bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch and TGF-β pathways cooperatively regulate receptor protein tyrosine phosphatase-κ (PTPRK) gene expression in human primary keratinocytes
Authors: Xu Yiru , Xue Siliang , Zhou Jin , Voorhees John J. , Fisher Gary J.
Published: January 2015

Receptor protein tyrosine phosphatase-κ (PTPRK) specifically and directly dephosphorylates epidermal growth factor receptor (EGFR), thereby limiting EGFR function in primary human keratinocytes. PTPRK expression is increased by the TGF-β/Smad3 pathway and cell–cell contact. Because the Notch receptor pathway is responsive to cell–cell contact and regulates keratinocyte growth and differentiation, we investigated the interplay between Notch and TGF-β pathways in regulation of PTPRK expression in human keratinocytes. Suppression of Notch signaling by γ-secretase inhibitors substantially reduced cell contact induction of PTPRK gene expression. In sparse keratinocyte cultures, addition of soluble Notch-activating ligand jagged one peptide (Jag1) induced PTPRK. Of interest, cell contact–induced expression of TGF-β1 and TGF-β receptor inhibitor SB431542 inhibited contact-induced expression of PTPRK. Furthermore, inhibition of Notch signaling, via knockdown of Notch1 or by γ-secretase inhibitors, significantly reduced TGF-β–induced PTPRK gene expression, indicating that Notch and TGF-β pathways function together to regulate PTPRK. Of importance, the combination of Jag1 plus TGF-β results in greater PTPRK expression and lower EGFR tyrosine phosphorylation than either ligand alone. These data indicate that Notch and TGF-β act in concert to stimulate induction of PTPRK, which suppresses EGFR activation in human keratinocytes.
Pentecostals, Proselytization, and Anti-Christian Violence in Contemporary India
Authors: Bauman Chad M.
Published: January 2015

Every year, there are several hundred attacks on India’s Christians carried out by violent anti-minority activists, many of them provoked by what they perceive to be Christians’ propensity for aggressive proselytization, and/or by rumored or real conversions to the faith. In this violence, Pentecostal Christians are disproportionately targeted. Based on extensive interviews and ethnographic work, and drawing upon the vast scholarly literature on interreligious violence in India, the volume attempts to account for this disproportionate targeting with reference to Indian Christian history, contemporary Indian politics, Indian social and cultural characteristics, and Pentecostal belief and practice. While some of the factors in the targeting of Pentecostals are obvious and expected (e.g., their relatively greater evangelical assertiveness), other factors also play a significant role, among them the marginalization of Pentecostals by “mainstream” Christians, the social location of Pentecostals, and transnational flows of missionary personnel, theories, and funds.
Pentecostalism in the Context of Indian History and Politics
Authors: Bauman Chad M.
Published: January 2015

The first half of the chapter traces the history of Hindu–Christian relations from the establishment of Indian Christianity, through the British colonial period, to contemporary times and seeks to account, with reference to this history, for the growing animosity between Hindus and Christians. Then, the second half of the chapter pauses to consider the development of a relatively common critique of Christianity in India, a critique focusing on its putative foreign funding and aggressive evangelical tendencies (and articulated by Mohandas Gandhi, Sita Ram Goel, Ram Swarup, Swami Dayananda Saraswati, Arun Shourie, and others). Finally, the chapter locates Pentecostal Christianity within the historical trajectory described in the first part of the chapter, and the anti-Christian critique described in the second.
Force, Fraud, and Inducement?
Authors: Bauman Chad M.
Published: January 2015

One of the claims commonly made against Indian Christianity is that the physical healing provided in its medical hospitals has served as an illegitimate inducement to Christian faith, either because non-Christians who receive healing feel obligated toward the Christians who provided it, or because non-Christians are impressed and attracted by the great displays of western wealth and technological power on display in Indian Christian hospitals. This claim is in many ways undermined by the growing prevalence of Christian faith healing, and what the chapter calls “recuperative conversions,” that is, conversions to Christianity brought about by spiritual or physical healing wrought by the prayerful interventions of Christian thaumaturges, many of them Pentecostal. Whatever else they may be, these healings are not dependent on displays of western wealth and power, and so they alter the contours of the debate about inducement in significant ways.
Competing motivation models and diachrony: What evidence for what motivations?
Authors: Cristofaro Sonia
Published: January 2015

Competing motivation models are usually established on synchronic grounds. The chapter discusses several diachronic processes that give rise to patterns that have been accounted for in terms of competing motivations, such as the development of different alignment systems and that of overt, as opposed to zero marking for number. These processes challenge the relevant competing motivations models both in the sense that they provide no evidence for the principles postulated in these models, and in the sense that they do not point to a competition between different principles pertaining to the encoding of the same grammatical domain.
Orconstructions: Monosemy vs. polysemy
Authors: Ariel Mira
Published: January 2015

