bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of MADS-domain transcription factor complexes in
Arabidopsis
flower development
Authors: Smaczniak Cezary , Immink Richard G. H. , Muiño Jose M. , Blanvillain Robert , Busscher Marco , Busscher-Lange Jacqueline , Dinh Q. D. (Peter) , Liu Shujing , Westphal Adrie H. , Boeren Sjef , Parcy François , Xu Lin , Carles Cristel C. , Angenent Gerco C. , Kaufmann Kerstin
Published: January 2012

Floral organs are specified by the combinatorial action of MADS-domain transcription factors, yet the mechanisms by which MADS-domain proteins activate or repress the expression of their target genes and the nature of their cofactors are still largely unknown. Here, we show using affinity purification and mass spectrometry that five major floral homeotic MADS-domain proteins (AP1, AP3, PI, AG, and SEP3) interact in floral tissues as proposed in the “floral quartet” model. In vitro studies confirmed a flexible composition of MADS-domain protein complexes depending on relative protein concentrations and DNA sequence. In situ bimolecular fluorescent complementation assays demonstrate that MADS-domain proteins interact during meristematic stages of flower development. By applying a targeted proteomics approach we were able to establish a MADS-domain protein interactome that strongly supports a mechanistic link between MADS-domain proteins and chromatin remodeling factors. Furthermore, members of other transcription factor families were identified as interaction partners of floral MADS-domain proteins suggesting various specific combinatorial modes of action.
Production and diagnosis of energetic particles in FAST
Authors: Tardocchi M. , Bruschi A. , Figini L. , Grossetti G. , Marocco D. , Nocente M. , Calabrò G. , Cardinali A. , Crisanti F. , Esposito B. , Gorini G. , Grosso G. , Lontano M. , Nowak S. , Orsitto F. , Tartari U. , Tudisco O.
Published: January 2012

The Fusion Advanced Study Torus (FAST) has been proposed as a possible European satellite facility to study fast-ion physics in deuterium plasmas under conditions relevant to a burning plasma. Energetic minority ions (H or 3He) accelerated by ion cyclotron resonance heating (ICRH), with dimensionless parameters close to those of fusion-born alphas in ITER, can be produced in FAST via 30 MW power ICRH minority heating. This work provides a first assessment of the extent to which the 3He fast-ion population can be diagnosed in FAST with a set of dedicated diagnostics for confined fast particles. Neutron emission spectroscopy (NES), gamma-ray spectroscopy (GRS) and collective Thomson scattering (CTS) diagnostics have been reviewed with a description of the state-of-the-art hardware and a preliminary analysis of the required lines of sight. The results of the analysis, based on numerical simulations of the spatial and energetic particle distribution function of the ICRH-accelerated ions for the standard FAST H-mode scenario, suggest that NES and GRS measurements can provide information on the fast 3He population effective tail temperature, with time resolutions in the range 20–100 ms. The proposed CTS diagnostic can measure the fast-ion parallel and perpendicular temperature with a spatial resolution of 5–10 cm and a time resolution of 10 ms. The paper provides a scientific basis for the prediction of the production and diagnosis of energetic ions in FAST.
Sensitivity to error fields in NSTX high β plasmas
Authors: Park Jong-Kyu , Menard Jonathan E. , Gerhardt Stefan P. , Buttery Richard J. , Sabbagh Steve A. , Bell Ronald E. , LeBlanc Benoit P.
Published: January 2012

It was found that error field threshold decreases for high β in NSTX, although the density correlation in conventional threshold scaling implies the threshold would increase since higher β plasmas in our study have higher plasma density. This greater sensitivity to error field in higher β plasmas is due to error field amplification by plasmas. When the effect of amplification is included with ideal plasma response calculations, the conventional density correlation can be restored and threshold scaling becomes more consistent with low β plasmas. However, it was also found that the threshold can be significantly changed depending on plasma rotation. When plasma rotation was reduced by non-resonant magnetic braking, the further increase in sensitivity to error field was observed.
RIBER/DIBER: a software suite for crystal content analysis in the studies of protein–nucleic acid complexes
Authors: Chojnowski Grzegorz , Bujnicki Janusz M. , Bochtler Matthias
Published: January 2012

Summary: Co-crystallization experiments of proteins with nucleic acids do not guarantee that both components are present in the crystal. We have previously developed DIBER to predict crystal content when protein and DNA are present in the crystallization mix. Here, we present RIBER, which should be used when protein and RNA are in the crystallization drop. The combined RIBER/DIBER suite builds on machine learning techniques to make reliable, quantitative predictions of crystal content for non-expert users and high-throughput crystallography.

Availability: The program source code, Linux binaries and a web server are available at http://diber.iimcb.gov.pl/ RIBER/DIBER requires diffraction data to at least 3.0 Å resolution in MTZ or CIF (web server only) format. The RIBER/DIBER code is subject to the GNU Public License.

