bluuebunny/crossref_metadata_2025 huggingface dataset:
A Complete Public Domain Family Genomics Dataset
Authors: Corpas Manuel , Cariaso Mike , Coletta Alain , Weiss David , Harrison Andrew , Moran Federico , Yang Huanming
Published: November 2013

Background

The availability of open access genomic data is essential for the personal genomics field. Public genomic data allow comparative analyses, testing of new tools and genotype-phenotype association studies. Personal genomics data of unrelated individuals are available in the public domain, notably the Personal Genome Project; however, to date genomics family data and metadata are severely lacking, mainly due to cost, privacy concerns or restricted access to Next Generation Sequencing (NGS) technology. Family data have a lot to offer as they allow the study of heritability, something which is impossible to do just by using unrelated individuals.

Findings

A whole family from Southern Spain decided to genotype, sequence and analyse their personal genomes making them publicly available under a Creative Commons 0 license (CC0; commonly denominated as public domain). These data include a) five 23andMe SNP chip genotype bed files, b) four raw exomes with their assorted bam files and VCF files, c) a metagenomic raw sequencing data file and d) derived data of likely phenotypes using SNPedia-derived tools.

Conclusions

To our knowledge this is the first CC0 released set of genomic, phenotypic and metagenomic data for a whole family. This dataset is also unique in that it was obtained through direct-to-consumer genetic tests. Hence any ordinary citizen with enough budget and samples should be able to reproduce this experiment. We envisage this dataset to be a useful resource for a variety of applications in the personal genomics field as a) negative control data for trait association discovery, b) testing data for development of new software and c) sample data for heritability studies. We encourage prospective users to share with us derived results so that they can be added to our existing collection.
Water and the biology of prions and plaques
Authors: Steel Graham K. , Wiggins Philippa M.
Published: November 2013

This is an attempt to account for the insolubility and/or aggregation of prions and plaques in terms of a model of water consisting of an equilibrium between high density and low density microdomains. Hydrophobic molecules, including proteins, accumulate selectively into stable populations, enriched in high density water, at charged sites on biopolymers. In enriched high density water, proteins are probably partially unfolded and may precipitate out when released. All extracellular matrices contain such charged polymers. Prions, which have been shown to accumulate in soils and clays containing silicates and aluminates also probably accumulate in extracellular matrices.

Release of proteins follows hydrolysis of the charged groups by highly reactive high density water. This is normally a slow process but is greatly accelerated by urea. Plaques may form with age and disease because of accumulation of urea and, perhaps, glucose in the blood. This favours precipitation of proteins emerging from matrices, rather than refolding and solution. Dialysis should, therefore, interfere with plaque formation and impede the development of some age-related diseases.
Matchmaker, Matchmaker, Make Me a Match: Migration of Populations via Marriages in the Past
Authors: Lee Sang Hoon , Ffrancon Robyn , Abrams Daniel M. , Kim Beom Jun , Porter Mason A.
Published: November 2013

The study of human mobility is both of fundamental importance and of great potential value. For example, it can be leveraged to facilitate efficient city planning and improve prevention strategies when faced with epidemics. The newfound wealth of rich sources of data—including banknote flows, mobile phone records, and transportation data—has led to an explosion of attempts to characterize modern human mobility. Unfortunately, the dearth of comparable historical data makes it much more difficult to study human mobility patterns from the past. In this paper, we present an analysis of long-term human migration, which is important for processes such as urbanization and the spread of ideas. We demonstrate that the data record from Korean family books (called “jokbo”) can be used to estimate migration patterns via marriages from the past 750 years. We apply two generative models of long-term human mobility to quantify the relevance of geographical information to human marriage records in the data, and we find that the wide variety in the geographical distributions of the clans poses interesting challenges for the direct application of these models. Using the different geographical distributions of clans, we quantify the “ergodicity” of clans in terms of how widely and uniformly they have spread across Korea, and we compare these results to those obtained using surname data from the Czech Republic. To examine population flow in more detail, we also construct and examine a population-flow network between regions. Based on the correlation between ergodicity and migration in Korea, we identify two different types of migration patterns: diffusive and convective. We expect the analysis of diffusive versus convective effects in population flows to be widely applicable to the study of mobility and migration patterns across different cultures.
On the Reproducibility of TCGA Ovarian Cancer MicroRNA Profiles
Authors: Wan Ying-Wooi , Mach Claire M. , Allen Genevera I. , Anderson Matthew L. , Liu Zhandong
Published: November 2013

Dysregulated microRNA (miRNA) expression is a well-established feature of human cancer. However, the role of specific miRNAs in determining cancer outcomes remains unclear. Using Level 3 expression data from the Cancer Genome Atlas (TCGA), we identified 61 miRNAs that are associated with overall survival in 469 ovarian cancers profiled by microarray (p<0.01). We also identified 12 miRNAs that are associated with survival when miRNAs were profiled in the same specimens using Next Generation Sequencing (miRNA-Seq) (p<0.01). Surprisingly, only 1 miRNA transcript is associated with ovarian cancer survival in both datasets. Our analyses indicate that this discrepancy is due to the fact that miRNA levels reported by the two platforms correlate poorly, even after correcting for potential issues inherent to signal detection algorithms. Further investigation is warranted.
Filling up the tree: considering the self-organization of avian roosting behavior
Authors: Alicea Bradly
Published: November 2013

