function from both known mutations in large cancer cohorts and interactions in biological networks. Second, using a multitask learning strategy, it can predict different driver genes for different cancer types, while sharing information between them to improve the prediction for every type. We provide experimental results showing that LOTUS significantly outperforms several state-of-the-art cancer gene prediction softwares.
Linking Fungal and Bacterial Proliferation to Microbiologically Influenced Corrosion in B20 Biodiesel Storage Tanks
Authors: Stamps Blake W. , Bojanowski Caitlin L. , Drake Carrie A. , Nunn Heather S. , Lloyd Pamela F. , Floyd James G. , Berberich Katelyn A. , Neal Abby R. , Crookes-Goodson Wendy J. , Stevenson Bradley S.
Published: August 2018

Biodiesel is a renewable substitute, or extender, for petroleum diesel that is composed of a mixture of fatty acid methyl esters (FAME) derived from plant and animal fats. Ultra-low sulfur diesel (ULSD) blended with up to 20% FAME can be used interchangeably with ULSD, is compatible with existing infrastructure, but is also more susceptible to biodegradation. Microbial proliferation and fuel degradation in biodiesel blends has not been directly linked in situ to microbiologically influenced corrosion. We, therefore, conducted a yearlong study of B20 storage tanks in operation at two locations, identified the microorganisms responsible for observed fuel fouling and degradation, and measured in situ corrosion. The bacterial populations were more diverse than the fungal populations, and largely unique to each location. The bacterial populations included members of the Acetobacteraceae, Clostridiaceae, and Proteobacteria. The abundant Eukaryotes at both locations consisted of the same taxa, including a filamentous fungus within the family Trichocomaceae, and the Saccharomycetaceae family of yeasts. Increases in the absolute and relative abundances of the Trichocomaceae were correlated with significant, visible fouling and pitting corrosion. This study identified the relationship between recurrent fouling of B20 with increased rates of corrosion, largely at the bottom of the sampled storage tanks.
Genomic signatures accompanying the dietary shift to phytophagy in polyphagan beetles
Authors: Seppey Mathieu , Ioannidis Panagiotis , Emerson Brent C. , Pitteloud Camille , Robinson-Rechavi Marc , Roux Julien , Escalona Hermes E. , McKenna Duane D. , Misof Bernhard , Shin Seunggwan , Zhou Xin , Waterhouse Robert M. , Alvarez Nadir
Published: August 2018

Background

The diversity and evolutionary success of beetles (Coleoptera) are proposed to be related to the diversity of plants on which they feed. Indeed the largest beetle suborder, Polyphaga, mostly includes plant-eaters among its ~315,000 species. In particular, plants defend themselves with a diversity of specialized toxic chemicals. These may impose selective pressures that drive genomic diversification and speciation in phytophagous beetles. However, evidence of changes in beetle gene repertoires driven by such interactions remains largely anecdotal and without explicit hypothesis testing.

Results

To address this, we explored the genomic consequences of beetle-plant trophic interactions by performing comparative gene family analyses across 18 species representing the two most species-rich beetle suborders. We contrasted the gene contents of species from the mostly plant-eating suborder Polyphaga with those of the mainly predatory Adephaga. We found gene repertoire evolution to be more dynamic, with significantly more adaptive lineage-specific expansions, in the more speciose Polyphaga. Testing the specific hypothesis of adaptation to plant-feeding, we identified families of enzymes putatively involved in beetle-plant interactions that underwent adaptive expansions in Polyphaga. There was especially strong support for the selection hypothesis on large gene families for glutathione S-transferase and carboxylesterase detoxification enzymes.

Conclusions

Our explicit modeling of the evolution of gene repertoires across 18 species identifies adaptive lineage-specific gene family expansions that accompany the dietary shift towards plants in beetles. These genomic signatures support the popular hypothesis of a key role for interactions with plant chemical defenses, and for plant-feeding in general, in driving beetle diversification.
Topological data analysis quantifies biological nano-structure from single molecule localization microscopy
Authors: Pike Jeremy A. , Khan Abdullah O. , Pallini Chiara , Thomas Steven G. , Mund Markus , Ries Jonas , Poulter Natalie S. , Styles Iain B.
Published: August 2018

The study of complex molecular organisation and nano-structure by localization based microscopy is limited by the available analysis tools. We present a segmentation protocol which, through the application of persistence based clustering, is capable of probing densely packed structures which vary in scale. An increase in segmentation performance over state-of-the-art methods is demonstrated. Moreover we employ persistent homology to move beyond clustering, and quantify the topological structure within data. This provides new information about the preserved shapes formed by molecular architecture. Our methods are flexible and we demonstrate this by applying them to receptor clustering in platelets, nuclear pore components and endocytic proteins. Both 2D and 3D implementations are provided within RSMLM, an R package for pointillist based analysis and batch processing of localization microscopy data.
High resolution evolutionary analysis of within-host hepatitis C virus infection
Authors: Raghwani Jayna , Wu Chieh-Hsi , Ho Cynthia K. Y. , de Jong Menno , Molenkamp Richard , Schinkel Janke , Pybus Oliver G. , Lythgoe Katrina A.
Published: August 2018

