bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Basis of Disulfide Bond Formation in the Bacterial Periplasm and Mammalian
ER
Authors: Kojima Rieko , Okumura Masaki , Inaba Kenji 
Published: September 2013

Abstract

Cellular quality control systems rely on the maintenance of protein and redox homoeostasis, in which the formation, reduction and isomerisation of protein disulfide bonds play important roles. The biological kingdoms have evolved catalytic systems that greatly promote oxidative protein folding. Remarkable progress in structural biology in this field has provided molecular views on how protein disulfide bonds are generated
de novo
and transferred to downstream folding substrates. Very recently, a novel concept has emerged, proposing that multiple oxidative pathways work redundantly, distinctly and in a complementary manner in the endoplasmic reticulum of mammalian cells to efficiently produce large quantities, and a wide variety, of secretory proteins. Thus, the oxidative protein folding network is even more complicated in higher eukaryotes than previously thought.

Key Concepts:

Almost all organisms, from bacteria to humans, possess catalytic systems that promote protein‐disulfide bond formation.

Disulfide bond formation networks have diversified dramatically, as evidenced by the appearance of a large number of disulfide oxidoreductases in higher eukaryotes.

High‐resolution structures have been solved for an increasing number of disulfide oxidoreductases, thereby revealing the structural and mechanistic basis of cellular disulfide bond formation systems.

Disulfide bonds play an important role in folding, assembly and stabilisation of various proteins.

Disulfide bond formation networks are closely related to the protein and redox homeostasis in the cell.
A‐to‐I
RNA
Editing and Human Genetic Disease
Authors: Maas Stefan 
Published: September 2013

Abstract

The regulation of when, where and how genomic information is utilised in cells and organisms is just as important for normal physiology as the
deoxyribonucleic acid
sequence itself. One important molecular tool at the disposal of eukaryotic cells is the process of
ribonucleic acid (RNA)
editing, which involves the recoding of genomically specified sequences within primary RNA transcripts. One kind of RNA editing, A‐to‐I modification, turns out to regulate the expression and function of various genes as well as enhance the functional and phenotypic diversity within the transcriptome and proteome. Recent insights on the A‐to‐I RNA‐editing machinery and the discovery of many additional editing targets, especially within mammalian species, underscore the importance of editing for normal physiology and also uncover strong links to human genetic diseases. Harnessing that knowledge could lead to approaches for treating RNA editing‐related disorders or even to the development of RNA‐directed gene therapy technologies.

Key Concepts:

RNA editing regulates protein function.

RNA editing diversifies the transcriptome and proteome.

ADARs mediate A‐to‐I RNA editing.

Important editing sites include many noncoding RNAs.

Some editing events are essential for survival.

Many editing sites await functional characterisation.

Deregulation of RNA editing can lead to disease.
Gene Therapy for Amyotrophic Lateral Sclerosis
Authors: McEachin Zachary , O'Connor Deirdre , Boulis Nicholas 
Published: September 2013

Abstract
Amyotrophic lateral sclerosis (ALS), commonly referred to as Lou Gehrig's disease, is a chronic, neurodegenerative disease with no known cure. ALS is characterised by the loss of both upper and lower motor neurons. On becoming symptomatic, patients with ALS survive between 1–5 years. The aetiology and pathogenesis of ALS is complex and can vary among cases; however, some forms of ALS have been identified to be genetic in origin. In particular, 20% of familial ALS cases have been attributed to a gain‐of‐function mutation in the SOD1 gene. Thus, gene therapy has been an attractive method to potentially treat ALS. The intention of this article is to provide the reader a summary of common gene therapy strategies for ALS.

Key Concepts:

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease with no known cure.

ALS exists in two forms: familial ALS and sporadic ALS.

Twenty per cent of fALS cases are due to a mutation in the SOD1 gene.

SOD1 murine models have been valuable in the advancement of gene therapy for ALS.

