bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges and obstacles related to solving the codon bias riddles
Authors: Tuller Tamir
Published: January 2014

Dozens of papers have been written about the relationship between codon bias, transcript features and gene translation. Even though answering these questions may sound straightforward, apparently many of these studies seem to contradict each other. In the present article, I provide four major non-mutually exclusive explanations related to this issue: (i) there are dozens of related relevant variables with unknown causal relationships; (ii) various biases in the relevant experimental data; (iii) drawing conclusions from specific examples; and (iv) challenges in experimentally modifying one biological variable without affecting the system via multiple biological feedback mechanisms. Specifically, some of the contradictions can be settled when considering these four points and/or via a multidisciplinary approach. The discussion reported in the present article is also relevant to many other biological/medical questions/fields.
Functions of inorganic polyphosphates in eukaryotic cells: a coat of many colours
Authors: Azevedo Cristina , Saiardi Adolfo
Published: January 2014

PolyP (inorganic polyphosphate) is a linear polymer of tens to hundreds of orthophosphate residues linked by high-energy phosphoanhydride bonds. This polymer is present in all living organisms from bacteria to mammals. Until recently, most of the studies on polyP have focused on its function in prokaryotes. In prokaryotes, polyP has been implicated in many unrelated processes ranging from basic metabolism to structural functions. However, polyP analysis and function in higher eukaryotes has been gaining momentum recently. In the present review, we mainly aim to discuss the proposed intracellular functions of polyP in higher eukaryotes and its detection methods.
Tight junction regulation through vesicle trafficking: bringing cells together
Authors: Fletcher Sarah J. , Rappoport Joshua Z.
Published: January 2014

Epithelial layers are integral for many physiological processes and are maintained by intercellular adhesive structures. During disease, these structures can disassemble, leading to breakdown of epithelia. TJs (tight junctions) are one type of intercellular adhesion. Loss of TJs has been linked to the pathogenesis of many diseases. The present review focuses on the role of vesicle trafficking in regulation of TJs, in particular trafficking of the TJ protein occludin. We examine how endocytosis and endosomal recycling modulate occludin localization under steady-state conditions and during stimulated TJ disassembly.
Rethinking the clockwork: redox cycles and non-transcriptional control of circadian rhythms
Authors: Wu Lisa , Reddy Akhilesh B.
Published: January 2014

Circadian rhythms are a hallmark of living organisms, observable in all walks of life from primitive bacteria to highly complex humans. They are believed to have evolved to co-ordinate the timing of biological and behavioural processes to the changing environmental needs brought on by the progression of day and night through the 24-h cycle. Most of the modern study of circadian rhythms has centred on so-called TTFLs (transcription–translation feedback loops), wherein a core group of ‘clock’ genes, capable of negatively regulating themselves, produce oscillations with a period of approximately 24 h. Recently, however, the prevalence of the TTFL paradigm has been challenged by a series of findings wherein circadian rhythms, in the form of redox reactions, persist in the absence of transcriptional cycles. We have found that circadian cycles of oxidation and reduction are conserved across all domains of life, strongly suggesting that non-TTFL mechanisms work in parallel with the canonical genetic processes of timekeeping to generate the cyclical cellular and behavioural phenotypes that we commonly recognize as circadian rhythms.
mRNA deadenylation by Pan2–Pan3
Authors: Wolf Jana , Passmore Lori A.
Published: January 2014

Poly(A) tails are important regulators of mRNA stability and translational efficiency. Cytoplasmic removal of poly(A) tails by 3′→5′ exonucleases (deadenylation) is the rate-limiting step in mRNA degradation. Two exonuclease complexes contribute the majority of the deadenylation activity in eukaryotes: Ccr4–Not and Pan2–Pan3. These can be specifically recruited to mRNA to regulate mRNA stability or translational efficiency, thereby fine-tuning gene expression. In the present review, we discuss the activities and roles of the Pan2–Pan3 deadenylation complex.
Recent advances in the structural molecular biology of Ets transcription factors: interactions, interfaces and inhibition
Authors: Cooper Christopher D.O. , Newman Joseph A. , Gileadi Opher
Published: January 2014

The Ets family of eukaryotic transcription factors is based around the conserved Ets DNA-binding domain. Although their DNA-binding selectivity is biochemically and structurally well characterized, structures of homodimeric and ternary complexes point to Ets domains functioning as versatile protein-interaction modules. In the present paper, we review the progress made over the last decade to elucidate the structural mechanisms involved in modulation of DNA binding and protein partner selection during dimerization. We see that Ets domains, although conserved around a core architecture, have evolved to utilize a variety of interaction surfaces and binding mechanisms, reflecting Ets domains as dynamic interfaces for both DNA and protein interaction. Furthermore, we discuss recent advances in drug development for inhibition of Ets factors, and the roles structural biology can play in their future.
HDX-MS takes centre stage at unravelling kinase dynamics
Authors: Lorenzen Kristina , Pawson Tony
Published: January 2014

