bluuebunny/crossref_metadata_2025 huggingface dataset:
A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer
Authors: Gallon Matthew , Clairfeuille Thomas , Steinberg Florian , Mas Caroline , Ghai Rajesh , Sessions Richard B. , Teasdale Rohan D. , Collins Brett M. , Cullen Peter J.
Published: August 2014

Significance

Cell surface proteins are regulated by a constant cycle of internalization and recycling from intracellular compartments called endosomes. From these organelles, two protein sorting platforms, sorting nexin 27 (SNX27) and the retromer complex, play a critical role in the retrieval of various proteins responsible for ion transport, glucose metabolism, neurotransmission, and other cell functions. Based on the three-dimensional structure of SNX27 in complex with the retromer subunit VPS26, we define the mechanism by which these proteins cooperate to drive endosomal cargo sorting. Retromer and SNX27 dysfunction is implicated in various disorders, including diabetes, Down syndrome, Parkinson disease, and Alzheimer’s disease, and this work provides important insights into the assembly of this essential endosomal sorting machinery.
Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns
Authors: Bergman Peter , Adori Csaba , Vas Szilvia , Kai-Larsen Ylva , Sarkanen Tomi , Cederlund Andreas , Agerberth Birgitta , Julkunen Ilkka , Horvath Beata , Kostyalik Diana , Kalmár Lajos , Bagdy Gyorgy , Huutoniemi Anne , Partinen Markku , Hökfelt Tomas
Published: August 2014

Significance

Narcolepsy is a chronic sleep disease with autoimmune origin. We explored occurrence of autoantibodies in narcolepsy and other sleep-related disorders (OSRDs) by screening human sera with immunohistochemistry on rat brains. Hypocretin/orexinergic neurons were not stained, but a prominent immunostaining pattern of hypothalamic melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) neurons was overrepresented in cases of narcolepsy and OSRD patients. The autoantigen was identified as the common C-terminal epitope of neuropeptide glutamic acid-isoleucine/α–melanocyte-stimulating hormone (NEI/αMSH). Purified IgGs from a patient with MCH/POMC staining injected intracerebroventricularly to rats caused disturbed sleep patterns. Also, GABAergic cortical interneurons were stained with other narcolepsy and OSRD sera. Thus, autoantibodies are frequent in patients with sleep disorders, and NEI/αMSH may be a previously unidentified autoantigen involved in pathomechanism(s). These findings indicate possible diagnostic/therapeutic targets.
Electrostatics-driven shape transitions in soft shells
Authors: Jadhao Vikram , Thomas Creighton K. , Olvera de la Cruz Monica
Published: August 2014

Significance

Shape is a fundamental property of an object that influences its interaction with the environment and often determines the object’s functional capabilities. Understanding how to generate and control shape by modifying the environmental conditions is of primary importance in designing systems that respond to external cues. We show here that electrostatic interactions can be used to change the equilibrium shape of soft, nanometer-sized shells. We find that a uniformly charged, spherical shell undergoes shape changes, transforming into ellipsoids, discs, and bowls, as the electrolyte concentration in the environment is decreased. This electrostatics-based shape design mechanism, regulated by varying properties external to the shell, can be used to build efficient nanocontainers for various medical and technological applications.
Towards interlingual constructicography
Authors: Bäckström Linnéa , Lyngfelt Benjamin , Sköldberg Emma
Published: August 2014

This article addresses the possibility of linking constructicon resources for different languages, in particular English and Swedish. The entries in Berkeley’s English constructicon have been compared to Swedish, with a focus on potential correspondences in a Swedish constructicon. In most cases, approximately corresponding Swedish constructions could be established, although typically with minor differences, often concerning grammatical markers. The closest equivalents are, typically, relatively general grammatical constructions, whereas constructions containing specific lexical elements tend to differ more. In order to link all corresponding constructions between the two resources, a combination of strategies seems to be required. Constructions with a referential meaning may be linked via FrameNet frames, while those with a more abstract grammatical function may be related in terms of their grammatical properties.
Automatic expansion of the Swedish FrameNet lexicon
Authors: Johansson Richard
Published: August 2014

We evaluate several lexicon-based and corpus-based methods to automatically induce new lexical units for the Swedish FrameNet, and we see that the best-performing setup uses a combination of both types of methods. A particular challenge for Swedish is the absence of a lexical resource such as WordNet; however, we show that the semantic network SALDO, which is organized according to lexicographical principles quite different from those of WordNet, is very useful for our purposes.
Social behaviours in dog-owner interactions can serve as a model for designing social robots
Authors: Faragó Tamás , Miklósi Ádám , Korcsok Beáta , Száraz Judit , Gácsi Márta
Published: August 2014