Codes and inferences compete in language, and the competition manifests itself at the level of the language system and in real‐time interactions. Grammars sometimes offer a monosemous code for some messages, but sometimes a form not coded for the intended message can (or must) be mobilized to serve the speaker's message. This is polysemy, where the speaker relies on a rich context which helps the addressee derive the interpretation via inference. This chapter examines various disjunctive interpretations and finds a number of competitions for expressing them. First, the disjunctive idea may be expressed by a dedicated construction, e.g. [X or Y], but it may be left to inference, when derived on a series of questions, for example. Second, specialized disjunctive interpretations may be conveyed by the general, polysemous construction, with the help of context‐driven inferences, or by dedicated, monosemous sub‐constructions, which encode the specialized meaning (e.g. [X or something]).
Conclusions: Competition across time
Authors: MacWhinney Brian
Published: January 2015

Like other biological systems, language emerges as a product of competing motivations that interact at the moment of speaking. These many different motivations are each linked to different timeframes for neural processing, social usage, and consolidation. Functionalist accounts of language usage need to pay increased attention to the ways in which motivations are distributed across timeframes in order to understand how the meshing of motivations at the moment of speaking produces long‐term impacts on speakers and language communities. Adoption of this perspective provides us with ways of integrating the many insights presented in the chapters in the current volume.
The Political Economy of Food Price Policy in Ethiopia
Authors: Admassie Assefa
Published: January 2015

Food prices increased significantly in 2007–8 in Ethiopia due to several supply- and demand-side factors. The Ethiopian government released emergency food grain reserves, imported and distributed wheat at subsidized price, banned the export of staple cereals, and removed value added and turnover taxes on food items. It also increased the reserve requirement of commercial banks and reduced domestic borrowing by public enterprises. These measures were mostly initiated by the government and the role of interest groups as well as local and international actors has been limited. These measures were taken to prevent potential social unrest and maintain macro-economic stability. A combination of factors including export bans, structural and cyclical factors, and developments in international markets have been cited as the main causes of the price increase.
The Political Economy of Food Price Policy in Mozambique
Authors: Nhate Virgulino , Massingarela Claudio , Salvucci Vincenzo
Published: January 2015

The 2007–9 food price shocks affected in particular the prices of food commodities and fuel. As a consequence, Mozambique experienced reduced exports, more expensive imports and increased food and oil prices, contributing to the stagnant poverty rates registered in 2008/9. Our analysis finds, first, that domestic prices for imported food crops followed the international trends only partially and remained high even after international prices declined. And second, the policy responses adopted by the Mozambican government to stabilize the impact of price shocks in the domestic market seem to have been effective, even though they turned out to be costly in terms of lost revenue and increased debt.
The Political Economy of Food Price Policy in Senegal
Authors: Resnick Danielle
Published: January 2015

Since independence, Senegal has been highly reliant on international markets to meet its food needs, this tendency has only increased with rapid levels of urbanization in recent decades. Poor domestic cereal harvests prior to 2007 exacerbated this import-dependence during a time of high global food prices, resulting in the cost of rice sky-rocketing. Government response was to suspend customs duties and value added taxes, providing consumer subsidies and other modes of social protection, and launching a high-profile agricultural initiative. This chapter argues that the policies which emerged reflected the confluence of a strong, diverse civil society placing disparate pressures on a government increasingly centralized around the personality and populist impulses of its former president. Senegal remains vulnerable to future food price crises, learning from these policy mistakes should be a key priority for government.
The Politics—and Process—of Rule of Law Systems in Developmental States
Authors: Desai Deval , Woolcock Michael
Published: January 2015

This chapter discusses the role of the rule of law in securing inclusive development outcomes in the context of an evolving political settlement. It offers a critique of the analytical deployment of political settlements, suggesting that the rule of law must be understood not only instrumentally but also in terms of the legitimacy it derives from the processes in and through which it has emerged and, in turn, the value with which it imbues those processes. Drawing on an extensive literature it explores how contests among and between elites and end users shape institutions through a contested, iterative, and dynamic process that, in any given setting, is likely to yield an idiosyncratic outcome borne of a unique hybrid mix of local and external inputs. It concludes with suggestions for how to enhance the rigour and relevance of rule-of-law research and interventions from both an analytical and practical standpoint.
Vanishing act
Authors: Kelly Saul
Published: January 2015

With few exceptions, Britain’s abandonment of Aden and retreat from the Gulf has been presented by contemporary commentators and later historians, in an almost Whiggish or Marxist manner, as a seemingly inevitable result of the retreat of the British Empire in the face of the inexorable march of Arab nationalism. It is designed to still any qualms about the manner of Britain leaving South Arabia and the Gulf. For, far from being an orderly ‘transfer’ of ‘power’, or’ transition’ from Britain to the successor states, the British fled Arabia in a mood of panic and confusion. It is not an edifying story, but it needs to be told.
Stopping the cycles of violence
Authors: Evans Martin
Published: January 2015

