bluuebunny/crossref_metadata_2025 huggingface dataset:
An
in silico
method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case
Authors: Wong Anthony F , Pielmeier Ulrike , Haug Peter J , Andreassen Steen , Morris Alan H
Published: July 2015

Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark.

Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low.

Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P  = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P  < .001), and clinically different.

Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols.

Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials.
Cranial Nerves I and II
Authors: Flemming Kelly D. , Leavitt Jacqueline A. , Benarroch Eduardo E.
Published: July 2015

Cranial nerves I and II are supratentorial, paired cranial nerves serving olfaction and vision, respectively. This chapter provides an overview of their anatomy. Clinical disorders of cranial nerves are reviewed elsewhere.
Autonomic Nervous System
Authors: Tracy Jennifer A. , Benarroch Eduardo E. , Flemming Kelly D.
Published: July 2015

The autonomic nervous system is involved in many important unconscious body functions. It aids in maintaining the internal environment and responds and adapts to the external environment. The autonomic nervous system consists of peripheral components (sympathetic and parasympathetic nerves) and central components (ventrolateral medulla, nucleus ambiguus, nucleus of the solitary tract, periaqueductal gray, anterior cingulate gyrus, insular cortex, amygdala, and hypothalamus). This chapter briefly reviews the anatomy and functional components of the autonomic nervous system and the anatomical clinical correlations.
Cortical Circuitry, Networks, and Function
Authors: Jones David T.
Published: July 2015

The human brain is a complex information processing system whose proper functioning depends on the organization of its processing units. The scale of these processing units spans multiple levels from the genetic to systems level. A complete understanding of any 1 of these levels necessitates understanding each level because they are interdependent. Functional magnetic resonance imaging has revolutionized the understanding of the functional and structural architecture of the brain and serves as the lens through which we will review this complex system. This chapter reviews cortical circuitry and networks of the cerebral cortex.
Cellular Injury and Death
Authors: Katz Brian S. , Benarroch Eduardo E.
Published: July 2015

Cell death is a result of several complex interconnected mechanisms simultaneously occurring in the cell’s organelles, namely, necrosis, apoptosis, and autophagy. While different morphologically and biochemically, these processes are not mutually exclusive and commonly coexist in cell loss in vascular, inflammatory, and degenerative conditions. The 3 pathways of cellular injury and death are 1) external forced cell death or necrosis; 2) programmed nuclear cell death, including apoptosis; and 3) autophagic cell death. These processes may affect neurons, glial cells, endothelial cells, and ependymal cells. The cell death pathways differ in their triggering factors, temporal profile, biochemical mechanisms, and morphologic markers.
Psychological Development Through the Life Cycle
Authors: Lapid Maria I. , Olsen Mark W.
Published: July 2015

Human development from conception to death can be viewed from a number of perspectives, including biologic, cognitive, emotional, social, and moral. This chapter reviews major features of various facets of development from infancy through toddlerhood, preschool, school-aged, preadolescence, adolescence, the transition into early adulthood, adulthood, and late adulthood. It includes consideration of developmental tasks and challenges as well as the importance of the environmental influence of family, peers, school, and the broader social milieu. Psychological aspects and specific stages in the elderly are also described.
Psychiatric Disorders Associated With Infancy, Childhood, and Adolescence
Authors: Bhagia Jyoti
Published: July 2015

This chapter covers key psychiatric disorders of infancy, childhood, and adolescence (eg, ADHD, learning disorder, autism spectrum disorder, mental retardation, tic disorders, motor skills disorder, communication disorders, elimination disorders). In some instances, the disorders are briefly mentioned here and covered in more detail in other chapters as indicated.
Substance Use Disorders
Authors: Dolenc Tamara J.
Published: July 2015

Substance dependence is a chronic, relapsing illness. Episodes of intoxication are common, along with significant medical and social consequences. Substance dependence is accompanied by loss of control over the amount used, continued use despite negative consequences, preoccupation with use, and dysphoria during abstinence. In heavy and long-term users, abrupt cessation or reduction in substance use results in withdrawal syndrome. Risk of substance dependence is influenced by genetic, psychosocial, and environmental factors. Patients with substance use disorders come from all age groups and from all ethnic, cultural, and socioeconomic backgrounds.
Small cell lung cancer (SCLC) and syndrome of inappropriate antidiurectic hormone (SIADH)
Authors: Darby Angela , Lee Alex
Published: July 2015