In this paper, models for understanding bird roosting will be considered for purposes of developing better Artificial Life models of complex behavior. Roosting involves multiple flocks of birds picking a single tree limb to rest on for the night, and can be considered an iterative, time-dependent process that unfolds over a 45-minute interval roughly corresponding to twilight. Two models will be used to better understand the main components of this behavior. The constrained dynamics model, which represents continuous random absorption on a one-dimensional lattice, will be used to characterize the dynamics of crowding in the tree structure over time. A second approach involves the relationships between complex networks and roosting behaviors, in particular the evolution of structured networks via rules of incorporation and interaction. Finally, the percolation model will be proposed as a way to bridge behaviors explained by the constrained dynamics and complex network models.
Sampling principles for biodiversity study
Authors: Pan Xubin
Published: November 2013

Sampling is a fundamental tool in ecology and critical for biodiversity measurement. However, basic principles of biodiversity sampling have been overlooked for many years. In this paper, I proposed and explored five principles of sampling for a specific area and biodiversity study. The first principle of sampling,species increasing with area, is that the number of species increases with the area. The second principle of sampling,individuals increasing with area, is that the number of individuals increases with the area. The third principle of sampling,sum of species number, is that the sum of species number in one area and species number in another area is no less than the total species number in the two areas. The fourth principle of sampling,individual complement, is that the sum of the mathematical expectation of individual number of one or several species in the areaaand that of the same one or several species in the areaA-ais the total individual numberNof the same one or several species in the total areaA. The fifth principle of sampling,species-area theory, is that the sum of the mathematical expectation of number of species in the areaaand that of number of species lost if areaA-ais cleared is the total species numberMin the total areaA.
The Origin of Human-infecting Avian Influenza A H6N1 Virus
Authors: Zhang Liangsheng , Zhang Zhenguo
Published: November 2013

In this study, we retraced the origin of the reported avian influenza A H6N1 virus infecting a 20-year-old woman in Taiwan. As we know, this is the first reported case of human infection by the H6N1 virus, because this subtype virus usually circulates in birds and poultry. Therefore it is crucial to know how this virus attained the ability to infect humans. Using phylogenetic analysis, we found that this virus was derived from reassortments of multiple lineages of H6N1 viruses and H5N2 viruses. The results deepen our understanding of how the new human-infecting virus originated and based on these we discussed possible explanations for the H6N1 infection of humans. Our results, together with recent studies of H7N9 viruses which result in severe disorders, suggest that reassortments among avian-type viruses are quite often, which may sometimes result in fatal infections in humans. Thus a close watch on the circulation of avian influenza viruses is pretty necessary.
The evolution of sex differences in disease genetics
Authors: Gilks William P. , Abbott Jessica K. , Morrow Edward H.
Published: November 2013

There are significant differences in the biology of males and females, ranging from biochemical pathways to behavioural responses, which are relevant to modern medicine. Broad-sense heritability estimates differ between the sexes for many common medical disorders, indicating that genetic architecture can be sex-dependent. Recent genome-wide association studies (GWAS) have successfully identified sex-specific and sex-biased effects, where in addition to sex-specific effects on gene expression, twenty-two medical traits have sex-specific or sex-biased loci. Sex-specific genetic architecture of complex traits is also extensively documented in model organisms using genome-wide linkage or association mapping, and in gene disruption studies. The evolutionary origins of sex-specific genetic architecture and sexual dimorphism lie in the fact that males and females share most of their genetic variation yet experience different selection pressures. At the extreme is sexual antagonism, where selection on an allele acts in opposite directions between the sexes. Sexual antagonism has been repeatedly identified via a number of experimental methods in a range of different taxa. Although the molecular basis remains to be identified, mathematical models predict the maintenance of deleterious variants that experience selection in a sex-dependent manner. There are multiple mechanisms by which sexual antagonism and alleles under sex-differential selection could contribute toward the genetics of common, complex disorders. The evidence we review clearly indicates that further research into sex-dependent selection and the sex-specific genetic architecture of diseases would be rewarding. This would be aided by studies of laboratory and wild animal populations, and by modelling sex-specific effects in genome-wide association data with joint, gene-by-sex interaction tests. We predict that even sexually monomorphic diseases may harbour cryptic sex-specific genetic architecture. Furthermore, empirical evidence suggests that investigating sex-dependent epistasis may be especially rewarding. Finally, the prevalent nature of sex-specific genetic architecture in disease offers scope for the development of more effective, sex-specific therapies.