It is essential for social robots to fit in the human society. In order to facilitate this process we propose to use the family dog’s social behaviour shown towards humans as an inspiration. In this study we explored dogs’ low level social monitoring in dog-human interactions and extracted individually consistent and context dependent behaviours in simple everyday social scenarios. We found that proximity seeking and tail wagging were most individually distinctive in dogs, while activity, orientation towards the owner, and exploration were dependent on the context and/or the activity of the owner. The functional analogues of these dog behaviours can be implemented in social robots of different embodiments in order to make them acceptable and more believable for humans. Keywords: dog-owner interaction; social robotics; low-level social monitoring; greeting behaviour; individually distinctive behaviours
Analysis of the RNA content of the exosomes derived from blood serum and urine and its potential as biomarkers
Authors: Li Mu , Zeringer Emily , Barta Timothy , Schageman Jeoffrey , Cheng Angie , Vlassov Alexander V.
Published: August 2014

Exosomes are tiny vesicles (30–150 nm) constantly secreted by all healthy and abnormal cells, and found in abundance in all body fluids. These vesicles, loaded with unique RNA and protein cargo, have a wide range of biological functions, including cell-to-cell communication and signalling. As such, exosomes hold tremendous potential as biomarkers and could lead to the development of minimally invasive diagnostics and next generation therapies within the next few years. Here, we describe the strategies for isolation of exosomes from human blood serum and urine, characterization of their RNA cargo by sequencing, and present the initial data on exosome labelling and uptake tracing in a cell culture model. The value of exosomes for clinical applications is discussed with an emphasis on their potential for diagnosing and treating neurodegenerative diseases and brain cancer.
MicroRNAs and synaptic plasticity—a mutual relationship
Authors: Aksoy-Aksel Ayla , Zampa Federico , Schratt Gerhard
Published: August 2014

MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain- and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.
Extracellular vesicles as modulators of cell-to-cell communication in the healthy and diseased brain
Authors: Pegtel D. M. , Peferoen L. , Amor S.
Published: August 2014

Homeostasis relies heavily on effective cell-to-cell communication. In the central nervous system (CNS), probably more so than in other organs, such communication is crucial to support and protect neurons especially during ageing, as well as to control inflammation, remove debris and infectious agents. Emerging evidence indicates that extracellular vesicles (EVs) including endosome-derived exosomes and fragments of the cellular plasma membrane play a key role in intercellular communication by transporting messenger RNA, microRNA (miRNA) and proteins. In neurodegenerative diseases, secreted vesicles not only remove misfolded proteins, but also transfer aggregated proteins and prions and are thus thought to perpetuate diseases by ‘infecting’ neighbouring cells with these pathogenic proteins. Conversely, in other CNS disorders signals from stressed cells may help control inflammation and inhibit degeneration. EVs may also reflect the status of the CNS and are present in the cerebrospinal fluid indicating that exosomes may act as biomarkers of disease. That extracellular RNA and in particular miRNA, can be transferred by EV also indicates that these vesicles could be used as carriers to specifically target the CNS to deliver immune modulatory drugs, neuroprotective agents and anti-cancer drugs. Here, we discuss the recent evidence indicating the potential role of exosomes in neurological disorders and how knowledge of their biology may enable a Trojan-horse approach to deliver drugs into the CNS and treat neurodegenerative and other disorders of the CNS.
The role of epigenetic-related codes in neurocomputation: dynamic hardware in the brain
Authors: Edelstein Lawrence , Smythies John
Published: August 2014

This paper presents a review of recent work on the role that two epigenetic-related systems may play in information processing mechanisms in the brain. The first consists of exosomes that transport epigenetic-related molecules between neurons. The second consists of homeoproteins like Otx2 that carry information from sense organs to primary sensory cortex. There is developing evidence that presynaptic neurons may be able to modulate the fine microanatomical structure in the postsynaptic neuron. This may be conducted by three mechanisms, of which the first is well established and the latter two are novel. (i) By the well-established activation of receptors that trigger a chain of signalling molecules (second messengers) that result in the upregulation and/or activation of a transcription factor. The two novel systems are the exosome system and homeoproteins. (ii) Exosomes are small vesicles that are released upon activation of the axon terminal, traverse the synaptic cleft, probably via astrocytes and are taken up by the postsynaptic neuron. They carry a load of signalling proteins and a variety of forms of RNA. These loads may then be transported widely throughout the postsynaptic neuron and engineer modulations in the fine structure of computational machinery by epigenetic-related processes. (iii) Otx2 is a transcription factor that,
inter alia
, controls the development and survival of PV+ GABAergic interneurons (PV cells) in the primary visual cortex. It is synthesized in the retina and is transported to the cortex by a presently unknown mechanism that probably includes direct cell-to-cell transfer, and may, or may not, include transfer by the dynein and exosome systems in addition. These three mechanisms explain a quantity of data from the field of de- and reafferentation plasticity. These data show that the modality of the presynaptic neuron controls to a large extent the modality of the postsynaptic neuron. However, the mechanism that effects this is currently unknown. The exosome and the homeoprotein hypotheses provide novel explanations to add to the well-established earlier mechanism described above.
CAPRI: Efficient Inference of Cancer Progression Models from Cross-sectional Data
Authors: Ramazzotti Daniele , Caravagna Giulio , Loohuis Loes Olde , Graudenzi Alex , Korsunsky Ilya , Mauri Giancarlo , Antoniotti Marco , Mishra Bud
Published: August 2014