Despite the breakthroughs in the treatment of HCV infection in recent years, we have a limited understanding of how virus diversity generated within individuals impacts the evolution and spread of HCV variants at the population scale. Addressing this gap will be important for building models for molecular epidemiology, which can identify main sources of disease transmission and evaluate the risks of drug-resistance mutations emerging and disseminating in a population. Here, we have undertaken a high-resolution analysis of HCV within-host evolution from four individuals co-infected with HIV. Specifically, we used long-read, deep-sequenced data of the full-length HCV envelope glycoprotein, longitudinally sampled from acute to chronic HCV infection to investigate the underlying viral evolutionary dynamics. In three individuals we found strong statistical support for population structure maintaining within-host HCV genetic diversity. Furthermore, we found significant variation in rates of molecular evolution among different regions of the HCV envelope region, both within and between individuals. Lastly, we report the first estimate of the within-host population genetic rate of recombination for HCV (0.28 x 10-7recombinations per site per day; interquartile range: 0.13-1.05 x 10-7), which is two orders of magnitude lower than that estimated for HIV-1, and four orders of magnitude lower than the nucleotide substitution rate of the HCV envelope gene. Together, these observations indicate that population structure and strong genetic linkage shapes within-host HCV evolutionary dynamics. These results will guide the future investigation of potential HCV drug resistance adaptation during infection, and at the population scale.
ENRICH: a fast method to improve the quality of flexible macromolecular reconstructions
Authors: Kazemi M. , Sorzano C. O. S. , Des Georges A. , Carazo J. M. , Vargas J.
Published: August 2018

Cryo-electron microscopy using single particle analysis requires the computational averaging of thousands of projection images captured from identical macromolecules. However, macromolecules usually present some degree of flexibility showing different conformations. Computational approaches are then required to classify heterogeneous single particle images into homogeneous sets corresponding to different structural states. Nonetheless, sometimes the attainable resolution of reconstructions obtained from these smaller homogeneous sets is compromised because of reduced number of particles or lack of images at certain macromolecular orientations. In these situations, the current solution to improve map resolution is returning to the electron microscope and collect more data. In this work, we present a fast approach to partially overcome this limitation for heterogeneous data sets. Our method is based on deforming and then moving particles between different conformations using an optical flow approach. Particles are then merged into a unique conformation obtaining reconstructions with improved resolution, contrast and signal-to-noise ratio, then, partially circumventing many issues that impact obtaining high quality reconstructions from small data sets. We present experimental results that show clear improvements in the quality of obtained 3D maps, however, there are also limits to this approach, which we discuss in the manuscript.
Mutations generated by repair of Cas9-induced double strand breaks are predictable from surrounding sequence
Authors: Allen Felicity , Crepaldi Luca , Alsinet Clara , Strong Alexander J. , Kleshchevnikov Vitalii , Angeli Pietro De , Palenikova Petra , Kosicki Michael , Bassett Andrew R. , Harding Heather , Galanty Yaron , Muñoz-Martínez Francisco , Metzakopian Emmanouil , Jackson Stephen P. , Parts Leopold
Published: August 2018

The exact DNA mutation produced by cellular repair of a CRISPR/Cas9-generated double strand break determines its phenotypic effect. It is known that the mutational outcomes are not random, and depend on DNA sequence at the targeted location. Here, we present a systematic study of this link. We created a high throughput assay to directly measure the edits generated by over 40,000 guide RNAs, and applied it in a range of genetic backgrounds and for alternative CRISPR/Cas9 reagents. In total, we gathered data for over 1,000,000,000 mutational outcomes in synthetic constructs, which mirror those at endogenous loci. The majority of reproducible mutations are insertions of a single base, short deletions, or long microhomology-mediated deletions. gRNAs have a cell-line dependent preference for particular outcomes, especially favouring single base insertions and microhomology-mediated deletions. We uncover sequence determinants of the produced mutations at individual loci, and use these to derive a predictor of Cas9 editing outcomes with accuracy close to the theoretical maximum. This improved understanding of sequence repair allows better design of editing experiments, and may lead to future therapeutic applications.
Signatures of negative frequency dependent selection in colonisation factors and the evolution of a multi-drug resistant lineage of Escherichia coli
Authors: McNally Alan , Kallonen Teemu , Connor Christopher , Abudahab Khalil , Aanensen David M. , Horner Carolyne , Peacock Sharon J. , Parkhill Julian , Croucher Nicholas J. , Corander Jukka
Published: August 2018

Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multi-drug resistant (MDR) strains of extra-intestinal pathogenic E. coli (ExPEC) poses a rapidly increasing public health burden due to narrowed treatment options and increased risk of failure to clear an infection. Here, we present a detailed population genomic analysis of the ExPEC ST131 clone, in which we seek explanations for its success as an emerging pathogenic strain beyond the acquisition of antimicrobial resistance (AMR) genes. We show evidence for evolution towards separate ecological niches for the main clades of ST131 and differential evolution of anaerobic metabolism, key colonisation and virulence factors. We further demonstrate that negative frequency-dependent selection acting across accessory loci is a major mechanism that has shaped the population evolution of this pathogen.
Local membrane charge regulates ல2 adrenergic receptor coupling to Gi
Authors: Strohman M.J. , Maeda S. , Hilger D. , Masureel M. , Du Y. , Kobilka B.K.
Published: August 2018

G protein coupled receptors (GPCRs) are transmembrane receptors that signal through heterotrimeric G proteins. Lipid modifications anchor G proteins to the plasma membrane; however, little is known about the effect of phospholipid composition on GPCR-G protein coupling. The β2adrenergic receptor (β2AR) signals through both Gsand Giin cardiac myocytes where studies suggest that Gisignaling may be cardioprotective. However, Gicoupling is much less efficient than Gscoupling in most cell-based and biochemical assays, making it difficult to study β2AR-Giinteractions. To investigate the role of phospholipid composition on Gsand Gicoupling, we reconstituted β2AR in detergent/lipid mixed micelles and found that negatively charged phospholipids (PS and PG) inhibit β2AR-Gi3coupling. Replacing negatively charged lipids with neutral lipids (PC or PE) facilitated the formation of a functional β2AR-Gi3interaction that activated Gi3. Ca2+, known to interact with negatively charged PS, facilitated β2AR-Gi3interaction in PS. Mutational analysis suggested that Ca2+interacts with the negatively charged EDGE motif on the carboxyl-terminal end of the αN helix of Gi3and coordinates an EDGE-PS interaction. These results were confirmed in β2AR reconstituted into nanodisc phospholipid bilayers. β2AR-Gi3interaction was favored in neutral lipids (PE and PC) over negatively charged lipids (PG and PS). In contrast, basal β2AR-Gsinteraction was favored in negatively charged lipids over neutral lipids. In negatively-charged lipids, Ca2+and Mg2+facilitated β2AR-Gi3interaction. Taken together, our observations suggest that local membrane charge modulates the interaction between β2AR and competing G protein subtypes.
LittleBrain: a gradient-based tool for the topographical interpretation of cerebellar neuroimaging findings
Authors: Guell Xavier , Goncalves Mathias , Kaczmarzyk Jakub R , Gabrieli John DE , Schmahmann Jeremy D , Ghosh Satrajit S
Published: August 2018

Gradient-based approaches to brain function have recently unmasked fundamental properties of brain organization. Diffusion map embedding analysis of resting-state fMRI data revealed a primary-to-transmodal axis of cerebral cortical macroscale functional organization. The same method was recently used to analyze resting-state data within the cerebellum, revealing for the first time a sensorimotor-fugal macroscale organization principle of cerebellar function. Cerebellar gradient 1 extended from motor to non-motor task-unfocused (default-mode network) areas, and cerebellar gradient 2 isolated task-focused processing regions. Here we present a freely available and easily accessible tool that applies this new knowledge to the topographical interpretation of cerebellar neuroimaging findings. LittleBrain generates scatterplots that illustrate the relationship between cerebellar data (e.g., volumetric patient study clusters, task activation maps, etc.) and cerebellar gradients 1 and 2. This novel method of data mapping provides alternative, gradual visualizations that complement discrete parcellation maps of cerebellar functional neuroanatomy. We present application examples to show that LittleBrain can also capture subtle, progressive aspects of cerebellar functional neuroanatomy that would be difficult to visualize using conventional mapping techniques. Download and use instructions can be found at https://xaviergp.github.io/littlebrain.
IPSE, a parasite-derived host immunomodulatory protein, is a promising therapeutic for hemorrhagic cystitis
Authors: Zee Rebecca S. , Mbanefo Evaristus C. , Le Loc H. , Pennington Luke F. , Odegaard Justin , Jardetzky Theodore S. , Alouffi Abdulaziz , Akinwale Jude , Falcone Franco H. , Hsieh Michael H.
Published: August 2018