Funding

This work was supported by the European Research Council (WPG and EHM; Starting Grant #280632), a Royal Society University Research Fellowship (EHM), the Swedish Research Council (JKA), and the Volkswagen Foundation (JKA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests

The authors declare that they have no competing financial interests.
On the optimal trimming of high-throughput mRNA sequence data
Authors: MacManes Matthew D.
Published: November 2013

The widespread and rapid adoption of high-throughput sequencing technologies has afforded researchers the opportunity to gain a deep understanding of genome level processes that underlie evolutionary change, and perhaps more importantly, the links between genotype and phenotype. In particular, researchers interested in functional biology and adaptation have used these technologies to sequence mRNA transcriptomes of specific tissues, which in turn are often compared to other tissues, or other individuals with different phenotypes. While these techniques are extremely powerful, careful attention to data quality is required. In particular, because high-throughput sequencing is more error-prone than traditional Sanger sequencing, quality trimming of sequence reads should be an important step in all data processing pipelines. While several software packages for quality trimming exist, no general guidelines for the specifics of trimming have been developed. Here, using empirically derived sequence data, I provide general recommendations regarding the optimal strength of trimming, specifically in mRNA-Seq studies. Although very aggressive quality trimming is common, this study suggests that a more gentle trimming, specifically of those nucleotides whose Phredscore<2 or<5, is optimal for most studies across a wide variety of metrics.
Design and implementation of a synthetic biomolecular concentration tracker
Authors: Hsiao Victoria , de los Santos Emmanuel LC , Whitaker Weston R. , Dueber John E. , Murray Richard M.
Published: November 2013

As a field, synthetic biology strives to engineer increasingly complex artificial systems in living cells. Active feedback in closed loop systems offers a dynamic and adaptive way to ensure constant relative activity independent of intrinsic and extrinsic noise. In this work, we design, model, and implement a biomolecular concentration tracker, in which an output protein tracks the concentration of an input protein. Using synthetic scaffolds built from small, modular protein-protein interaction domains to colocalize a two-component system, the circuit design relies on a single negative feedback loop to modulate the production of the output protein. Using a combination of modeling and experimental work, we show that the circuit achieves real-time protein concentration tracking inEscherichia coliand that steady state outputs can be tuned.
A data repository and analysis framework for spontaneous neural activity recordings in developing retina
Authors: Eglen Stephen John , Weeks Michael , Jessop Mark , Simonotto Jennifer , Jackson Tom , Sernagor Evelyne
Published: November 2013

Background

During early development, neural circuits fire spontaneously, generating activity episodes with complex spatiotemporal patterns. Recordings of spontaneous activity have been made in many parts of the nervous system over the last 25 years, reporting developmental changes in activity patterns and the effects of various genetic perturbations.

Results

We present a curated repository of multielectrode array recordings of spontaneous activity in developing mouse and ferret retina. The data have been annotated with minimal metadata and converted into HDF5. This paper describes the structure of the data, along with examples of reproducible research using these data files. We also demonstrate how these data can be analysed in the CARMEN workflow system. This article is written as a literate programming document; all programs and data described here are freely available.

Conclusions

1. We hope this repository will lead to novel analysis of spontaneous activity recorded in different laboratories. 2. We encourage published data to be added to the repository. 3. This repository serves as an example of how multielectrode array recordings can be stored for long-term reuse.
Unexpected links reflect the noise in networks
Authors: Yambartsev Anatoly , Perlin Michael , Kovchegov Yevgeniy , Shulzhenko Natalia , Mine Karina L. , Morgun Andrey
Published: November 2013

Gene regulatory networks are commonly used for modeling biological processes and revealing underlying molecular mechanisms. The reconstruction of gene regulatory networks from observational data is a challenging task, especially, considering the large number of involved players (e.g. genes) and much fewer biological replicates available for analysis. Herein, we proposed a new statistical method of estimating the number of erroneous edges that strongly enhances the commonly used inference approaches. This method is based on special relationship between correlation and causality, and allows to identify and to remove approximately half of erroneous edges. Using the mathematical model of Bayesian networks and positive correlation inequalities we established a mathematical foundation for our method. Analyzing real biological datasets, we found a strong correlation between the results of our method and the commonly used false discovery rate (FDR) technique. Furthermore, the simulation analysis demonstrates that in large networks, our new method provides a more precise estimation of the proportion of erroneous links than FDR.
Lack of evidence for the presence of an interferon in invertebrate
Authors: Wang Pei-Hui
Published: November 2013

In vertebrates, the interferon (IFN) response is the primary form of innate antiviral defense. Previously (2005), a partial cDNA which could encode an interferon-like protein (IntlP) is reported in shrimp, later Rosa et al. (2008) argue that this partial cDNA should encode a portion of insect mitochondrial ATP synthase (MAS) B-chain. Recently (2009), it is demonstrated IntlP also possess antibacterial activity beside antiviral activity reported before. Lacking of a consensus opinion to the question of whether this gene encodes IntlP or MAS, we try to provide more evidences to identify this gene exactly. Here we obtain the full length cDNAs of IntlP/ MAS inLitopenaeus vannamei, and perform the tissue distribution and induced expression analysis. Our results confirm that IntlP is coded by a mistaken ORF and the actual protein indeed is aL. vannameimitochondrial ATP synthase (LvMAS) whose function is unknown in antiviral responses.
Pathways to social evolution: reciprocity, relatedness, and synergy
Authors: Cleve Jeremy Van , Akçay Erol
Published: November 2013