Gene therapy is a promising therapeutic option for ALS.
Gene Therapy for Duchenne Muscular Dystrophy
Authors: van Putten Maaike , Aartsma‐Rus Annemieke 
Published: September 2013

Abstract

Duchenne muscular dystrophy is a severe muscle wasting disorder caused by lack of functional dystrophin, due to reading‐frame disrupting mutations in the
DMD
gene. There is no cure, but several genetic therapeutic approaches aiming to delay disease progression by restoring, manipulating or replacing the
DMD
gene are under investigation in (pre)clinical settings. The antisense‐mediated exon skipping approach, which restores the disrupted reading frame allowing synthesis of partly functional dystrophin proteins is closest to clinical application. The first trials with viral vectors to deliver minidystrophin genes and compounds to force readthrough of premature stop codons by the translation machinery have also been undertaken, whereas other approaches, like genome editing, are still in the early development phase. Despite some remaining hurdles that have to be overcome, lessons learned can be used to catalyse the development of potential therapies.

Key Concepts:

Duchenne muscular dystrophy (DMD) is caused by reading‐frame disrupting mutations in the
DMD
gene, resulting in premature termination of dystrophin synthesis.

Inframe mutations allow synthesis of shorter, but partly functional dystrophin proteins, resulting in the milder Becker muscular dystrophy (BMD) phenotype.

Antisense oligonucleotide‐mediated exon skipping aims to restore the reading frame enabling synthesis of BMD‐like dystrophins, thereby converting the severe DMD into the milder BMD disease.

Gene replacement therapy (replacing the dysfunctional dystrophin cDNA) is hampered by the size and complexity of the
DMD
gene and dystrophin cDNA.

AAV vectors have a limited loading capacity of ∼4.5 kb, requiring the use of mini‐, or microdystrophin genes that encode only the most crucial functional domains.

Ataluren can be used to force the translational machinery to ignore premature stop codons enabling synthesis of intact dystrophin.

Endonuclease‐mediated generation of double‐strand breaks can be used to correct the genetic mutation or restore the reading frame.

Many therapeutic approaches have progressed to clinical trials.
History of the Signal Hypothesis
Authors: Matlin Karl S 
Published: September 2013

AbstractThe signal hypothesis, which describes how secretory and membrane proteins are targeted to the endoplasmic reticulum, was proposed in 1971 by Günter Blobel and David Sabatini and demonstrated by Blobel and Bernhard Dobberstein in 1975. Subsequent research identified the key components of the membrane insertion and translocation machinery, including the signal recognition particle (SRP), the SRP receptor and the protein‐conducting channel. Ultimately, the signal hypothesis was shown to be true for not only eukaryotes but also prokaryotes. Most importantly, the concept of signal‐mediated targeting was expanded into a general hypothesis of cellular topogenesis that helps to explain how proteins are distributed to their correct locations within the cell following their synthesis in the cytoplasm.Key Concepts:Modern cell biology was developed in the post‐World War II period.Cell biological research in the 30 years after World War II was characterised by a multidisciplinary approach that combined electron microscopy, cell fractionation, biochemical analysis and radioactive pulse‐labelling of proteins.Formulation of the signal hypothesis was an outgrowth of protein synthesis and secretion research carried out at the Rockefeller University beginning in the late 1940s.The signal hypothesis was originally proposed by Günter Blobel and David Sabatini in 1971, and demonstrated by Blobel and colleagues in 1975.The signal hypothesis showed that cytoplasmically synthesised proteins targeted to the ER use a signal sequence to direct them to the ER membrane.A signal sequence is a short peptide that is part of the original translation product of proteins targeted to the ER, often at theN‐terminus of the protein, and is frequently removed proteolytically after translocation of the nascent polypeptide through the ER membrane.The mechanism of protein translocation was established through the isolation and characterisation of SRP, the SRP‐receptor and the protein‐conducting channel.The signal hypothesis was found to be applicable to protein translocation in all eukaryotes and prokaryotes.Although the original signal hypothesis proposed translocation of proteins during the elongation of the polypeptide chain (cotranslational), translocation was found to also occur in some instances after protein synthesis was complete (post‐translational), primarily through studies of bacteria and yeast.The concept of signal‐mediated targeting of proteins was expanded into a generalised hypothesis of protein topogenesis by Günter Blobel in 1980.
Membrane Dynamics: Fluorescence Spectroscopy
Authors: Subburaj Yamunadevi , Gallego Raquel Salvador , García‐Sáez Ana J. 
Published: September 2013