This chapter offers a brief history of the roots political and terrorist violence in Algeria from the 1960s and situates the Algerian violence of the 1990s in a broader context that compares post-independence Algeria with decolonization processes as well as post-violence transitions in Latin America, Morocco, Spain, and South Africa. As well as documenting six strands of the violence—terrorism and counter-terrorism; violence against the ordinary population; the targeting of foreigners; infighting between Islamist groups; violence within the regime; and extortion by guerrillas and pro-government militias—the chapter identifies six models of transition: amnesia; trial and justice; lustrative; negotiated restitution; political re-education; and truth commissions, to which Evans adds a seventh: political expediency. The chapter argues that Algeria was the product of a particular symmetry which was driven by internal rather than external factors.
News media, communications, and the limits of perception management and propaganda during military operations
Authors: Robinson Piers
Published: January 2015

This chapter explores debates over public opinion, media, and war, addressing the extent to which public perceptions can be shaped via propaganda and perception management. The historical backdrop to contemporary media management operations is outlined through an examination of the so-called Vietnam syndrome. Contemporary research into wartime media–state–public opinion dynamics is then discussed. Concerning domestic audiences, it is argued that early in a conflict government has considerable scope to influence opinions via propaganda activities. However, as a conflict becomes extended, and certainly by the point of ‘tactical transition’, the combination of rising casualties and elite debate reduce the potency of propaganda activities. Within a conflict zone, the utility of propaganda and perception management is significantly less, at all stages of a conflict. It is concluded that greater focus should be placed on substantive policy, as opposed to propaganda and perception-management activities, when seeking to ‘win hearts and minds’.
Negotiated agreements in tactical transitions
Authors: Beautement Mark
Published: January 2015

In 2011, Sangin District, in Helmand Province was considered the most dangerous place not only in Afghanistan but the whole world. Nevertheless, Afghan Government officials received a written offer of peace from the principal local grouping aligned to the Taliban on 29 May 2010, before NATO’s surge, or Sangin’s handover from UK to US forces. This offer evolved into the local negotiated agreement known as the Sangin Accord, announced in January 2011. This chapter considers relationships between motivations for negotiation and international policy and actions, notably military power, stabilization activities, and the co-option and legitimation of enemies. It compares explanations for negotiated agreements from academic theory and military doctrine, notably I. William Zartman’s ripeness theory and its evolutions, and offers suggestions for other local reintegration or reconciliation scenarios.
The development and diversification of West Germanic
Authors: Ringe Don , Taylor Ann
Published: January 2015

This chapter sketches the development from Proto-Northwest Germanic to Proto-West Germanic and discusses some subsequent changes that were widely shared among West Germanic dialects. It resembles the preceding chapter in organization but is much more detailed because of the much greater number of West Germanic changes. Topics covered include: Proto-West Germanic sound changes; Proto-West Germanic morphological innovations; parallel developments in West Germanic, divided into post-PWGmc sound changes and post-PWGmc morphological changes. A chart of the relative chronology of sound changes from Proto-Germanic to and beyond Proto-West Germanic closes the chapter.
The interaction of adjectival passive and Voice
Authors: Doron Edit
Published: January 2015

Adjectival passive participles typically denote states resulting from the events described by the corresponding active verbs. For a particular subclass of passive participles in Hebrew (the causative-template participles), the characterization of these states always implicitly includes the verb's external argument, even for verbs where the external argument is optional in the active voice. Such passive participles are thus parallel to passive verbs, which also obligatorily include implicit external arguments. Adjectival passive participles in other templates are parallel to middle-voice verbs, which do not include external arguments. This indicates that the structure of adjectival passives is specified for voice. Moreover, the voice specification of adjectival passives is determined by the non-active voice values available to the corresponding verbs.
Basic considerations in experimental design
Authors: Gibson David J.
Published: January 2015

Three main topics are covered in this chapter: design considerations (experiments and observations), where and how studies should be conducted (choosing sites, plots, and plants), and statistical issues in conducting experiments. The advantages and limitations of field, greenhouse, and laboratory experiments are discussed. How to choose the most appropriate plants to address particular questions is described along with listings of popular or ‘model’ plants, and plant phytometers. The increasing emphasis on phylogenetics is described along with an introduction to accounting for phylogenetic relatedness in comparative studies through the use of phylogenetically independent contrasts (PICs). Important statistical issues in conducting experiments are described including the use of controls, adequate replication, precision versus accuracy, sample adequacy, type I and type II errors, power, and experimental designs to avoid pseudoreplication. Darwin’s ‘Vitality of seeds’ experiment is described as the first plant population ecology experiment.
Experimental treatments
Authors: Gibson David J.
Published: January 2015