Many organisms live in populations structured by space and by class, exhibit plastic responses to their social partners, and are subject to non-additive ecological and fitness effects. Social evolution theory has long recognized that all of these factors can lead to different selection pressures but has only recently attempted to synthesize how these factors interact. Using models for both discrete and continuous phenotypes, we show that analyzing these factors in a consistent framework reveals that they interact with one another in ways previously overlooked. Specifically, behavioral responses (reciprocity), genetic relatedness, and synergy interact in non-trivial ways that cannot be easily captured by simple summary indices of assortment. We demonstrate the importance of these interactions by showing how they have been neglected in previous synthetic models of social behavior both within and between species. These interactions also affect the level of behavioral responses that can evolve in the long run; proximate biological mechanisms are evolutionarily stable when they generate enough responsiveness relative to the level of responsiveness that exactly balances the ecological costs and benefits. Given the richness of social behavior across taxa, these interactions should be a boon for empirical research as they are likely crucial for describing the complex relationship linking ecology, demography, and social behavior.
Varing chemical equilibrium gives kinetic parameters
Authors: Flach Edward , Schnell Santiago
Published: November 2013

We are interested in finding the kinetic parameters of a chemical reaction. Previous methods for finding these parameters rely on the dynamic behaviour of the system. This means that the methods are time-sensitive and often rely on non-linear curve fitting.
Lipoproteins carry endocannabinoids that inhibit the Hedgehog pathway
Authors: Khaliullina Helena , Bilgin Mesut , Sampaio Julio L. , Shevchenko Andrej , Eaton Suzanne
Published: November 2013

Hedgehog proteins are lipid-modified secreted signaling molecules that regulate tissue development and homeostasis. Lipids contained in circulating lipoproteins repress the Hedgehog signaling pathway in the absence of Hedgehog ligand, but the identity of these lipids is unknown. Here, using biochemical fractionation and lipid mass spectrometry, we identify these inhibitory lipids as endocannabinoids. Endocannabinoids are present in lipoproteins of both flies and humans, and repress the pathway in both mammalian signaling assays andDrosophilawing imaginal discs. InDrosophila, endocannabinoids are requiredin vivoto keep the levels of Smoothened and full-length Cubitus interruptus (Ci155) low in the absence of Hedgehog. Furthermore, elevating their endogenous levels inhibits Hedgehog-dependent accumulation of Smoothened and Ci155. Interestingly,cannabis-derived phytocannabinoids are also potent pathway inhibitors in flies and mammals. These findings constitute a novel link between organismal metabolism and local Hedgehog signaling, and suggest previously unsuspected mechanisms for the broad physiological activities of cannabinoids.
On the concept of biological function, junk DNA and the gospels of ENCODE and Grauret al.
Authors: Bandea Claudiu I.
Published: November 2013

In a recent article entitled “On the immortality of television sets: “function” in the human genome according to the evolution-free gospel of ENCODE”, Grauret al. dismantle ENCODE’s evidence and conclusion that 80% of the human genome is functional. However, the article by Grauret al.contains assumptions and statements that are questionable. Primarily, the authors limit their evaluation of DNA’s biological functions to informational roles, sidestepping putative non-informational functions. Here, I bring forward an old hypothesis on the evolution of genome size and on the role of so called ‘junk DNA’ (jDNA), which might explain C-value enigma. According to this hypothesis, the jDNA functions as a defense mechanism against insertion mutagenesis by endogenous and exogenous inserting elements such as retroviruses, thereby protecting informational DNA sequences from inactivation or alteration of their expression. Notably, this model couples the mechanisms and the selective forces responsible for the origin of jDNA with its putative protective biological function, which represents a classic example of ‘fighting fire with fire.’ One of the key tenets of this theory is that in humans and many other species, jDNAs serves as a protective mechanism against insertional oncogenic transformation. As an adaptive defense mechanism, the amount of protective DNA varies from one species to another based on the rate of its origin, insertional mutagenesis activity, and evolutionary constraints on genome size.
Aβ, tau, α-synuclein, huntingtin, TDP-43, PrP and AA are members of the innate immune system: a unifying hypothesis on the etiology of AD, PD, HD, ALS, CJD and RSA as innate immunity disorders
Authors: Bandea Claudiu I.
Published: November 2013