In recent years, HDX-MS (hydrogen–deuterium exchange coupled to MS) on biomolecules has evolved from a niche technique to a powerful method in the investigation of protein dynamics. Protein kinases, in particular, represent an area of active study using this technique owing to their well-characterized protein structures and their relevance to diseases such as cancer, immune disorders and neurodegenerative defects. In the present review, we describe how HDX-MS has revealed important dynamic properties of protein kinases and provided insight into the mechanisms of drug binding.
Control and regulation of mRNA translation
Authors: Mead Emma J. , Masterton Rosalyn J. , von der Haar Tobias , Tuite Mick F. , Smales C. Mark
Published: January 2014

Translational control is central to the gene expression pathway and was the focus of the 2013 annual Translation UK meeting held at the University of Kent. The meeting brought together scientists at all career stages to present and discuss research in the mRNA translation field, with an emphasis on the presentations on the research of early career scientists. The diverse nature of this field was represented by the broad range of papers presented at the meeting. The complexity of mRNA translation and its control is emphasized by the interdisciplinary research approaches required to address this area with speakers highlighting emerging systems biology techniques and their application to understanding mRNA translation and the network of pathways controlling it.
Rho-GTPase-regulated vesicle trafficking in plant cell polarity
Authors: Chen Xu , Friml Jiří
Published: January 2014

ROPs (Rho of plants) belong to a large family of plant-specific Rho-like small GTPases that function as essential molecular switches to control diverse cellular processes including cytoskeleton organization, cell polarization, cytokinesis, cell differentiation and vesicle trafficking. Although the machineries of vesicle trafficking and cell polarity in plants have been individually well addressed, how ROPs co-ordinate those processes is still largely unclear. Recent progress has been made towards an understanding of the co-ordination of ROP signalling and trafficking of PIN (PINFORMED) transporters for the plant hormone auxin in both root and leaf pavement cells. PIN transporters constantly shuttle between the endosomal compartments and the polar plasma membrane domains, therefore the modulation of PIN-dependent auxin transport between cells is a main developmental output of ROP-regulated vesicle trafficking. The present review focuses on these cellular mechanisms, especially the integration of ROP-based vesicle trafficking and plant cell polarity.
Study on the effect of artificial radiation simulating terrestrial solar ultraviolet radiation on negative DC discharge performance of air gap
Authors: Lichun Shu , Zhangang Yang , Xingliang Jiang , Qin Hu , Zongkui Qiu
Published: January 2014

It is important to reveal the effect of terrestrial solar ultraviolet radiation (TSUVR) on discharge performance of external insulation for the design and operation of a power system in regions with strong TSUVR, especially in Tibet. However, no research was carried out in this field until now. In this study, an artificial UV lamp was used to imitate TSUVR in the relevant experiments to research on the effect of negative DC discharge. It was found that artificial radiation simulating terrestrial solar UV radiation (STSUVR) does not affect appreciably the negative DC corona characteristics and breakdown voltage of short rod‐plane air gaps of several electrode materials. That is because the wavelength of the STSUVR is in the range of 290–400 nm, and its intensity is less than 200 W/m2. Thus, air, Cu and Fe cannot be photoionised by STSUVR. There is also no effect of the STSUVR on arc propagation because of energy. Although a part of the photons in the TSUVR has higher energy than the work function of Al, it is very easy for the Al to be oxidised, and the oxide film (Al2O3) can prevent Al from being ionised by TSUVR. Therefore the TSUVR does not have an obvious effect on negative DC discharge performance of air gap.
Two‐stage power network reconfiguration strategy considering node importance and restored generation capacity
Authors: Zhang Can , Lin Zhenzhi , Wen Fushuan , Ledwich Gerard , Xue Yusheng
Published: January 2014

Network reconfiguration after complete blackout of a power system is an essential step for power system restoration. A new node importance evaluation method is presented based on the concept of regret, and maximisation of the average importance of a path is employed as the objective of finding the optimal restoration path. Then, a two‐stage method is presented to optimise the network reconfiguration strategy. Specifically, the restoration sequence of generating units is first optimised so as to maximise the restored generation capacity, then the optimal restoration path is selected to restore the generating nodes concerned and the issues of selecting a serial or parallel restoration mode and the reconnecting failure of a transmission line are next considered. Both the restoration path selection and skeleton‐network determination are implemented together in the proposed method, which overcomes the shortcoming of separate decision‐making in the existing methods. Finally, the New England 10‐unit 39‐bus power system and the Guangzhou power system in South China are employed to demonstrate the basic features of the proposed method.
Autonomous operation of distributed storages in microgrids
Authors: Loh Poh Chiang , Chai Yi Kai , Li Ding , Blaabjerg Frede
Published: January 2014

Operation of distributed generators in microgrids has been widely discussed, but would not be fully autonomous if distributed energy storages are not considered. Storages are important since they provide energy buffering to load changes, energy levelling to source variations and ride‐through enhancement to the microgrids. Recognising their importance, this study presents a scheme for sharing power among multiple distributed storages in coordination with the distributed sources and loads. The scheme prompts the storages to autonomously sense for local operating conditions, requesting for maximum charging energy only when excess generation capacity is available. As generation capacity drops or demand increases, energy drawn by the storages decreases spontaneously to avoid over‐stressing the sources. When full generation capacity is near, the storages will automatically release their stored energy to help with meeting the extra load demand. The described process takes place autonomously with energy eventually shared among the storages in proportion to their ratings. To test the concepts discussed, experiments have been performed with favourable results obtained for performance verification.
Study of safety operation of AC resistance spot welding system
Authors: Zhou Kang , Cai Lilong
Published: January 2014