Contact:  gchojnowski@genesilico.pl

Supplementary information:  Supplementary data are available at Bioinformatics online.
Estimating abundances of retroviral insertion sites from DNA fragment length data
Authors: Berry Charles C. , Gillet Nicolas A. , Melamed Anat , Gormley Niall , Bangham Charles R. M. , Bushman Frederic D.
Published: January 2012

Motivation: The relative abundance of retroviral insertions in a host genome is important in understanding the persistence and pathogenesis of both natural retroviral infections and retroviral gene therapy vectors. It could be estimated from a sample of cells if only the host genomic sites of retroviral insertions could be directly counted. When host genomic DNA is randomly broken via sonication and then amplified, amplicons of varying lengths are produced. The number of unique lengths of amplicons of an insertion site tends to increase according to its abundance, providing a basis for estimating relative abundance. However, as abundance increases amplicons of the same length arise by chance leading to a non-linear relation between the number of unique lengths and relative abundance. The difficulty in calibrating this relation is compounded by sample-specific variations in the relative frequencies of clones of each length.

Results: A likelihood function is proposed for the discrete lengths observed in each of a collection of insertion sites and is maximized with a hybrid expectation–maximization algorithm. Patient data illustrate the method and simulations show that relative abundance can be estimated with little bias, but that variation in highly abundant sites can be large. In replicated patient samples, variation exceeds what the model implies—requiring adjustment as in Efron (2004) or using jackknife standard errors. Consequently, it is advantageous to collect replicate samples to strengthen inferences about relative abundance.

Availability: An R package implements the algorithm described here. It is available at http://soniclength.r-forge.r-project.org/

Contact:  ccberry@ucsd.edu

Supplementary information:  Supplementary data are available at at Bioinformatics online.
Predicting folding free energy changes upon single point mutations
Authors: Zhang Zhe , Wang Lin , Gao Yang , Zhang Jie , Zhenirovskyy Maxim , Alexov Emil
Published: January 2012

Motivation: The folding free energy is an important characteristic of proteins stability and is directly related to protein's wild-type function. The changes of protein's stability due to naturally occurring mutations, missense mutations, are typically causing diseases. Single point mutations made in vitro are frequently used to assess the contribution of given amino acid to the stability of the protein. In both cases, it is desirable to predict the change of the folding free energy upon single point mutations in order to either provide insights of the molecular mechanism of the change or to design new experimental studies.

Results: We report an approach that predicts the free energy change upon single point mutation by utilizing the 3D structure of the wild-type protein. It is based on variation of the molecular mechanics Generalized Born (MMGB) method, scaled with optimized parameters (sMMGB) and utilizing specific model of unfolded state. The corresponding mutations are built in silico and the predictions are tested against large dataset of 1109 mutations with experimentally measured changes of the folding free energy. Benchmarking resulted in root mean square deviation = 1.78 kcal/mol and slope of the linear regression fit between the experimental data and the calculations was 1.04. The sMMGB is compared with other leading methods of predicting folding free energy changes upon single mutations and results discussed with respect to various parameters.

Availability: All the pdb files we used in this article can be downloaded from http://compbio.clemson.edu/downloadDir/mentaldisorders/sMMGB_pdb.rar

Contact:  ealexov@clemson.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
The evolution of nitrogen fixation in cyanobacteria
Authors: Latysheva Natasha , Junker Vivien L. , Palmer William J. , Codd Geoffrey A. , Barker Daniel
Published: January 2012

Motivation: Fixed nitrogen is an essential requirement for the biosynthesis of cellular nitrogenous compounds. Some cyanobacteria can fix nitrogen, contributing significantly to the nitrogen cycle, agriculture and biogeochemical history of Earth. The rate and position on the species phylogeny of gains and losses of this ability, as well as of the underlying nif genes, are controversial.

Results: We use probabilistic models of trait evolution to investigate the presence and absence of cyanobacterial nitrogen-fixing ability. We estimate rates of change on the species phylogeny, pinpoint probable changes and reconstruct the state and nif gene complement of the ancestor. Our results are consistent with a nitrogen-fixing cyanobacterial ancestor, repeated loss of nitrogen fixation and vertical descent, with little horizontal transfer of the genes involved.

Contact:  db60@st-andrews.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
PHACTS, a computational approach to classifying the lifestyle of phages
Authors: McNair Katelyn , Bailey Barbara A. , Edwards Robert A.
Published: January 2012

Motivation: Bacteriophages have two distinct lifestyles: virulent and temperate. The virulent lifestyle has many implications for phage therapy, genomics and microbiology. Determining which lifestyle a newly sequenced phage falls into is currently determined using standard culturing techniques. Such laboratory work is not only costly and time consuming, but also cannot be used on phage genomes constructed from environmental sequencing. Therefore, a computational method that utilizes the sequence data of phage genomes is needed.

