bluuebunny/crossref_metadata_2025 huggingface dataset:
Rab5-family guanine nucleotide exchange factors bind retromer and promote its recruitment to endosomes
Authors: Bean Bjorn D. M. , Davey Michael , Snider Jamie , Jessulat Matthew , Deineko Viktor , Tinney Matthew , Stagljar Igor , Babu Mohan , Conibear Elizabeth
Published: January 2015

The retromer complex facilitates the sorting of integral membrane proteins from the endosome to the late Golgi. In mammalian cells, the efficient recruitment of retromer to endosomes requires the lipid phosphatidylinositol 3-phosphate (PI3P) as well as Rab5 and Rab7 GTPases. However, in yeast, the role of Rabs in recruiting retromer to endosomes is less clear. We identified novel physical interactions between retromer and the Saccharomyces cerevisiae VPS9-domain Rab5-family guanine nucleotide exchange factors (GEFs) Muk1 and Vps9. Furthermore, we identified a new yeast VPS9 domain-containing protein, VARP-like 1 (Vrl1), which is related to the human VARP protein. All three VPS9 domain–containing proteins show localization to endosomes, and the presence of any one of them is necessary for the endosomal recruitment of retromer. We find that expression of an active VPS9-domain protein is required for correct localization of the phosphatidylinositol 3-kinase Vps34 and the production of endosomal PI3P. These results suggest that VPS9 GEFs promote retromer recruitment by establishing PI3P-enriched domains at the endosomal membrane. The interaction of retromer with distinct VPS9 GEFs could thus link GEF-dependent regulatory inputs to the temporal or spatial coordination of retromer assembly or function.
Who Are India’s Pentecostals?
Authors: Bauman Chad M.
Published: January 2015

There is much debate in scholarly circles about how to define Pentecostals and differentiate them from other Christian groups. This chapter takes up the question of definition, with special attention to the Indian context and to the history of Pentecostalism in the subcontinent. Defining Pentecostalism and determining the central characteristics of Indian Pentecostalism is important in the context of this book precisely because many of the factors in the disproportionate targeting of Pentecostals are related to their distinctive characteristics. Moreover, for similar reasons, it is important that we attempt to clearly delineate what makes Pentecostals different from other kinds of Indian Christians. As the chapter argues, however, differentiating Indian Pentecostals from other Evangelicals is incredibly difficult, particularly because of the Pentecostalization of all forms of Indian Christianity.
Competition all the way down: How children learn word order cues to sentence meaning
Authors: Rowland Caroline F. , Noble Claire , Chan Angel
Published: January 2015

Most work on competing cues in language acquisition has focused on what happens when cues compete within a certain construction. There has been far less work on what happens when constructions themselves compete. This chapter aims to explore how the acquisition mechanism copes when constructions compete in a language. It presents three experimental studies, all of which focus on the acquisition of the syntactic function of word order as a marker of the Theme–Recipient relation in ditransitives. It concludes that there is not only competition between cues but competition between constructions from the very beginning of the language acquisition process.
Conflicting vs. convergent vs. interdependent motivations in morphology
Authors: Dressler Wolfgang U. , Libben Gary , Korecky‐Kröll Katharina
Published: January 2015

This chapter distinguishes among different types of competing motivations and discusses examples of competing motivations in morphology on its own (notably affix order and markedness vs. frequency) or in its interface either with the lexicon or with discourse (in compounding) or with phonology (in morphonotactics). It also discusses competing motivations in the context of investigations of first language acquisition and experiments on the acquisition and processing of actual vs. potential vs. illegal German plurals. It is concluded by discussing the implications of the nature of competing motivation in these different types of research for the notion of competing motivation in general and for the manner in which the resolution of conflict in language research can lead to the advancement of knowledge in linguistics and psycholinguistics.
Politeness distinctions in personal pronouns: A case study on competing motivations
Authors: Helmbrecht Johannes
Published: January 2015

Most European languages display politeness distinctions in personal pronouns similar to the one between the second‐person singular address pronouns tu (2SG) and vous (2SG.HON) in French. The goal of this chapter is to present a functional analysis of the emergence and diffusion of politeness distinctions in personal pronouns in terms of a competing motivations approach. First, the relevant functional motivations for this historical process will be identified in a criteria‐bound way. Second, it will be shown that the social or pragmatic functions—politeness (Brown and Levinson) and prestige—are in conflict with the cognitive/psychological factor of economy. It will be argued that the different degrees of grammatical integration of the polite pronouns into the pronominal paradigm of the respective languages may be explained by this conflict, not in terms of a winning and a losing factor but in terms of a compromise between the factors involved.
International to Domestic Price Transmission in Fourteen Developing Countries during the 2007–8 Food Crisis
Authors: Baltzer Kenneth
Published: January 2015