This study deals with the safety operation of AC resistance spot welding (RSW) system. The input of the RSW system is the firing angle of the silicon‐controlled rectifier (SCR) during each control cycle. Wrongly choosing a firing angle may induce disastrous consequence. The range of firing angle depends on the system's power factor angle; the relation between the firing angle, power factor angle and conduction angle is highly non‐linear. After comparing three methods, a simple mathematical model is proposed in this study to facilitate the online calculation of the power factor angle and selection of the proper firing angle, so that the safety operation of RSW system can be guaranteed. In this condition, the RSW machine can work at the machine's the most capacity, the calculated value of power factor angle should be the lowest limit for actual selected firing angle of SCR. Finally, experimental results confirmed the effectiveness of the proposed mathematical model.
From Rhetoric to Reality: Which Resilience, Why Resilience, and Whose Resilience in Spatial Planning?
Authors: White Iain , O'Hare Paul
Published: January 2014

This paper analyses contrasting academic understandings of ‘equilibrium resilience’ and ‘evolutionary resilience’ and investigates how these nuances are reflected within both policy and practice. We reveal that there is a lack of clarity in policy, where these differences are not acknowledged with resilience mainly discussed as a singular, vague, but optimistic aim. This opaque political treatment of the term and the lack of guidance has affected practice by privileging an equilibrist interpretation over more transformative, evolutionary measures. In short, resilience within spatial planning is characterised by a simple return to normality that is more analogous with planning norms, engineered responses, dominant interests, and technomanagerial trends. The paper argues that, although presented as a possible paradigm shift, resilience policy and practice underpin existing behaviour and normalise risk. It leaves unaddressed wider sociocultural concerns and instead emerges as a narrow, regressive, technorational frame centred on reactive measures at the building scale.
Dopamine prediction error responses integrate subjective value from different reward dimensions
Authors: Lak Armin , Stauffer William R. , Schultz Wolfram
Published: January 2014

Significance

Most real-world rewards have multiple dimensions, such as amount, risk, and type. Here we show that within a bounded set of such multidimensional rewards monkeys’ choice behavior fulfilled several core tenets of rational choice theory; namely, their choices were stochastically complete and transitive. As such, in selecting between rewards, the monkeys behaved as if they maximized value on a common scale. Dopamine neurons encoded prediction errors that reflected that scale. A particular reward dimension influenced dopamine activity only to the extent that it influenced choice. Thus, vastly different reward types such as juice and food activated dopamine neurons in accordance with subjective value derived from the different rewards. This neuronal signal could serve to update value signals for economic choice.
Structure of sugar-bound LacY
Authors: Kumar Hemant , Kasho Vladimir , Smirnova Irina , Finer-Moore Janet S. , Kaback H. Ronald , Stroud Robert M.
Published: January 2014

Significance

The lactose permease of
Escherichia coli
(LacY), a model for the major facilitator superfamily, catalyzes the symport of a galactopyranoside and an H
+
across the membrane by a mechanism in which the sugar-binding site in the middle of the protein becomes alternately accessible to either side of the membrane. However, all X-ray structures thus far show LacY in an inward-facing conformation with a tightly sealed periplasmic side. Significantly, by using a double-Trp mutant, we now describe an almost occluded, outward-open conformation with bound sugar, confirming more than two decades of biochemical and biophysical findings. We also present evidence that protonated LacY specifically binds D-galactopyranosides, inducing an occluded state that can open to either side of the membrane.
Violence in Acute Psychiatric Patients: A Cumulative Increased Risk with Polysubstance Abuse?
Authors: Fosse Roar , Olsen BrittMarie , Bjørkly Stål
Published: January 2014

While comorbidity of serious mental illness (SMI) and substance abuse increases violence risk, less is known about additional effects of multiple substance abuse. By using a check list, data on substance abuse, violence, diagnoses, and Perceived Threat Control Override symptoms (TCO) were extracted from electronic patient files in 146 male patients who were extensive users of acute psychiatric services. Variables that were significant in univariate analysis were entered into a stepwise multivariate regression analysis. Odds ratios for violence increased from 5.3 in patients who abused one substance to 153.4 with the abuse of four or five substances (Step 1). The effect was moderated in Step 2 by having a diagnosis of mood disorder (OR = .17). In Step 3, only a trend indicated that one TCO component, “others control my thoughts and feelings,” increased the risk of violence (OR = 3.7). The positive effect sizes for polysubstance abuse were about two times larger in Step 3 than in Step 1. The findings indicate that including the number of abused substances may improve violence risk assessment in patients with SMI.
Assessment and Support Consultation: Enhancing Social Support for Sexual Offenders
Authors: Hawkins Katherine , Eddie David
Published: January 2014