Small cell lung cancer (SCLC) is a smoking-associated malignancy. Accounting for 15-20% of lung cancers, the onset is typically rapid. In localized disease, surgical resection can be considered. High rates of response to first-line chemotherapy are seen, with the addition of concurrent radiotherapy improving survival in disease restricted to the ipsilateral hemithorax, as illustrated by this case. Prophylactic cranial irradiation, following response to induction therapy, reduces the rate of brain metastases and prolongs survival. Disease relapse occurs in a large proportion of cases, frequently within 1 year of induction treatment. Second-line options have a modest impact, in terms of response and survival. So far, there has been limited success of novel targeted agents in the treatment of SCLC treatment. This case discusses the recurrence of SCLC with the syndrome of inappropriate anti-diuretic hormone (SIADH) secretion. It is the cancer most commonly associated with paraneoplastic endocrine and neurological syndromes.
Ovarian cancer and malignant bowel obstruction
Authors: McNeish Iain , Chau Caroline
Published: July 2015

Ovarian cancer typically presents at an advanced stage and requires a multidisciplinary approach in its management. This chapter covers the diagnosis, evidence-based treatments, and recent advances in ovarian cancer. The case study outlines the presentation and clinical course of a patient with advanced ovarian cancer. It summarizes the role of surgery, chemotherapy, and bevacizumab in first-line and in disease relapse settings, with reference to landmark trials such as ICON4, ICON7, OCEANS, and CALYPSO. Bowel obstruction is a common complication of this disease, seen in the acute oncology setting. Topical issues, such as routine germline BRCA1/2 testing and CA125 monitoring, have also been discussed.
Metastatic prostate cancer and spinal cord compression
Authors: O’Donnell Helen , Bhattacharya Indrani
Published: July 2015

The managements of localized and metastatic prostate cancer are distinct. Prostate cancer management has undergone many changes, due to developments in our understanding of the natural history of prostate cancer and its response to treatment, and the introduction of functional imaging and technological advances in both radiotherapy and surgery. This case demonstrates the issues surrounding diagnosis and risk stratification of prostate cancer, such that treatment options can be presented and an informed decision made. The issue of prostate-specific antigen recurrence, subsequent metastatic disease, and its sequelae are discussed. There have been significant advances in drug development in metastatic prostate cancer, which have been discussed, as well as the diagnosis and management of spinal cord compression. The limitations of success from radical local treatment relate either to resistant disease locally or the presence of early micrometastatic disease at diagnosis, which is not treated with local therapy.
The Neuron
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

The Fourth Edition of The Neuron provides a comprehensive first course in the cell and molecular biology of nerve cells. It begins with properties of the many newly discovered ion channels that have emerged through mapping of the genome and which shape the way a single neuron generates varied patterns of electrical activity. It also covers the molecular mechanisms that convert electrical activity into the secretion of neurotransmitter hormones at synaptic junctions between neurons. It discusses the biochemical pathways that are linked to the action of neurotransmitters and that can alter the cellular properties of neurons or sensory cells that transduce information from the outside world into the electrical code used by neurons, and the rapidly expanding knowledge of the molecular factors that induce an undifferentiated cell to become a neuron, and then guide it to form appropriate synaptic connections with its partners. Also addressed is the role of ongoing experience and activity in shaping these connections, and the mechanisms thought to underlie the phenomena of learning and memory.
Ion Channels Are Membrane Proteins
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

Molecular structures of voltage-gated sodium and potassium channels both have 24 membrane-spanning segments, in addition to a domain that contributes to the channel pore. In sodium channels, this overall structure is achieved with a single primary subunit containing four homologous domains, each with six membrane-spanning segments. The primary subunit of potassium channels, however, is smaller and resembles one of the four homologous domains in the sodium channel; four of these primary subunits come together to form a functional potassium channel. Experiments have revealed channel protein regions involved in such functions as voltage-dependent activation, inactivation, and ion selectivity. Some functions of voltage-dependent channels do not involve global changes in protein conformation but can be assigned to discrete structural modules in the channel protein. Inferences from mutational analysis, particularly those related to channel gating, conduction, and selectivity, have been confirmed and extended by elucidating the three-dimensional structures of several voltage-dependent ion channels.
Sensory Receptors
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

Sensory cells have evolved pathways that allow ion channels to be regulated by external stimuli such as movement, light, or chemicals. In some cases, such as in photoreceptors and olfactory and taste receptors, the means by which the external stimulus is transduced is reasonably well understood. Such cells appear to handle information in ways similar to those used by neurons that deal with information coming from a presynaptic pathway, by altering the levels of second messengers such as cyclic nucleotides, which then open or close ion channels in the plasma membrane. In contrast, in mechanoreceptors, which include touch receptors and hair cells of the cochlea that are required for hearing, movement is directly linked to the gating of ion channels.
The Birth and Death of a Neuron
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

The development of the nervous system requires the participation of a variety of factors that influence neuronal determination, proliferation, migration, and differentiation. The earliest steps in the formation of a neuron involve the actions of factors such as the bone morphogenetic proteins and neural inducers. Acting on cells that still have the potential to develop into many different types of cells, these factors control the synthesis of transcription factors and determine whether the complement of genes that becomes activated corresponds to those required for building a neuron. The birth of new neurons occurs at a high rate early in development, but in some brain regions persists in adults. The normal formation of the nervous system also requires the programmed death of many neurons. Decisions as to whether a specific neuron survives or perishes during development are made by factors that control the permeability of the outer mitochondrial membrane.
Learning and Memory
Authors: Levitan Irwin B. , Kaczmarek Leonard K.
Published: July 2015