This chapter synthesizes the evidence on price transmission from international maize, rice and wheat markets to domestic markets in fourteen developing countries during the global food crisis in 2007–8. A great variation in the price transmission patterns is observed; from almost no price pass-through in China and India, over close relationship between international and domestic prices in Brazil and South Africa, to substantial domestic price overshooting in Ethiopia and Nigeria. Much of this variation can be explained by price stabilization policies, public policy failure, incomplete market integration, and coinciding domestic shocks.
The Political Economy of Food Price Policy in Kenya
Authors: Makau Nzuma Jonathan
Published: January 2015

This chapter evaluates Kenya’s food price crisis over 2002–11 using a political economy approach. Kenya’s food prices have been high and volatile relative to world food prices. Moreover, domestic food markets are highly integrated while about 30 per cent of the changes in world market prices are transmitted to domestic markets in Kenya. The study finds a relatively slow speed of adjustment of domestic food prices in Kenya of between three to five months. In response, the government implemented both supply-side and demand-side policies. However, the implementation of these policies has not been fully institutionalized and relies on the most part on the executive. These findings lend credence to calls to institutionalize the policy-making process in Kenya.
The Political Economy of Food Price Policy in Egypt
Authors: Farouk Ghoneim Ahmed
Published: January 2015

The study focuses on the period 2004–9 during which Egypt experienced food crisis. The political economy context on how the government responded to the crisis is analysed while pinpointing to what extent there was a pass-through effect from international to domestic prices. The complexity of food price policy issues and their entanglement with poverty, agricultural, and economic policies in Egypt together with the structural aspects of the food subsidy policies are discussed and evaluated from a political economy perspective. Prospects for reform or lack thereof are also analysed in the context of the 25 January 2011 revolution and new political set-up. Dramatic shifts in food prices and their significant impact on many variables implied that countries have been experiencing a new situation where the interaction of economic and social policies need to be altered to face this new challenge.
The Political Economy of Food Price Policy in Nigeria
Authors: Olomola Aderibigbe S.
Published: January 2015

The food crisis of 2008 in Nigeria was influenced by price changes in the world market and the escalation of the price of imported fuel into Nigeria which led to sharp increases in the prices of agricultural inputs and transportation cost. The soaring prices of food staples benefited the producers whereas there was a worsening of malnutrition among the poor. To cushion the effects within the short-term, the government released grains from the reserve, ordered the import of half a million tonnes of rice to be sold at a subsidized rate and suspended the tariff on rice imports. The short-term price reduction could not be sustained, however, due to food supply shortages, weakness of the Nigerian currency, and the poor implementation of projects.
Food Price Volatility and EU Policies
Authors: Swinnen Johan , Knops Louise , van Herck Kristine
Published: January 2015

Changes in global food prices have affected EU producers and consumers and have triggered policy reactions through the EU’s political process. In particular, the EU and member states responded by social policies to protect their consumers, attempts to regulate ‘speculation’ on agricultural commodities, revisions of sustainability requirements for biofuels, international development and food aid, and changes in the EU’s Common Agricultural Policy (CAP). With the exception of biofuel regulations, policy changes have been relatively limited and the effects on global food markets minor. The reasons are that the impact of global price volatility on EU consumers has been limited and the link between the CAP and the world market is much smaller than it was twenty years ago.
The Politics of What Works for the Poor in Public Expenditure and Taxation
Authors: Mosley Paul
Published: January 2015

This chapter examines which fiscal options work in terms of poverty reduction. It argues that although the poor, acting on their own, are politically weak, there are ways in which they can make themselves essential to the elite This in combination with relevant policies and institutions has enabled poverty, in some countries and regions, to fall dramatically. Nonetheless some have been excluded from this process. The chapter identifies the following areas of policy and institutional development as requiring further exploration and testing: (1) the distributional impact of public expenditure and taxation, with emphasis on the sectors of agriculture and social protection, and on the instruments of input subsidy and ‘progressive’ export taxation; (2) the politics of pro-poor coalitions, with emphasis on reforms of distributive justice as an instrument for achieving this; (3) the politics of escaping from the low-tax trap, with emphasis on the role of aid donors.
Governing Natural Resources for Inclusive Development
Authors: Bebbington Anthony
Published: January 2015

This chapter addresses institutional and political relationships that govern the interactions between natural resource extraction, economy and society with a focus on the mining and hydrocarbon sectors. These relationships help define the implications of resource extraction for democracy and the qualities of growth. On that basis it explores the conditions under which these relationships are likely to be reproduced or changed, and the ways in which they might mediate the interactions between extraction and inclusion. The chapter uses a framework that draws from two perspectives: political settlements, contentious politics, and the politics of ideas; and another that engages with the specific relationships of scale, space, and time. The implication is that any effort to understand the governance of extraction and of its relationships to development must be spatially and historically explicit.
China in Africa: Impacts and Prospects for Accountable Development
Authors: Mohan Giles
Published: January 2015

China is the major ‘new’ player in Africa and impacts on development and politics in numerous ways. The chapter sets out an analytical framework which identifies the channels through which China engages with African development and the role the African state plays in mediating these interactions. It applies this framework to three case studies that are emblematic of differing African state types. Analysis shows that China impacts on African development in multiple ways that go well beyond aid. A feature of this engagement is inter-elite brokerage which tends to bypass domestic channels of accountability and so undermines good governance. However, China usually delivers much-needed infrastructure which benefits wider society. Crucially, as civil and political society in Africa has started to contest this elitism, more transparent attempts to negotiate the relationship are visible. The chapter concludes with an outline of emerging trends and proposes themes for future research.
Transitions
Authors: Johnson Robert
Published: January 2015