Social support is a known predictor of both sexual offender recidivism (Andrews & Bonta, 2010) and client recovery from numerous clinical disorders (Drake, O’Neal, & Wallach, 2008; Schön, Denhov, & Topor, 2009). Interventions that engage social supports have demonstrated positive outcomes in many clinical treatments for a wide range of psychopathologies (Rea et al., 2003; Shimazu et al., 2011), but have not yet been broadly incorporated into forensic practice. Furthermore, some criminogenic risk assessment measures do not routinely seek collateral information from social supports, despite the benefits of doing so (Bonta, 2002; Doren, 2004). This article reviews extant work, and proposes a methodology—Assessment and Support Consultation (ASC)—aimed at bringing support systems into the sexual offender assessment and treatment milieu. Aims for this model and suggestions for its development and implementation are discussed.
The Validity of the Short-Term Assessment of Risk and Treatability (START) in a UK Medium Secure Forensic Mental Health Service
Authors: Quinn Rachel , Miles Helen , Kinane Catherine
Published: January 2014

This study aimed to evaluate the validity of the Short-Term Assessment of Risk and Treatability (START) within a UK medium-secure hospital (665 STARTs derived from N = 80 individuals). Findings showed that START Total Vulnerability and Mean Risk Rating Scores were significantly predictive of Total Aversive incidents at one month, decreasing over time to a nonsignificant small/medium effect at six months. START Total Strength Scores were not predictive at any time point. START scores could discriminate between mentally disordered offenders at different stages of their care-pathway. Females were rated as having significantly less strengths and more risks than males. The START correlates with the HCR-20 and HoNOS Secure, and a crude cost analysis was undertaken. These results suggest that the START is a valid tool in this population.
Response of White Seabass to Practical Diets with Varying Levels of Protein
Authors: Jirsa Dave , Davis D Allen , Barrows Frederic T , Roy Luke A , Drawbridge Mark
Published: January 2014

Interest in the commercial culture of White Seabass Atractoscion nobilis on the western coast of the United States has been increasing in recent years. Despite this interest, there is a scarcity of knowledge on the dietary requirements of this species, particularly as it relates to basic nutrient requirements and selection of feeds. Hence, we evaluated a wide range of protein levels (31, 34, 37, 40, 43, and 46%) with practical lipid levels (5.75, 7, 8.25, 9.5, 10.75, and 12%) to initiate the development of a species-specific commercial diet for White Seabass. A 56-d trial was conducted in a recirculating system at Hubbs–SeaWorld Research Institute's marine fish hatchery in Carlsbad, California. Diets were formulated to contain 20–30% fish meal and offered to juvenile White Seabass (3.6 g mean initial weight). At the conclusion of the growth trial final weights ranged from 13.9 to 15.9 g, and percent weight gain ranged from 278.2% to 345.6% and generally increased with protein level. Protein retention ranged from 25.2% to 33.7% and was significantly lower for fish offered the diets containing 43% and 46% protein. Based on growth and protein retention, the use of a diet incorporating 40% protein and 10% lipid is recommended for juvenile White Seabass.
Effects of Abrupt pH Changes on Survival of Goldfish Fry
Authors: Chen Yushun , Kelly Anita M , Kumaran Sathyanand
Published: January 2014

Abrupt pH changes from hatchery to pond water may affect survival of Goldfish Carassius auratus fry after stocking. A total of 12 triplicate pH treatments ranging from 3.57 to 11.50 were used to assess a gradient of abrupt pH changes on survival of 3-d posthatch (dph) Goldfish fry in aquaria during a 24-h exposure experiment. The experiment indicated that the 24-h LC10, LC50, and LC90 pH values for 3 dph Goldfish fry was 9.99, 10.52, and 11.08, respectively, based on an initial pH = 8.38. When pH was decreased below 8.38, the 24-h LC10, LC50, and LC90 occurred at a pH of 4.68, 4.27, and 3.89, respectively. Baitfish farmers should avoid pond water with high pH to reduce fry mortality during the early fry stocking period when the upper lethal pH limit (i.e., LC10, for practical consideration) of 9.99 will become possible.
Winter Pond Fertilization Can Increase Phytoplankton Density in Aquaculture Ponds
Authors: Mischke Charles C
Published: January 2014