AbstractMembranes are dynamic lipophilic structures that constitute a selective barrier essential for the smooth functioning of cellular machinery. Their complex and highly heterogeneous composition, as well as the intricate diffusion patterns that they display, have been intensely studied in the past decades. Several innovative microscopy techniques have recently been developed to gain insight into the basis of membrane dynamics, interactions, and molecular organization. In this article, we introduce four pioneer fluorescence‐based approaches that have substantially broadened our overall understanding of membranes: fluorescence correlation spectroscopy (FCS), single particle tracking (SPT), fluorescence recovery after photobleaching (FRAP), and 6‐lauroyl‐2‐(dimethylamino)‐naphtalene (LAURDAN) microscopy. We discuss each technique in detail, explaining their principles, methodology, and applications in the research of the dynamic processes controlled by membranes.
Probing Membrane Protein Structure and Dynamics by Fluorescence Spectroscopy
Authors: Kang Guipeun , López‐Peña Ignacio , Bhakta Saajan , Kim Judy E. 
Published: September 2013

ABSTRACT
Applications of fluorescence spectroscopy to biomolecules, with focus on membrane proteins, are discussed in this article. A broad range of molecular insights can be gained with this simple technique because the emission properties of a chromophore are typically sensitive to the environment. The intensities and maximum wavelengths of steady‐state fluorescence spectra are used to elucidate the thermodynamics of membrane protein folding, monitor the extent of solvent exposure of chromophores, determine the depths of insertion into synthetic bilayers, probe the degree of rotational freedom in solvent‐exposed and buried regions, and measure the evolution of distances between donor and acceptor moieties. We also address some of the challenges associated with fluorescence measurements of integral membrane proteins. An important goal is to provide a practical guide for laboratory measurements as well as examples of analyses related to membrane protein structure and dynamics.
WHY IS IT SO DIFFICULT TO REFORM SOME ASIAN BUREAUCRACIES? BUILDING THEORY FROM CAMBODIAN EVIDENCE
Authors: Turner Mark 
Published: September 2013

SUMMARYThis article demonstrates how theory can be built to explain cases of public administration reform failure in Asia. Drawing on the methodologies of middle range theory and grounded theory, qualitative data are gathered from the case of Cambodia and then analyzed. The result is the proposition that a specific constellation of reform‐inhibiting factors explains the slow progress of public administration reform in Cambodia. At the center of the constellation is patronage. The cluster of surrounding and interrelated factors includes weak accountability, hegemonic political regime, high and legitimate power distance, low wages, and bureaucratic dysfunction. The chances of reform success increase with the removal or absence of these inhibiting factors. The analysis emphasizes the importance of political economy factors in determining the success or failure of public administration reform. Copyright © 2013 John Wiley & Sons, Ltd.
REVISITING CONFUCIAN BUREAUCRACY: ROOTS OF THE KOREAN GOVERNMENT'S CULTURE AND COMPETITIVENESS
Authors: Im Tobin , Campbell Jesse W. , Cha Seyeong 
Published: September 2013

SUMMARYThis paper looks at Korea's Chosun dynasty bureaucracy and the Neo‐Confucian principles that formed the basis of its governing philosophy. We argue that Korea's traditional bureaucracy had a number of modern characteristics, including a system of formal and informal checks on the powers of the sovereign and a decision‐making system that encouraged deliberation among highly qualified civil servants. On the basis of this exposition, we also argue that there are strong links between the traditional bureaucracy and its current, modern form. We firstly show how the institutionalization of a strong state during the period of rapid development was as much a return to traditional governing principles as it was a revolution and, secondly, how contemporary organizational culture is shaped by Korea's Confucian heritage. In the final section, we argue that the distinctive characteristics of the Korean bureaucracy have played an important role in limiting the success of a number of Western‐oriented reform efforts. Copyright © 2013 John Wiley & Sons, Ltd.
CAN THERE BE AN ASIAN MODEL OF PUBLIC ADMINISTRATION?
Authors: Cheung Anthony B. L. 
Published: September 2013