In this chapter, Johnson analyses the processes and calculations that led to the British withdrawal from India and Pakistan in 1947–48. This was not simply a case of the British being driven out, but rather a combination of unrest in India and new priorities for the British at home, set against an exceptionally short timeline for transition. The deteriorating security situation illustrated the limitations of force, but also the inadequacy of the new administrations to agree on a political settlement. These left Britain with responsibilities it no longer had the power to discharge. Maintaining a good relationship with the successor governments was prioritized over former efforts to transfer power gradually. The war had transformed India dramatically, but transition, including the break-up of the security forces, took place amid shocking communal violence.
Transitioning in and out of COIN
Authors: Worrall James
Published: January 2015

This chapter explores Britain’s role in Oman, specifically from the start of its deepening involvement in the COIN campaign in the southern province of Dhofar in 1970 until the withdrawal of most of its military assets in 1976. There were a number of key transitions, both during this period and beyond, which this chapter identifies. This is accompanied by an examination of how decisions were made to pursue these transitions in the context of their in-depth understanding of conditions on the ground, as well as the wider interests and constraints operating on Britain at that time. The chapter also attempts to place the critical counter-insurgency period, 1970–1976, into a wider context of state-building, development programmes, and legitimacy building in order to show how transitions are best conducted through a relationship which has a much longer-term perspective than that associated with the usual narratives of exit, retreat, and withdrawal.
Political analysis and understanding in Afghanistan
Authors: King Anthony
Published: January 2015

For the last decade, the ISAF campaign has been prosecuted on the basis of a political conception of the Afghanistan initially articulated in the Bonn Accords and London Compact. The aim has been to connect a centralized, accountable, and democratic state with a unified population whose consent it has earned through the provision of security, governance, and development. Examining General McChrystal’s plan for the surge in 2009, Operation OMID, this chapter argues that the failure to recognize the patrimonialism of the Afghan political system has substantially undermined ISAF’s efforts. It proposes an alternative political strategy for transition.
Local and tactical political accommodation
Authors: Giustozzi Antonio
Published: January 2015

The chapter describes local deal-making between the Taliban insurgents and various branches of the Afghan government, including the army, police, security services, civilian officials, but also pro-government militias. Deal-making has been quite widespread since at least 2006, when the Taliban emerged as a major force. In some areas of government, such as education, deal-making has been particularly widespread. The chapter discusses the implications of this deal-making and concludes that it could favour either side, depending on the wider context. Once channels of communication are open, they can be exploited for different purposes. If the current stalemate between government and insurgents were to be broken, these channels of communication could favour a rapid collapse of the weaker side.
The changing role of contractors in security transition in Southern Afghanistan
Authors: Dunsby James
Published: January 2015

Dunsby argues that contractors have become more significant in Western military operations, but their role is not well understood. Having defined contractors and their role, Dunsby examines their contribution to the stabilization of southern Afghanistan, but notes that private contractors have been strangely absent from planning in transition. He acknowledges some of the problems with local contractors, difficult relationships with governments, and the business imperative for all companies, but argues that they have been useful in training local security forces, protection, and logistics. They may develop their coordination systems for reconstruction but re-tasking during withdrawal presents contractors with very similar problems as state organizations.
The other side of COIN
Authors: Clutterbuck Lindsay
Published: January 2015

This chapter reviews how the development of UK policing has been influenced by domestic and foreign counter-insurgencies and the need to interact with the military to counter them. It commenced in Ireland in the nineteenth century and then occurred extensively overseas. Police counter-insurgency techniques were used and developed in Palestine from 1921, then in Malaya and elsewhere after the Second World War and, by the 1970s, in Northern Ireland. The role of police in gathering human intelligence from within communities was central to COIN successes. However, in both Iraq and Afghanistan, building capacity in partner nation police forces was dominated by the military, thus minimizing the role of the UK police and producing negative consequences for both short-term COIN HUMINT requirements and the longer-term objective of creating an effective and sustainable local police force.
Introduction
Authors: Ringe Don , Taylor Ann
Published: January 2015

After a general introduction to the volume, this short chapter outlines some basic facts about Old English c. ad 900. The system of surface-contrastive sounds is described in detail, with discussion of controversial points and of indeterminacies in the orthography of the manuscripts. The system of morphosyntactic categories is described briefly in terms useful for an assessment of the linguistic typology of Old English. The attested dialects of the language and the documentation of the dialects are briefly outlined.
A grammatical sketch of Proto-West Germanic
Authors: Ringe Don , Taylor Ann
Published: January 2015