Results: Phage Classification Tool Set (PHACTS) utilizes a novel similarity algorithm and a supervised Random Forest classifier to make a prediction whether the lifestyle of a phage, described by its proteome, is virulent or temperate. The similarity algorithm creates a training set from phages with known lifestyles and along with the lifestyle annotation, trains a Random Forest to classify the lifestyle of a phage. PHACTS predictions are shown to have a 99% precision rate.

Availability and implementation: PHACTS was implemented in the PERL programming language and utilizes the FASTA program (Pearson and Lipman, 1988) and the R programming language library ‘Random Forest’ (Liaw and Weiner, 2010). The PHACTS software is open source and is available as downloadable stand-alone version or can be accessed online as a user-friendly web interface. The source code, help files and online version are available at http://www.phantome.org/PHACTS/.

Contact:  katelyn@rohan.sdsu.edu; redwards@sciences.sdsu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
SSuMMo: rapid analysis, comparison and visualization of microbial communities
Authors: Leach Alex L. B. , Chong James P. J. , Redeker Kelly R.
Published: January 2012

Motivation: Next-generation sequencing methods are generating increasingly massive datasets, yet still do not fully capture genetic diversity in the richest environments. To understand such complicated and elusive systems, effective tools are needed to assist with delineating the differences found in and between community datasets.

Results: The Small Subunit Markov Modeler (SSuMMo) was developed to probabilistically assign SSU rRNA gene fragments from any sequence dataset to recognized taxonomic clades, producing consistent, comparable cladograms. Accuracy tests predicted >90% of genera correctly for sequences downloaded from public reference databases. Sequences from a next-generation sequence dataset, sampled from lean, overweight and obese individuals, were analysed to demonstrate parallel visualization of comparable datasets. SSuMMo shows potential as a valuable curatorial tool, as numerous incorrect and outdated taxonomic entries and annotations were identified in public databases.

Availability and implementation: SSuMMo is GPLv3 open source Python software, available at http://code.google.com/p/ssummo/. Taxonomy and HMM databases can be downloaded from http://bioltfws1.york.ac.uk/ssummo/.

Contact:  albl500@york.ac.uk

Supplementary information: Supplemental materials are available at Bioinformatics Online.
Detecting genomic indel variants with exact breakpoints in single- and paired-end sequencing data using SplazerS
Authors: Emde Anne-Katrin , Schulz Marcel H. , Weese David , Sun Ruping , Vingron Martin , Kalscheuer Vera M. , Haas Stefan A. , Reinert Knut
Published: January 2012

Motivation: The reliable detection of genomic variation in resequencing data is still a major challenge, especially for variants larger than a few base pairs. Sequencing reads crossing boundaries of structural variation carry the potential for their identification, but are difficult to map.

Results: Here we present a method for ‘split’ read mapping, where prefix and suffix match of a read may be interrupted by a longer gap in the read-to-reference alignment. We use this method to accurately detect medium-sized insertions and long deletions with precise breakpoints in genomic resequencing data. Compared with alternative split mapping methods, SplazerS significantly improves sensitivity for detecting large indel events, especially in variant-rich regions. Our method is robust in the presence of sequencing errors as well as alignment errors due to genomic mutations/divergence, and can be used on reads of variable lengths. Our analysis shows that SplazerS is a versatile tool applicable to unanchored or single-end as well as anchored paired-end reads. In addition, application of SplazerS to targeted resequencing data led to the interesting discovery of a complete, possibly functional gene retrocopy variant.

Availability: SplazerS is available from http://www.seqan.de/projects/ splazers.

Contact:  emde@inf.fu-berlin.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
GROMACS molecule & liquid database
Authors: van der Spoel David , van Maaren Paul J. , Caleman Carl
Published: January 2012

Motivation: The molecular dynamics simulation package GROMACS is a widely used tool used in a broad range of different applications within physics, chemistry and biology. It is freely available, user friendly and extremely efficient. The GROMACS software is force field agnostic, and compatible with many molecular dynamics force fields; coarse-grained, unified atom, all atom as well as polarizable models based on the charge on a spring concept. To validate simulations, it is necessary to compare results from the simulations to experimental data. To ease the process of setting up topologies and structures for simulations, as well as providing pre-calculated physical properties along with experimental values for the same we provide a web-based database, containing 145 organic molecules at present.

Results: Liquid properties of 145 organic molecules have been simulated using two different force fields, OPLS all atom and Generalized Amber Force Field. So far, eight properties have been calculated (the density, enthalpy of vaporization, surface tension, heat capacity at constant volume and pressure, isothermal compressibility, volumetric expansion coefficient and the static dielectric constant). The results, together with experimental values are available through the database, along with liquid structures and topologies for the 145 molecules, in the two force fields.

Availability: The database is freely available under http://virtualchemistry.org.

