bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNAJ Proteins in neurodegeneration: essential and protective factors
Authors: Zarouchlioti Christina , Parfitt David A. , Li Wenwen , Gittings Lauren M. , Cheetham Michael E. 
Published: December 2017

Maintenance of protein homeostasis is vitally important in post-mitotic cells, particularly neurons. Neurodegenerative diseases such as polyglutamine expansion disorders—like Huntington's disease or spinocerebellar ataxia (SCA), Alzheimer's disease, fronto-temporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease—are often characterized by the presence of inclusions of aggregated protein. Neurons contain complex protein networks dedicated to protein quality control and maintaining protein homeostasis, or proteostasis. Molecular chaperones are a class of proteins with prominent roles in maintaining proteostasis, which act to bind and shield hydrophobic regions of nascent or misfolded proteins while allowing correct folding, conformational changes and enabling quality control. There are many different families of molecular chaperones with multiple functions in proteostasis. The DNAJ family of molecular chaperones is the largest chaperone family and is defined by the J-domain, which regulates the function of HSP70 chaperones. DNAJ proteins can also have multiple other protein domains such as ubiquitin-interacting motifs or clathrin-binding domains leading to diverse and specific roles in the cell, including targeting client proteins for degradation via the proteasome, chaperone-mediated autophagy and uncoating clathrin-coated vesicles. DNAJ proteins can also contain ER-signal peptides or mitochondrial leader sequences, targeting them to specific organelles in the cell. In this review, we discuss the multiple roles of DNAJ proteins and in particular focus on the role of DNAJ proteins in protecting against neurodegenerative diseases caused by misfolded proteins. We also discuss the role of DNAJ proteins as direct causes of inherited neurodegeneration via mutations inDNAJfamily genes.This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
Comparative genomics of bdelloid rotifers: evaluating the effects of asexuality and desiccation tolerance on genome evolution
Authors: Nowell Reuben W. , Almeida Pedro , Wilson Christopher G. , Smith Thomas P. , Fontaneto Diego , Crisp Alastair , Micklem Gos , Tunnacliffe Alan , Boschetti Chiara , Barraclough Timothy G 
Published: December 2017

AbstractBdelloid rotifers are microscopic invertebrates that have existed for millions of years apparently without sex or meiosis. They inhabit a variety of temporary and permanent freshwater habitats globally, and many species are remarkably tolerant of desiccation. Bdelloids offer an opportunity to better understand the evolution of sex and recombination, but previous work has emphasized desiccation as the cause of several unusual genomic features in this group. Here, we evaluate the relative effects of asexuality and desiccation tolerance on genome evolution by comparing whole genome sequences for three bdelloid species:Adineta ricciae(desiccation tolerant),Rotaria macruraandRotaria magnacalcarata(both desiccation intolerant) to the only published bdelloid genome to date, that ofAdineta vaga(also desiccation tolerant). We find that tetraploidy is conserved among all four bdelloid species, but homologous divergence in obligately aquaticRotariagenomes is low, well within the range observed between alleles in obligately sexual, diploid animals. In addition, we find that homologous regions inA. ricciaeare largely collinear and do not form palindromic repeats as observed in the publishedA. vagaassembly. These findings are contrary to current understanding of the role of desiccation in shaping the bdelloid genome, and indicate that various features interpreted as genomic evidence for long-term ameiotic evolution are not general to all bdelloid species, even within the same genus. Finally, we substantiate previous findings of high levels of horizontally transferred non-metazoan genes encoded in both desiccating and non-desiccating bdelloid species, and show that this is a unique feature of bdelloids among related animal phyla. Comparisons within bdelloids and to other desiccation-tolerant animals, however, again call into question the purported role of desiccation in horizontal transfer.
The emerging role of physical modeling in the future of structure determination
Authors: Gaalswyk Kari , Muniyat Mir Ishruna , MacCallum Justin L. 
Published: December 2017