Psychologists have described different kinds of learning and memory, and there is an ongoing search for the physical basis of these distinctions and for the cellular and molecular mechanisms responsible. Because of the complexity of most nervous systems, the search has focused to a large extent on animals with relatively simple nervous systems and on reduced preparations. Common themes have emerged, such as the requirement for signaling pathways linked to calcium and cyclic AMP, and the fact that pathways used in normal development continue to be used for plasticity in adults. At the same time, it is clear that there is an enormous diversity of cellular mechanisms that contribute to short-term and long-term phases of memory formation. These include long-term potentiation (LTP), long-term depression (LTD), spike-timing dependent plasticity, synaptic tagging, and synaptic scaling. Each type of synaptic connection has its own personality such that, in response to a particular pattern of stimulation, one synapse may increase its postsynaptic receptors while another may expand its presynaptic terminals.
Characterization of systemic disease in primary Sjögren's syndrome: EULAR-SS Task Force recommendations for articular, cutaneous, pulmonary and renal involvements
Authors: Ramos-Casals Manuel , Brito-Zerón Pilar , Seror Raphaèle , Bootsma Hendrika , Bowman Simon J. , Dörner Thomas , Gottenberg Jacques-Eric , Mariette Xavier , Theander Elke , Bombardieri Stefano , De Vita Salvatore , Mandl Thomas , Ng Wan-Fai , Kruize Aike , Tzioufas Athanasios , Vitali Claudio ,   on behalf of the EULAR Sjögren Syndrome Task Force
Published: July 2015

Objective. To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS.

Methods. The EULAR-SS Task Force Group steering committee agreed to approach SS-related systemic involvement according to the EULAR SS Disease Activity Index (ESSDAI) classification and proposed the preparation of four separate manuscripts: articular, cutaneous, pulmonary and renal ESSDAI involvement; muscular, peripheral nervous system, CNS and haematological ESSDAI involvement; organs not included in the ESSDAI classification; and lymphoproliferative disease. Currently available evidence was obtained by a systematic literature review focused on SS-related systemic features.

Results. The following information was summarized for articular, cutaneous, pulmonary and renal involvement: a clear, consensual definition of the clinical feature, a brief epidemiological description including an estimate of the prevalence reported in the main clinical series and a brief list of the key clinical and diagnostic features that could help physicians clearly identify these features. Unfortunately we found that the body of evidence relied predominantly on information retrieved from individual cases, and the scientific information provided was heterogeneous. The analysis of types of involvement was biased due to the unbalanced reporting of severe cases over non-severe cases, although the main sources of bias were the heterogeneous definitions of organ involvement (or even the lack of definition in some studies) and the heterogeneous diagnostic approach used in studies to investigate involvment of each organ.

Conclusion. The proposals included in this article are a first step to developing an optimal diagnostic approach to systemic involvement in primary SS and may pave the way for further development of evidence-based diagnostic and therapeutic guidelines.
Breast Milk Protects Against Gastrointestinal Symptoms in Infants at High Risk for Autism During Early Development
Authors: Penn Alexander H. , Carver Leslie J. , Herbert Carrie A. , Lai Tiffany S. , McIntire Melissa J. , Howard Jeffrey T. , Taylor Sharon F. , Schmid‐Schönbein Geert W. , Dobkins Karen R.
Published: July 2015

Objectives:

Parents of children with autism spectrum disorders (ASDs) often report gastrointestinal (GI) dysfunction in their children. The objectives of the present study were to determine whether infants at high risk for developing ASD (ie, siblings of children diagnosed as having ASD) show greater prevalence of GI problems and whether this prevalence is associated with diet and age at weaning from breast milk.

Methods:

Using questionnaires, diet history and GI problems were tracked prospectively and retrospectively in 57 high‐risk infants and for comparison in 114 low‐risk infants (infants from families without ASD history).

Results:

In low‐risk infants, prevalence of GI symptoms, in aggregate, did not vary with diet or age of weaning. By contrast, high‐risk infants with GI symptoms were weaned earlier than those without symptoms (P < 0.04), and high‐risk infants showed greater prevalence of GI symptoms, in aggregate, on a no breast milk diet than on an exclusive breast milk diet (P < 0.017). Constipation, in particular, was more prevalent in high‐risk infants compared with low‐risk infants (P = 0.01), especially on a no breast milk diet (P = 0.002). High‐risk infants who completed weaning earlier than 6 months showed greater prevalence of constipation (P = 0.001) and abdominal distress (P = 0.004) than those fully weaned after 6 months.