Effective winter fertilization would be beneficial under certain production systems in the southeastern USA. Maintaining a phytoplankton bloom during the winter has the potential to shade macrophytes, discourage filamentous algae, and provide natural foraging opportunities for fish during warmer days; this would be advantageous. An additional benefit of a winter bloom would be to produce turbidity, thereby possibly reducing bird predation. The objective of this study was to determine if winter fertilization could increase phytoplankton to greater biomass than in nonfertilized control ponds. Six ponds served as controls and six ponds received an initial dose of nitrogen at 20 kg/ha and phosphorus at 2 kg/ha in mid-November. Over the following five weeks, treatment ponds received one-half the initial dose once per week, and then continued to receive the half dose once per month in January, February, and March. Fertilization led to increases in total ammonia nitrogen, nitrite, and nitrate. The water temperature ranged from a low of 5°C to a high of 16.8°C (mean of 10.2°C) over the entire study. Even though water temperatures were low and light intensity is less in winter, fertilization caused a significant increase in chlorophyll a over the study. The increase in total algal biomass was not due to an increase in any specific algal group, but rather a general biomass increase in most algal groups. Cryptophyta tended to be the most common phytoplankton division throughout the study. Although this fertilization protocol increased algal biomass, there were no differences in zooplankton abundance between fertilized and nonfertilized ponds. In contrast to the currently held belief that winter fertilization is ineffective, this study shows that winter fertilization can increase algal blooms. Therefore, future studies should determine if blooms created from winter fertilization can increase growth of planktivorous fish, shade macrophytes, discourage filamentous algae, or produce turbidity which could reduce bird predation.
Computation and theory of extended Mordell-Tornheim-Witten sums
Authors: Bailey David , Borwein Jonathan , Crandall Richard
Published: January 2014

We consider some fundamental generalized Mordell–Tornheim–Witten (MTW) zeta-function values along with their derivatives, and explore connections with multiple-zeta values (MZVs). To achieve this, we make use of symbolic integration, high precision numerical integration, and some interesting combinatorics and special-function theory. Our original motivation was to represent unresolved constructs such as Eulerian log-gamma integrals. We are able to resolve all such integrals in terms of an MTW basis. We also present, for a substantial subset of MTW values, explicit closed-form expressions. In the process, we significantly extend methods for high-precision numerical computation of polylogarithms and their derivatives with respect to order.
On relations among 1-cycles on cubic hypersurfaces
Authors: Shen Mingmin
Published: January 2014

In this paper we give two explicit relations among

1
1

-cycles modulo rational equivalence on a smooth cubic hypersurface

X
X

. Such a relation is given in terms of a (pair of) curve(s) and its secant lines. As the first application, we reprove Paranjape’s theorem that

C
H

1

(
X
)

\mathrm {CH}_1(X)

is always generated by lines and that it is isomorphic to

Z

\mathbb {Z}

if the dimension of

X
X

is at least 5. Another application is to the intermediate jacobian of a cubic threefold

X
X

. To be more precise, we show that the intermediate jacobian of

X
X

is naturally isomorphic to the Prym–Tjurin variety constructed from the curve parameterizing all lines meeting a given rational curve on

X
X

. The incidence correspondences play an important role in this study. We also give a description of the Abel–Jacobi map for 1-cycles in this setting.
Aim44p regulates phosphorylation of Hof1p to promote contractile ring closure during cytokinesis in budding yeast
Authors: Wolken Dana M. Alessi , McInnes Joseph , Pon Liza A.
Published: January 2014

Whereas actomyosin and septin ring organization and function in cytokinesis are thoroughly described, little is known regarding the mechanisms by which the actomyosin ring interacts with septins and associated proteins to coordinate cell division. Here we show that the protein product of YPL158C, Aim44p, undergoes septin-dependent recruitment to the site of cell division. Aim44p colocalizes with Myo1p, the type II myosin of the contractile ring, throughout most of the cell cycle. The Aim44p ring does not contract when the actomyosin ring closes. Instead, it forms a double ring that associates with septin rings on mother and daughter cells after cell separation. Deletion of AIM44 results in defects in contractile ring closure. Aim44p coimmunoprecipitates with Hof1p, a conserved F-BAR protein that binds both septins and type II myosins and promotes contractile ring closure. Deletion of AIM44 results in a delay in Hof1p phosphorylation and altered Hof1p localization. Finally, overexpression of Dbf2p, a kinase that phosphorylates Hof1p and is required for relocalization of Hof1p from septin rings to the contractile ring and for Hof1p-triggered contractile ring closure, rescues the cytokinesis defect observed in aim44∆ cells. Our studies reveal a novel role for Aim44p in regulating contractile ring closure through effects on Hof1p.
BLESS: Bloom filter-based error correction solution for high-throughput sequencing reads
Authors: Heo Yun , Wu Xiao-Long , Chen Deming , Ma Jian , Hwu Wen-Mei
Published: January 2014

Motivation: Rapid advances in next-generation sequencing (NGS) technology have led to exponential increase in the amount of genomic information. However, NGS reads contain far more errors than data from traditional sequencing methods, and downstream genomic analysis results can be improved by correcting the errors. Unfortunately, all the previous error correction methods required a large amount of memory, making it unsuitable to process reads from large genomes with commodity computers.

Results: We present a novel algorithm that produces accurate correction results with much less memory compared with previous solutions. The algorithm, named BLoom-filter-based Error correction Solution for high-throughput Sequencing reads (BLESS), uses a single minimum-sized Bloom filter, and is also able to tolerate a higher false-positive rate, thus allowing us to correct errors with a 40× memory usage reduction on average compared with previous methods. Meanwhile, BLESS can extend reads like DNA assemblers to correct errors at the end of reads. Evaluations using real and simulated reads showed that BLESS could generate more accurate results than existing solutions. After errors were corrected using BLESS, 69% of initially unaligned reads could be aligned correctly. Additionally, de novo assembly results became 50% longer with 66% fewer assembly errors.