The first section of this chapter provides advice on issues related to appropriate establishment of experimental treatments including identification of the experimental unit and avoiding hidden treatment effects. Experimental treatments also need to consider various aspects of the plants that are being tested including age, ontogeny, gender, density, and genetic identity. The main focus of this chapter is on establishing biotic and abiotic experimental treatments. Biotic treatments include population sources (including ecotypes and reaction norms), neighbour effects, manipulating reproduction (fecundity and pollinators), herbivory, pathogens, and allelopathy. Abiotic treatments discussed include the soil environment, temperature, light, atmospheric change, and disturbance (including mowing, fire, and burial). Designs for establishing experimental treatments to study plant interactions both above- and belowground are presented.
Rural Bound: Determinants of Metro to Non‐Metro Migration in the United States
Authors: Rupasingha Anil , Liu Yongzheng , Partridge Mark
Published: January 2015

A general global precept is that agglomeration forces lead to migration from rural to urban areas. Yet for much of the time since the early 1970s, more people have moved from metro to nonmetro U.S. counties. The underlying causes of this pattern have changed over time with economic shocks and changing household preferences. For instance, the post 2000 period has seen a significant decline in domestic migration rates, a significant increase in commodity prices that favor rural areas, and potential changes in the valuation of natural amenities that would affect migration. This article investigates the determinants of U.S. gross migration from metro to nonmetro counties and nonmetro to metro counties for the 1995–2000 and 2005–2009 periods in order to compare the differences in rural to urban and urban to rural migration, as well as compare the 1990s to the 2005–2009 periods. More specifically, the present study extends the literature by more broadly examining the underlying factors associated with deconcentration and economic restructuring arguments of metro to nonmetro migration. The article uses (1) extensive county‐to‐county migration flows and (2) the utility maximization theory that extends the framework of a discrete choice model. The results show that population density, distance to urban areas, industry mix employment growth, natural amenities, and percentage of older people are key factors underlying these migration patterns. We also find a slight fading of effects of natural amenities and population density, and a slight increase in the effects of wage and employment growth from 2005–2009.
Plasma and target-site subcutaneous tissue population pharmacokinetics and dosing simulations of cefazolin in post-trauma critically ill patients
Authors: Roberts Jason A. , Udy Andrew A. , Jarrett Paul , Wallis Steven C. , Hope William W. , Sharma Raman , Kirkpatrick Carl M. J. , Kruger Peter S. , Roberts Michael S. , Lipman Jeffrey
Published: January 2015

Objectives

The objective of this study was to describe the population pharmacokinetics of cefazolin in plasma and the interstitial fluid of subcutaneous tissue of post-trauma critically ill patients and provide clinically relevant dosing recommendations that result in optimal concentrations at the target site.

Patients and methods

This was a pharmacokinetic study in a tertiary referral ICU. We recruited 30 post-trauma critically ill adult patients and collected serial total and unbound plasma cefazolin concentrations. Interstitial fluid concentrations were determined using in vivo microdialysis. Population pharmacokinetic analysis and Monte Carlo simulations were undertaken with Pmetrics®. Fractional target attainment against an MIC distribution for Staphylococcus aureus isolates was calculated.

Results

The mean (SD) age, weight, APACHE II score and CLCR were 37.0 (14.1) years, 86.8 (22.7) kg, 16.9 (5.3) and 163 (44) mL/min, respectively. A three-compartment linear population pharmacokinetic model was most appropriate. Covariates included in the model were CLCR on drug clearance and serum albumin concentration and body weight on the volume of the central compartment. The fractional target attainment for a 1 g intravenous 8-hourly dose for a CLCR of 50 mL/min was 88%, whereas for a patient with a CLCR of 215 mL/min, a dose of 2 g 6-hourly achieved 84% fractional target attainment.

Conclusions

Clinicians should be mindful of the effects of elevated CLCR and serum albumin concentrations on dosing requirements for post-trauma critically ill patients.
RPI-Pred: predicting ncRNA-protein interaction using sequence and structural information
Authors: Suresh V. , Liu Liang , Adjeroh Donald , Zhou Xiaobo
Published: January 2015

RNA-protein complexes are essential in mediating important fundamental cellular processes, such as transport and localization. In particular, ncRNA-protein interactions play an important role in post-transcriptional gene regulation like mRNA localization, mRNA stabilization, poly-adenylation, splicing and translation. The experimental methods to solve RNA-protein interaction prediction problem remain expensive and time-consuming. Here, we present the RPI-Pred (RNA-protein interaction predictor), a new support-vector machine-based method, to predict protein-RNA interaction pairs, based on both the sequences and structures. The results show that RPI-Pred can correctly predict RNA-protein interaction pairs with ∼94% prediction accuracy when using sequence and experimentally determined protein and RNA structures, and with ∼83% when using sequences and predicted protein and RNA structures. Further, our proposed method RPI-Pred was superior to other existing ones by predicting more experimentally validated ncRNA-protein interaction pairs from different organisms. Motivated by the improved performance of RPI-Pred, we further applied our method for reliable construction of ncRNA-protein interaction networks. The RPI-Pred is publicly available at: http://ctsb.is.wfubmc.edu/projects/rpi-pred.
A Less-Invasive Retroperitoneal Lumbar Approach
Authors: Qian Yu , Lin Zhen , Jin Cong , Zhao Xing , Zheng Minghao
Published: January 2015

