bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the concept of biological function, junk DNA and the gospels of ENCODE and Grauret al.
Authors: Bandea Claudiu I. 
Published: November 2013

AbstractIn 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

AbstractDespite 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.
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

AbstractTelomeres 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.
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

AbstractContinuous 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

AbstractAnnotations 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

AbstractBiodiversity 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

HighlightsBiological complexity cannot be reduced to chemistry and physicsComplex living states are: multicomponent, multiphase, ‘crowded’, andre-emergentLiving states arise naturallyonlyby the action of cycling physicochemical gradientsBacterial cells can be modeled as viscoelastic capacitors with sol-gel transitionsEvolving living states can be investigated via ‘biotic soup’ experimentationDarwinian evolution arises from the process errors of the cell cycleSynthetic biology heralds the transition from unintentional Darwinian evolution to intentional anthropic evolutionAbstractWithin 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

AbstractAn 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

AbstractBoth 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

AbstractThe 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

AbstractThere 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

AbstractColorectal 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.
The-LHON-Enigma: explaining the behaviour of Leber’s Hereditary Optic Neuropathy by the use of a simple computer model
Authors: Logan Ian 
Published: November 2013

AbstractLeber’s Hereditary Optic Neuropathy (LHON) appears as anenigmaticcondition; affecting only certain families and often causing a severe loss of vision seemingly at random amongst family members. The first breakthrough came in 1988 with the linking of the condition to a mutation in the mitochondrial DNA (mtDNA). Now it is known that about 90% of cases are linked to 3 mutations. In this paper thehypothesisis suggested that a LHON mutation decreases the function of the mitochondrial enzyme, Complex I, by 50% and this alone critically endangers the survival of cells - especially the fragile cells of the optic nerves. A computer model has been written to illustrate how thehypothesiscan produce anatural historyfor the condition of LHON that has features similar to those observed in practice; thereby successfully explaining the behaviour of thisenigmaticcondition.