SUMMARYThis article examines the conceptual possibilities of an Asian model of public administration, challenging some pre‐established paradigms along the way. There are two basic contentions. First, there is no such thing as one universal model of public administration that satisfies all national political and cultural situations so that each public administration system is also shaped by its own national tradition and historical evolution. The historical process is as important as the horizontal process of policy learning and transfer from others in the world. Second, Asia has its unique administrative civilization that has been under‐studied in the larger context of contemporary public administration theories and practices. The article does not argue for an Asian‐dominated governance model per se. Rather, the point is that the rapid social and economic growth of some emerging Asian nations has cast further doubt on any deterministic ‘good governance’ model driven predominantly by the Western growth experience. No definite thesis is concluded, and this must involve a process of drawing wisdoms from more Asian ‘national’ and local narratives of administrative histories and practices. Copyright © 2013 John Wiley & Sons, Ltd.
KNOWLEDGE ACCUMULATION IN ASIAN PUBLIC ADMINISTRATION RESEARCH: A CRITICAL REVIEW
Authors: Ko Kilkon 
Published: September 2013

SUMMARYGiven the growing controversy over the relevance of Anglo‐Saxon style public administration to developing countries and a greater demand for more context‐relevant theories of public administration in Asia, we should expect that Asian scholars achieve a certain level of knowledge growth in line with this controversy and demand. On the basis of the review of 8810 articles published in nine major international journals during 1990–2011, the author found that the number of articles on Asian public administration is very small, and there is no strong pattern of growth in this regard. In addition, there are very few studies adopting a comparative approach covering multiple Asian countries. Copyright © 2013 John Wiley & Sons, Ltd.
KNOWLEDGE‐BUILDING IN ASIAN PUBLIC ADMINISTRATION: AN INTRODUCTORY OVERVIEW
Authors: Haque M. Shamsul , Turner Mark 
Published: September 2013

SUMMARYIn recent years, the re‐emergence of Asia as a global power coincided with the proliferation of Asian studies in diverse disciplines and institutions worldwide. However, although the state and its administrative apparatus have been directly instrumental to this Asian success story, there is still inadequate research on the role of public administration in Asia. Thus, there is a need for exploring major issues related to research and knowledge building in Asian public administration. Copyright © 2013 John Wiley & Sons, Ltd.
Induced Pluripotency for Translational Research
Authors: Wu Menghua , Chen Guilai , Hu Baoyang 
Published: September 2013

Abstract
The advent of induced pluripotent stem cells (iPSCs) has revolutionized the concept of cellular reprogramming and potentially will solve the immunological compatibility issues that have so far hindered the application of human pluripotent stem cells in regenerative medicine. Recent findings showed that pluripotency is defined by a state of balanced lineage potency, which can be artificially instated through various procedures, including the conventional Yamanaka strategy. As a type of pluripotent stem cell, iPSCs are subject to the usual concerns over purity of differentiated derivatives and risks of tumor formation when used for cell-based therapy, though they provide certain advantages in translational research, especially in the areas of personalized medicine, disease modeling and drug screening. iPSC-based technology, human embryonic stem cells (hESCs) and direct lineage conversion each will play distinct roles in specific aspects of translational medicine, and continue yielding surprises for scientists and the public.
Particle capture by a circular cylinder in the vortex-shedding regime
Authors: Espinosa-Gayosso Alexis , Ghisalberti Marco , Ivey Gregory N. , Jones Nicole L. 
Published: September 2013

AbstractParticle capture, whereby suspended particles contact and adhere to a solid surface (a ‘collector’), is an important mechanism for a range of environmental processes including suspension feeding by corals and ‘filtering’ by aquatic vegetation. In this paper, we use two- and three-dimensional direct numerical simulations to quantify the capture efficiency ($\eta $) of low-inertia particles by a circular cylindrical collector at intermediate Reynolds numbers in the vortex-shedding regime (i.e. for$47\lt \mathit{Re}\leq 1000$, where$\mathit{Re}$is the collector Reynolds number). We demonstrate that vortex shedding induces oscillations near the leading face of the collector which greatly affect the quantity and distribution of captured particles. Unlike in steady, low-$\mathit{Re}$flow, particles directly upstream of the collector are not the most likely to be captured. Our results demonstrate the dependence of the time-averaged capture efficiency on$\mathit{Re}$and particle size, improving the predictive capability for the capture of particles by aquatic collectors. The transition to theoretical high-Reynolds-number behaviour (i.e. $\eta \sim {\mathit{Re}}^{1/ 2} $) is complex due to comparatively rapid changes in wake conditions in this Reynolds number range.
Scaling of streamwise boundary layer streaks and their ability to reduce skin-friction drag
Authors: Shahinfar S. , Fransson J. H. M. , Sattarzadeh S. S. , Talamelli A. 
Published: September 2013