Study Design:

Surgical approach development in an animal model, and a prospective study comparing clinical outcomes between novel and conventional approaches in thoracolumbar burst fracture fixation.

Objective:

To investigate the feasibility of a less-invasive retroperitoneal approach to the lumbar spine in a sheep model and to compare the clinical outcomes of anterior reconstruction in the treatment of thoracolumbar burst fractures using novel and conventional approaches.

Summary of Background Data:

The anterior retroperitoneal lumbar approach is well established for anterior lumbar surgical procedures in both humans and animal models. However, potential concerns include the increased risk of complications such as soft-tissue trauma, and extended periods of rehabilitation postoperatively.

Materials and Methods:

A less-invasive retroperitoneal approach was designed in a sheep model with minimal soft-tissue dissection to keep the abdominal and paravertebral muscles intact. Eight sheep underwent anterior lumbar interbody fusion using this approach. In the clinical study, 48 patients with thoracolumbar burst fractures underwent anterior decompression and reconstruction. The less-invasive approach and conventional approach were applied in 12 and 36 cases, respectively. The clinical outcomes during the minimum 12-month follow-up of the 2 groups were compared.

Results:

With the less-invasive approach, anterior lumbar interbody fusion was accomplished in all sheep, and no surgical complications were observed. In the clinical study, operation time, blood loss, and duration of hospitalization were comparable between 2 groups. Using the less-invasive approach decreased the length of incision, 3-day postoperative visual analogue scale score, postoperative independent standing, and narcotic-dependent duration. No surgical complications were observed in either group.

Conclusions:

Our results and early experience suggests that the less-invasive retroperitoneal approach is safe and effective for anterior lumbar surgery. Compared with the conventional approach, significantly better postoperative rehabilitation and abdominal muscle preservation were seen with this novel approach.
Nutrient Adequacy and Associated Factors in a Nationwide Sample of German Toddlers
Authors: Hilbig Annett , Drossard Claudia , Kersting Mathilde , Alexy Ute
Published: January 2015

Objectives:

Nutrition in toddlerhood may have short‐ and long‐term impacts on health and nutrition behavior. The objectives of the present article are to describe intake of energy and nutrients from the end of infancy to toddlerhood, and to examine dietary and socioeconomic factors (socioeconomic status [SES]) associated with total nutrient adequacy measured by a nutrient‐based index (Nutrient Quality Index [NQI]).

Methods:

In the German Representative Study of Toddler Alimentation from 2008, 7‐day estimated dietary records were collected cross‐sectionally from toddlers ages 10 to 36 months (n = 525). The study population was recruited in the TNS access panel. The intakes of energy and 18 nutrients were evaluated and the NQI was determined. Age trends in nutrient intake were tested with analysis of variance. Analysis of the association between SES and the NQI was performed by multiple linear regression analysis.

Results:

In all of the age groups, energy intake was close to the reference value representing moderate physical activity. The mean intake of most vitamins and minerals reached the respective reference values, but nutrient density decreased with age. Dietary intakes of iron, iodine, and vitamin D are low in our study. The NQI reached approximately 80 points and was lower in older children than in younger children. NQI was not affected by SES but by formula use.

Conclusions:

Nutritional quality measured by total nutrient intake is altogether high in German toddlers, although NQI decreased with increasing age. The NQI is independent of social class. The positive association with formula intake can be explained by the general enrichment of vitamins and minerals of these products.
Information use by humans during dynamic route choice in virtual crowd evacuations
Authors: Bode Nikolai W. F. , Kemloh Wagoum Armel U. , Codling Edward A.
Published: January 2015

We conducted a computer-based experiment with over 450 human participants and used a Bayesian model selection approach to explore dynamic exit route choice mechanisms of individuals in simulated crowd evacuations. In contrast to previous work, we explicitly explore the use of time-dependent and time-independent information in decision-making. Our findings suggest that participants tended to base their exit choices on time-dependent information, such as differences in queue lengths and queue speeds at exits rather than on time-independent information, such as differences in exit widths or exit route length. We found weak support for similar decision-making mechanisms under a stress-inducing experimental treatment. However, under this treatment participants were less able or willing to adjust their original exit choice in the course of the evacuation. Our experiment is not a direct test of behaviour in real evacuations, but it does highlight the role different types of information and stress play in real human decision-making in a virtual environment. Our findings may be useful in identifying topics for future study on real human crowd movements or for developing more realistic agent-based simulations.
Top carnivores increase their kill rates on prey as a response to human-induced fear
Authors: Smith Justine A. , Wang Yiwei , Wilmers Christopher C.
Published: January 2015