This chapter is a brief description of the phonology and morphology of Proto-West Germanic, as well as of several dialect divisions that already existed in that prehistoric speech community; it is meant to highlight the differences between Proto-Germanic (described in vol. i) and Proto-West Germanic as a result of the large number of distinctive West Germanic changes, and it also serves as a point of departure for the chapters that follow. The phonology of the language (which still resembled that of PGmc) is briefly described; the inflectional morphology is described in much greater detail, with sample paradigms. There is also a section on the PWGmc lexicon, listing lexemes and meanings unique to PWgmc, discussing productive innovations in word derivation, and considering in detail the Latin loanwords that can be ascribed to the period when the West Germanic dialects were still mutually intelligible dialects of a single language.
The separate prehistory of Old English: sound changes
Authors: Ringe Don , Taylor Ann
Published: January 2015

This very long chapter discusses and exemplifies in detail the important regular sound changes that occurred in the separate prehistory of Old English (down to about the year 900) and the phonological phenomena to which those sound changes gave rise. The relative chronology of those changes that can be shown to have interacted with each other is discussed fully. The more important changes are addressed in chronological order. The first few sections deal with those changes that can be shown to have preceded i-umlaut; a long section on i-umlaut follows, then substantial sections on syncope, apocope, and the changes that interacted with them. The last few sections deal with changes whose course can be traced in the earliest Old English documents, and with changes that affected only a few words.
The separate prehistory of Old English: morphological changes
Authors: Ringe Don , Taylor Ann
Published: January 2015

This chapter sketches the changes in inflectional morphology that occurred in the separate prehistory of Old English (down to about the year 900). These are far fewer, and less drastic in their overall effects, than the phonological changes, since many of the most important morphological changes had occurred in Proto-West Germanic or while its northern dialects were still diversifying. However, some of the Old English morphological changes require extensive discussion, especially the development of the third class of weak verbs, case syncretism and the syntactic merger of cases, and the substantial reduction in the inflectional classes of nouns.
Domains within words and their meanings
Authors: Anagnostopoulou Elena , Samioti Yota
Published: January 2015

The aim of this chapter is to investigate the conditions under which idiosyncratic meaning arises in word formation. It discusses the issue of (non-)compositionality of meaning on the basis of a case study, namely Greek ‘-menos’ participles and ‘-tos’ verbal adjectives denoting characteristic state, negation, and ability/possibility, and it uses these to test the Arad/Marantz hypothesis. These suffixes provide extensive evidence for attachment below vs. above higher heads. The chapter proposes that the domain for special meaning in single word idioms is larger than the first phase head.
Derivational affixes as roots
Authors: Lowenstamm Jean
Published: January 2015

This chapter proposes that English stress-shifting affixes are effectively transitive roots, rather than categorial labels. Thus, the domains of phonological rule application and spellout cannot be characterized usefully along the lines of + boundaries vs. # boundaries. Rather, phases, or domains for the application of phonological rules should instead be defined on roots.
Advanced statistical techniques: spatial patterns, life tables, modelling, and population viability analysis
Authors: Gibson David J.
Published: January 2015

This chapter moves forward from Chapter 7 (planning, choosing, and using statistics) and introduces some more advanced statistical methods that are of particular importance to plant population ecologists. The general goal of these methods is to quantify the spatiotemporal dynamics of plant populations. The basis for ecological modelling is described and advanced methods are described in four sections: first- and second-order spatial pattern analysis (including tessellation models); life table response experiments (LTREs), survivorship curves, and matrix models; cellular automata models, individual-based dynamic population models (e.g., SORTIE), and integral projection models (IPMs); and population viability analysis (PVA). Methods of spatial analysis are illustrated through use of a completely mapped plant dataset. Matrix models are illustrated through reanalysis of a published example. Recommended R packages for each method are provided.
Religion of a Different Color
Authors: Reeve W. Paul
Published: January 2015

The Protestant white majority in the nineteenth century was convinced that Mormonism represented a racial—not merely religious—departure from the mainstream, and they spent considerable effort attempting to substantiate their claims. At least some of that effort came through persistent attacks on the collective Mormon body: outsiders suggested that Mormons were physically different and racially more similar to marginalized groups than to white people. One Senate report argued that someone on the outside could distinguish a Mormon “at a glance,” especially because of the degenerate nature of their bodies. Medical doctors went so far as to suggest that Mormon polygamy had spawned a “new race” that represented a backward evolutionary descent into barbarism and savagery. Mormons responded with aspirations toward whiteness. It was a back-and-forth struggle between what outsiders imagined and what Mormons believed. Mormons ultimately emerged triumphant but not unscathed. At least a portion of the cost of their struggle came at the expense of their own black converts. Mormon leaders moved away from universalistic ideals toward segregated priesthood and temples—a story told here in gripping detail and based upon newly uncovered sources. So successful were Mormons at claiming whiteness for themselves, that by the time Mitt Romney sought the White House in 2012, he was labeled the whitest white man to run for office in recent memory. Mormons once again found themselves on the wrong side of white.
Red, White, and Mormon: White Indians
Authors: Reeve W. Paul
Published: January 2015