Contact:  spoel@xray.bmc.uu.se; carl.caleman@cfel.de
Surrogate variable analysis using partial least squares (SVA-PLS) in gene expression studies
Authors: Chakraborty Sutirtha , Datta Somnath , Datta Susmita
Published: January 2012

Motivation: In a typical gene expression profiling study, our prime objective is to identify the genes that are differentially expressed between the samples from two different tissue types. Commonly, standard analysis of variance (ANOVA)/regression is implemented to identify the relative effects of these genes over the two types of samples from their respective arrays of expression levels. But, this technique becomes fundamentally flawed when there are unaccounted sources of variability in these arrays (latent variables attributable to different biological, environmental or other factors relevant in the context). These factors distort the true picture of differential gene expression between the two tissue types and introduce spurious signals of expression heterogeneity. As a result, many genes which are actually differentially expressed are not detected, whereas many others are falsely identified as positives. Moreover, these distortions can be different for different genes. Thus, it is also not possible to get rid of these variations by simple array normalizations. This both-way error can lead to a serious loss in sensitivity and specificity, thereby causing a severe inefficiency in the underlying multiple testing problem. In this work, we attempt to identify the hidden effects of the underlying latent factors in a gene expression profiling study by partial least squares (PLS) and apply ANCOVA technique with the PLS-identified signatures of these hidden effects as covariates, in order to identify the genes that are truly differentially expressed between the two concerned tissue types.

Results: We compare the performance of our method SVA-PLS with standard ANOVA and a relatively recent technique of surrogate variable analysis (SVA), on a wide variety of simulation settings (incorporating different effects of the hidden variable, under situations with varying signal intensities and gene groupings). In all settings, our method yields the highest sensitivity while maintaining relatively reasonable values for the specificity, false discovery rate and false non-discovery rate. Application of our method to gene expression profiling for acute megakaryoblastic leukemia shows that our method detects an additional six genes, that are missed by both the standard ANOVA method as well as SVA, but may be relevant to this disease, as can be seen from mining the existing literature.

Availability: The R code for our method, SVA-PLS, is freely available on the Supplementary website http://www.somnathdatta.org/Supp/SVPLS/

Contact:  s0chak10@louisville.edu; susmita.datta@louisville.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Interactome–transcriptome integration for predicting distant metastasis in breast cancer
Authors: Garcia Maxime , Millat-Carus Raphaelle , Bertucci François , Finetti Pascal , Birnbaum Daniel , Bidaut Ghislain
Published: January 2012

Motivation: High-throughput gene expression profiling yields genomic signatures that allow the prediction of clinical conditions including patient outcome. However, these signatures have limitations, such as dependency on the training set, and worse, lack of generalization.

Results: We propose a novel algorithm called ITI (interactome–transcriptome integration), to extract a genomic signature predicting distant metastasis in breast cancer by superimposition of large-scale protein–protein interaction data over a compendium of several gene expression datasets. Training on two different compendia showed that the estrogen receptor-specific signatures obtained are more stable (11–35% stability), can be generalized on independent data and performs better than previously published methods (53–74% accuracy).

Availability: The ITI algorithm source code from analysis are available under CeCILL from the ITI companion website: http://bioinformatique.marseille.inserm.fr/iti.

Contact:  maxime.garcia@inserm.fr; ghislain.bidaut@inserm.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
‘The World Palpitates’: Globalization and the Religious Faith and Practices of Latin American Women
Authors: Bedford Nancy E.
Published: January 2012

Given the fact that religion and globalization are significantly intertwined, what should we make of the contemporary religious faith and practices of Latin American women? Do religious conversion and active participation in a community of faith amount to “adaptive solutions” to the crisis unleashed by capitalist globalization, analogous to those made by women as economic agents? From the perspective of the sociology of religion, it has become a byword that the faith and religious community-building of women—be it the Pentecostalism of Maya women in Guatemala or the activism of Brazilian women in Roman Catholic base communities—can and do serve as coping or indeed as survival strategies in times of globalization. A theological perspective does not necessarily contradict the sociological insight that discovers ways in which religious faith and practices serve in coping and surviving. Because theology speaks in an engaged voice from within the realm of faith, however, it can allow itself—indeed it must—to delve differently than the social sciences. This chapter explores the observation that religious faith and practices of Latin American women, in these economically globalized times, often serve in rather unexpected ways to make space for life, in all of its messiness and materiality.
First Nation, Empire, and Globalization
Authors: Smith Andrea
Published: January 2012

In his analysis of postmodern theology, which details the imbrication of theology in discourses of power, Gavin Hyman casually evokes the term “Indian territory” to connote the space from which the theologian must resort to the tactics of the “outlaw.” In his larger argument, he evokes an Agamban-like state of exception for theology, where theology must be conducted in the realm of radical undecidability, a theology excluded from but belonging to the law, as it were. So, it is significant that, to make this argument, Hyman relies on the obvious racist connotation of Natives as “outlaws” who live in a place without a home. This chapter argues that this tendency to depict Natives as “outlaws” is not unique to Hyman, but exists even within feminist and liberation theologies. That is, the United States, despite the critiques which many theologians make of it, is still envisaged as a place of law, thereby rending Native peoples, whose genocide is the foundation of the USA, outside the law. Consequently, the theological strategy of engagement with Native peoples does resemble the tactic of “raid and return”: that is, a selective use of “indigenous” principles without engagement in the fundamental contradiction indigenous peoples expose in the project of liberation. Furthermore, this problematic engagement is fundamentally gendered.
Globalization and Women's Bodies in Latin America
Authors: Ventura María Cristina
Published: January 2012