Chemotherapy-induced hemorrhagic cystitis is characterized by bladder pain and voiding dysfunction caused by hemorrhage and inflammation. Of currently available therapies, prophylactic 2-mercaptoethanesulfonic acid (MESNA) has limited efficacy and cannot treat pre-existing lesions. Therefore, novel therapeutic options to treat hemorrhagic cystitis are needed. We previously reported that systemic administration of the Schistosomiasis haematobium-derived protein H-IPSEH06 (IL-4-inducing principle from Schistosoma mansonieggs), is superior to 3 doses of MESNA in alleviating hemorrhagic cystitis. Based on prior reports by others on S. mansoni IPSE and additional work by our group, we reasoned that H-IPSEH06 mediates its effects on hemorrhagic cystitis by binding IgE on basophils and inducing IL-4 expression, promoting urothelial proliferation, and translocating to the nucleus to modulate expression of genes implicated in relieving bladder dysfunction. We speculated that local bladder injection of the S. haematobium IPSE ortholog IPSEH03, hereafter called H-IPSEH03, might be more efficacious in preventing hemorrhagic cystitis compared to systemic administration of IPSEH06. We demonstrate herein that H-IPSEH03 is a promising therapeutic for the treatment of voiding dysfunction and bladder pain in hemorrhagic cystitis. Namely, it attenuates ifosfamide-induced increases in bladder wet weight in an IL-4-dependent fashion. H-IPSEH03 relieves hemorrhagic cystitis-associated allodynia. Finally, H-IPSEH03 drives increased urothelial cell proliferation. This indicates that IPSE induces bladder healing mechanisms, which suggests that it may be a novel non-opioid analgesic to treat bladder pain syndromes.
The deadly touch: protein denaturation at the water-air interface and how to prevent it
Authors: D’Imprima Edoardo , Floris Davide , Joppe Mirko , Sánchez Ricardo , Grininger Martin , Kühlbrandt Werner
Published: August 2018

Electron cryo-microscopy analyzes the structure of proteins and protein complexes in vitrified solution. Proteins tend to adsorb to the air-water interface in unsupported films of aqueous solution, which can result in partial or complete denaturation of the protein. We investigated the structure of yeast fatty acid synthase at the air-water interface by electron cryo-tomography and single-particle image processing. Around 90% of complexes adsorbed to the air-water interface are partly denatured. We show that the unfolded regions are those facing the air-water interface. Denaturation by contact with air may happen at any stage of specimen preparation. Denaturation at the air-water interface is completely avoided when the complex is plunge-frozen on a substrate of hydrophilized graphene.
Goalkeeper game: a new assessment instrument in neurology showed higher predictive power than moca for gait performance in people with parkinson’s disease
Authors: Stern Rafael B. , d’Alencar Matheus , Uscapi Yanina L. , Gubitoso Marco D. , Roque Antonio C. , Helene André F. , Piemonte Maria Elisa P.
Published: August 2018

Objective

To investigate the use of the Goalkeeper Game (GG) to assess gait automaticity decline under dual task conditions in people with Parkinson’s disease (PPD) and compare its predictive power with the one of the MoCA test.

Materials and Methods

74 PPD (H&Y stages: 23 in stage 1; 31 in stage 2; 20 in stage 3), without dementia (MoCA cut-off 23), tested in ON period with dopaminergic medication were submitted to single individual cognitive/motor evaluation sessions. The tests applied were: MoCA, GG, dynamic gait index (DGI) task and timed up and go test (TUG) under single and dual-task (DT) conditions. GG test resulted in 9 measures extracted via a statistical model. The predictive power of the GG measures and the MoCA score with respect to gait performance, as assessed by DGI and DT-TUG, were compared.

Results

The predictive models based on GG measures and MoCA score obtained, respectively, sensitivities of 65% and 56% for DGI scores and 59% and 57% for DT-TUG cost at a 50% specificity. GG application proved to be feasible and aroused more motivation in PPDs than MoCa.

Conclusion

GG, a friendly and ludic game, was able to reach a good power of gait performance prediction in people at initial and intermediate stages of PD evolution.
Why do phylogenomic analyses of early animal evolution continue to disagree? Sites in different structural environments yield different answers
Authors: Pandey Akanksha , Braun Edward L.
Published: August 2018

Phylogenomics has revolutionized the study of evolutionary relationships. However, genome-scale data have not been able to resolve all relationships in the tree of life. This could reflect the poor-fit of the models used to analyze heterogeneous datasets; that heterogeneity is likely to have many explanations. However, it seems reasonable to hypothesize that the different patterns of selection on proteins based on their structures might represent a source of heterogeneity. To test that hypothesis, we developed an efficient pipeline to divide phylogenomic datasets that comprise proteins into subsets based on secondary structure and relative solvent accessibility. We then tested whether amino acids in different structural environments had different signals for the deepest branches in the metazoan tree of life. Sites located in different structural environments did support distinct tree topologies. The most striking difference in phylogenetic signal reflected relative solvent accessibility; analyses of sites on the surface of proteins yielded a tree that placed ctenophores sister to all other animals whereas sites buried inside proteins yielded a tree with a sponge-ctenophore clade. These differences in phylogenetic signal were not ameliorated when we repeated our analyses using the site-heterogeneous CAT model, a mixture model that is often used for analyses of protein datasets. In fact, analyses using the CAT model actually resulted in rearrangements that are unlikely to represent evolutionary history. These results provide striking evidence that it will be necessary to achieve a better understanding the constraints due to protein structure to improve phylogenetic estimation.
The dimensions of species diversity
Authors: Larcombe Matthew J. , Jordan Gregory J. , Bryant David , Higgins Steven I.
Published: August 2018