This chapter considers the ways in which Mormons were derisively labeled “white Indians.” Outsiders continued to imagine Mormon-Indian conspiracies against white America. Especially during the Utah War and Mountain Meadows massacre, outsiders suggested that Mormons dressed like Indians to commit murder and mayhem, an accusation that predated the massacre by at least seven years. It also evaluates Mormon efforts to marry among the Indians and the way in which outsiders imagined that effort producing degraded offspring. Mormons were sometimes conflated with Native Americans as a perceived threat to American democracy. Some people suggested that the best solution to the Mormon problem was the Indian solution.
Black, White, and Mormon: Miscegenation
Authors: Reeve W. Paul
Published: January 2015

This chapter considers the ways in which outsiders imagined Mormonism as facilitating race mixing. Race, as something ascribed from the outside, is the focus here, especially as a lack of information invited many dubious depictions and racial characterizations of Mormons. Political cartoons imagined interracial polygamous families among Mormons and suggested that polygamy was darkening the white race and making it unfit for democracy. By the end of the century the “Mormon coon” emerged as a culture discourse to define a philandering black man. Mormonism in these depictions was associated with miscegenation and, as a result, was seen as a threat to American democracy.
Serum Uric Acid and Pulse Wave Velocity Among Healthy Adults: Baseline Data From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Baena Cristina Pellegrino , Lotufo Paulo Andrade , Mill José Geraldo , Cunha Roberto de Sa , Benseñor Isabela J
Published: January 2015

BACKGROUND

We aimed to evaluate a possible association between serum uric acid (SUA) levels and carotid-to-femoral pulse wave velocity (cf-PWV) among healthy participants of the ELSA-Brasil.

METHODS

We excluded subjects using antihypertensive medication, diuretics, allopurinol, binge drinkers, body mass index (BMI) >35kg/m2, and those with history of cardiovascular diseases (CVD). In a cross-sectional and sex-specific analysis, linear regression models were built having cf-PWV as dependent variable and SUA as independent variable. Multiple adjustments were subsequently made for age, heart rate and blood pressure, BMI, and fasting glucose levels as covariates. Product interaction terms were built to test interaction between SUA and other covariates.

RESULTS

We analyzed 1,875 men and 1,713 women (mean ages, 48.9±8.4 and 50.2±8.7 years, respectively). SUA was linearly associated with cf-PWV in men (P = 0.01) and in women (P = 0.01). After full adjustment, the association remained significant for men (P = 0.01) and no longer significant for women (P = 0.10). Fully adjusted linear coefficients β (95% CI) were 0.06 (0.015; 0.112) and 0.04 (−0.01; 0.12) in men and women, respectively. Significant interaction between SUA and age (P = 0.02) fasting glucose (P < 0.01) and BMI (P = 0.02) was found only for women.

CONCLUSION

In an apparently healthy population, SUA was significantly associated to cf-PWV in men but not in women.
MethylMix: an R package for identifying DNA methylation-driven genes
Authors: Gevaert Olivier
Published: January 2015

Summary: DNA methylation is an important mechanism regulating gene transcription, and its role in carcinogenesis has been extensively studied. Hyper and hypomethylation of genes is an alternative mechanism to deregulate gene expression in a wide range of diseases. At the same time, high-throughput DNA methylation assays have been developed generating vast amounts of genome wide DNA methylation measurements. Yet, few tools exist that can formally identify hypo and hypermethylated genes that are predictive of transcription and thus functionally relevant for a particular disease. To accommodate this lack of tools, we developed MethylMix, an algorithm implemented in R to identify disease specific hyper and hypomethylated genes. MethylMix is based on a beta mixture model to identify methylation states and compares them with the normal DNA methylation state. MethylMix introduces a novel metric, the ‘Differential Methylation value’ or DM-value defined as the difference of a methylation state with the normal methylation state. Finally, matched gene expression data are used to identify, besides differential, transcriptionally predictive methylation states by focusing on methylation changes that effect gene expression.

Availability and implementation: MethylMix was implemented as an R package and is available in bioconductor.

Contact:  olivier.gevaert@stanford.edu
dslice: an R package for nonparametric testing of associations with application in QTL and gene set analysis
Authors: Ye Chao , Jiang Bo , Zhang Xuegong , Liu Jun S.
Published: January 2015

Summary : Many statistical problems in bioinformatics and genetics can be formulated as the testing of associations between a categorical variable and a continuous variable. A dynamic slicing method was proposed for non-parametric dependence testing, which has been demonstrated to have higher powers compared with traditional methods such as Kolmogorov–Smirnov test. We introduce an R package dslice to facilitate the use of dynamic slicing method in bioinformatic applications such as quantitative trait loci study and gene set enrichment analysis.

Availability and implementation : dslice is implemented in Rcpp and available in the Comprehensive R Archive Network. The package is distributed under the GNU General Public License (version 2 or later).