Conclusions:

The greater prevalence of GI symptoms in high‐risk infants suggests that GI dysfunction during early infant development may be a part of the ASD endophenotype. Late weaning and exclusive breast milk were associated with protection against GI symptoms in high‐risk infants.
Adherence to Oral Maintenance Treatment in Adolescents With Inflammatory Bowel Disease
Authors: Spekhorst Lieke M. , Hummel Thalia Z. , Benninga Marc A. , van Rheenen Patrick F. , Kindermann Angelika
Published: July 2015

Objectives:

The aim of this study was to systematically review the rates of nonadherence to oral maintenance treatment in adolescents with inflammatory bowel disease (IBD), and to describe perceived barriers to adherence and psychosocial factors involved.

Methods:

The article considered studies published in MEDLINE, Embase, and PsycINFO up to March 2015. Studies that had collected data on adherence to thiopurines or aminosalicylates in a cohort of adolescents with IBD. Case reports and case series were excluded.

Results:

A total of 25 studies were included. Lack of uniformity of outcome measures made pooling of data impossible. Rates of medication nonadherence ranged from 2% to 93%. The most frequently reported barriers were “just forgot,” “wasn’t home,” and “interferes with activity.” Family dysfunction, peer victimization, poor health‐related quality of life, poor child‐coping strategies, anxiety, and depressive symptoms were associated with medication nonadherence.

Conclusions:

Nonadherence to oral maintenance therapy in adolescents with IBD is a significant health care problem and can lead to unnecessary escalation in therapy. Difficulties in family and social interactions, and psychosocial dysfunction can jeopardize IBD treatment outcome and should receive attention early in the course of the disease.
Early Gut Colonization With Lactobacilli and Staphylococcus in Infants
Authors: Salminen Seppo , Endo Akihito , Isolauri Erika , Scalabrin Deolinda
Published: July 2015

Objectives:

The aim of the present study was to assess the mode of delivery and type‐of‐feeding impact on gut microbiota. We demonstrated higher fecal bifidobacteria in infants who were breast‐fed (BF) or fed formula with prebiotics polydextrose (PDX) and galactooligosaccharides (GOS) versus formula without prebiotics. Here, we tested feces of that cohort for lactobacilli and Staphylococcus aureus, 2 types of bacteria present in breast milk.

Methods:

In a double‐blind, randomized study, 21‐ to 30‐day‐old term infants vaginally delivered and exclusively formula‐fed received a cow's milk–based formula (control, n = 80) or the same formula with 4 g/L (1:1 ratio) of PDX/GOS (PDX/GOS, n = 77). A reference BF group (n = 71) was included. Stool samples were obtained at baseline and after 30 and 60 days of feeding to assess fecal bacteria by quantitative real‐time polymerase chain reaction.

Results:

Pairwise comparisons between baseline‐adjusted means log10 colony‐forming unit per gram feces of total lactobacilli counts (8.37 in control, 8.46 in PDX/GOS, and 8.42 in BF) showed a significant difference only between PDX/GOS and control at 30 and 60 days combined (P = 0.035), utilizing generalized estimating equations method. Baseline‐adjusted odds ratio (OR) of colonization with S aureus was lower in control (OR 0.47, 95% confidence interval 0.22–1.00, P = 0.049) and PDX/GOS (OR 0.44, 95% confidence interval 0.21–0.94, P = 0.03) groups versus the BF group.

Conclusions:

Bacteria found in breast milk, such as lactobacilli and S aureus can also be found in infant feces. S aureus, traditionally considered harmful, may aid in educating the coevolving immune system. Modifying formula by adding prebiotics may bring gut microbiota closer to that of BF infants in terms of beneficial microbes.
Pedobacter alpinus sp. nov., isolated from a plateau lake
Authors: Li Ai-Hua , Liu Hong-Can , Zhou Yu-Guang
Published: July 2015

Two Gram-staining-negative, aerobic, non-motile, red-pigment and rod-shaped bacterial strains, designated RSP19T and RSR28, were isolated from lake water and subjected to polyphasic taxonomic studies. Based on 16S rRNA gene sequence analysis, strains RSP19T and RSR28 exhibited 91.4–95.7 % similarity to the type strains of existing species of the genus Pedobacter. The species most closely related phylogenetically were Pedobacter daechungensis (95.7 % sequence similarity), Pedobacter lentus (95.4 %), Pedobacter glucosidilyticus (94.5 %), Pedobacter panaciterrae (94.5 %) and Pedobacter terricola (94.2 %). MK-7 was the sole respiratory quinone. The major polar lipids were phosphatidylethanolamine, one unidentified aminolipid and several unidentified polar lipids. The predominant fatty acids were C16 : 1ω7c, iso-C15 : 0 and iso-C17 : 0 3-OH. The genomic DNA G+C contents were 34.3 and 33.9 mol% for strains RSP19T and RSR28, respectively. Based on the phenotypic characteristics, biochemical properties and genetic analysis, strains RSP19T and RSR28 clearly represent a novel species of the genus Pedobacter, for which the name Pedobacter alpinus is proposed. The type strain is RSP19T ( = CGMCC 1.14040T = KCTC 42456T = NBRC 110967T).
Structural modeling of the flagellum MS ring protein FliF reveals similarities to the type III secretion system and sporulation complex
Authors: Bergeron Julien
Published: July 2015