We devise a novel inference algorithm to effectively solve thecancer progression model reconstructionproblem. Our empirical analysis of the accuracy and convergence rate of our algorithm,CAncer PRogression Inference(CAPRI), shows that it outperforms the state-of-the-art algorithms addressing similar problems.

Motivation

Several cancer-related genomic data have become available (e.g.,The Cancer Genome Atlas, TCGA) typically involving hundreds of patients. At present, most of these data are aggregated in across-sectionalfashion providing all measurements at the time of diagnosis.

Our goal is to infer cancer “progression” models from such data. These models are represented as directed acyclic graphs (DAGs) of collections of “selectivity” relations, where a mutation in a geneA“selects” for a later mutation in a geneB. Gaining insight into the structure of such progressions has the potential to improve both the stratification of patients and personalized therapy choices.

Results

The CAPRI algorithm relies on a scoring method based on aprobabilistic theorydeveloped by Suppes, coupled withbootstrapandmaximum likelihoodinference. The resulting algorithm is efficient, achieves high accuracy, and has good complexity, also, in terms of convergence properties. CAPRI performs especially well in the presence of noise in the data, and with limited sample sizes. Moreover CAPRI, in contrast to other approaches, robustly reconstructs different types of confluent trajectories despite irregularities in the data.

We also report on an ongoing investigation using CAPRI to studyatypical Chronic Myeloid Leukemia, in which we uncovered non trivial selectivity relations and exclusivity patterns among key genomic events.

Availability

CAPRI is part of theTRanslational ONCOlogyR package and is freely available on the web at:http://bimib.disco.unimib.it/index.php/Tronco

Contact

daniele.ramazzotti@disco.unimib.it
Dual autogenous control of the multiple antibiotic resistance phenotype inEscherichia coli
Authors: Rodrigo Guillermo , Bajić Djordje , Elola Ignacio , Poyatos Juan F.
Published: August 2014

Bacteria can defend against diverse antibiotics by mounting a multiple antibiotic resistance (mar) phenotype. The resistance is linked to a chromosomal locus that encodes an activator and a repressor regulating their own expression. Here, we investigated how this dual autogenous control determines the dynamics of the response. We found that the regulatory architecture provides a mechanism to enable rapid induction, generate pulses of activation, and increase the range of sensing. The response is also graded and homogeneous across the population. Moreover, the interaction of a third regulator with the core module fine tunes the previous features, while limiting the cross-talk with metabolic signals. A minimal model accurately anticipates these properties, and emphasizes how specific attributes of the circuit components constrain the appearance of other potential behaviors associated to the regulatory design. Our results integrate both molecular and circuit-level characteristics to fully elucidate the dynamic emergence of themarphenotype.
RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas
Authors: Bao Zhao-Shi , Chen Hui-Min , Yang Ming-Yu , Zhang Chuan-Bao , Yu Kai , Ye Wan-Lu , Hu Bo-Qiang , Yan Wei , Zhang Wei , Akers Johnny , Ramakrishnan Valya , Li Jie , Carter Bob , Liu Yan-Wei , Hu Hui-Min , Wang Zheng , Li Ming-Yang , Yao Kun , Qiu Xiao-Guang , Kang Chun-Sheng , You Yong-Ping , Fan Xiao-Long , Song Wei Sonya , Li Rui-Qiang , Su Xiao-Dong , Chen Clark C. , Jiang Tao
Published: August 2014

Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs.
Safety signals as instrumental reinforcers during free-operant avoidance
Authors: Fernando Anushka B.P. , Urcelay Gonzalo P. , Mar Adam C. , Dickinson Anthony , Robbins Trevor W.
Published: August 2014