AbstractBiomolecular structure determination has long relied on heuristics based on physical insight; however, recent efforts to model conformational ensembles and to make sense of sparse, ambiguous, and noisy data have revealed the value of detailed, quantitative physical models in structure determination. We review these two key challenges, describe different approaches to physical modeling in structure determination, and illustrate several successes and emerging technologies enabled by physical modeling.HighlightsQuantitative physical modeling is emerging as a key tool in structure determinationThere are different approaches to incorporate physical modeling into structure determinationModeling conformational ensembles and making sense of sparse, noisy, and ambiguous data are two challenges where physical modeling can play a prominent role
Plant–soil feedbacks between arbuscular- and ecto-mycorrhizal communities
Authors: Kadowaki Kohmei , Yamamoto Satoshi , Sato Hirotoshi , Tanabe Akifumi S. , Hidaka Amane , Toju Hirokazu 
Published: December 2017

AbstractSoil microbiomes of adult trees exert species-specific effects on the survival and growth of seedlings1-6, yet empirical evidence that such plant–soil microbiome interaction drives seedling community assembly remains scarce. Here we show that mycorrhizal fungal communities determine seedling community assembly by controlling how resident plant communities alter the growth of newly established seedlings. We reciprocally introduced seedling communities of arbuscular-and ecto-mycorrhizal plant species to replicated mesocosms to follow the effects of mycorrhizal type match/mismatch with resident plant communities on seedling growth rates. The growth rates of recruited seedlings were generally higher under resident trees of the same mycorrhizal types than under those of different mycorrhizal types, generating positive plant–soil feedbacks through mycorrhizal-type matching. Such positive effects of matching were linked with seedlings’ greater acquisition rates of mycorrhizal symbionts from matched resident plants than from mismatched plants, and such linkage was pronounced for ecto-mycorrhizal plant species. In contrast, under the condition of mycorrhizal-type matching between resident plants and seedlings (i.e., within-mycorrhizal-type comparison), plant–soil feedback effects varied considerably in their sign and strength among resident–seedling species combinations. Consequently, the assembly of a temperate tree seedling community is driven by a combination of species-specific plant–soil feedbacks and the match/mismatch of mycorrhizal type between resident plants and seedlings.
Natural Variation of OsLG3 Controls Drought Stress Tolerance in Rice by Inducing ROS Scavenging
Authors: Xiong Haiyan , Yu Jianping , Li Jinjie , Wang Xin , Liu Pengli , Zhang Hongliang , Zhao Yan , Yin Zhigang , Li Yang , Guo Yan , Fu Binying , Wang Wensheng , Li Zhikang , Ali Jauhar , Li Zichao 
Published: December 2017

AbstractBackgroundImproving performance of rice under drought stress has potential to significant impact on rice productivity. Previously we reported that OsLG3 positively control rice grain length and yield.ResultsIn this study, we found that OsLG3 was more strongly expressed in upland rice compared to lowland rice under drought stress condition. Candidate gene association analysis showed that the natural variation in OsLG3 was associated with tolerance to water deficit stress in germinating rice seeds. Transgenic rice with enhanced OsLG3 expression exhibited improved tolerance to drought and that is most likely due to enhanced ROS scavenging efficiency. Phylogenetic analysis and pedigree records indicated that the tolerant allele of OsLG3 has potential to improve drought tolerance of japonica rice.ConclusionsCollectively, our work revealed that the natural variation of OsLG3 contributes to rice drought tolerance and the elite allele of OsLG3 is a promising genetic resource for the development of drought-tolerant and high-yield rice varieties.
polyCluster: Defining Communities of Reconciled Cancer Subtypes with Biological and Prognostic Significance
Authors: Eason Katherine , Nyamundanda Gift , Sadanandam Anguraj 
Published: December 2017

AbstractTo stratify cancer patients for most beneficial therapies, it is a priority to define robust molecular subtypes using clustering methods and “big data”. If each of these methods produces different numbers of clusters for the same data, it is difficult to achieve an optimal solution. Here, we introduce “polyCluster”, a tool that reconciles clusters identified by different methods into context-specific subtype “communities” using a hypergeometric test or a measure of relative proportion of common samples. The polycluster was tested using a breast cancer dataset, and latter using uveal melanoma datasets to identify novel subtype communities with significant metastasis-free prognostic differences. Available at: https://github.com/syspremed/polyClustR
Accurate Determination of Bacterial Abundances in Human Metagenomes Using Full-length 16S Sequencing Reads
Authors: Perraudeau Fanny , Dudoit Sandrine , Bullard James H. 
Published: December 2017