This chapter considers globalization and its relationship to women's bodies in Latin America, both the effects this new face of capitalism is having on women's bodies in this part of the world and the ways in which women construct modalities as creative resistance strategies. It goes beyond a mere analysis of the socioeconomic impact in a variety of situations to examine what women invent, represent, and endow with power in their discourse, practices, and collective quest to redefine the status of all women, and particularly of women excluded from the so-called global economic system.
Globalization, Women's Transnational Migration, and Religious De-traditioning
Authors: Tanner Kathryn
Published: January 2012

Far-flung movements of women from disadvantaged areas of the world to more advantaged ones are at the heart of the present configuration of global capitalism. Rather than simply leaving their countries of origin to set up temporary or permanent residence elsewhere, women who move in today's global economy, in order to take jobs as housekeepers or nannies (for example), are typically transnational migrants. Even as they settle into new places, their lives remain bound up with where they came from, in virtue of rather dense social and familial networks bridging national boundaries. Connected simultaneously in this way to at least two places at once, these women are working out in their everyday lives a fundamental reconfiguration of the way cultural traditions are set up and maintained, with significant implications for the understanding of religious traditions in particular. This chapter shows that, in the lives of these women, coming undone is the familiar association of tradition with the intergenerational transmission of an already established way of life by means of face-to-face interactions in a single location.
Editors' Introduction
Authors: Kuusela Oskari , McGinn Marie
Published: January 2012

This Introduction starts by stating that Wittgenstein is a contested figure on the philosophical scene. It talks further about Wittgenstein’s philosophy and his relation to, what is now called, analytical philosophy. It then goes on to talk about the various literature that has been generated by the study of Wittgenstein philosophy, stating that Wittgenstein is best known for his work in the philosophy of language, mind, and mathematics. The Introduction also talks about the differences between Wittgenstein’s views and mainstream analytical philosophy. Finally the topics covered in this book are introduced.
Wittgenstein and Biography
Authors: McGuinness Brian
Published: January 2012

There are obvious ways in which the study of Ludwig Wittgenstein's thought must have recourse to the facts of his life. Much of the most intimate part of Wittgenstein's own diaries was written in a simple code understood in his family, as if it were addressed to them, like one of the ‘confessions’ he often talked about and more than once made. In the notebooks in which he recorded his thoughts for future reflection or use, personal reflections abound. He interrupts his philosophical writing to exclaim, sometimes but not always in code, on his weaknesses, his vanity, his sins, or his aspirations — all of which of course might infect his philosophical writing as much as any other aspect of his life. He constantly felt that he could easily relapse into vanity, in philosophy as elsewhere. In the case of autobiography itself (he said, reflecting on his current activity), this would compound his faults, make him yet schmutziger (sully him yet further).
Assertion, Saying, and Propositional Complexity in Wittgenstein's Tractatus
Authors: Johnston Colin
Published: January 2012

Ludwig Wittgenstein responds in his Notes on Logic to a discussion of Bertrand Russell's 1903 Principles of Mathematics concerning assertion. In Principles of Mathematics, Russell makes a distinction between asserted and unasserted propositions. Whilst this distinction is not given a fully worked-out account, Russell sees it as a point of considerable theoretical importance. It is introduced in the context of a separation by Russell of modus ponens from the proposition that ‘if p and q be propositions then p together with p implies q’. In reply to Russell, Wittgenstein argues that ‘Assertion is merely psychological. In not-p, p is exactly the same as if it stands alone; this point is absolutely fundamental’. Wittgenstein's response is intriguing, not least because of the centrality to his Tractatus Logico-Philosophicus of the idea that a proposition says something.
Wittgenstein and Frege
Authors: Kienzler Wolfgang
Published: January 2012

In the Preface to Tractatus Logico-Philosophicus, Ludwig Wittgenstein acknowledges his debt to ‘the great works of Gottlob Frege’; and even during the years in which he resigned from doing philosophy Wittgenstein directed others to read Frege, even when he himself did not continue to do so. This article describes Wittgenstein and Frege's personal relationship and examines how much we know about the extent to which Wittgenstein studied Frege's work. It gives a systematic account of Frege's most basic approach and compares it to some suggestions by Cora Diamond. Frege's mature logical system is organized around the basic distinction between function and object. Wittgenstein's fundamental insight that the language of logic and mathematics works in a totally different way from the language of empirical statements organizes his Tractatus. Frege, on the other hand, develops a model where all statements, whether they be empirical, logical, or mathematical, are fashioned on one and the same basic pattern, namely, that of function and argument, supplemented by sense and reference.
The Proposition's Progress
Authors: Travis Charles
Published: January 2012