Contact : zhangxg@tsinghua.edu.cn or jliu@stat.harvard.edu .
Topology-function conservation in protein–protein interaction networks
Authors: Davis Darren , Yaveroğlu Ömer Nebil , Malod-Dognin Noël , Stojmirovic Aleksandar , Pržulj Nataša
Published: January 2015

Motivation: Proteins underlay the functioning of a cell and the wiring of proteins in protein–protein interaction network (PIN) relates to their biological functions. Proteins with similar wiring in the PIN (topology around them) have been shown to have similar functions. This property has been successfully exploited for predicting protein functions. Topological similarity is also used to guide network alignment algorithms that find similarly wired proteins between PINs of different species; these similarities are used to transfer annotation across PINs, e.g. from model organisms to human. To refine these functional predictions and annotation transfers, we need to gain insight into the variability of the topology-function relationships. For example, a function may be significantly associated with specific topologies, while another function may be weakly associated with several different topologies. Also, the topology-function relationships may differ between different species.

Results: To improve our understanding of topology-function relationships and of their conservation among species, we develop a statistical framework that is built upon canonical correlation analysis. Using the graphlet degrees to represent the wiring around proteins in PINs and gene ontology (GO) annotations to describe their functions, our framework: (i) characterizes statistically significant topology-function relationships in a given species, and (ii) uncovers the functions that have conserved topology in PINs of different species, which we term topologically orthologous functions. We apply our framework to PINs of yeast and human, identifying seven biological process and two cellular component GO terms to be topologically orthologous for the two organisms.

Availability and implementation:  http://bio-nets.doc.ic.ac.uk/goCCA.zip

Contact:  natasha@imperial.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Isoniazid treatment to prevent TB in kidney and pancreas transplant recipients based on an interferon-γ-releasing assay: an exploratory randomized controlled trial
Authors: Kim Sung-Han , Lee Sang-Oh , Park In-Ah , Kim Sun-Mi , Park Su Jin , Yun Sung-Cheol , Jung Joo Hee , Shin Sung , Kim Young Hoon , Choi Sang-Ho , Kim Yang Soo , Woo Jun Hee , Park Su-Kil , Park Jung Sik , Han Duck Jong
Published: January 2015

Background

We performed a randomized trial of isoniazid treatment based on interferon-γ-releasing assay (IGRA) in kidney transplant (KT) recipients in an intermediate-TB-burden country.

Methods

All adult patients admitted to a KT institute between June 2010 and May 2013 were enrolled. The IGRA (T-SPOT.TB assay) was performed on all patients, and isoniazid treatment was given to those with clinical risk factors for latent TB infection (LTBI). Patients with positive IGRA who had no clinical risk factors for LTBI were randomly assigned to isoniazid treatment or a control group. The development of TB after KT was monitored between June 2010 and November 2013. The primary endpoint was the development of TB.

Results

Of the 784 patients who had no clinical risk factors for LTBI, 445 (57%) gave negative results in the IGRA, 76 (10%) indeterminate results and 263 (33%) positive results. Of the latter, 131 were allocated to isoniazid treatment and 132 to the control group. Three (2%) of the control group developed TB, whereas none of the isoniazid treatment group developed TB (rate difference 1.22 per 100 person-years, P = 0.09). Of the 521 patients with negative or indeterminate IGRA results, 4 [0.8%, 0.43 per 100 person-years (95% CI 0.12–1.09)] developed TB after KT.

Conclusions

IGRA-based isoniazid treatment has a trend towards reducing TB development in KT recipients without clinical risk factors, but careful monitoring of TB development is needed in negative-IGRA KT recipients.
Performance of commonly used genotypic assays and comparison with phenotypic assays of HIV-1 coreceptor tropism in acutely HIV-1-infected patients
Authors: Ceresola Elisa Rita , Nozza Silvia , Sampaolo Michela , Pignataro Angela Rosa , Saita Diego , Ferrarese Roberto , Ripa Marco , Deng Wenjie , Mullins James I. , Boeri Enzo , Tambussi Giuseppe , Toniolo Antonio , Lazzarin Adriano , Clementi Massimo , Canducci Filippo
Published: January 2015

Objectives

Although founder viruses in primary HIV-1 infections (PHIs) typically use the CCR5 coreceptor (R5-tropic), 3%–19% of subjects also harbour CXCR4-using viruses (X4-tropic), making tropism determination before CCR5 antagonist usage mandatory. Genotypic methods can be used to accurately determine HIV-1 tropism in chronically infected patients.

Methods

We compared the results of genotypic methods [geno2pheno, PSSMx4r5 including a novel nucleotide-input version (ntPSSM) and distant segments (ds)Kernel] to predict coreceptor usage in a cohort of 67 PHIs. Specimens with discrepant results were phenotypically tested after cloning the V3 gene region into proviral backbones. Recombinant viruses were used to infect U87 indicator cell lines bearing CD4 and either CCR5 or CXCR4.

Results

Geno2pheno10%, PSSMx4r5 and (ds)Kernel gave identical predictions in 85% of cases. Geno2pheno10% predicted the presence of CXCR4 viruses in 18% of patients. Two patients were predicted to carry X4-tropic viruses by all algorithms and X4-tropic viruses were detected in at least one of the recombinant AD8 or NL4-3 backbone-based assays. Ten samples resulted in discordant predictions with at least one algorithm. Full concordance between tropism prediction by using population sequencing and phenotypic assays was observed only with ntPSSM. Geno2pheno prediction and the phenotypic assay gave the same results in a minority of ‘discordant’ patients.