Despite decades of research, thousands of studies and numerous advances, the etiologies of Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD), Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Lobar Degeneration (FTLD-U), Creutzfeldt-Jakob Disease (CJD), Reactive Systemic Amyloidosis (RSA) and many other neurodegenerative and systemic amyloid diseases have not been defined, nor have the pathogenic mechanisms leading to cellular death and disease. Moreover, the biological functions of APP/amyloid-β (Aβ), tau, α-synuclein, huntingtin, TAR DNA-binding protein 43 (TDP-43), prion protein (PrP), amyloid A (AA) and some of the other primary proteins implicated in amyloid diseases are not known. And, there are no successful preventive or therapeutic approaches. Based on a comprehensive analysis and new interpretation of the existing data in context of an evolutionary framework, it is proposed that: (i) Aβ, tau, α-synuclein, huntingtin, TDP-43, PrP and AA are members of the innate immune system, (ii) the isomeric conformational changes of these proteins and their assembly into various oligomers, plaques, and tangles are not protein misfolding events as defined for decades, nor are they prion-replication activities, but part of their normal, evolutionarily selected innate immune repertoire, and (iii) the immune reactions and activities associated with the function of these proteins in innate immunity lead to AD, PD, HD, ALS, CJD, RSA and other related diseases, which are innate immunity disorders.
An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells
Authors: Turner David A , Trott Jamie , Hayward Penelope , Rué Pau , Martinez Arias Alfonso
Published: November 2013

Embryonic Stem cells derived from the epiblast tissue of the mammalian blastocyst retain the capability to differentiate into any adult cell type and are able to self-renew indefinitely under appropriate culture conditions. Despite the large amount of knowledge that we have accumulated to date about the regulation and control of self-renewal, efficient directed differentiation into specific tissues remains elusive. In this work, we have analysed in a systematic manner the interaction between the dynamics of loss of pluripotency and Activin/Nodal, BMP4 and Wnt signalling in fate assignment during the early stages of differentiation of mouse ES cells in culture. During the initial period of differentiation, cells exit from pluripotency and enter an Epi-like state. Following this transient stage, and under the influence of Activin/Nodal and BMP signalling, cells face a fate choice between differentiating into neuroectoderm and contributing to Primitive Streak fates. We find that Wnt signalling does not suppress neural development as previously thought and that it aids both fates in a context dependent manner. Our results suggest that as cells exit pluripotency they are endowed with a primary neuroectodermal fate and that the potency to become endomesodermal rises with time. We suggest that this situation translates into a ?race for fates? in which the neuroectodermal fate has an advantage.
Differentiation-dependent telomeric long non-coding transcription in a model of skeletal myogenesis
Authors: Brouilette Scott W. , Ounzain Samir , Sawhney Vinit , Yashiro Kenta , Shintani Yasunori , Takahashi Kunihiko , Coppen Steven R. , Narita Takuya , Torsney Kelli , Carrier Martin , Campbell Niall , Suzuki Ken
Published: November 2013

Telomeres comprise the distal ends of eukaryotic chromosomes, serve to maintain genomic integrity and are extended by the ribonucleoprotein telomerase. Recent evidence indicates that telomeres are transcribed to generate long non-coding RNAs (lncRNAs) and that these transcripts (TERRA) may inhibit telomerase activity. In this study we assessed telomerase activity and telomeric lncRNA expression in a mouse model of skeletal myogenesis. Using the C2C12 cell line we demonstrated decreased telomerase activity during differentiation into terminally-differentiated skeletal myotubes. Despite existing in a post-mitotic state, residual telomerase activity remained in C2C12 myotubes, indicating a role independent of telomere extension. Telomeric transcripts were detected in both myoblasts and myotubes, with reduced expression during differentiation correlating with reduced telomerase expression. Our data indicate that in a mouse model of skeletal myogenesis TERRA expression does not reduce telomerase activity, suggesting that their relationship is more complex than originally perceived; the role of telomeric derived lncRNAs in relation to telomerase activity may be cell-type specific. These findings raise the possibility for novel non-telomerase regulatory function for TERRA-lncRNAs during skeletal myogenesis.
Human genetics and clinical aspects of neurodevelopmental disorders
Authors: Lyon Gholson J , O'Rawe Jason
Published: November 2013

There are ~12 billion nucleotides in every cell of the human body, and there are ~25-100 trillion cells in each human body. Given somatic mosaicism, epigenetic changes and environmental differences, no two human beings are the same, particularly as there are only ~7 billion people on the planet. One of the next great challenges for studying human genetics will be to acknowledge and embrace complexity. Every human is unique, and the study of human disease phenotypes (and phenotypes in general) will be greatly enriched by moving from a deterministic to a more stochastic/probabilistic model. The dichotomous distinction between simple and complex diseases is completely artificial, and we argue instead for a model that considers a spectrum of diseases that are variably manifesting in each person. The rapid adoption of whole genome sequencing (WGS) and the Internet-mediated networking of people promise to yield more insight into this century-old debate. Comprehensive ancestry tracking and detailed family history data, when combined with WGS or at least cascade-carrier screening, might eventually facilitate a degree of genetic prediction for some diseases in the context of their familial and ancestral etiologies. However, it is important to remain humble, as our current state of knowledge is not yet sufficient, and in principle, any number of nucleotides in the genome, if mutated or modified in a certain way and at a certain time and place, might influence some phenotype during embryogenesis or postnatal life.
Sap flow through petioles and petiolules reveals leaf-level responses to light and vapor pressure deficit in the tropical treeTabebuia rosea(Bignoniaceae)
Authors: Roddy Adam B. , Winter Klaus , Dawson Todd E.
Published: November 2013