This article explores Ludwig Wittgenstein's views on the proposition by tracing a path, in steps, from Tractatus Logico-Philosophicus to Philosophical Investigations. It focuses on one intermediate step, found in Philosophical Grammar. As things now stand, a language unfolds the notions proposition and truth. In one way among indefinitely many it adds enough content to these notions for there to be an extension for ‘is a proposition’ and for ‘is either true or false’. Its grammar provides this content. Still bracketing conflict between grammar and logic, there is no perspective from outside a language from which its grammar is criticisable. The idea of language-games as objects of comparison gives the parochial a certain purchase on thought and its objects. Among other things, the parochial gains a role in how logic applies to thought, which raises questions about Gottlob Frege's conception of logic's distance from psychology.
Very General Facts of Nature
Authors: Hertzberg Lars
Published: January 2012

In Philosophical Investigations §415, Ludwig Wittgenstein gives what appears to be a general characterisation of his method in philosophy: ‘What we are supplying are really remarks on the natural history of human beings; we are not contributing curiosities however, but observations which no one has doubted, but which have escaped remark only because they are always before our eyes’. This article argues that this remark points to quite an important dimension of Wittgenstein's later thought, a dimension that has largely been bypassed or underplayed (perhaps even by Wittgenstein himself). It concerns the importance, for our way of thinking about language, of recognising the ways in which the language we speak is contingent on the circumstances of our lives. In Philosophical Investigations, II, xii, Wittgenstein is contrasting two approaches to the dependence of our concepts on facts of nature. From large parts of Philosophical Investigations one may get the impression that the recognition problem is the central issue where language learning is concerned.
Wittgenstein on Criteria and The Problem Of Other Minds
Authors: Witherspoon Edward
Published: January 2012

In Philosophical Investigations, Ludwig Wittgenstein explores the grammar of our concepts — especially the grammar of concepts that describe the mind — by looking at the grounds on which we apply them. Wittgenstein usually employs the term ‘criteria’ for the grounds on which we apply a concept, so we may say that a major aim of Wittgenstein's philosophical enterprise is to understand and clarify the logic of psychological concepts through an examination of their criteria. This article examines two very different interpretations of Wittgenstein on criteria. The first reader is Rogers Albritton, who interprets criteria as conventions linking behaviour with mental states. The second is John McDowell, who identifies the defects of that approach and offers a radically different way of thinking about criteria of mental concepts. The article concludes by arguing that Wittgenstein's remarks about criteria are a crucial part of his critique of skepticism.
Wittgenstein on Intuition, Rule-Following, and Certainty: Exchanges with Brouwer and Russell
Authors: Gennip Kim van
Published: January 2012

This article focuses on the debate on perception or intuition between Bertrand Russell and Ludwig Wittgenstein as constructed largely from ‘The Limits of Empiricism’ and ‘Cause and Effect: Intuitive Awareness’. In consulting several Nachlass items as written in 1935–1936, it shows, first, that Wittgenstein puts forward a detailed criticism of Russell's account of perception, as Russell presents it in the context of a discussion on causation. This criticism is interesting in that it leads up to an account of knowledge and certainty that foreshadows the position known from On Certainty. In addition, the article demonstrates that a crucial element in Wittgenstein's critique of Russell is similar to his critique of L. E. J. Brouwer's intuitionist stance in mathematics, a criticism that Wittgenstein expressed in the early 1930s. Russell presents an account of the relation between sense experience and knowledge that should produce propositions functioning as examples of our most immediate knowledge.
The Development of Wittgenstein's Philosophy
Authors: Kuusela Oskari
Published: January 2012

In the Preface to Philosophical Investigations, Ludwig Wittgenstein distinguishes between two aspects of the relation of his later work to his early philosophy, and between two senses in which knowledge of his early work can help in the interpretation of his later philosophy. On the one hand, he suggests that his later philosophy can ‘be seen in the right light only...against the background’ of his ‘old way of thinking’. Presumably this is so because the later work develops further certain ideas that were present already in Tractatus Logico-Philosophicus and make Wittgenstein's philosophy a distinctive contribution to the tradition of philosophy. A proper grasp of the way in which Wittgenstein seeks to correct his early view of logic and language in his later philosophy requires understanding the development of his conception of philosophy and its methodology.
Writing Philosophy as Poetry: Literary form in Wittgenstein
Authors: Perloff Marjorie
Published: January 2012

Ludwig Wittgenstein, hoping, in 1919, to persuade Ludwig von Ficker, the editor of the literary journal Der Brenner, to publish his controversial Tractatus Logico-Philosophicus, remarked, ‘The work is strictly philosophical and at the same time literary’. In Tractatus, Wittgenstein concerns himself with tautology: ‘the fact that the propositions of logic are tautologies shows the formal — logical — properties of language, of the world’. In the much-cited Preface to Philosophical Investigations, Wittgenstein describes the method whereby he ordered the ‘remarks, short paragraphs, of which there is sometimes a fairly long chain about the same subject’ into the larger structure of the book. Wittgenstein's writings enact their central motive: words and phrases can be understood only in their particular context, their use. Not what one says but how one says it is the key to doing philosophy. And that, of course, is what makes it poetry as well.
Do females preferentially associate with males given a better start in life?
Authors: Kahn Andrew T. , Livingston Julianne D. , Jennions Michael D.
Published: January 2012