The fear induced by predators on their prey is well known to cause behavioural adjustments by prey that can ripple through food webs. Little is known, however, about the analogous impacts of humans as perceived top predators on the foraging behaviour of carnivores. Here, we investigate the influence of human-induced fear on puma foraging behaviour using location and prey consumption data from 30 tagged individuals living along a gradient of human development. We observed strong behavioural responses by female pumas to human development, whereby their fidelity to kill sites and overall consumption time of prey declined with increasing housing density by 36 and 42%, respectively. Females responded to this decline in prey consumption time by increasing the number of deer they killed in high housing density areas by 36% over what they killed in areas with little residential development. The loss of food from declines in prey consumption time paired with increases in energetic costs associated with killing more prey may have consequences for puma populations, particularly with regard to reproductive success. In addition, greater carcass availability is likely to alter community dynamics by augmenting food resources for scavengers. In light of the extensive and growing impact of habitat modification, our study emphasizes that knowledge of the indirect effects of human activity on animal behaviour is a necessary component in understanding anthropogenic impacts on community dynamics and food web function.
Structural and biochemical characterization of the laminarinaseZgLamCGH16fromZobellia galactanivoranssuggests preferred recognition of branched laminarin
Authors: Labourel Aurore , Jam Murielle , Legentil Laurent , Sylla Balla , Hehemann Jan-Hendrik , Ferrières Vincent , Czjzek Mirjam , Michel Gurvan
Published: January 2015

Laminarin is a β-1,3-D-glucan displaying occasional β-1,6 branches. This storage polysaccharide of brown algae constitutes an abundant source of carbon for marine bacteria such asZobellia galactanivorans. This marine member of the Bacteroidetes possesses five putative β-1,3-glucanases [four belonging to glycosyl hydrolase family 16 (GH16) and one to GH64] with various modular architectures. Here, the characterization of the β-glucanaseZgLamC is reported. The catalytic GH16 module (ZgLamCGH16) was produced inEscherichia coliand purified. This recombinant enzyme has a preferential specificity for laminarin but also a significant activity on mixed-linked glucan (MLG). The structure of an inactive mutant ofZgLamCGH16in complex with a thio-β-1,3-hexaglucan substrate unravelled a straight active-site cleft with three additional pockets flanking subsites −1, −2 and −3. These lateral pockets are occupied by a glycerol, an acetate ion and a chloride ion, respectively. The presence of these molecules in the vicinity of the O6 hydroxyl group of each glucose moiety suggests thatZgLamCGH16accommodates branched laminarins as substrates. Altogether,ZgLamC is a secreted laminarinase that is likely to be involved in the initial step of degradation of branched laminarin, while the previously characterizedZgLamA efficiently degrades unbranched laminarin and oligo-laminarins.
Structures of lactate dehydrogenase A (LDHA) in apo, ternary and inhibitor-bound forms
Authors: Kolappan Subramaniapillai , Shen David L. , Mosi Renee , Sun Jianyu , McEachern Ernest J. , Vocadlo David J. , Craig Lisa
Published: January 2015

Lactate dehydrogenase (LDH) is an essential metabolic enzyme that catalyzes the interconversion of pyruvate and lactate using NADH/NAD+as a co-substrate. Many cancer cells exhibit a glycolytic phenotype known as the Warburg effect, in which elevated LDH levels enhance the conversion of glucose to lactate, making LDH an attractive therapeutic target for oncology. Two known inhibitors of the human muscle LDH isoform, LDHA, designated1and2, were selected, and their IC50values were determined to be 14.4 ± 3.77 and 2.20 ± 0.15 µM, respectively. The X-ray crystal structures of LDHA in complex with each inhibitor were determined; both inhibitors bind to a site overlapping with the NADH-binding site. Further, an apo LDHA crystal structure solved in a new space group is reported, as well as a complex with both NADH and the substrate analogue oxalate bound in seven of the eight molecules and an oxalate only bound in the eighth molecule in the asymmetric unit. In this latter structure, a kanamycin molecule is located in the inhibitor-binding site, thereby blocking NADH binding. These structures provide insights into LDHA enzyme mechanism and inhibition and a framework for structure-assisted drug design that may contribute to new cancer therapies.
Analysis of the HindIII-catalyzed reaction by time-resolved crystallography
Authors: Kawamura Takashi , Kobayashi Tomoki , Watanabe Nobuhisa
Published: January 2015