Diversification processes underpin the patterns of species diversity that fascinate biologists. Two competing hypotheses disagree about the effect of competition on these processes. The bounded hypothesis suggests that species diversity is limited (bounded) by competition between species for finite niche space, while the unbounded hypothesis proposes that evolution and ecological opportunity associated with speciation, render competition unimportant. We use phylogenetically structured niche modelling, to show that processes consistent with both these diversification models have driven species accumulation in conifers. In agreement with the bounded hypothesis, niche competition constrained diversification, and in line with the unbounded hypothesis, niche evolution and partitioning promoted diversification. We then analyse niche traits to show that these diversification enhancing and inhibiting processes can occur simultaneously on different niche dimensions. Together these results suggests a new hypothesis for lineage diversification based on the multi-dimensional nature of ecological niches that accommodates both bounded and unbounded diversification processes.
Heat Shock Factor 1 Drives Intergenic Association of Its Target Gene Loci Upon Heat Shock
Authors: Chowdhary Surabhi , Kainth Amoldeep S. , Pincus David , Gross David S.
Published: August 2018

Transcriptional induction ofHeat Shock Protein(HSP) genes in yeast is accompanied by dynamic changes in their 3D structure and spatial organization, yet the molecular basis for these phenomena remains unknown. Using chromosome conformation capture and single cell imaging, we show that genes transcriptionally activated by Heat Shock Factor 1 (Hsf1) specifically interact across chromosomes and coalesce into diffraction-limited intranuclear foci. Genes activated by the alternative stress regulators Msn2 and Msn4, in contrast, do not interact among themselves nor with Hsf1 targets. Likewise, constitutively expressed genes, even those interposed betweenHSPgenes, show no detectable interaction. Hsf1 forms discrete subnuclear puncta when stress-activated, and these puncta dissolve in concert with transcriptional attenuation, paralleling the kinetics ofHSPgene coalescence and dissolution. Nuclear Hsf1 and RNA Pol II are both necessary for intergenicHSPgene interactions, while DNA-bound Hsf1 is necessary and sufficient to drive coalescence of a heterologous gene. Our findings demonstrate that Hsf1 can dynamically restructure the yeast genome.
Translocation and duplication from CRISPR-Cas9 editing inArabidopsis thaliana
Authors: Lynagh Peter G. , Inagaki Soichi , Amundson Kirk R. , Marimuthu Mohan P.A. , Pike Brett Randolph , Henry Isabelle M. , Tan Ek Han , Comai Luca
Published: August 2018

Cut DNA ends in plants may recombine to form novel molecules. We asked whether CRISPR-Cas9 expression in plants could induce nonhomologous recombination between diverse and heterologous broken DNA ends. We induced two breaks separated by 2.3 or by 8.5 kilobases leading to duplication of the intervening DNA and meiotic transmission of the 2.3kb duplication. Two or more dsDNA breaks in nonhomologous chromosomes led to ligation of breakpoints consistent with chromosome arm translocations. Screening 881 primary transformants we obtained 195 PCR products spanning independent, expected translocation junctions involving ends produced by cutting different loci. Sequencing indicated a true positive rate of 84/91 and demonstrated the occurrence of different junction alleles. A majority of the resulting structures would be deleterious and none were transmitted meiotically. Ligation of interchromosomal, heterologous dsDNA ends suggest that the CRISPR-Cas9 can be used to engineer plant genes and chromosomes in vivo.