Safety signals provide “relief” through predicting the absence of an aversive event. At issue is whether these signals also act as instrumental reinforcers. Four experiments were conducted using a free-operant lever-press avoidance paradigm in which each press avoided shock and was followed by the presentation of a 5-sec auditory safety signal. When given a choice between two levers in Experiment 1, both avoiding shock, rats preferentially responded on the lever that produced the safety signal as feedback, even when footshock was omitted. Following avoidance training with a single lever in Experiment 2, removal of the signal led to a decrease in avoidance responses and an increase in responses during the safety period normally denoted by the signal. These behavioral changes demonstrate the dual conditioned reinforcing and fear inhibiting properties of the safety signal. The associative processes that support the reinforcing properties of a safety signal were tested using a novel revaluation procedure. Prior experience of systemic morphine during safety signal presentations resulted in an increased rate of avoidance responses to produce the safety signal during a drug-free extinction test, a finding not seen with d-amphetamine in Experiment 3. Morphine revaluation of the safety signal was repeated in Experiment 4 followed by a drug-free extinction test in which responses did not produce the signal for the first 10 min of the session. Instrumental avoidance in the absence of the signal was shown to be insensitive to prior signal revaluation, suggesting that the signal reinforces free-operant avoidance behavior through a habit-like mechanism.
Crystal structure ofN-(1-allyl-3-chloro-4-ethoxy-1H-indazol-5-yl)-4-methoxybenzenesulfonamide
Authors: Chicha Hakima , Rakib El Mostapha , Bouissane Latifa , Saadi Mohamed , El Ammari Lahcen
Published: August 2014

In the title compound, C19H20ClN3O4S, the benzene ring is inclined to the indazole ring system (r.m.s. deviation = 0.014 Å) by 65.07 (8)°. The allyl and ethoxy groups are almost normal to the indazole ring, as indicated by the respective torsion angles [N—N—C—C = 111.6 (2) and C—C—O—C = −88.1 (2)°]. In the crystal, molecules are connected by N—H...N hydrogen bonds, forming helical chains propagating along [010]. The chains are linked by C—H...O hydrogen bonds, forming a three-dimensional network.
Ac-Cent-Tchu-Ate the positive
Authors: M. Watson Ann
Published: August 2014

Purpose

– The purpose of this column is to address how utilizing positive psychology can be beneficial in solving complex problems and increasing staff productivity.

Design/methodology/approach

– This is a viewpoint column.

Findings

– Many academic libraries, along with their parent institutions, are facing difficult challenges. Finding ways to maintain a positive outlook can be beneficial in meeting these obstacles and keeping staff motivated and productive.

Originality/value

– This column addresses how the author’s history of reading self-help books has been beneficial in providing leadership tools and in helping overcome challenging circumstances in academic libraries.
Reward systems promote high-performance work teams achieving library mission
Authors: D. Hall-Ellis Sylvia
Published: August 2014

Purpose

– The purpose of this paper is to discuss that development and recognition of human capital is a shared responsibility reflecting a delicate balance with employees on one side and the organization on the other. Conveying the message that employees matter, are valued contributors and will be rewarded improves morale, builds trust and expands opportunities for growth, through challenging assignments, improving performance and furthering skill development.

Design/methodology/approach

– The typical organizational structure in a library is made up of three key components: formal reporting relationships, the identification of groupings of individuals into departments or teams and the design of systems that ensures effective communication, coordination and integration of efforts across units. What steps can a library administrator take to reimagine and implement a responsive rewards system?

Findings

– There are five recommendations for library administrators to develop and implement a rewards system.

Originality/value

– New thought piece on this topic.
Can a mentoring program save you money?
Authors: A. Crumpton Michael
Published: August 2014

Purpose

– The purpose of this article is to suggest that a benefit-cost analysis should be performed for mentoring activities so as to justify the effort and expense and as a tool for measuring effectiveness.

Design/methodology/approach

– Pulling from field literature, this article provides some examples of mentoring programs and resources as well as an example for conducting an analysis.

Findings

– The author feels that applying a cost model to mentoring programs can strengthen their appeal overall.

Originality/value

– The article and its conclusions are the product of this author and his experiences with such programs.
Work characteristics and work performance of knowledge workers
Authors: Hernaus Tomislav , Mikulić Josip
Published: August 2014

Purpose

– The purpose of this paper is to investigate a specific pattern of relationships among various task, knowledge and social characteristics of work design and work outcomes. It clearly shows how particular work characteristics influence task and contextual performance.

Design/methodology/approach

– The empirical research was conducted through a field survey of the largest Croatian organizations with more than 500 employees. A cross-sectional and cross-occupational sample of 512 knowledge workers from 48 organizations is analyzed by applying the partial least squares structural equation modeling technique.

Findings

– The results confirmed the existence and importance of the interaction between work characteristics and work outcomes. However, the findings suggest that only knowledge characteristics of work design exhibit a significant effect on both dimensions of work behavior, while task and social characteristics showed different effects on task and contextual performance, respectively.

Practical implications

– The research findings clearly show that work design efforts are not straightforward but rather context-specific, and with diverging performance effects. Organizations can significantly enhance their bottom-line performance by designing challenging and cognitively demanding configurations of work tasks for their knowledge workers.