A poor start in life owing to a restricted diet can have readily detectable detrimental consequences for many adult life-history traits. However, some costs such as smaller adult body size are potentially eliminated when individuals modify their development. For example, male mosquitofish (Gambusia holbrooki) that have reduced early food intake undergo compensatory growth and delay maturation so that they eventually mature at the same size as males that develop normally. But do subtle effects of a poor start persist? Specifically, does a male's developmental history affect his subsequent attractiveness to females? Females prefer to associate with larger males but, controlling for body length, we show that females spent less time in association with males that underwent compensatory growth than with males that developed normally.
Hotter nests produce smarter young lizards
Authors: Amiel Joshua J. , Shine Richard
Published: January 2012

A hatchling reptile's sex, body size and shape, and locomotor performance can be influenced not only by its genes, but also by the temperature that it experiences during incubation. Can incubation temperature also affect a hatchling's cognitive skills? In the scincid lizard
Bassiana duperreyi
, higher incubation temperatures enhanced the resultant hatchling's learning performance. Hence, factors such as maternal nest-site selection and climate change affect not only the size, shape and athletic abilities of hatchling reptiles, but also their ability to learn novel tasks.
Stochastic steady state gain in a gene expression process with mRNA degradation control
Authors: Kuwahara Hiroyuki , Schwartz Russell
Published: January 2012

Recent analyses with high-resolution single-molecule experimental methods have shown highly irregular and variable bursting of mRNA in a wide range of organisms. Noise in gene expression is thought to be beneficial in cell fate specifications, as it can lay a foundation for phenotypic diversification of isogenetic cells in the homogeneous environment. However, because the stability of proteins is, in many cases, higher than that of mRNAs, noise from transcriptional bursting can be considerably buffered at the protein level, limiting the effect of noisy mRNAs at a more global regulation level. This raises a question as to what constructive role noisy mRNAs can play in the system-level dynamics. In this study, we have addressed this question using the computational models that extend the conventional transcriptional bursting model with a post-transcriptional regulation step. Surprisingly, by comparing this stochastic model with the corresponding deterministic model, we find that intrinsic fluctuations can substantially increase the expected mRNA level. Because effects of a higher mRNA level can be transmitted to the protein level even with slow protein degradation rates, this finding suggests that an increase in the protein level is another potential effect of transcriptional bursting. Here, we show that this striking steady state increase is caused by the asynchronous nature of molecular reactions, which allows the transcriptional regulation model to create additional modes of qualitatively distinct dynamics. Our results illustrate non-intuitive effects of reaction asynchronicity on system dynamics that cannot be captured by the traditional deterministic framework. Because molecular reactions are intrinsically stochastic and asynchronous, these findings may have broad implications in modelling and understanding complex biological systems.
Meta-DNA: synthetic biology via DNA nanostructures and hybridization reactions
Authors: Chandran Harish , Gopalkrishnan Nikhil , Yurke Bernard , Reif John
Published: January 2012

Can a wide range of complex biochemical behaviour arise from repeated applications of a highly reduced class of interactions? In particular, can the range of DNA manipulations achieved by protein enzymes be simulated via simple DNA hybridization chemistry? In this work, we develop a biochemical system which we call meta-DNA (abbreviated as mDNA), based on strands of DNA as the only component molecules. Various enzymatic manipulations of these mDNA molecules are simulated via toehold-mediated DNA strand displacement reactions. We provide a formal model to describe the required properties and operations of our mDNA, and show that our proposed DNA nanostructures and hybridization reactions provide these properties and functionality. Our meta-nucleotides are designed to form flexible linear assemblies (single-stranded mDNA (
ss
mDNA)) analogous to single-stranded DNA. We describe various isothermal hybridization reactions that manipulate our mDNA in powerful ways analogous to DNA–DNA reactions and the action of various enzymes on DNA. These operations on mDNA include (i) hybridization of
ss
mDNA into a double-stranded mDNA (
ds
mDNA) and heat denaturation of a
ds
mDNA into its component
ss
mDNA, (ii) strand displacement of one
ss
mDNA by another, (iii) restriction cuts on the backbones of
ss
mDNA and
ds
mDNA, (iv) polymerization reactions that extend
ss
mDNA on a template to form a complete
ds
mDNA, (v) synthesis of mDNA sequences via mDNA polymerase chain reaction, (vi) isothermal denaturation of a
ds
mDNA into its component
ss
mDNA, and (vii) an isothermal replicator reaction that exponentially amplifies
ss
mDNA strands and may be modified to allow for mutations.
Structure and function of the transketolase from
Mycobacterium tuberculosis
and comparison with the human enzyme
Authors: Fullam Elizabeth , Pojer Florence , Bergfors Terese , Jones T. Alwyn , Cole Stewart T.
Published: January 2012