Significance Statement

We explored how genome editing tools such as CRISPR-Cas9 could provide new ways to tailor novel genomic combinations and arrangements. We show that distant cut ends often precisely come together, that cuts in different chromosomes can result in translocations, and that two cuts within a chromosome often result in the duplication of the intervening segment. Formation of multiple structures with precise junctions will enable engineered rearrangements that can be predicted with accuracy.
Characterization for Drought Tolerance and Physiological Efficiency in Novel Cytoplasmic Male Sterile Sources of Sunflower (Helianthus annuus L.)
Authors: Tyagi Vikrant , Kaur Gurpreet , Kaushik Prashant , Dhillon Satwinder Kaur
Published: August 2018

Sunflower is sensitive to drought and its hybrids have a limited cytoplasmic diversity. The wild cytoplasmic sources of sunflower are not well exploited to their potential for drought tolerance and hybrid development. In this respect, we carried out a Line × Tester based genetic study using 19 sunflower genotypes representing, 13 cytoplasmic male sterile (CMS) lines from wild and conventional sources, 2 maintainer lines, and 4 restorer lines. The CMS and maintainer lines were crossed with restorer lines to develop sixty one-way F1 hybrids. The parents and their hybrids were evaluated under two water regimes viz., normal irrigated and water stress. A total of twelve important plant descriptors were studied over a period of two years. The significant differences were observed between parents and hybrids in both water regimes. Hybrids were higher in average values for all the descriptors than parents. The role of female parent was more prominent in the expression of traits in hybrids as compared to male parents. The CMS sources varied significantly regarding seed yield per plant and other physiological traits. Proline content was three times higher in parents and their hybrids under water stress, and it was not correlated with any other descriptor. Accession CMS-PKU-2A was identified as the best general combiner for leaf area and specific leaf weight. Whereas, CMS-234A was the best general combiner for biological yield and photosynthetic efficiency under both the conditions. The cross combinations CMS-ARG-2A × RCR-8297, CMS-234A × P124R, and CMS-38A × P124R were found significant for biological yield, seed yield and oil content under both environments. Overall, this study provides useful information about the cytoplasmic effects on important sunflower traits and drought stress tolerance when used in the different combinations.
Dual role for fungal-specific outer kinetochore proteins during cell cycle and development in Magnaporthe oryzae
Authors: Shah Hiral , Rawat Kanika , Ashar Harsh , Patkar Rajesh , Manjrekar Johannes
Published: August 2018

The outer kinetochore DASH/DAM complex ensures proper spindle structure and chromosome segregation. While DASH complex protein requirement diverges among different yeasts, its role in filamentous fungi has not been investigated so far. We studied the dynamics and role of middle (Mis12) and outer (Dam1 and Ask1) kinetochore proteins in the filamentous fungal pathogen, Magnaporthe oryzae, which undergoes multiple cell cycle linked developmental transitions. Both Dam1 and Ask1, unlike Mis12, were recruited to the nucleus specifically during mitosis. While Dam1 was not required for viability, loss of its function (dam1Δ mutant) delayed mitotic progression, resulting in impaired conidial and hyphal development in Magnaporthe. Intriguingly, both Dam1 and Ask1 also localised to the hyphal tips, in the form of punctae oscillating back and forth from the growing ends, suggesting that Magnaporthe DASH complex proteins may play a non-canonical role in polarised growth during interphase, in addition to their function in nuclear segregation during mitosis. Impaired appressorial (infection structure) development and function in the dam1Δ mutant suggest that fungus-specific Dam1 complex proteins could be an attractive target for a novel anti-fungal strategy.

Summary Statement

DASH complex proteins are differentially recruited to the nucleus during cell division and are intriguingly involved in polarised growth during development and differentiation in the rice blast fungus.
Evolution of mating types in finite populations: the precarious advantage of being rare
Authors: Czuppon Peter , Rogers David W.
Published: August 2018

Sexually reproducing populations with self-incompatibility bear the cost of limiting potential mates to individuals of a different type. Rare mating types escape this cost since they are unlikely to encounter incompatible partners, leading to the deterministic prediction of continuous invasion by new mutants and an ever increasing number of types. However, rare types are also at an increased risk of being lost by random drift. Calculating the number of mating types that a population can maintain requires consideration of both the deterministic advantages and the stochastic risks. By comparing the relative importance of selection and drift, we show that a population of sizeNcan maintain a maximum of approximatelyN1/3mating types for intermediate population sizes while for largeNwe derive a formal estimate. Although the number of mating types in a population is quite stable, the rare type advantage promotes turnover of types. We derive explicit formulas for both the invasion and turnover probabilities in finite populations.
Development of Coupling Controlled Polymerizations by Adapter-ligation in Mate-pair Sequencing for Detection of Various Genomic Variants in One Single Assay
Authors: Dong Zirui , Zhao Xia , Li Qiaoling , Yang Zhenjun , Xi Yang , Alexeev Andrei , Shen Hanjie , Wang Ou , Ruan Jie , Ren Han , Wei Hanmin , Qi Xiaojuan , Li Jiguang , Zhu Xiaofan , Zhang Yanyan , Dai Peng , Kong Xiangdong , Kirkconnell Killeen , Alferov Oleg , Giles Shane , Yamtich Jennifer , Kermani Bahram G. , Dong Chao , Liu Pengjuan , Mi Zilan , Zhang Wenwei , Xu Xun , Drmanac Radoje , Choy Kwong Wai , Jiang Yuan
Published: August 2018