Originality/value

– The paper extends previous research by capturing a broader set of work characteristics of knowledge workers. The results suggest that different categories of work characteristics have different effects on task and contextual performance. By revealing the nature of work design in the central and eastern European context, this study indicates the existence of possible differences in work design practices in various backgrounds.
Paradigm debates and marketing theory, thought and practice
Authors: Tadajewski Mark
Published: August 2014

Purpose

– This paper aims to provide a history of a number of intellectual debates in marketing theory and consumer research. It outlines the key arguments involved, highlights the politics and acrimoniousness that often accompanied the competition for academic prestige or practitioner remuneration. It weaves the contents of the special issue into its narrative.

Design/methodology/approach

– This article engages in a broad historical survey of the history of marketing thought, as it pertains to intellectual debate and disputation.

Findings

– While scholars often articulate objectivity as an intellectual ideal, many of the debates that are explored reveal a degree of intellectual intolerance and this is refracted through the institutional system that structures marketing discourse.

Originality/value

– This account provides an introduction to the intellectual debates of the last century, highlighting the ebb and flow of marketing thought. It calls attention to debates that are largely under explored and highlights the politics of knowledge production in marketing and consumer research.
Economic Losers, Protestors, Islamophobes or Xenophobes? Predicting Public Support for a Counter-Jihad Movement
Authors: Goodwin Matthew J. , Cutts David , Janta-Lipinski Laurence
Published: August 2014

In recent years several European states have seen the emergence of ‘counter-Jihad’ movements, which in contrast to the established populist radical right eschew electoral politics and put stronger emphasis on mobilising opposition to Islam and Muslims. Despite attracting attention, counter-Jihad movements and the predictors of their support are under-researched. Drawing on a new survey and sample of self-identified supporters, this article investigates the predictors of public support for the English Defence League (EDL), the inaugural ‘defence league’ in Europe. Contrary to accounts that stress unemployment, apathy or single issues, it is found that support is concentrated among male workers, citizens with school-level education, who read tabloid newspapers and vote for right-wing parties, but who are not more likely to be unemployed, in social housing, have no qualifications or be politically apathetic. Foremost, regression analysis confirms that the strongest predictor of their support is xenophobic hostility toward Muslims, and ethnic minorities more generally.
Mode of delivery and the probability of subsequent childbearing: a population‐based register study
Authors: Elvander C , Dahlberg J , Andersson G , Cnattingius S
Published: August 2014

Objective

To investigate the relationship between mode of first delivery and probability of subsequent childbearing.

Design

Population‐based study.

Setting

Nationwide study in Sweden.

Population

A cohort of 771 690 women who delivered their first singleton infant in Sweden between 1992 and 2010.

Methods

Using Cox's proportional‐hazards regression models, risks of subsequent childbearing were compared across four modes of delivery. Hazard ratios (HRs) were calculated, using 95% confidence intervals (95% CIs).

Main outcome measures

Probability of having a second and third child; interpregnancy interval.

Results

Compared with women who had a spontaneous vaginal first delivery, women who delivered by vacuum extraction were less likely to have a second pregnancy (HR 0.96, 95% CI 0.95–0.97), and the probabilities of a second childbirth were substantially lower among women with a previous emergency caesarean section (HR 0.85, 95% CI 0.84–0.86) or an elective caesarean section (HR 0.82, 95% CI 0.80–0.83). There were no clinically important differences in the median time between first and second pregnancy by mode of first delivery. Compared with women younger than 30 years of age, older women were more negatively affected by a vacuum extraction with respect to the probability of having a second child. A primary vacuum extraction decreased the probability of having a third child by 4%, but having two consecutive vacuum extraction deliveries did not further alter the probability.

Conclusions

A first delivery by vacuum extraction does not reduce the probability of subsequent childbearing to the same extent as a first delivery by emergency or elective caesarean section.
Ultrasound prediction of perinatal outcome: the unrecognised value of sibling data
Authors: Morken N–H , Skjaerven R , Wilcox AJ
Published: August 2014

Objective

To identify high‐risk fetuses at the first routinely performed ultrasound examination by making use of information from the mother's previous pregnancy.

Design

A population‐based cohort study.

Setting

Norway, 1999–2009.

Population

All singleton first live births and their second‐born siblings registered in the Medical Birth Registry of Norway (166 786 eligible sibling pairs).

Methods

Odds ratios were calculated by logistic regression.

Main outcome measures

Very small for gestational age (vSGA; birthweight ≤−1.96 standard deviations) and perinatal death (stillbirth at ≥22 weeks of gestation or death within 28 days of life).

Results

Small fetal size at ultrasound (i.e. a fetus smaller than expected by last menstrual period, LMP) is only weakly predictive of vSGA or perinatal death; however, if the firstborn sibling was vSGA at birth, ultrasound measures in the next pregnancy become strongly informative of risk. The smaller the fetal size on ultrasound, the higher its risk of vSGA (3–18%; Ptrend < 0.0001) and perinatal death (4–19 per thousand, Ptrend = 0.012). In contrast, if the first baby was not vSGA, small fetal size on ultrasound is uninformative.