In order to investigate the mechanism of the reaction catalyzed by HindIII, structures of HindIII–DNA complexes with varying durations of soaking time in cryoprotectant buffer containing manganese ions were determined by the freeze-trap method. In the crystal structures of the complexes obtained after soaking for a longer duration, two manganese ions, indicated by relatively higher electron density, are clearly observed at the two metal ion-binding sites in the active site of HindIII. The increase in the electron density of the two metal-ion peaks followed distinct pathways with increasing soaking times, suggesting variation in the binding rate constant for the two metal sites. DNA cleavage is observed when the second manganese ion appears, suggesting that HindIII uses the two-metal-ion mechanism, or alternatively that its reactivity is enhanced by the binding of the second metal ion. In addition, conformational change in a loop near the active site accompanies the catalytic reaction.
Ligand-bound structures of 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase fromMoraxella catarrhalisreveal a water channel connecting to the active site for the second step of catalysis
Authors: Dhindwal Sonali , Priyadarshini Priyanka , Patil Dipak N. , Tapas Satya , Kumar Pramod , Tomar Shailly , Kumar Pravindra
Published: January 2015

KdsC, the third enzyme of the 3-deoxy-D-manno-octulosonic acid (KDO) biosynthetic pathway, catalyzes a substrate-specific reaction to hydrolyze 3-deoxy-D-manno-octulosonate 8-phosphate to generate a molecule of KDO and phosphate. KdsC is a phosphatase that belongs to the C0 subfamily of the HAD superfamily. To understand the molecular basis for the substrate specificity of this tetrameric enzyme, the crystal structures of KdsC fromMoraxella catarrhalis(Mc-KdsC) with several combinations of ligands, namely metal ion, citrate and products, were determined. Various transition states of the enzyme have been captured in these crystal forms. The ligand-free and ligand-bound crystal forms reveal that the binding of ligands does not cause any specific conformational changes in the active site. However, the electron-density maps clearly showed that the conformation of KDO as a substrate is different from the conformation adopted by KDO when it binds as a cleaved product. Furthermore, structural evidence for the existence of an intersubunit tunnel has been reported for the first time in the C0 subfamily of enzymes. A role for this tunnel in transferring water molecules from the interior of the tetrameric structure to the active-site cleft has been proposed. At the active site, water molecules are required for the formation of a water bridge that participates as a proton shuttle during the second step of the two-step phosphoryl-transfer reaction. In addition, as the KDO biosynthesis pathway is a potential antibacterial target, pharmacophore-based virtual screening was employed to identify inhibitor molecules for theMc-KdsC enzyme.
A fragmentation and reassembly method forab initiophasing
Authors: Shrestha Rojan , Zhang Kam Y. J.
Published: January 2015

Ab initiophasing withde novomodels has become a viable approach for structural solution from protein crystallographic diffraction data. This approach takes advantage of the known protein sequence information, predictsde novomodels and uses them for structure determination by molecular replacement. However, even the current state-of-the-artde novomodelling method has a limit as to the accuracy of the model predicted, which is sometimes insufficient to be used as a template for successful molecular replacement. A fragment-assembly phasing method has been developed that starts from an ensemble of low-accuracyde novomodels, disassembles them into fragments, places them independently in the crystallographic unit cell by molecular replacement and then reassembles them into a whole structure that can provide sufficient phase information to enable complete structure determination by automated model building. Tests on ten protein targets showed that the method could solve structures for eight of these targets, although the predictedde novomodels cannot be used as templates for successful molecular replacement since the best model for each target is on average more than 4.0 Å away from the native structure. The method has extended the applicability of theab initiophasing byde novomodels approach. The method can be used to solve structures when the bestde novomodels are still of low accuracy.
The affine and Euclidean normalizers of the subperiodic groups
Authors: VanLeeuwen Brian Kevin , Valentín De Jesús Pedro , Litvin Daniel B. , Gopalan Venkatraman
Published: January 2015

The affine and Euclidean normalizers of the subperiodic groups, the frieze groups, the rod groups and the layer groups, are derived and listed. For the layer groups, the special metrics used for plane-group Euclidean normalizers have been considered.
Understanding students’ preferences on school mid-day meal menu in India
Authors: Ali Jabir , Akbar Mohammad
Published: January 2015

Purpose

– The purpose of this paper is to analyze the difference in students’ preferences on weekly menu of school mid-day meal (MDM) program in Uttar Pradesh, India.

Design/methodology/approach

– The study is based on primary structured questionnaire survey through personal interviews using multi-stage stratified sampling technique. This comprehensive survey covered 2,400 primary and upper primary students belonging to eight districts of Uttar Pradesh – Allahabad, Balrampur, Gautam Buddh Nagar, Hathras, Kanpur Nagar, Mathura, Shahjahanpur and Varanasi. A total of 60 schools have been selected from each district, covering a total of 480 primary and upper primary schools. Simple statistical tools have been used to analyze the surveyed data such as cross-tabulation, percentage distribution and rank analysis. Further, six research hypotheses have been formulated to analyze the difference in school meal menu preferences among the students and χ2-statistics has been used to test the significance level of these hypotheses.