The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick-translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter ligation reaction 3’ branch ligation, we evidenced that CP-AL significantly increased DNA-circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ~50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases.
Deep attention networks reveal the rules of collective motion in zebrafish
Authors: Heras Francisco J.H. , Romero-Ferrero Francisco , Hinz Robert C. , Polavieja Gonzalo G. de
Published: August 2018

A variety of simple models has been proposed to understand the collective motion of animals. These models can be insightful but lack important elements necessary to predict the motion of each individual in the collective. Adding more detail increases predictability but can make models too complex to be insightful. Here we report that deep attention networks can obtain in a data-driven way a model of collective behavior that is simultaneously predictive and insightful thanks to an organization in modules. The model obtains that interactions between two zebrafish, Danio rerio, in a large groups of 60-100, can be approximately be described as repulsive, attractive or as alignment, but only when moving slowly. At high velocities, interactions correspond only to alignment or alignment mixed with repulsion at close distances. The model also shows that each zebrafish decides where to move by aggregating information from the group as a weighted average over neighbours. Weights are higher for neighbours that are close, in a collision path or moving faster in frontal and lateral locations. These weights effectively select 5 relevant neighbours on average, but this number is dynamical, changing between a single neighbour to up to 12, often in less than a second. Our results suggest that each animal in a group decides by dynamically selecting information from the group.

Highlights

At 30 days postfertilization, zebrafish, Danio rerio, can move in very cohesive and predictable large groups

Deep attention networks obtain a predictive and understadable model of collective motion

When moving slowly, interations between pairs of zebrafish have clear components of repulsion, attraction and alignment

When moving fast, interactions correspond to alignment and a mixture of alignment and repulsion at close distances

Zebrafish turn left or right depending on a weighted average of interaction information with other fish, with weights higher for close fish, those in a collision path or those moving fast in front or to the sides

Aggregation is dynamical, oscillating between 1 and 12 neighbouring fish, with 5 on average
Environmental programming of adult foraging behavior in C. elegans
Authors: Pradhan Sreeparna , Quilez Sabrina , Homer Kai , Hendricks Michael
Published: August 2018

Foraging strategies must be tuned to the availability and distribution of resources in the environment. This can occur over generations and lead to genetic differences in foraging behavior, or it can occur on shorter time scales within an individual’s life span. Both genetic and experience-based strategies must be implemented by neural circuits that respond to environmental cues and track internal states, and the analysis of such circuits provides insight into the neural basis of complex decision making. In C. elegans, between-strain genetic differences and within-strain plasticity in foraging has been observed. Most individual changes in foraging are short-term, based on experience over several hours. Here, we tested if developmental experience could permanently alter foraging. We found that in wild strains that are normally highly exploratory, early-life starvation leads to “cautious” foraging behavior in which exploration is reduced. We characterize the behavioral bases for these strategies and identify changes in the dynamics of a locomotory circuit involved in navigation. Overall, we show that some C. elegans strains exhibit adaptive tuning of their foraging behavior based on early-life experience, and this is associated with changes in a core navigation circuit.
gFACs: Filtering, Analysis, and Conversion to Unify Genome Annotations Across Alignment and Gene Prediction Frameworks
Authors: Caballero Madison , Wegrzyn Jill
Published: August 2018

Published genome annotations are filled with erroneous gene models that represent issues associated with frame, start side identification, splice sites, and related structural features. The source of these inconsistencies can often be traced to translated text file formats designed to describe long read alignments and predicted gene structures. The majority of gene prediction frameworks do not provide downstream filtering to remove problematic gene annotations, nor do they represent these annotations in a format consistent with current file standards. In addition, these frameworks lack consideration for functional attributes, such as the presence or absence of protein domains which can be used for gene model validation. To provide oversight to the increasing number of published genome annotations, we present gFACs as a software package to filter, analyze, and convert predicted gene models and alignments. gFACs operates across a wide range of alignment, analysis, and gene prediction software inputs with a flexible framework for defining gene models with reliable structural and functional attributes. gFACs supports common downstream applications, including genome browsers and generates extensive details on the filtering process, including distributions that can be visualized to further assess the proposed gene space.
Gridlock from Diagnosis to Treatment of Multidrug Resistant Tuberculosis (MDR-TB) in Tanzania: Patients’ Perspectives from the Focus Group Discussion
Authors: Mpagama Stellah G , Mangi Ezekiel , Mbelele Peter M , Chongolo Anna M , Kibiki Gibson S , Heysell Scott K
Published: August 2018

Introduction

Molecular diagnostics have revolutionized the diagnosis of multidrug resistant tuberculosis (MDR-TB). Yet in Tanzania we found delay in diagnosis with more than 70% of MDR-TB patients having history of several previous treatment courses for TB signaling complications of prior missed diagnosis. We aimed to explore patients’ viewpoints and experiences with personal and socio-behavioral obstacles from MDR-TB diagnosis to treatment in an attempt to understand these prior findings.