Conclusions

When the firstborn baby is vSGA, discrepancies between fetal size on ultrasound and LMP become highly predictive of risk of vSGA and perinatal mortality in the second‐born infant. The value of combining these routinely collected clinical data has not previously been recognised.
Novel Approaches in Gluten‐Free Breadmaking: Interface between Food Science, Nutrition, and Health
Authors: Capriles Vanessa D. , Arêas José Alfredo G.
Published: August 2014

The evidence that celiac disease is one of the commonest food intolerances in the world is driving an increasing demand for gluten‐free foods. However, gluten is a structure‐building protein essential for formulating leavened baked goods. Therefore, obtaining high‐quality gluten‐free bread (GFB) is a technological challenge. This review focuses on contemporary approaches in gluten‐free baking that allow improvements at the structure, texture, acceptability, nutritive value, and shelf life of GFB. Gluten‐free breadmaking is a relatively new, emerging research topic that is attracting worldwide attention in order to develop different kinds of GFB, including regional varieties. Several approaches have been used to understand and improve GFB systems by evaluating different flours and starch sources, ingredients added for nutritional purposes, additives, and technologies or a combination of these elements. Some studies aimed to assess or improve GFB's technological or nutritional properties, while others had multiple objectives. Several studies used food science tools in order to improve technological and sensory quality of GFB, together with nutritional value. Some GFBs are vehicles of nutrients and bioactive compounds. Furthermore, extensive research on interfacing food science, nutrition, and health is needed so that a GFB with both good technological and nutritional properties can be prepared and made more available to those with celiac disease, which will help them adhere to a strict gluten‐free diet, increase social inclusion, and improve their quality of life.
Effect of Food Matrix on Saltiness Perception—Implications for Sodium Reduction
Authors: Kuo Wan‐Yuan , Lee Youngsoo
Published: August 2014

Enhancing sodium release from the food matrix, thus increasing saltiness perception, is a promising strategy to reduce the amount of salt needed in foods. However, the complex nature of the effect of the food matrix on saltiness perception makes it difficult to control saltiness perception when designing food products. The aim of this review is to provide an overview of the food matrix effects on saltiness perception of sodium chloride. The effects are discussed in the order of 3 stages in saltiness perception: release of sodium from food matrix into oral cavity (1st stage), delivery of sodium within oral cavity (2nd stage), and detection of sodium by the taste receptor cells (TRCs) (3rd stage). In the 1st stage, the food matrix affects the initial availability of sodium to be released, and also affects the spontaneous and facilitated migration of sodium from the matrix into the oral cavity. In the 2nd stage, the food matrix affects the availability of sodium and the mixing efficiency of sodium with saliva. The relationship between food matrix and oral processing of food that may affect the sodium release (1st stage) and the delivery (2nd stage) is also discussed. In the 3rd stage, the food matrix affects the physical availability of sodium for the TRCs, the physiological activity of TRCs, and the central activities involved in the perception process. Based on the understanding of complex nature of the matrix effects on saltiness perception discussed in this review, the properties of food matrix may be controlled effectively to enhance saltiness perception and achieve sodium reduction.
Bacterial role in pine wilt disease development – review and future perspectives
Authors: Nascimento Francisco X. , Hasegawa Koichi , Mota Manuel , Vicente Cláudia S. L.
Published: August 2014

Mutualistic and beneficial relationships between nematodes and bacteria are highly present in nature, mostly occurring because of nutritional dependence and pathogen protection, and intrinsically related with the environment, the ecological conditions and the nematode life stages. Thirty‐four years have passed since the first hypothesis suggesting a bacterial role in pine wilt disease (PWD), associated with the pinewood nematode (PWN), Bursaphelenchus xylophilus. In 1980, researchers reported that bacteria associated with the PWN could produce toxins that lead to PWD development in pine seedlings. It was also suggested a double vector system for PWD, where bacteria were vectored by the PWN and the PWN vectored by an insect from the Monochamus genus. Presently, the specific involvement of bacteria in such complex disease is still controversial, even though the increased number of studies focused on the potential bacteria role has increased considerably. This review is an up‐to‐date comprehensive perspective and brings new insights on the role of PWN‐associated bacteria in PWD.
Interactive transmission of two phytoplasmas by the vector insect
Authors: Rashidi M. , D'Amelio R. , Galetto L. , Marzachì C. , Bosco D.
Published: August 2014