AbstractDNA sequencing of PCR-amplified marker genes, especially but not limited to the 16S rRNA gene, is perhaps the most common approach for profiling microbial communities. Due to technological constraints of commonly available DNA sequencing, these approaches usually take the form of short reads sequenced from a narrow, targeted variable region, with a corresponding loss of taxonomic resolution relative to the full length marker gene. We use Pacific Biosciences single-molecule, real-time circular consensus sequencing to sequence amplicons spanning the entire length of the 16S rRNA gene. However, this sequencing technology suffers from high sequencing error rate that needs to be addressed in order to take full advantage of the longer sequence. Here, we present a method to model the sequencing error process using a generalized pair hidden Markov chain model and estimate bacterial abundances in microbial samples. We demonstrate, with simulated and real data, that our model and its associated estimation procedure are able to give accurate estimates at the species (or subspecies) level, and is more flexible than existing methods like SImple Non-Bayesian TAXonomy (SINTAX).
Structurally informed evolutionary models improve phylogenetic reconstruction for emerging, seasonal, and pandemic influenza viruses
Authors: Qiu Xueting , Bahl Justin 
Published: December 2017

AbstractPrecise estimation of genetic substitution patterns is critical for accurate reconstruction of pathogen phylogenies. Few studies of viral evolution account for variations of mutation rate across a single gene. This is especially true when considering evolution of segmented viruses where individual segments are short, encoding for few proteins. However, the structural and functional partitions of these proteins could provide valuable information for more accurate inference of viral evolution, due to the disparate immune selection pressure on different functional domains. Accurately reconstructed evolutionary features on specific functional domains can in turn provide biological information on viral protein and immune targets for vaccine design. In this study we developed and evaluated a structurally informed partitioning scheme that accounts for rate variation among immunogenic head and stalk domains of the surface protein hemagglutinin (HA) of influenza viruses. We evaluated the model fit and performance of four different models - HKY, SRD06 codon, HKY with a structurally informed partitioning scheme, SRD06 with a structurally informed partitioning scheme on pandemic A/H1N1pdm09, seasonal A/H1N1postpdm, A/H3N2, B-Yamagata-like and Victoria-like lineages, and two highly pathogenic avian influenza A viruses H5Nx and H7N9. Results showed that structurally informed partitioning with SRD06 performed better for all datasets with decisively statistical support. Significantly faster nucleotide substitution rates for head domain, compared to stalk domain was observed and may provide insight for stalk derived broadly-reactive vaccine design. Taken together, integrating a functionally informed partitioning scheme based on protein structures of immune targets allows for significant improvement of phylogenetic analysis and providing important biological insights.
Defining the relevant combinatorial space of the PKC/CARD-CC signal transduction nodes
Authors: Staal Jens , Driege Yasmine , Haegman Mira , Kreike Marja , Iliaki Styliani , Vanneste Domien , Affonina Inna , Braun Harald , Beyaert Rudi 
Published: December 2017

AbstractBiological signal transduction typically display a so-called bow-tie or hour glass topology: Multiple receptors lead to multiple cellular responses but the signals all pass through a narrow waist of central signaling nodes. One such critical signaling node for several inflammatory and oncogenic signaling pathways in humans are the CARD-CC / Bcl10 / MALT1 (CBM) complexes, which get activated by upstream protein kinase C (PKC). In humans, there are four phylogenetically distinct CARD-CC family (CARD9, −10, −11 and −14) proteins and 9 true PKC isozymes (α to ι). At this moment, less than a handful of PKC/CARD-CC relationships are known from experimental evidence. In order to explore the biologically relevant combinatorial space out of all 36 potential permutations in this two-component signaling event, we made use of CRISPR/Cas9 genome-edited HEK293T cells to mutate CARD10 for subsequent pairwise cotransfections of all CARD-CC family members and activated mutants of all true PKCs. By quantitative reporter gene expression readout, we could define specific strong and weak PKC/CARD-CC relationships. Surprisingly as many as 21 PKC/CARD-CC combinations were found to have synergistic effects. We also discovered heterodimerization between different CARD-CC proteins, and that this can influence their PKC response profile. This information will be valuable for future studies of novel signaling pathways dependent on the CBM complex signaling nodes.
Pneumococcal vaccine impacts on the population genomics of non-typeable Haemophilus influenzae
Authors: Cleary David W. , Devine Vanessa T. , Morris Denise E. , Osman Karen L. , Gladstone Rebecca A. , Bentley Stephen D. , Faust Saul N. , Clarke Stuart C. 
Published: December 2017