Conclusions

Compared with both PSSMx4r5 versions, (ds)Kernel and our phenotypic assay, geno2pheno10% overestimated the frequency of X4-tropic viruses (18% versus 3%). ntPSSM was able to detect one additional X4 virus compared with (ds)Kernel that was confirmed with the phenotypic assay.
Global Oct4 target gene analysis reveals novel downstream PTEN and TNC genes required for drug-resistance and metastasis in lung cancer
Authors: Tang Yen-An , Chen Chi-Hsin , Sun H. Sunny , Cheng Chun-Pei , Tseng Vincent S. , Hsu Han-Shui , Su Wu-Chou , Lai Wu-Wei , Wang Yi-Ching
Published: January 2015

Overexpression of Oct4, a stemness gene encoding a transcription factor, has been reported in several cancers. However, the mechanism by which Oct4 directs transcriptional program that leads to somatic cancer progression remains unclear. In this study, we provide mechanistic insight into Oct4-driven transcriptional network promoting drug-resistance and metastasis in lung cancer cell, animal and clinical studies. Through an integrative approach combining our Oct4 chromatin-immunoprecipitation sequencing and ENCODE datasets, we identified the genome-wide binding regions of Oct4 in lung cancer at promoter and enhancer of numerous genes involved in critical pathways which promote tumorigenesis. Notably, PTEN and TNC were previously undefined targets of Oct4. In addition, novel Oct4-binding motifs were found to overlap with DNA elements for Sp1 transcription factor. We provided evidence that Oct4 suppressed PTEN in an Sp1-dependent manner by recruitment of HDAC1/2, leading to activation of AKT signaling and drug-resistance. In contrast, Oct4 transactivated TNC independent of Sp1 and resulted in cancer metastasis. Clinically, lung cancer patients with Oct4 high, PTEN low and TNC high expression profile significantly correlated with poor disease-free survival. Our study reveals a critical Oct4-driven transcriptional program that promotes lung cancer progression, illustrating the therapeutic potential of targeting Oc4 transcriptionally regulated genes.
Metabolic Imaging Using Proton Magnetic Spectroscopy as a Predictor of Outcome After Surgery for Cervical Spondylotic Myelopathy
Authors: Holly Langston T. , Ellingson Benjamin M. , Salamon Noriko
Published: January 2015

Study Design:

A single-center magnetic resonance spectroscopy (MRS) imaging and surgical outcome study involving 16 patients with cervical spondylotic myelopathy (CSM).

Objective:

In the present study, we assess the utility of MRS to quantify metabolic changes within the spinal cord and predict surgical outcome in CSM patients.

Summary of Background Data:

MRS is an advanced spinal imaging modality that can provide pertinent metabolic and biochemical information regarding spinal cord function. Previous studies have demonstrated significant abnormalities in specific cellular metabolite concentrations in CSM patients.

Methods:

Sixteen patients with CSM were evaluated. Single voxel MRS was performed in the cervical cord. N-acetyl-aspartate (NAA) and choline metabolite concentration ratios with respect to creatine were quantified, as well as the presence or absence of a lactate peak. The modified Japanese Orthopaedic Association (mJOA) scale was used as the functional assessment measure. Correlation of MRS metabolites with change in mJOA score was performed.

Results:

The mean follow-up time was 19 months. There was a statistically significant improvement between mean preoperative and postoperative mJOA score after surgery (P<0.0001). The NAA/Cr ratio demonstrated a significant relationship to the change in mJOA score after surgery (P=0.0479; R
2=0.2513). The Cho/NAA ratio demonstrated an even stronger correlation with the change in mJOA score after surgery (P=0.0065; R
2=0.4219). Neither the Cho/Cr ratio, nor the presence of a lactate peak or T2-weighted signal change was significantly correlated with change in mJOA score after surgery.

Conclusions:

MRS is a novel, noninvasive imaging modality that provides pertinent information regarding spinal cord cellular and metabolic function. In a cohort of operatively treated CSM patients, the NAA/Cr and Cho/NAA ratios were predictive of neurological outcome, as both were significantly associated with change in mJOA score after surgery.
Management of Ingested Foreign Bodies in Children
Authors: Kramer Robert E. , Lerner Diana G. , Lin Tom , Manfredi Michael , Shah Manoj , Stephen Thomas C. , Gibbons Troy E. , Pall Harpreet , Sahn Ben , McOmber Mark , Zacur George , Friedlander Joel , Quiros Antonio J. , Fishman Douglas S. , Mamula Petar
Published: January 2015