Continuous measurements of sap flow have been widely used to measure water flux through tree stems and branches. However, these measurements lack the resolution necessary for determining fine-scale, leaf-level responses to environmental variables. We used the heat ratio method to measure sap flow rates through leaf petioles and leaflet petiolules of saplings of the tropical treeTabebuia rosea(Bignoniaceae) to determine how leaf and leaflet sap flow responds to variation in light and vapor pressure deficit (VPD). We found that in the morning sap flow rates to east-facing leaves increased 26 minutes before adjacent west-facing leaves. Although leaves had higher integrated sap flow than their largest leaflet, this difference was not proportional to the difference in leaf area, which could be due to lower conduit area in petiolules than in petioles. In contrast to measurements on main stems, integrated daily sap flow was negatively correlated with daily mean VPD. Furthermore, leaves exhibited previously undescribed patterns of hysteresis in the sap flow-VPD and sap flow-PAR relationships. When hysteresis in the sap flow-PAR relationship was clockwise, the sap flow-VPD relationship was also clockwise; however, when hysteresis in the sap flow-PAR relationship was counterclockwise, the sap flow-VPD relationship displayed an intersected loop. These pattern differences highlight how substantially leaf-level processes may vary within a canopy and how leaf-level processes may not scale predictably to the stem level.
Joint analysis of functional genomic data and genome-wide association studies of 18 human traits
Authors: Pickrell Joseph K.
Published: November 2013

Annotations of gene structures and regulatory elements can inform genome-wide association studies (GWAS). However, choosing the relevant annotations for interpreting an association study of a given trait remains challenging. We describe a statistical model that uses association statistics computed across the genome to identify classes of genomic element that are enriched or depleted for loci that influence a trait. The model naturally incorporates multiple types of annotations. We applied the model to GWAS of 18 human traits, including red blood cell traits, platelet traits, glucose levels, lipid levels, height, BMI, and Crohn’s disease. For each trait, we evaluated the relevance of 450 different genomic annotations, including protein-coding genes, enhancers, and DNase-I hypersensitive sites in over a hundred tissues and cell lines. We show that the fraction of phenotype-associated SNPs that influence protein sequence ranges from around 2% (for platelet volume) up to around 20% (for LDL cholesterol); that repressed chromatin is significantly depleted for SNPs associated with several traits; and that cell type-specific DNase-I hypersensitive sites are enriched for SNPs associated with several traits (for example, the spleen in platelet volume). Finally, by re-weighting each GWAS using information from functional genomics, we increase the number of loci with high-confidence associations by around 5%.
Linking indices for biodiversity monitoring to extinction risk theory
Authors: McCarthy Michael A. , Moore Alana L. , Krauss Jochen , Morgan John W. , Clements Christopher F.
Published: November 2013

Biodiversity indices often combine data from different species when used in monitoring programs. Heuristic properties can suggest preferred indices, but we lack objective ways to discriminate between indices with similar heuristics. Biodiversity indices can be evaluated by determining how well they reflect management objectives that a monitoring program aims to support. For example, the Convention on Biological Diversity requires reporting about extinction rates, so simple indices that reflect extinction risk would be valuable. Here we develop three biodiversity indices that are based on simple models of population viability that relate extinction risk to abundance. The first index is based on the geometric mean abundance of species. A second uses a more general power mean. A third integrates both the geometric mean abundance and trend. These indices require the same data as previous indices, but they also relate directly to extinction risk. Field data for butterflies and woodland plants, and experimental studies of protozoan communities show that the indices correlate with local extinction rates. Applying the index based on the geometric mean to global data on changes in avian abundance suggests that the average extinction probability of birds has increased approximately 1% from 1970 to 2009.
Cycling Physicochemical Gradients as ‘Evolutionary Drivers’: From Complex Matter to Complex Living States
Authors: Spitzer Jan
Published: November 2013

Highlights

Biological complexity cannot be reduced to chemistry and physics

Complex living states are: multicomponent, multiphase, ‘crowded’, andre-emergent

Living states arise naturallyonlyby the action of cycling physicochemical gradients

Bacterial cells can be modeled as viscoelastic capacitors with sol-gel transitions

Evolving living states can be investigated via ‘biotic soup’ experimentation

Darwinian evolution arises from the process errors of the cell cycle

Synthetic biology heralds the transition from unintentional Darwinian evolution to intentional anthropic evolution

Within the overlap of physics, chemistry and biology, complex matter becomes ‘more deeply’ understood when high level mathematics converts regularities of experimental data into scientific laws, theories, and models (Krakauer et al., 2011.The challenges and scope of theoretical biology. J. Theoret. Biol. 276: 269–276). The simplest kinds of complex biological matter are bacterial cells; they appear complex–from a physicochemical standpoint–because they are multicomponent, multiphase, biomacromolecularly crowded, and re-emergent; the property of re-emergence differentiates biological matter from complex chemical and physical matter.