Phytoplasmas are wall‐less bacteria associated with many plant diseases of wild and cultivated plants, transmitted by hemipteran insects. In nature, vectors can acquire more than one phytoplasma by feeding on multiple‐infected source plants or sequentially on plants infected by different phytoplasmas. The acquisition of multiple phytoplasmas may lead to their interaction in the insects. In this work, nymphs of the leafhopper Euscelidius variegatus were allowed to feed sequentially on Flavescence dorée (FDP)‐infected and chrysanthemum yellows (CYP)‐infected source plants and vice‐versa. Following the acquisition feeding, the titre of the two phytoplasmas in the insect was measured over time. FDP and CYP transmission capability of the doubly infected leafhoppers was studied by transmission to Vicia faba and to artificial feeding medium. Both phytoplasmas were acquired by the vector regardless of the feeding order and FDP titre, but not CYP titre, was affected by double infection. FDP and CYP persisted in the insect for life. Only CYP was consistently and efficiently transmitted by doubly infected leafhoppers. Consistently, FDP was seldom detected in the salivary glands and never in the artificial feeding medium of doubly infected leafhoppers. In conclusion, competition between CYP and FDP affected only salivary gland colonisation, while it had almost no effect on phytoplasma acquisition. Competition among phytoplasma strains in an evolutionary time scale may explain the greater ability of CYP to colonise the insect body and be transmitted.
Molecular biology and pathogenicity of phytoplasmas
Authors: Marcone C.
Published: August 2014

Phytoplasmas are a large group of plant‐pathogenic wall‐less, non‐helical, bacteria associated with diseases, collectively referred to as yellows diseases, in more than a thousand plant species worldwide. Many of these diseases are of great economic importance. Phytoplasmas are difficult to study, in particular because all attempts at culturing these plant pathogens under axenic conditions have failed. With the introduction of molecular methods into phytoplasmology about two decades ago, the genetic diversity of phytoplasmas could be elucidated and a system for their taxonomic classification based on phylogenetic traits established. In addition, a wealth of information was generated on phytoplasma ecology and genomics, phytoplasma–plant host interactions and phytoplasma–insect vector relationships. Taxonomically, phytoplasmas are placed in the class Mollicutes, closely related to acholeplasmas, and are currently classified within the provisional genus ‘Candidatus Phytoplasma’ based primarily on 16S rDNA sequence analysis. Phytoplasmas are characterised by a small genome. The sizes vary considerably, ranging from 530 to 1350 kilobases (kb), with overlapping values between the various taxonomic groups and subgroups, resembling in this respect the culturable mollicutes. The smallest chromosome, about 530 kb, is known to occur in the Bermuda grass white leaf agent ‘Ca. Phytoplasma cynodontis’. This value represents the smallest mollicute chromosome reported to date. In diseased plants, phytoplasmas reside almost exclusively in the phloem sieve tube elements and are transmitted from plant to plant by phloem‐feeding homopteran insects, mainly leafhoppers and planthoppers, and less frequently psyllids. Most of the phytoplasma host plants are angiosperms in which a wide range of specific and non‐specific symptoms are induced. Phytoplasmas have a unique and complex life cycle that involves colonisation of different environments, the plant phloem and various organs of the insect vectors. Furthermore, many phytoplasmas have an extremely wide plant host range. The dynamic architecture of phytoplasma genomes, due to the occurrence of repetitive elements of various types, may account for variation in their genome size and adaptation of phytoplasmas to the diverse environments of their plant and insect hosts. The availability of five complete phytoplasma genome sequences has made it possible to identify a considerable number of genes that are likely to play major roles in phytoplasma–host interactions. Among these, there are genes encoding surface membrane proteins and effector proteins. Also, it has been shown that phytoplasmas dramatically alter their gene expression upon switching between plant and insect hosts.
Changeable naevi in people at high risk for melanoma
Authors: Abbott Nicola CD , Pandeya Nirmala , Ong Natalie , McClenahan Phil , Smithers B Mark , Green Adele , Soyer H Peter
Published: August 2014

Background and Objectives

Naevi may change in size, shape and colour due to multiple inherent and external factors. We observed naevi changing size in adults at high risk of melanoma, and assessed associations of change with demographic factors, skin type, sites of naevi and history of melanoma.

Methods

In total, 29 participants with a personal or first‐degree family history of melanoma or those deemed at high risk with multiple naevi of variable morphologies had all melanocytic naevi 0.5–1 cm imaged and their maximum diameter recorded. Maximum diameters from repeat imaging of naevi 12 months later were compared to baseline measurements. Newly appearing naevi ≥5 mm and naevi that grew or decreased in size by 20% or more were defined as changeable naevi. Associations between changeable naevi and participants' age, sex, skin type, body sites of naevi and personal and family history of melanoma were assessed.

Results

There was no difference in changeable naevus rates among sex, age or skin type. Among the body sites, the head and neck were most likely to have changeable naevi, and the upper limbs the least likely. A family history of melanoma almost tripled the likelihood of having changeable naevi compared with those without both personal and family melanoma history.