The flagellum is a large proteinaceous organelle found at the surface of many bacteria, whose primary role is to allow motility through the rotation of a long extracellular filament. It is an essential virulence factor in many pathogenic species, and is also a priming component in the formation of antibiotic-resistant biofilms. The flagellum consists of the export apparatus and stator in the cytosol; the basal body, spanning the bacterial membrane(s) and periplasm; and the hook-filament, that protrudes away from the bacterial surface. Assembly of the bacterial flagellum is initiated by the formation of the basal body MS ring region, constituted of multiple copies of the protein FliF. Here, I report an analysis of the FliF sequence from various bacterial species, demonstrating that its periplasmic region is composed of a domain homologuous to that of the type III secretion system proteins PrgK, and of a second globular domain that possesses a similar fold to that of the sporulation complex component SpoIIIAG. I also describe that Chlamydia possesses an unusual FliF protein, lacking part of the PrgK homology domain and the SpoIIIAG-like domain, and fused to FliG at its C-terminus. Finally, I have combined the sequence analysis of FliF with the EM map of the MS ring, to propose the first atomic model for the FliF oligomer. These results further emphasize the similarity between the flagellum, T3SS and sporulation complex, and will facilitate further structural studies.
The frequent evolutionary birth and death of functional promoters in mouse and human
Authors: Young Robert S. , Hayashizaki Yoshihide , Andersson Robin , Sandelin Albin , Kawaji Hideya , Itoh Masayoshi , Lassmann Timo , Carninci Piero ,   The FANTOM Consortium, Bickmore Wendy A. , Forrest Alistair R. , Taylor Martin S.
Published: July 2015

Promoters are central to the regulation of gene expression. Changes in gene regulation are thought to underlie much of the adaptive diversification between species and phenotypic variation within populations. In contrast to earlier work emphasizing the importance of enhancer evolution and subtle sequence changes at promoters, we show that dramatic changes such as the complete gain and loss (collectively, turnover) of functional promoters are common. Using quantitative measures of transcription initiation in both humans and mice across 52 matched tissues, we discriminate promoter sequence gains from losses and resolve the lineage of changes. We also identify expression divergence and functional turnover between orthologous promoters, finding only the latter is associated with local sequence changes. Promoter turnover has occurred at the majority (>56%) of protein-coding genes since humans and mice diverged. Tissue-restricted promoters are the most evolutionarily volatile where retrotransposition is an important, but not the sole, source of innovation. There is considerable heterogeneity of turnover rates between promoters in different tissues, but the consistency of these in both lineages suggests that the same biological systems are similarly inclined to transcriptional rewiring. The genes affected by promoter turnover show evidence of adaptive evolution. In mice, promoters are primarily lost through deletion of the promoter containing sequence, whereas in humans, many promoters appear to be gradually decaying with weak transcriptional output and relaxed selective constraint. Our results suggest that promoter gain and loss is an important process in the evolutionary rewiring of gene regulation and may be a significant source of phenotypic diversification.
Combining `dry' co-crystallization andin situdiffraction to facilitate ligand screening by X-ray crystallography
Authors: Gelin Muriel , Delfosse Vanessa , Allemand Frédéric , Hoh François , Sallaz-Damaz Yoann , Pirocchi Michel , Bourguet William , Ferrer Jean-Luc , Labesse Gilles , Guichou Jean-François
Published: July 2015

X-ray crystallography is an established technique for ligand screening in fragment-based drug-design projects, but the required manual handling steps – soaking crystals with ligand and the subsequent harvesting – are tedious and limit the throughput of the process. Here, an alternative approach is reported: crystallization plates are pre-coated with potential binders prior to protein crystallization and X-ray diffraction is performed directly `in situ' (or in-plate). Its performance is demonstrated on distinct and relevant therapeutic targets currently being studied for ligand screening by X-ray crystallography using either a bending-magnet beamline or a rotating-anode generator. The possibility of using DMSO stock solutions of the ligands to be coated opens up a route to screening most chemical libraries.
Three-dimensional structure of the human breast cancer resistance protein (BCRP/ABCG2) in an inward-facing conformation
Authors: Rosenberg Mark F. , Bikadi Zsolt , Hazai Eszter , Starborg Tobias , Kelley Lawrence , Chayen Naomi E. , Ford Robert C. , Mao Qingcheng
Published: July 2015