Bacterial cells cannot self-reassemble spontaneously from their biomolecules and biomacromolecules (via non-covalent molecular forces) without the action of external ‘drivers’; on Earth, such drivers have been diurnal (cycling) physicochemical gradients,i.e. temperature, water activity, etc. brought about by solar radiation striking the Earth’s rotating surface. About 3.5 billion years ago, these cycling gradients drove complex chemical ‘prebiotic soups’ toward progenotic living states from which extant bacteria evolved (Spitzer and Poolman, 2009;The role of biomacromolecular crowding, ionic strength and physicochemical gradients in the complexities of life’s emergence. Microbiol. Mol. Biol. Revs. 73:371–388). Thus there is historical non-equilibrium continuity between complex ‘dead’ chemical matter and complex living states of bacterial cells. This historical continuity becomes accessible to present-day experimentation, when cycling physicochemical gradients act on ‘dead’ biomacromolecules obtained from (suitably) killed bacterial populations – on a ‘biotic soup’ of chemicals (Harold, 2005,Molecules into cells: specifying spatial architecture. Microbiol. Mol. Biol. Rev. 69:544–564). The making of biotic soups and recovering living states from them is briefly discussed in terms of novel concepts and experimental possibilities.

In principle, emergent living states contingently arise and evolve when cycling physicochemical gradients continuously act on complex chemical mass; once living states become dynamically stabilized, the inevitable process errors of ‘primitive’ cell cycles become the roots of Darwinian evolution.
Generation of high-resolutiona prioriY-chromosome phylogenies using “next-generation” sequencing data
Authors: Magoon Gregory R. , Banks Raymond H. , Rottensteiner Christian , Schrack Bonnie E. , Tilroe Vincent O. , Robb Terry , Grierson Andrew J.
Published: November 2013

An approach for generating high-resolutiona priorimaximum parsimony Y-chromosome (“chrY”) phylogenies based on SNP and small INDEL variant data from massively-parallel short-read (“next-generation”) sequencing data is described; the tree-generation methodology produces annotations localizing mutations to individual branches of the tree, along with indications of mutation placement uncertainty in cases for which “no-calls” (through lack of mapped reads or otherwise) at particular sites precludes precise phylogenetic placement of mutations. The approach leverages careful variant site filtering and a novel iterative reweighting procedure to generate high-accuracy trees while considering variants in regions of chrY that had previously been excluded from analyses based on short-read sequencing data. It is argued that the proposed approach is also superior to previous region-based filtering approaches in that it adapts to the quality of the underlying data and will automatically allow the scope of sites considered to expand as the underlying data quality improves (e.g. through longer read lengths). Key related issues, including calling of genotypes for the hemizygous chrY, reliability of variant results, read mismappings and “heterozygous” genotype calls, and the mutational stability of different variants are discussed and taken into account. The methodology is demonstrated through application to a dataset consisting of 1292 male samples from diverse populations and haplogroups, with the majority coming from low-coverage sequencing by the 1000 Genomes Project. Application of the tree-generation approach to these data produces a tree involving over 120,000 chrY variant sites (about 45,000 sites if “singletons” are excluded). The utility of this approach in refining the Y-chromosome phylogenetic tree is demonstrated by examining results for several haplogroups. The results indicate a number of new branches on the Y-chromosome phylogenetic tree, many of them subdividing known branches, but also including some that inform the presence of additional levels along the “trunk” of the tree. Finally, opportunities for extensions of this phylogenetic analysis approach to other types of genetic data are noted.
Virulence in aPseudomonas syringaeStrain with a Small Repertoire of Predicted Effectors
Authors: Hockett Kevin L. , Nishimura Marc T. , Karlsrud Erick , Dougherty Kevin , Baltrus David A.
Published: November 2013

Both type III effector proteins and non-ribosomal peptide toxins play important roles forPseudomonas syringaepathogenicity in host plants, but whether and how these virulence pathways interact to promote infection remains unclear. Genomic evidence from one clade ofP. syringaesuggests a tradeoff between the total number of type III effector proteins and presence of syringomycin, syringopeptin, and syringolin A toxins. Here we report the complete genome sequence fromP. syringaeCC1557, which contains the lowest number of known type III effectors to date and has also acquired genes similar to sequences encoding syringomycin pathways from other strains. We demonstrate that this strain is pathogenic onNicotiana benthamianaand that both the type III secretion system and a new type III effector family,hopBJ1, contribute to virulence. We further demonstrate that virulence activity of HopBJ1 is dependent on similar catalytic sites as theE. coliCNF1 toxin. Taken together, our results provide additional support for a negative correlation between type III effector repertoires and the potential to produce syringomycin-like toxins while also highlighting how genomic synteny and bioinformatics can be used to identify and characterize novel virulence proteins.
Gene circuit performance characterization and resource usage in a cell-free ‘breadboard’
Authors: Siegal-Gaskins Dan , Tuza Zoltan A. , Kim Jongmin , Noireaux Vincent , Murray Richard M.
Published: November 2013