Findings

– Survey results indicate that more than 90 percent students eat MDM in the school as per the weekly menu. Result of χ2-test indicates that choices on school meal menu among the students differ significantly across weekdays. Rice-pulses or rice-sambar served on Tuesday is reported to be the first preferred food of children given first preference by around 30 percent, followed by kadi-rice or kheer which is served on Wednesday. The results of χ2-tests exhibited a significant difference on weekly menu choices by gender, kitchen types, rural and urban locations and geographical regions. About 27 percent of the students reported that they want to have a change in the menu. When further probed about the kind of changes desired in the menu, puri-vegetables was found to be the most preferred choice of the respondents, beside halwa/kheer and rice with pulses/vegetables/kadi being the next preferred choices.

Practical implications

– The present study provides managerial implications to the policy makers and scheme/program implementers for better understanding of the students’ preferences on school MDM weekly menu.

Originality/value

– There are several evaluation studies undertaken by various agencies to assess the impact of MDM program on school attendance, retention and nutritional status of children. However, there are limited numbers of studies available, which have measured the students’ preferences on school MDM menu.
Why investors use technical analysis? Information discovery versus herding behavior
Authors: Wang Tiandu , Sun Qian
Published: January 2015

Purpose

– The purpose of this paper is to establish two competitive models to explain why investors use technical analysis (TA).

Design/methodology/approach

– Information Discovery Model suggests that technical traders are able to infer non-public information; Herding Behavior Model argues that TA is a kind of irrational herding behavior that can make profit when other noise traders exist.

Findings

– The empirical results from Chinese stock market show that some technical trading rules generate significant excess returns.

Research limitations/implications

– The empirical results from Chinese stock market show that some technical trading rules generate significant excess returns. Stocks with stronger information asymmetry and lower liquidity experiences higher excess return, which support the Information Discovery Model that TA is a method of information discovery for rational investors when the market is not fully efficient.

Originality/value

– Stocks with stronger information asymmetry and lower liquidity experiences higher excess return, which support the Information Discovery Model that TA is a method of information discovery for rational investors when the market is not fully efficient.
Corporate social and environmental disclosure and corporate performance
Authors: Khlif Hichem , Guidara Achraf , Souissi Mohsen
Published: January 2015

Purpose

– The purpose of this paper is to investigate the relationship between corporate performance and social and environmental disclosure for two African leading countries namely, South Africa (common law country) and Morocco (civil law country).

Design/methodology/approach

– The sample consists of 168 annual reports spanning from 2004 to 2009. A content analysis of companies’ annual reports is used to measure the extent of voluntary social and environmental disclosure.

Findings

– Results show that social and environmental disclosure has a significant positive effect on corporate performance only in the South African setting.

Originality/value

– The findings emphasize the need to explicitly consider the legal and institutional setting prevailing in each context. For instance, social and environmental organizations in South Africa enjoy more power to influence companies’ social and environmental reporting policy, whereas, their counterparts in Morocco, enjoy less power to place pressure on companies to incorporate social and environmental considerations into business operations.
Does ownership structure affect the degree of corporate financial distress in China?
Authors: Hu Dan , Zheng Haiyan
Published: January 2015

Purpose

– The purpose of this paper is to investigate the degree of corporate financial distress (DOFD) and relationship between ownership structure and the DOFD in China.

Design/methodology/approach

– The authors estimate the DOFD across a sample of 378 Chinese-listed companies that got into financial distress between 2000 and 2008. The DOFD reflects long-term solvency capability, short-term liquidity capability, development capability, risk level, profitability capability, operating capacity, and cash flow capability. The authors analyze the relationship between ownership structure and the DOFD in these companies, using the panel data analysis method.

Findings

– The authors find that a concentrated ownership structure is negatively related to the DOFD. Further, the results indicate that a state-owned status helps firms in decreasing their DOFD and that the separation of cash-flow rights and control rights is positively related to the DOFD. The authors also found that the Chinese special treatment (ST) system needs further improvement. The reason is that ST firms can be classified into “value” ST firms and “garbage” ST firms. They have different DOFD and change trend, so they should not be treated equally.

Originality/value

– This paper find that Chinese ST system and previous research are not helpful for risk-seeking investor to distinguish and evaluate “value” ST firms and “garbage” ST firms. It is unfair to warn and punish this two kinds of firms equally, so ST system should be improved. The authors also suggest that risk-seeking investor can choose ST firms that have a concentrated ownership structure and are controlled by the state or local government. These findings are not observed in previous studies.