ABCG2 is an efflux drug transporter that plays an important role in drug resistance and drug disposition. In this study, the first three-dimensional structure of human full-length ABCG2 analysed by electron crystallography from two-dimensional crystals in the absence of nucleotides and transported substrates is reported at 2 nm resolution. In this state, ABCG2 forms a symmetric homodimer with a noncrystallographic twofold axis perpendicular to the two-dimensional crystal plane, as confirmed by subtomogram averaging. This configuration suggests an inward-facing configuration similar to murine ABCB1, with the nucleotide-binding domains (NBDs) widely separated from each other. In the three-dimensional map, densities representing the long cytoplasmic extensions from the transmembrane domains that connect the NBDs are clearly visible. The structural data have allowed the atomic model of ABCG2 to be refined, in which the two arms of the V-shaped ABCG2 homodimeric complex are in a more closed and narrower conformation. The structural data and the refined model of ABCG2 are compatible with the biochemical analysis of the previously published mutagenesis studies, providing novel insight into the structure and function of the transporter.
The first crystal structure of a glycoside hydrolase family 17 β-1,3-glucanosyltransferase displays a unique catalytic cleft
Authors: Qin Zhen , Yan Qiaojuan , Lei Jian , Yang Shaoqing , Jiang Zhengqiang , Wu Shiwang
Published: July 2015

β-1,3-Glucanosyltransferase (EC 2.4.1.–) plays an important role in the formation of branched glucans, as well as in cell-wall assembly and rearrangement in fungi and yeasts. The crystal structures of a novel glycoside hydrolase (GH) family 17 β-1,3-glucanosyltransferase fromRhizomucor miehei(RmBgt17A) and the complexes of its active-site mutant (E189A) with two substrates were solved at resolutions of 1.30, 2.30 and 2.27 Å, respectively. The overall structure ofRmBgt17A had the characteristic (β/α)8TIM-barrel fold. The structures ofRmBgt17A and other GH family 17 members were compared: it was found that a conserved subdomain located in the region near helix α6 and part of the catalytic cleft in other GH family 17 members was absent inRmBgt17A. Instead, four amino-acid residues exposed to the surface of the enzyme (Tyr135, Tyr136, Glu158 and His172) were found in the reducing terminus of subsite +2 ofRmBgt17A, hindering access to the catalytic cleft. This distinct region ofRmBgt17A makes its catalytic cleft shorter than those of other reported GH family 17 enzymes. The complex structures also illustrated thatRmBgt17A can only provide subsites −3 to +2. This structural evidence provides a clear explanation of the catalytic mode ofRmBgt17A, in which laminaribiose is released from the reducing end of linear β-1,3-glucan and the remaining glucan is transferred to the end of another β-1,3-glucan acceptor. The first crystal structure of a GH family 17 β-1,3-glucanosyltransferase may be useful in studies of the catalytic mechanism of GH family 17 proteins, and provides a basis for further enzymatic engineering or antifungal drug screening.
Fully automatic characterization and data collection from crystals of biological macromolecules
Authors: Svensson Olof , Malbet-Monaco Stéphanie , Popov Alexander , Nurizzo Didier , Bowler Matthew W.
Published: July 2015

Considerable effort is dedicated to evaluating macromolecular crystals at synchrotron sources, even for well established and robust systems. Much of this work is repetitive, and the time spent could be better invested in the interpretation of the results. In order to decrease the need for manual intervention in the most repetitive steps of structural biology projects, initial screening and data collection, a fully automatic system has been developed to mount, locate, centre to the optimal diffraction volume, characterize and, if possible, collect data from multiple cryocooled crystals. Using the capabilities of pixel-array detectors, the system is as fast as a human operator, taking an average of 6 min per sample depending on the sample size and the level of characterization required. Using a fast X-ray-based routine, samples are located and centred systematically at the position of highest diffraction signal and important parameters for sample characterization, such as flux, beam size and crystal volume, are automatically taken into account, ensuring the calculation of optimal data-collection strategies. The system is now in operation at the new ESRF beamline MASSIF-1 and has been used by both industrial and academic users for many different sample types, including crystals of less than 20 µm in the smallest dimension. To date, over 8000 samples have been evaluated on MASSIF-1 without any human intervention.
A comparative study of tourist attitudes towards culinary tourism in Spain and Slovenia
Authors: Sanchez-Cañizares Sandra , Castillo-Canalejo Ana M
Published: July 2015

Purpose

– The purpose of this paper is to determine the role of gastronomy as a destination attraction, tourists’ perception of culinary tourism, its influence on satisfaction with the trip, and the economic value tourist’s attach to the opportunity to try traditional cuisine. The paper also examines possible sociocultural differences between different tourist segments according to how they rate gastronomy in their motivations for travel.

Design/methodology/approach

– Data were collected by means of 392 questionnaires distributed in Ljubjlana (Slovenia) and Cordoba (Spain). Various bivariate and multivariate statistical techniques are used to perform a comprehensive econometric study.