The many successes of synthetic biology have come in a manner largely different from those in other engineering disciplines; in particular, without well-characterized and simplified prototyping environments to play a role analogous to wind-tunnels in aerodynamics and breadboards in electrical engineering. However, as the complexity of synthetic circuits increases, the benefits—in cost savings and design cycle time—of a more traditional engineering approach can be significant. We have recently developed anin vitro‘breadboard’ prototyping platform based onE. colicell extract that allows biocircuits to operate in an environment considerably simpler than but functionally similar toin vivo. The simplicity of this system makes it a promising tool for rapid biocircuit design and testing, as well as for probing fundamental aspects of gene circuit operation normally masked by cellular complexity. In this work we characterize the cell-free breadboard using real-time and simultaneous measurements of transcriptional and translational activities of a small set of reporter genes and a transcriptional activation cascade. We determine the effects of promoter strength, gene concentration, and nucleoside triphosphate concentration on biocircuit properties, and we isolate the specific contributions of essential biomolecular resources—core RNA polymerase and ribosomes—to overall performance. Importantly, we show how limits on resources, particularly those involved in translation, are manifested as reduced expression in the presence of orthogonal genes that serve as additional loads on the system.
The Effectiveness of China’s National Forest Protection Program and National-level Nature Reserves, 2000 to 2010: PREPRINT
Authors: Ren Guopeng , Young Stephen S. , Wang Lin , Wang Wei , Long Yongcheng , Wu Ruidong , Li Junsheng , Zhu Jianguo , Yu Douglas W.
Published: November 2013

There is profound interest in knowing the degree to which China’s institutions are capable of protecting its natural forests and biodiversity in the face of economic and political change. China’s two most important forest protection policies are its National Forest Protection Program (NFPP) and its National-level Nature Reserves (NNRs). The NFPP was implemented in 17 provinces starting in the year 2000 in response to deforestation-caused flooding. We used MODIS data (MOD13Q1) to estimate forest cover and forest loss across mainland China, and we report that 1.765 million km2or 18.7% of mainland China was covered in forest (12.3%, canopy cover > 70%) and woodland (6.4%, 40% ≤ canopy cover < 70%) in 2000. By 2010, a total of 480,203 km2of forest + woodland was lost, amounting to an annual deforestation rate of 2.7%. The forest-only loss was 127,473 km2, or 1.05% annually. The three most rapidly deforested provinces were outside NFPP jurisdiction, in the southeast. Within the NFPP provinces, the annual forest + woodland loss rate was 2.26%, and the forest-only rate was 0.62%. Because these loss rates are likely overestimates, China appears to have achieved, and even exceeded, its NFPP target of reducing deforestation to 1.1% annually in the target provinces. We also assemble the first-ever polygon dataset for China’s forested NNRs (n = 237), which covered 74,030 km2in 2000. Conventional unmatched and covariate-matching analyses both find that about two-thirds of China’s NNRs exhibit effectiveness in protecting forest cover and that within-NNR deforestation rates are higher in provinces that have higher overall deforestation.
Investigating the relation between stochastic differentiation and homeostasis in intestinal crypts via multiscale modeling
Authors: Graudenzi Alex , Caravagna Giulio , De Matteis Giovanni , Antoniotti Marco
Published: November 2013

Colorectal tumors originate and develop within intestinal crypts. Even though some of the essential phenomena that characterize crypt structure and dynamics have been effectively described in the past, the relation between the differentiation process and the overall crypt homeostasis is still partially understood. We here investigate this relation and other important biological phenomena by introducing a novel multiscale model that combines a morphological description of the crypt with a gene regulation model: the emergent dynamical behavior of the underlying gene regulatory network drives cell growth and differentiation processes, linking the two distinct spatio-temporal levels. The model relies on a few a priori assumptions, yet accounting for several key processes related to crypt functioning, such as: dynamic gene activation patterns, stochastic differentiation, signaling pathways ruling cell adhesion properties, cell displacement, cell growth, mitosis, apoptosis and the presence of biological noise.

We show that this modeling approach captures the major dynamical phenomena that characterize the regular physiology of crypts, such as cell sorting, coordinate migration, dynamic turnover, stem cell niche maintenance and clonal expansion. All in all, the model suggests that the process of stochastic differentiation might be sufficient to drive the crypt to homeostasis, under certain crypt configurations. Besides, our approach allows to make precise quantitative inferences that, when possible, were matched to the current biological knowledge and it permits to investigate the role of gene-level perturbations, with reference to cancer development. We also remark the theoretical framework is general and may applied to different tissues, organs or organisms.