AbstractBetween 2008/09 and 2012/13 the molecular epidemiology of non-typeable Haemophilus influenzae (NTHi) carriage in children <5 years of age was determined; a period that included pneumococcal conjugate vaccine (PCV) 13 introduction. Significantly increased carriage in post-PCV13 years was observed and lineage-specific associations with S. pneumoniae were observed before and after PCV13 introduction. NTHi were characterised into eleven discrete, temporally stable lineages, congruent with current knowledge regarding the clonality of NTHi. This increase could not be linked to the expansion of a particular clone and demonstrates different dynamics to before PCV13 implementation during which time NTHi co-carried with vaccine serotype pneumococci.
Gaze Bias Differences Capture Individual Choice Behavior
Authors: Thomas Armin W. , Molter Felix , Krajbich Ian , Heekeren Hauke R. , Mohr Peter N. C. 
Published: December 2017

AbstractHow do we make simple consumer choices (e.g., deciding between an apple, an orange, and a banana)? Recent empirical evidence suggests a close link between choice behavior and eye movements at the group level, with generally higher choice probabilities for items that were looked at longer during the decision process. However, it is unclear how variable this effect is across individuals. Here, we investigate this question in a multialternative forced-choice experiment using a novel computational model that can be easily applied to the individual participant level. We show that a link between gaze and choice is present for most individuals, but differs considerably in strength, namely, the choices of some individuals are almost independent of gaze allocation, while the choices of others are strongly associated with gaze behavior. Accounting for this variability in our model allows us to explain and accurately predict individual differences in observed choice behavior.
Electron microscopy reveals unique spore-like nano forms of Bacillus cereus
Authors: Ghosh Sumanta , Chakraborty Biprashekhar , Ghosh Shreya , Dey Sandip , Biswas Chiranjit , Chowdhury Rukhsana , Chattopadhyay Krishnananda , Sengupta Jayati 
Published: December 2017

AbstractEndospore formation under environmental stress conditions is a well-established phenomenon for members of bacterial phylum Firmicutes, among which the most well studied ones belong to genus Bacillus and Clostridium. So far, known sizes of the spores are all larger than 500 nm. Nano-forms of bacteria have been reported but the notion still remains controversial.In this study, we provide visual evidences of living nano-entities (named here as ‘nano-spores’) formed by a bacterial species Bacillus cereus under prolonged stress, which are capable of escaping though standard sterile filtration procedure. The existence of nano-forms of bacteria was initially identified in a yeast ribosome preparation. We further demonstrate the transformation of the ‘nano-spores’ into mature cells upon nutrient supply. Our study not only demonstrates the ability of bacteria to get transformed into yet-unknown form in order to survive under harsh environment, but also brings to light the existence of the smallest possible form of life.
The transcriptional dynamics of two filmy ferns from Hymenophyllaceae with different niche preferences unravel key aspects of their desiccation tolerance and vertical distribution along host trees
Authors: Larama Giovanni , Ostria-Gallardo Enrique , Berrios Graciela , Gutierrez Ana , Ensminger Ingo , Bravo Leon A. 
Published: December 2017