Findings

– Tourists exhibit greater interest in gastronomy as a travel motivation in the Spanish city, where they value aspects related to this activity more positively. However, the willingness to pay more to try traditional food is similar in both cities. No sociodemographic differences were found between the segments regarding the importance of gastronomy as a travel motivation.

Research limitations/implications

– Restaurateurs, hospitality associations, and other public or private stakeholders engaged in culinary tourism can benefit from this type of analysis. The study reveals the need to improve language skills, human capital formation, and the innovation of traditional dishes in the Spanish sample. It also shows that the future of culinary tourism in Slovenia will depend on enhancing the international visibility of this emerging tourism sector.

Originality/value

– Successful strategies to promote culinary tourism must take into account the views of its main target group, tourists. Many studies analyzing tourist profiles are mainly qualitative, with few providing a cross-country comparison. This analysis provides a comprehensive, quantitative econometric approach to tourists’ opinions, and compares two different countries that differ in terms of their international visibility regarding this type of activity; specifically, Spain, which is a consolidated and world-renowned culinary tourism destination, and Slovenia, which is in the process of developing a culinary tourism project. Segmenting tourists based on their interest in culinary tourism also allows designing promotional strategies specifically tailored to each segment.
Convergence of food systems: Kosher, Christian and Halal
Authors: Tieman Marco , Hassan Faridah Hj
Published: July 2015

Purpose

– The purpose of this paper is to investigate if religious food laws can provide answers to current issues with the food systems.

Design/methodology/approach

– This paper provides a discussion of the dietary and food system principles from a Judaism, Christianity and Islamic perspective for the design of a more sustainable and healthy food system.

Findings

– The commercialisation of the natural resources, industrial food production approach and consumerism is endangering the food security, health and environment. Current industry practices are not sustainable and do not comply with Jewish, Christian and Islamic scriptures. Kosher, Christian and halal food laws share common principles in prohibition of certain animals (like pig), prohibition of blood, role of fasting and animal welfare. As a change in the diet is the solution, there is a key role for the food industry to comply and for religious leaders to radically reduce meat consumption and food waste of its followers.

Research limitations/implications

– This viewpoint paper shows that religious food laws provide answers to current problems with the industrialised food production approach and consumerism.

Practical implications

– New food industry directives should convert meat-based to plant-based ingredients and additives; replace porcine by bovine sources; and emphasise on animal welfare to better serve the Jewish, Christian and Muslim consumer. Religious logos (kosher and halal) should incorporate nutrient profiling through a traffic light system to promote healthy food choice.

Originality/value

– Religious food laws are important for a big part of the world population (Jews, Christians and Muslims), which share many common principles. This study contributes to a better understanding of the commonalities and differences in these religious food laws.
A laboratory exploration for multi-period perishable food pricing
Authors: Wang Xiaohuan , Fan Zhi-Ping , Wang Yiming , Li Manning
Published: July 2015

Purpose

– The purpose of this paper is to put forward a multi-period dynamic pricing strategy for perishable food considering consumers’ price fairness perception. The impacts of the multi-period retail price, food freshness and inventory shortage risk on consumers’ heterogeneous willingness to pay (WTP) and their strategic purchasing behaviours are studied.

Design/methodology/approach

– The authors present a price optimization model for perishable food, and conduct a laboratory experiment to justify the theoretical model. The data collected are analysed by correlation analysis and nonparametric test.

Findings

– The results obtained reveal, first, food freshness and inventory shortage risk have effect on consumers’ heterogeneous WTP. Second, different retail prices lead to consumers’ strategically purchasing behaviours. Finally, consumers’ intertemporal price fairness perception and the food retailer’s long-term utility maximization can be achieved by developing multi-period dynamic pricing strategy.

Practical implications

– This study suggests the perishable food retailer to apply a step-by-step price markdown strategy. It aims at eliminating price unfairness perceptions caused by loss of freshness and high shortage risk of the perishable food in the subsequent selling periods within the shelf life. Some valuable managerial insights towards perishable pricing for food retailers are discussed.

Originality/value

– This study serves as the first step to utilize a laboratory experiment to dig out consumers’ intertemporal WTP towards perishable food. It also presents a novel way for describing consumers’ intertemporal price fairness perception by equalizing consumers’ average utilities considering consumer surplus, food freshness and shortage risk at different selling periods. The line of research on dynamic pricing concerning consumers’ price fairness perception is quite new in academic research, and has arisen due to its importance for food retailers of maximizing their long-term revenues and also of constructing mutual benefit and lasting connections with the consumers.
Studying the effect of spiritual leadership on organizational performance: an empirical study in hotel industry
Authors: Salehzadeh Reza , Khazaei Pool Javad , Kia Lashaki Jafar , Dolati Hasan , Balouei Jamkhaneh Hadi
Published: July 2015

Purpose

– The purpose of this paper is to investigate the effect of spiritual leadership on organizational performance based on the balanced scorecard (BSC).