Availability and implementation: Freely available at http://sourceforge.net/p/bless-ec

Contact:  dchen@illinois.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
InterProScan 5: genome-scale protein function classification
Authors: Jones Philip , Binns David , Chang Hsin-Yu , Fraser Matthew , Li Weizhong , McAnulla Craig , McWilliam Hamish , Maslen John , Mitchell Alex , Nuka Gift , Pesseat Sebastien , Quinn Antony F. , Sangrador-Vegas Amaia , Scheremetjew Maxim , Yong Siew-Yit , Lopez Rodrigo , Hunter Sarah
Published: January 2014

Motivation: Robust large-scale sequence analysis is a major challenge in modern genomic science, where biologists are frequently trying to characterize many millions of sequences. Here, we describe a new Java-based architecture for the widely used protein function prediction software package InterProScan. Developments include improvements and additions to the outputs of the software and the complete reimplementation of the software framework, resulting in a flexible and stable system that is able to use both multiprocessor machines and/or conventional clusters to achieve scalable distributed data analysis. InterProScan is freely available for download from the EMBl-EBI FTP site and the open source code is hosted at Google Code.

Availability and implementation: InterProScan is distributed via FTP at ftp://ftp.ebi.ac.uk/pub/software/unix/iprscan/5/ and the source code is available from http://code.google.com/p/interproscan/.

Contact:  http://www.ebi.ac.uk/support or interhelp@ebi.ac.uk or mitchell@ebi.ac.uk
jmodeltest.org: selection of nucleotide substitution models on the cloud
Authors: Santorum Jose Manuel , Darriba Diego , Taboada Guillermo L. , Posada David
Published: January 2014

Summary: The selection of models of nucleotide substitution is one of the major steps of modern phylogenetic analysis. Different tools exist to accomplish this task, among which jModelTest 2 (jMT2) is one of the most popular. Still, to deal with large DNA alignments with hundreds or thousands of loci, users of jMT2 need to have access to High Performance Computing clusters, including installation and configuration capabilities, conditions not always met. Here we present jmodeltest.org, a novel web server for the transparent execution of jMT2 across different platforms and for a wide range of users. Its main benefit is straightforward execution, avoiding any configuration/execution issues, and reducing significantly in most cases the time required to complete the analysis.

Availability and implementation:  jmodeltest.org is accessible using modern browsers, such as Firefox, Chrome, Opera, Safari and IE from http://jmodeltest.org. User registration is not mandatory, but users wanting to have additional functionalities, like access to previous analyses, have the possibility of opening a user account.

Contact:  info@jmodeltest.org
Purification, characterization and crystallization of the human 80S ribosome
Authors: Khatter Heena , Myasnikov Alexander G. , Mastio Leslie , Billas Isabelle M. L. , Birck Catherine , Stella Stefano , Klaholz Bruno P.
Published: January 2014

Ribosomes are key macromolecular protein synthesis machineries in the cell. Human ribosomes have so far not been studied to atomic resolution because of their particularly complex structure as compared with other eukaryotic or prokaryotic ribosomes, and they are difficult to prepare to high homogeneity, which is a key requisite for high-resolution structural work. We established a purification protocol for human 80S ribosomes isolated from HeLa cells that allows obtaining large quantities of homogenous samples as characterized by biophysical methods using analytical ultracentrifugation and multiangle laser light scattering. Samples prepared under different conditions were characterized by direct single particle imaging using cryo electron microscopy, which helped optimizing the preparation protocol. From a small data set, a 3D reconstruction at subnanometric resolution was obtained showing all prominent structural features of the human ribosome, and revealing a salt concentration dependence of the presence of the exit site tRNA, which we show is critical for obtaining crystals. With these well-characterized samples first human 80S ribosome crystals were obtained from several crystallization conditions in capillaries and sitting drops, which diffract to 26 Å resolution at cryo temperatures and for which the crystallographic parameters were determined, paving the way for future high-resolution work.
A ribozyme that triphosphorylates RNA 5′-hydroxyl groups
Authors: Moretti Janina E. , Müller Ulrich F.
Published: January 2014

The RNA world hypothesis describes a stage in the early evolution of life in which RNA served as genome and as the only genome-encoded catalyst. To test whether RNA world organisms could have used cyclic trimetaphosphate as an energy source, we developed an in vitro selection strategy for isolating ribozymes that catalyze the triphosphorylation of RNA 5′-hydroxyl groups with trimetaphosphate. Several active sequences were isolated, and one ribozyme was analyzed in more detail. The ribozyme was truncated to 96 nt, while retaining full activity. It was converted to a trans-format and reacted with rates of 0.16 min−1 under optimal conditions. The secondary structure appears to contain a four-helical junction motif. This study showed that ribozymes can use trimetaphosphate to triphosphorylate RNA 5′-hydroxyl groups and suggested that RNA world organisms could have used trimetaphosphate as their energy source.
Removal of Arterial Lines and Devices from the Ascending Aorta in Cardiac Surgery Patients
Authors: Brinster Derek R. , Chinichian Shideh
Published: January 2014