Methods

The study was conducted in December 2016 with MDR-TB patients admitted at Kibong’oto Infectious Diseases Hospital. We used semi-structured interviews and focus group discussion to examine patients’ views and experiences during MDR-TB diagnosis. Groups were sex aggregated to allow free interaction and to gauge gender specific issues in the social and behavioral contexts. The discussion – explored patients’ delivery factors that were impacting delay from MDR-TB diagnosis to treatment. Iterative data collection and analysis was applied with data, codes and categories being compared and refined.

Results

Forty-five MDR-TB patients participated in 6 focus group discussions. Challenges and barriers contributing to the delay from MDR-TB diagnosis to treatment were as follows: 1) The general population had differing understanding of MDR-TB that led to seeking services from traditional healers; 2) Also socio-economic adversity made health-seeking behavior difficult and often unproductive; 3) In the health system, challenges included inadequacy of MDR-TB diagnostic centers, lack of knowledge on behalf of health care providers to consider MDR-TB and order appropriate diagnostics; 4) Insufficiency in the specimen referral system for early diagnosis of MDR-TB. Non-adherence of TB patients to first-line anti-TB drugs prior to MDR-TB diagnosis given the multitude of barriers discussed was coupled with both intentional and unintentional non-adherence of health care providers to international standards of TB care.

Conclusion

Patient-centered strategies bridging communities and the health system are urgently required for optimum MDR-TB control in Tanzania.
The flower flies and the unknown diversity of Drosophilidae (Diptera): a biodiversity inventory in the Brazilian fauna
Authors: Schmitz Hermes J. , Valente Vera L. S.
Published: August 2018

Diptera is a megadiverse order, reaching its peak of diversity in Neotropics, although our knowledge of dipteran fauna of this region is grossly deficient. This applies even for the most studied families, as Drosophilidae. Despite its position of evidence, most aspects of the biology of these insects are still poorly understood, especially those linked to natural communities. Field studies on drosophilids are highly biased to fruit-breeders species. Flower-breeding drosophilids, however, are worldwide distributed, especially in tropical regions, although being mostly neglected. The present paper shows results of a biodiversity inventory of flower-breeding drosophilids carried out in several localities in Brazil, based on samples of 125 plant species, from 47 families. Drosophilids were found in flowers of 56 plant species, from 18 families. The fauna discovered showed to be highly unknown, comprising 28 species, 12 of them (>40%) still undescribed. Not taking in account opportunist species, two thirds of the diversity exclusive from flowers were undescribed. TheDrosophila bromeliaespecies group was the most representative taxon, with eight species (six undescribed), including four polyphagous and fourSolanum-specialised species. This specialisation onSolanumis reported for the first time forDrosophila. Other taxa of restrict flower-breeding drosophilids were theDrosophila lutziispecies group and the genusZygothrica. Some specimens of the generaCladochaeta, RhinoleucophengaandScaptomyzawere found, but their relations to flowers are unclear. Additionally, ten species of ample niche was found using flowers opportunistically. Localities and host plants are recorded for all species collected.
High-throughput single-cell transcriptome profiling of plant cell types
Authors: Shulse Christine N. , Cole Benjamin J. , Turco Gina M. , Zhu Yiwen , Brady Siobhan M. , Dickel Diane E.
Published: August 2018

Single-cell transcriptome analysis of heterogeneous tissues can provide high-resolution windows into the genomic basis and spatiotemporal dynamics of developmental processes. Here we demonstrate the feasibility of high-throughput single-cell RNA sequencing of plant tissue using the Drop-seq approach. Profiling of >4,000 individual cells from theArabidopsisroot provides transcriptomes and marker genes for a diversity of cell types and illuminates the gene expression changes that occur across endodermis development.
Functional Interpretation of Single-Cell Similarity Maps
Authors: DeTomaso David , Jones Matthew , Subramaniam Meena , Ashuach Tal , Ye Chun J. , Yosef Nir
Published: August 2018

We present VISION, a tool for annotating the sources of variation in single cell RNA-seq data in an automated, unbiased and scalable manner. VISION operates directly on the manifold of cell-cell similarity and employs a flexible annotation approach that can operate either with or without preconceived stratification of the cells into groups or along a continuum. We demonstrate the utility of VISION using a relatively homogeneous set of B cells from a cohort of lupus patients and healthy controls and show that it can derive important sources of cellular variation and link them to clinical phenotypes in a stratification free manner. VISION produces an interactive, low latency and feature rich web-based report that can be easily shared amongst researchers.