ABSTRACTFerns from the Hymenophyllaceae family are one of the main components of the epiphytic species diversity in the Chilean temperate rain forest. Having membranous fronds of a single layer of cells, they show a poikilohydric strategy most typical from bryophytes. Although Hymenophyllaceae species shows the ability to tolerate desiccation, there are interspecific differences in their water loss kinetic. Counter-intuitively, those species that have rapid desiccation kinetic are able to reach higher host height and tolerate higher light exposure and vapor pressure deficit. Therefore, what are the mechanisms (constitutive and/or induced) responsible of the desiccation tolerance in this fern family? As this primitive fern family is closely related with mosses, it can be hypothesized that desiccation tolerance in this particular group would be associated with constitutive features rather than induced responses during dehydration. However, the inter-specific differences in water loss and vertical distribution would be associated to different degrees of induction either within the dehydration or rehydration phases. We applied an ecophysiological transcriptomic approach to study the dynamic of gene expression in two species of filmy ferns with contrasting desiccation kinetics and vertical distribution on the host tree. Our analysis identified commonalities and differences in gene regulation, and key genes correlated with the fronds hydration state, providing the patterns of gene expression responding to microenvironmental signals and behind the physiology of their resurrection strategy
Identifying important interaction modifications in ecological systems
Authors: Terry J. Christopher D. , Bonsall Michael B. , Morris Rebecca J. 
Published: December 2017

AbstractTrophic interaction modifications, where a consumer-resource link is affected by additional species, are widespread and significant causes of indirect effects in ecological networks. The sheer number of potential interaction modifications in ecological systems poses a considerable challenge, making prioritisation for empirical study essential. Here, we introduce measures to quantify the topological relationship of individual interaction modifications relative to the underlying network. We use these, together with measures for the strength of trophic interaction modifications to identify modifications that are most likely to exert significant effects on the dynamics of whole systems. Using a set of simulated food webs and randomly distributed interaction modifications, we test whether a subset of interaction modifications important for the local stability and direction of species responses to perturbation of complex networks can be identified. We show that trophic interaction modifications affecting interactions with a high biomass flux, those that connect species otherwise distantly linked, and those where high trophic-level species modify to interactions lower in the web have particular importance for dynamics. In contrast, the centrality of modifications in the network provided little information. This work demonstrates that analyses of interaction modifications can be tractable at the network scale and highlights the importance of understanding the relationship between the distributions of trophic and non-trophic effects.
Antiretroviral treatment, prevention of transmission, and modeling the HIV epidemic: why the ART efficacy and effectiveness parameter matters
Authors: Granich Reuben , Gupta Somya , Wollmers Matt , Williams Brian 
Published: December 2017

AbstractIntroductionHIV remains a major public health threat with over 75 million deaths, 2 million annual infections and over 1 million HIV-associated TB cases a year. Population-based studies suggest a marked decline in incidence, prevalence and deaths, mostly likely due to treatment expansion, in countries in East and Southern Africa. This calls into question the ART efficacy, effectiveness and coverage parameters used by many modelers to project HIV incidence and prevalence.MethodsFor 2015 and 2016 we reviewed global and national mathematical modeling studies regarding ART impact (with or without other HIV prevention interventions) and/or 90-90-90 on either new HIV infections or investment or both. We reviewed these HIV epidemiologic and costing models for their structure and parameterization around ART; we directly compared two models to illustrate differences in outcome.ResultsThe nine models published in 2015 or 2016 included parameters for ART effectiveness ranging from 20% to 86% for ART effectiveness. Model 1 limits eligibility for ART initiation to 80% coverage of people living with HIV and with a CD4+ cell count below 350 cells/μL, 70% retention, and ART reduces transmission by 80%, with a derived ART effectiveness of 20%. Model 2 assumes 90-90-90 by 2020 (i.e., 73% viral suppression of estimated PLHIV), ART reduces transmission by 96% in those on ART and virally suppressed, and by 88% in those on ART but not virally suppressed with a derived effectiveness of 86% and consequent decline towards ending AIDS and HIV elimination. ART parameter selection and assumptions dominate and low ART effectiveness translates into lower impact.DiscussionUsing more realistic parameters for ART effectiveness suggests that through expanding access and supporting sustainable viral suppression it will be possible to significantly reduce transmission and eliminate HIV in many settings.