The use of monitoring or device lines through the ascending aorta may be necessary for a variety of clinical situations. The technique provided in this article allows percutaneous closure of these entry sites with a closed chest.
Cross-talk between Rho and Rac GTPases drives deterministic exploration of cellular shape space and morphological heterogeneity
Authors: Sailem Heba , Bousgouni Vicky , Cooper Sam , Bakal Chris
Published: January 2014

One goal of cell biology is to understand how cells adopt different shapes in response to varying environmental and cellular conditions. Achieving a comprehensive understanding of the relationship between cell shape and environment requires a systems-level understanding of the signalling networks that respond to external cues and regulate the cytoskeleton. Classical biochemical and genetic approaches have identified thousands of individual components that contribute to cell shape, but it remains difficult to predict how cell shape is generated by the activity of these components using bottom-up approaches because of the complex nature of their interactions in space and time. Here, we describe the regulation of cellular shape by signalling systems using a top-down approach. We first exploit the shape diversity generated by systematic RNAi screening and comprehensively define the shape space a migratory cell explores. We suggest a simple Boolean model involving the activation of Rac and Rho GTPases in two compartments to explain the basis for all cell shapes in the dataset. Critically, we also generate a probabilistic graphical model to show how cells explore this space in a deterministic, rather than a stochastic, fashion. We validate the predictions made by our model using live-cell imaging. Our work explains how cross-talk between Rho and Rac can generate different cell shapes, and thus morphological heterogeneity, in genetically identical populations.
Moheibacter sediminis gen. nov., sp. nov., a member of the family Flavobacteriaceae isolated from sediment, and emended descriptions of Empedobacter brevis, Wautersiella falsenii and Weeksella virosa
Authors: Zhang Ren-Gang , Tan Xu , Zhao Xing-Min , Deng Jian , Lv Jie
Published: January 2014

A Gram-reaction-negative, yellow-pigmented, strictly aerobic bacterium, designated M0116T, was isolated from the sediment of the Mohe Basin in north-east China. Flexirubin-type pigments were produced. Cells were catalase- and oxidase-positive and non-gliding rods. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain M0116T was a member of the family

Flavobacteriaceae

and was most closely related to members of the genera

Empedobacter

,

Wautersiella

and

Weeksella

with 90.5–91.0 % sequence similarities. The major cellular fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH. The major respiratory quinone was MK-6 and the major polar lipid was phosphatidylethanolamine. The DNA G+C content was 38.2 mol%. Based on phenotypic, phylogenetic and genotypic data, strain M0116T is considered to represent a novel species of a new genus in the family

Flavobacteriaceae

, for which the name Moheibacter sediminis gen. nov., sp. nov. is proposed. The type strain is M0116T ( = CGMCC 1.12708T = JCM 19634T). Emended descriptions of

Empedobacter brevis

,

Wautersiella falsenii

and

Weeksella virosa

are also proposed.
Joint Variant andDe NovoMutation Identification on Pedigrees from High-Throughput Sequencing Data
Authors: Cleary John G. , Braithwaite Ross , Gaastra Kurt , Hilbush Brian S. , Inglis Stuart , Irvine Sean A. , Jackson Alan , Littin Richard , Nohzadeh-Malakshah Sahar , Shah Minita , Rathod Mehul , Ware David , Trigg Len , De La Vega Francisco M.
Published: January 2014

The analysis of whole-genome or exome sequencing data from trios and pedigrees has being successfully applied to the identification of disease-causing mutations. However, most methods used to identify and genotype genetic variants from next-generation sequencing data ignore the relationships between samples, resulting in significant Mendelian errors, false positives and negatives. Here we present a Bayesian network framework that jointly analyses data from all members of a pedigree simultaneously using Mendelian segregation priors, yet providing the ability to detectde novomutations in offspring, and is scalable to large pedigrees. We evaluated our method by simulations and analysis of WGS data from a 17 individual, 3-generation CEPH pedigree sequenced to 50X average depth. Compared to singleton calling, our family caller produced more high quality variants and eliminated spurious calls as judged by common quality metrics such as Ti/Tv, Het/Hom ratios, and dbSNP/SNP array data concordance. We developed a ground truth dataset to further evaluate our calls by identifying recombination cross-overs in the pedigree and testing variants for consistency with the inferred phasing, and we show that our method significantly outperforms singleton and population variant calling in pedigrees. We identify all previously validatedde novomutations in NA12878, concurrent with a 7X precision improvement. Our results show that our method is scalable to large genomics and human disease studies and allows cost optimization by rational sequencing capacity distribution.
Single nucleotide polymorphisms shed light on correlations between environmental vairalbe and adaptive genetic divergence in Chum salmon (Oncorhynchus keta)
Authors: Deng Xilin , Henry Philippe
Published: January 2014