Design/methodology/approach

– Statistical population includes the middle managers of 60 hotels across eight provinces in Iran. For data analysis, 207 accurate completed questionnaires have been used. Structural equation modeling has been used to explore the relationships between the research variables.

Findings

– The findings showed that spiritual leadership has a significant positive effect on calling and membership. Also, spiritual leadership, calling and membership have a significant positive effect on organizational performance.

Originality/value

– This paper by presenting a comprehensive model provides a framework and approach for studying the performance consequences of spiritual leadership in the hotel industry using the BSC.
Perceived performance appraisal justice in Egyptian chain hotels
Authors: Nassar Mohamed A. , Zaitouni Michel
Published: July 2015

Purpose

– This paper aims to examine the relationships between perceptions of organisational justice, perceived competence of supervisor and perceived supervisory support (PSS) in hotel employees in Egypt.

Design/methodology/approach

– Employees who worked in chain hotels in two cities completed questionnaires on each dimension. Principal component analysis and hierarchical regression analysis were used to evaluate relationships among the dimensions to test the hypothesis that PSS mediates the relationship between perceived organisational justice and perceived competence of supervisor.

Findings

– Measures of organisational justice, perceived competence of supervisor and PSS were all positively related to one another. PSS partially mediated the relationship between organisational justice and perceived competence of supervisor.

Research limitations/implications

– Results indicate that employees who perceive their managers to be supportive and their organisations to be fair and just also believe that their supervisors are more competent. However, these results are only a cross-sectional snapshot, and future studies could examine how employee attitudes change over time and what factors contribute most to establishing perceptions of managerial competence and trust in the organisation.

Practical implications

– The findings suggest that organisations should develop policies that allow managers to foster supportive and transparent relationships with employees to establish confidence between employee and both manager and organisation.

Originality/value

– This study is the first of its kind to evaluate the mediating effects of PSS on organisational justice and perceived competence of supervisor in Egypt and in the hospitality industry.
Assessment of residents’ attitude towards ecotourism in KwaZulu-Natal protected areas
Authors: Adeleke Bola Olusola
Published: July 2015

Purpose

– The purpose of this paper was to assess the attitude of residents towards ecotourism in KwaZulu-Natal protected areas. It also determined how barriers to ecotourism trips could negatively affect the success of tourism development in protected areas. The new South Africa today has widely and innovatively embraced ecotourism based largely around the protected areas. Residents’ attitude towards tourism is one of the important indicators for sustainable development in protected areas.

Design/methodology/approach

– In total, 212 copies of structured questionnaires were used to collect information for the study. A purposive sampling technique was used to select the target population of the protected areas while respondents were selected from the communities based on random sampling technique. Mean scores for barriers to ecotourism trips were determined. Descriptive statistics and T-test inferential statistics were used to analyse the data.

Findings

– The results agree with the theory of planned behaviour where intentions of residents to participate in ecotourism were directly influenced by barriers such as no time, low income and no transportation. It was also found out that preference for ecotourism trips was significantly influenced by the various barriers to ecotourism activities. High level of unemployment and high level of illiteracy were considered to be responsible for poor attitude in Kwadlangezwa with many (43.4 per cent) unwilling to support ecotourism development projects.

Research limitations/implications

– The research implication infers that high level of poverty and illiteracy in communities surrounding protected areas could seriously indicate non-support for development projects.

Practical implications

– Ecotourism-related businesses need be developed in destinations to alleviate poverty.

Social implications

– The moral of residents need be boosted through workshops and educative seminars.

Originality/value

– The study was conducted during the author’s research fellowship with the Department of Recreation and Tourism, University of Zululand, Kwadlangezwa, South Africa.
Educational lessons from the past – marketing textbooks during the Age of Enlightenment (16th to 18th Centuries)
Authors: Shaw Eric
Published: July 2015

Purpose

– The purpose of this paper is to critique four marketing textbooks written during the Age of Enlightenment (sixteenth-eighteenth centuries) to understand the educational lessons they taught students of marketing at the time and the lessons they might hold for the present day.

Design/methodology/approach

– The method entails critically examining several marketing textbooks within the context of the great social, religious, intellectual, political and economic changes taking place at the time.

Findings

– Over the period, paralleling developments in the Enlightenment, the two earlier textbooks of the age have a heavier emphasis on religious and ethical concerns along with their discussions of business issues. The two later textbooks de-emphasize spiritual themes in favor of almost completely focusing on business matters. In addition to discussing themes relevant to their times, the books anticipate concepts found in marketing textbooks of today. Generally, there is also more stress placed on immediate facts rather than enduring business principles. Yet many principles are discussed, including the most fundamental and durable principle of merchandising: “buy cheape, sell deare”.

Originality/value

– There is no other review of a collection of marketing textbooks during the Age of Enlightenment in the published literature.