Conclusions

Naevi can continue to change in size throughout adulthood, showing both increases and decreases in size as well as the appearance of new naevi. This has important clinical implications, in particular for sequential body imaging used for the detection of melanoma.
A Phase IB multicentre dose‐determination study of BHQ880 in combination with anti‐myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal‐related events
Authors: Iyer Swaminathan P. , Beck Joseph Taddeus , Stewart A. Keith , Shah Jatin , Kelly Kevin R. , Isaacs Randi , Bilic Sanela , Sen Suman , Munshi Nikhil C.
Published: August 2014

Dickkopf‐1 (DKK1), expressed by myeloma cells, suppresses osteoblast function and plays a key role in bone disease in multiple myeloma. BHQ880, a human neutralizing IgG1 anti‐DKK1 monoclonal antibody, is being investigated for its impact on multiple myeloma‐related bone disease and as an agent with potential anti‐myeloma activity. The primary objectives of this Phase IB study were to determine the maximum tolerated dose (MTD) of BHQ880 and to characterize the dose‐limiting toxicity (DLT) of escalating doses in combination with anti‐myeloma therapy and zoledronic acid. Twenty‐eight patients were enrolled and received BHQ880 at doses of 3–40 mg/kg. No DLTs were reported, therefore, the MTD was not determined. The recommended Phase II dose was declared as 10 mg/kg, based mainly on saturation data. There was a general trend towards increased bone mineral density (BMD) observed over time; specific increases in spine BMD from Cycle 12 onwards irrespective of new skeletal‐related events on study were observed, and increases in bone strength at the spine and hip were also demonstrated in some patients. BHQ880 in combination with zoledronic acid and anti‐myeloma therapy was well tolerated and demonstrated potential clinical activity in patients with relapsed or refractory multiple myeloma.
Treatment of malignant phaeochromocytoma with a combination of cyclophosphamide, vincristine and dacarbazine: own experience and overview of the contemporary literature
Authors: Deutschbein Timo , Fassnacht Martin , Weismann Dirk , Reincke Martin , Mann Klaus , Petersenn Stephan
Published: August 2014

Objective

Malignant phaeochromocytomas are rare and highly aggressive tumours. This retrospective study evaluated the outcome of combined chemotherapy with cyclophosphamide, vincristine and dacarbazine (also known as CVD regimen).

Methods

Patients with histologically and radiologically confirmed malignant phaeochromocytoma who were treated with the CVD regimen for progressive disease were retrospectively identified from chart review. Treatment cycles were usually repeated at 21‐day intervals, with cyclophosphamide (750 mg/m2), vincristine (1·4 mg/m2) and dacarbazine (600 mg/m2) on day 1, and dacarbazine only (600 mg/m2) on day 2. The main outcome measures were best response during treatment and progression‐free survival.

Results

Eight patients (4 males; median age 55·5 (range 31–77) years) with progressive disease underwent a median of 6 (range 3–11) cycles. Best treatment responses were as follows: partial response, n = 2 (25%); stable disease, n = 3 (38%); and progressive disease, n = 3 (38%). The median progression‐free survival was 5·4 (range 2·5–26·8) months. After the initial administration of 6 cycles, two patients received a second course of chemotherapy with another 6 cycles after new progressive disease had been detected. Subsequently, these patients were progression‐free for another 6·0 and 6·4 months. Mild gastrointestinal symptoms and fatigue were the most common adverse events.

Conclusion

Although objective tumour response rates were lower than previously reported in small series, the CVD regimen allowed disease stabilization for a substantial period of time and may therefore be considered as a treatment option in advanced stages. To improve disease outcome, however, new therapeutic approaches and larger multicentre studies are needed.
How does obesity affect fertility in men – and what are the treatment options?
Authors: Stokes Victoria J. , Anderson Richard A. , George Jyothis T.
Published: August 2014

Adiposity is associated with reduced fertility in men. The aetiology is multifactorial, with obese men at greater risk of suffering from impaired spermatogenesis, reduced circulating testosterone levels, erectile dysfunction and poor libido. The diagnosis and treatment of reduced fertility observed in obese men therefore requires insight into the underlying pathology, which has hormonal, mechanical and psychosocial aspects. This article summarises the current epidemiological, experimental and clinical trial evidence from the perspective of a practicing clinician. The following conclusions and recommendations can be drawn: Obesity is associated with low serum testosterone concentrations, but treatment with exogenous testosterone is likely to adversely impact on fertility. It is important to discuss this with men prior to initiation of testosterone therapy. Obesity adversely affects sperm concentration and may affect sperm quality. However, whether or not weight loss will correct these factors remain to be established. Oestrogen receptor modulators (and aromatase inhibitors) are unlicensed in the treatment for male hypogonadism and/or infertility. These treatments should hence be considered experimental approach until ongoing clinical trials report their outcomes.