Foreign body ingestions in children are some of the most challenging clinical scenarios facing pediatric gastroenterologists. Determining the indications and timing for intervention requires assessment of patient size, type of object ingested, location, clinical symptoms, time since ingestion, and myriad other factors. Often the easiest and least anxiety‐producing decision is the one to proceed to endoscopic removal, instead of observation alone. Because of variability in pediatric patient size, there are less firm guidelines available to determine which type of object will safely pass, as opposed to the clearer guidelines in the adult population. In addition, the imprecise nature of the histories often leaves the clinician to question the timing and nature of the ingestion. Furthermore, changes in the types of ingestions encountered, specifically button batteries and high‐powered magnet ingestions, create an even greater potential for severe morbidity and mortality among children. As a result, clinical guidelines regarding management of these ingestions in children remain varied and sporadic, with little in the way of prospective data to guide their development. An expert panel of pediatric endoscopists was convened and produced the present article that outlines practical clinical approaches to the pediatric patient with a variety of foreign body ingestions. This guideline is intended as an educational tool that may help inform pediatric endoscopists in managing foreign body ingestions in children. Medical decision making, however, remains a complex process requiring integration of clinical data beyond the scope of these guidelines. These guidelines should therefore not be considered to be a rule or to be establishing a legal standard of care. Caregivers may well choose a course of action outside of those represented in these guidelines because of specific patient circumstances. Furthermore, additional clinical studies may be necessary to clarify aspects based on expert opinion instead of published data. Thus, these guidelines may be revised as needed to account for new data, changes in clinical practice, or availability of new technology.
A social insect fertility signal is dependent on chemical context
Authors: Smith Adrian A. , Millar Jocelyn G. , Suarez Andrew V.
Published: January 2015

Identifying group members and individuals' status within a group are fundamental tasks in animal societies. For ants, this information is coded in the cuticular hydrocarbon profile. We manipulated profiles of the ant
Odontomachus brunneus
to examine whether the releaser and primer effects of fertility signals are dependent on chemical context. Fertility status is signalled through increased abundance of (
Z
)-9-nonacosene (
Z
9 : C
29
). Across the ant's distribution, populations have distinct hydrocarbon profiles but the fertility signal is conserved. Foreign queens and fertility-signal-treated workers from the same population, sharing a similar chemical background, elicited releaser effects from workers, whereas queens and fertility-signal-treated workers from different populations did not.
Z
9 : C
29
presented without chemical background did not elicit releaser effects. A primer-effect experiment found that
Z
9 : C
29
, presented without a chemical background, did not inhibit worker reproduction. Our results demonstrate that a familiar chemical background is necessary for appropriate responses to fertility signals.
Generalist–specialist trade-off during thermal acclimation
Authors: Seebacher Frank , Ducret Varlérie , Little Alexander G. , Adriaenssens Bart
Published: January 2015

The shape of performance curves and their plasticity define how individuals and populations respond to environmental variability. In theory, maximum performance decreases with an increase in performance breadth. However, reversible acclimation may counteract this generalist–specialist trade-off, because performance optima track environmental conditions so that there is no benefit of generalist phenotypes. We tested this hypothesis by acclimating individual mosquitofish (
Gambusia holbrooki
) to cool and warm temperatures consecutively and measuring performance curves of swimming performance after each acclimation treatment. Individuals from the same population differed significantly in performance maxima, performance breadth and the capacity for acclimation. As predicted, acclimation resulted in a shift of the temperature at which maximal performance occurred. Within acclimation treatments, there was a significant generalist–specialist trade-off in responses to acute temperature change. Surprisingly, however, there was also a trade-off across acclimation treatments, and animals with greater capacity for cold acclimation had lower performance maxima under warm conditions. Hence, cold acclimation may be viewed as a generalist strategy that extends performance breadth at the colder seasons, but comes at the cost of reduced performance at the warmer time of year. Acclimation therefore does not counteract a generalist–specialist trade-off and, at least in mosquitofish, the trade-off seems to be a system property that persists despite phenotypic plasticity.
Protein and carbohydrate intake influence sperm number and fertility in male cockroaches, but not sperm viability
Authors: Bunning Harriet , Rapkin James , Belcher Laurence , Archer C. Ruth , Jensen Kim , Hunt John
Published: January 2015

It is commonly assumed that because males produce many, tiny sperm, they are cheap to produce. Recent work, however, suggests that sperm production is not cost-free. If sperm are costly to produce, sperm number and/or viability should be influenced by diet, and this has been documented in numerous species. Yet few studies have examined the exact nutrients responsible for mediating these effects. Here, we quantify the effects of protein (P) and carbohydrate (C) intake on sperm number and viability in the cockroachNauphoeta cinerea, as well as the consequences for male fertility. We found the intake of P and C influenced sperm number, being maximized at a high intake of diets with a P : C ratio of 1 : 2, but not sperm viability. The nutritional landscapes for male fertility and sperm number were closely aligned, suggesting that sperm number is the major determinant of male fertility inN. cinerea. Under dietary choice, males regulate nutrient intake at a P : C ratio of 1 : 4.95, which is midway between the ratios needed to maximize sperm production and pre-copulatory attractiveness in this species. This raises the possibility that males regulate nutrient intake to balance the trade-off between pre- and post-copulatory traits in this species.