Identifying the genetic and ecological basis of adaptation is of immense importance in evolutionary biology. In our study, we applied a panel of 58 biallelic single nucleotide polymorphisms (SNPs) for the economically and culturally important salmonidOncorhynchus keta.Samples included 4164 individuals from 43 populations ranging from Coastal Western Alaska to southern British Colombia and northern Washington. Signatures of natural selection were detected by identifying seven outlier loci using two independent approaches: one based on outlier detection and another based on environmental correlations. Evidence of divergent selection at two candidate SNP loci,Oke_RFC2-168 and Oke_MARCKS-362, indicates significant environmental correlations, particularly with the number of frost-free days (NFFD). Important associations found between environmental variables and outlier loci indicate that those environmental variables could be the major driving forces of allele frequency divergence at the candidate loci. NFFD, in particular, may play an important adaptive role in shaping genetic variation inO. keta.Correlations between divergent selection and local environmental variables will help shed light on processes of natural selection and molecular adaptation to local environmental conditions.
An accelerated miRNA-based screen implicates Atf-3 in odorant receptor expression
Authors: Bhat Shreelatha , Shin Minjung , Bahk Suhyoung , Kim Young-Joon , Jones Walton D.
Published: January 2014

Large scale genetic screening is tedious and time-consuming. To address this problem, we propose a novel two-tiered screening system comprising an initial “pooling” screen that identifies miRNAs whose tissue-specific over-expression causes a phenotype of interest followed by a more focused secondary screen that uses gene-specific RNAi. As miRNAs inhibit translation or direct the destruction of their target mRNAs, any phenotype observed with miRNA over-expression can be attributed to the loss-of-function of one or more target mRNAs. Since miRNA-target pairing is sequence-specific, a list of predicted targets for miRNAs identified in the initial screen serves as a list of candidates for the secondary RNAi-based screen. These predicted miRNA targets can be prioritized by expression pattern, and if multiple miRNAs produce the same phenotype, overlapping target predictions can be given higher priority in the follow-up screen.

Since miRNAs are short, miRNA misexpression will likely uncover artifactual miRNA-target relation-ships. Thus, we are using miRNAs as a tool to accelerate genetic screening rather than focus on the biology of miRNAs themselves. This two-tiered system allows us to rapidly identify individual target genes involved in a phenomenon of interest, often in less than 200 crosses. Here we demonstrate the effectiveness of this method by identifying miRNAs that alterDrosophilaodorant receptor expression. With subsequent miRNA target prediction and follow-up RNAi screening we identify and validate a novel role for the transcription factor Atf3 in the expression of the socially relevant receptor Or47b.
Information gathering during enterprise system selection: insight from practice
Authors: Lech Przemysław
Published: January 2014

Purpose

The purpose of this paper is to examine the information gathering methods used during enterprise system (ES) selection among Polish organizations and to have IT consulting experts evaluate these methods, which will result in identification of the preferred approach for the information‐gathering task during system selection.

Design/methodology/approach

The research has a qualitative exploratory design with grounded theory being the main research method. A mixed quantitative‐qualitative approach to data collection was used: an e‐mail‐based survey was used as an introductory stage to gather data on information‐gathering methods. The results of the survey were evaluated by ES experts during unstructured interviews. The interviews were then transcribed and coded according to the grounded theory coding techniques.

Findings

The evaluation of selection approaches revealed that the approach to information gathering should depend on the level of configurability of the systems subject to selection. Two generic approaches were identified: requirements driven – for highly configurable systems, and system functionality driven – for the systems offering limited configurability. Interaction between the customer and the bidder was also identified as the main condition for preparing the unbiased offer by the bidders.

Research limitations/implications

Regarding the survey study, as the survey sample was small and the sample selection process was not random, the results should not be generalised to the whole population of Polish enterprises. It would be also beneficial to test the validity of the findings from the grounded theory study on the big population of ES bidders with the use of statistical methods.

Practical implications

For highly configurable systems, a model that includes a business process analysis, detailed requirements' specification and dedicated system functionality presentation is the preferred approach. A workshop is preferred to obtaining a ready requirements list. For systems offering limited configurability, an approach centred on system presentation is more suitable. In this case the requirements should be gathered during the presentation on a “gap‐fit” basis.

Originality/value

There is a significant lack of research that explores the selection process, with the stress on organizational needs and system functionality information gathering and makes indications for improvement of this process from the consulting enterprise (bidder) point of view. The paper fills this gap by presenting the results of a survey among Polish enterprises regarding selection routines and the evaluation of these routines by expert ES professionals, resulting in the development of the preferred set of information‐gathering methods.
New developments in fuzzy logic computers
Authors: Stotts Linda , Kleiner Brian H.
Published: January 2014

Sets out to provide an understanding of the theory of fuzzy logic
by supplying background details concerning its evolution in mathematics
and computer science. Once a basic understanding of the theory is
obtained, then it is easier to understand the implications for computer
applications. Fuzzy logic processors and compilers have facilitated the
development of expert systems that typically use a lot of imprecise
data. These expert systems have been used successfully as control units
in industrial settings and as decision support systems in hospital
settings. Fuzzy logic has been found to be a practical and viable form
of artificial intelligence that mitigates the current drawbacks of other
forms of artificial intelligence. But the really exciting development
that is poised to emerge is the introduction of fuzzy logic appliances.
These appliances employ an expert system on a chip that is able to mimic
the range of flexibility of the human mind, while utilizing resources
more efficiently.