The transketolase (TKT) enzyme in
Mycobacterium tuberculosis
represents a novel drug target for tuberculosis treatment and has low homology with the orthologous human enzyme. Here, we report on the structural and kinetic characterization of the transketolase from
M. tuberculosis
(TBTKT), a homodimer whose monomers each comprise 700 amino acids. We show that TBTKT catalyses the oxidation of donor sugars xylulose-5-phosphate and fructose-6-phosphate as well as the reduction of the acceptor sugar ribose-5-phosphate. An invariant residue of the TKT consensus sequence required for thiamine cofactor binding is mutated in TBTKT; yet its catalytic activities are unaffected, and the 2.5 Å resolution structure of full-length TBTKT provides an explanation for this. Key structural differences between the human and mycobacterial TKT enzymes that impact both substrate and cofactor recognition and binding were uncovered. These changes explain the kinetic differences between TBTKT and its human counterpart, and their differential inhibition by small molecules. The availability of a detailed structural model of TBTKT will enable differences between human and
M. tuberculosis
TKT structures to be exploited to design selective inhibitors with potential antitubercular activity.
Prey community structure affects how predators select for Müllerian mimicry
Authors: Ihalainen Eira , Rowland Hannah M. , Speed Michael P. , Ruxton Graeme D. , Mappes Johanna
Published: January 2012

Müllerian mimicry describes the close resemblance between aposematic prey species; it is thought to be beneficial because sharing a warning signal decreases the mortality caused by sampling by inexperienced predators learning to avoid the signal. It has been hypothesized that selection for mimicry is strongest in multi-species prey communities where predators are more prone to misidentify the prey than in simple communities. In this study, wild great tits (
Parus major
) foraged from either simple (few prey appearances) or complex (several prey appearances) artificial prey communities where a specific model prey was always present. Owing to slower learning, the model did suffer higher mortality in complex communities when the birds were inexperienced. However, in a subsequent generalization test to potential mimics of the model prey (a continuum of signal accuracy), only birds that had foraged from simple communities selected against inaccurate mimics. Therefore, accurate mimicry is more likely to evolve in simple communities even though predator avoidance learning is slower in complex communities. For mimicry to evolve, prey species must have a common predator; the effective community consists of the predator's diet. In diverse environments, the limited diets of specialist predators could create ‘simple community pockets’ where accurate mimicry is selected for.
Two palmitylated cysteine residues of the severe acute respiratory syndrome coronavirus spike (S) protein are critical for S incorporation into virus-like particles, but not for M–S co-localization
Authors: Ujike Makoto , Huang Cheng , Shirato Kazuya , Matsuyama Shutoku , Makino Shinji , Taguchi Fumihiro
Published: January 2012

The endodomain of several coronavirus (CoV) spike (S) proteins contains palmitylated cysteine residues and enables co-localization and interaction with the CoV membrane (M) protein. Depalmitylation of mouse hepatitis virus S proteins abolished this interaction, resulting in the failure of S incorporation into virions. In contrast, an immunofluorescence assay (IFA) showed that depalmitylated severe acute respiratory syndrome coronavirus (SCoV) S proteins still co-localized with the M protein in the budding site. Here, we determined the ability of depalmitylated SCoV S mutants to incorporate S into virus-like particles (VLPs). IFA confirmed that all SCoV S mutants co-localized with the M protein intracellularly. However, the mutants lacking two cysteine residues (C1234/1235) failed to incorporate S into VLPs. This indicated that these palmitylated cysteines are essential for S incorporation, but are not involved in S co-localization mediated by the M protein. Our findings suggest that M–S co-localization and S incorporation occur independently of one another in SCoV virion assembly.
Mouse Models of Aneuploidy
Authors: Sheppard Olivia , Wiseman Frances K. , Ruparelia Aarti , Tybulewicz Victor L. J. , Fisher Elizabeth M. C.
Published: January 2012

Abnormalities of chromosome copy number are called aneuploidies and make up a large health load on the human population. Many aneuploidies are lethal because the resulting abnormal gene dosage is highly deleterious. Nevertheless, some whole chromosome aneuploidies can lead to live births. Alterations in the copy number of sections of chromosomes, which are also known as segmental aneuploidies, are also associated with deleterious effects. Here we examine how aneuploidy of whole chromosomes and segmental aneuploidy of chromosomal regions are modeled in the mouse. These models provide a whole animal system in which we aim to investigate the complex phenotype-genotype interactions that arise from alteration in the copy number of genes. Although our understanding of this subject is still in its infancy, already research in mouse models is highlighting possible therapies that might help alleviate the cognitive effects associated with changes in gene number. Thus, creating and studying mouse models of aneuploidy and copy number variation is important for understanding what it is to be human, in both the normal and genomically altered states.