AbstractSpanwise arrays of miniature vortex generators (MVGs) are used to generate energetic transient disturbance growth, which is able to modulate the boundary layer flow with steady and stable streak amplitudes up to 32 % of the free-stream velocity. This type of modulation has previously been shown to act in a stabilizing manner on modal disturbance growth described by classical instability theory. In an attempt to reproduce a more realistic flow configuration, in the present experimental set-up, Tollmien–Schlichting (TS) waves are generated upstream of the MVG array, allowing for a complete interaction of the incoming wave with the array. Fifteen new MVG configurations are investigated and the stabilizing effect on the TS waves is quantified. We show that the streak amplitude definition is very important when trying to relate it to the stabilization, since it may completely bypass information on the mean streamwise velocity gradient in the spanwise direction, which is an essential ingredient of the observed stabilization. Here, we use an integral-based streak amplitude definition along with a streak amplitude scaling relation based on empiricism, which takes the spanwise periodicity of the streaks into account. The results show that, applying the integral definition, the optimal streak amplitude for attenuating TS wave disturbance growth is around 30 % of the free-stream velocity, which corresponds to ${\sim }20\hspace{0.167em} \% $ in the conventional definition when keeping the spanwise wavelength constant. The experiments also show that the disturbance energy level, based on the full velocity signal, is significantly reduced in the controlled case, and that the onset of transition may be inhibited altogether throughout the measured region in the presence of an MVG array.
A bathtub vortex under the influence of a protruding cylinder in a rotating tank
Authors: Chen Yin-Chung , Huang Shih-Lin , Li Zi-Ya , Chang Chien-Cheng , Chu Chin-Chou 
Published: September 2013

AbstractNumerical simulations and laboratory experiments were jointly conducted to investigate a bathtub vortex under the influence of a protruding cylinder in a rotating tank. In the set-up, a central drain hole is placed at the bottom of the tank and a top-down cylinder is suspended from the rigid top lid, with fluid supplied from the sidewall for mass conservation. The cylinder is protruded to produce the Taylor column effect. The flow pattern depends on the Rossby number ($\mathit{Ro}= U/ fR$), the Ekman number ($\mathit{Ek}= \nu / f{R}^{2} )$ and the height ratio, $h/ H$, where $R$ is the radius of the cylinder, $f$ is the Coriolis parameter, $\nu $ is the kinematic viscosity of the fluid, $h$ is the vertical length of the cylinder and $H$ is the height of the tank. It is found appropriate to choose $U$ to be the average inflow velocity of fluid entering the column beneath the cylinder. Steady-state solutions obtained by numerically solving the Navier–Stokes equations in the rotating frame are shown to have a good agreement with flow visualizations and particle tracking velocimetry (PTV) measurements. It is known that at $\mathit{Ro}\sim 1{0}^{- 2} $, the central downward flow surrounded by the neighbouring Ekman pumping forms a classic one-celled bathtub vortex structure when there is no protruding cylinder ($h/ H= 0$). The influence of a suspended cylinder ($h/ H\not = 0$) leads to several findings. The bathtub vortex exhibits an interesting two-celled structure with an inner Ekman pumping (EP) and an outer up-drafting motion, termed Taylor upwelling (TU). The two regions of up-drafting motion are separated by a notable finite-thickness structure, identified as a (thin-walled) Taylor column. The thickness ${ \delta }_{T}^{\ast } $ of the Taylor column is found to be well correlated to the height ratio and the Ekman number by ${\delta }_{T} = { \delta }_{T}^{\ast } / R= {(1- h/ H)}^{- 0. 32} {\mathit{Ek}}^{0. 095} $. The Taylor column presents a barrier to the fluid flow such that the fluid from the inlet may only flow into the inner region through the narrow gaps, one above the Taylor column and one beneath it (conveniently called Ekman gaps). As a result, five types of routes along which the fluid may flow to and exit at the drain hole could be identified for the multi-celled vortex structure. Moreover, the flow rates associated with the five routes were calculated and compared to help understand the relative importance of the component flow structures. The weaker influence of the Taylor column effect on the bathtub vortex at $\mathit{Ro}\sim 1$ or even higher $\mathit{Ro}\sim 1{0}^{2} $ is also discussed.