bluuebunny/crossref_metadata_2025 huggingface dataset:
Basset: Learning the regulatory code of the accessible genome with deep convolutional neural networks
Authors: Kelley David R. , Snoek Jasper , Rinn John
Published: October 2015

The complex language of eukaryotic gene expression remains incompletely understood. Despite the importance suggested by many noncoding variants statistically associated with human disease, nearly all such variants have unknown mechanism. Here, we address this challenge using an approach based on a recent machine learning advance—deep convolutional neural networks (CNNs). We introduce an open source package Basset (https://github.com/davek44/Basset) to apply CNNs to learn the functional activity of DNA sequences from genomics data. We trained Basset on a compendium of accessible genomic sites mapped in 164 cell types by DNaseI-seq and demonstrate far greater predictive accuracy than previous methods. Basset predictions for the change in accessibility between variant alleles were far greater for GWAS SNPs that are likely to be causal relative to nearby SNPs in linkage disequilibrium with them. With Basset, a researcher can perform a single sequencing assay in their cell type of interest and simultaneously learn that cell’s chromatin accessibility code and annotate every mutation in the genome with its influence on present accessibility and latent potential for accessibility. Thus, Basset offers a powerful computational approach to annotate and interpret the noncoding genome.
Local regulation of the Srs2 helicase by the SUMO-like domain protein Esc2 promotes recombination at sites of stalled replication
Authors: Urulangodi Madhusoodanan , Sebesta Marek , Menolfi Demis , Szakal Barnabas , Sollier Julie , Sisakova Alexandra , Krejci Lumir , Branzei Dana
Published: October 2015

Accurate completion of replication relies on the ability of cells to activate error-free recombination-mediated DNA damage bypass at sites of perturbed replication. However, as anti-recombinase activities are also recruited to replication forks, how recombination-mediated damage bypass is enabled at replication stress sites remained puzzling. Here we uncovered that the conserved SUMO-like domain-containing Saccharomyces cerevisiae protein Esc2 facilitates recombination-mediated DNA damage tolerance by allowing optimal recruitment of the Rad51 recombinase specifically at sites of perturbed replication. Mechanistically, Esc2 binds stalled replication forks and counteracts the anti-recombinase Srs2 helicase via a two-faceted mechanism involving chromatin recruitment and turnover of Srs2. Importantly, point mutations in the SUMO-like domains of Esc2 that reduce its interaction with Srs2 cause suboptimal levels of Rad51 recruitment at damaged replication forks. In conclusion, our results reveal how recombination-mediated DNA damage tolerance is locally enabled at sites of replication stress and globally prevented at undamaged replicating chromosomes.
The Y3** ncRNA promotes the 3′ end processing of histone mRNAs
Authors: Köhn Marcel , Ihling Christian , Sinz Andrea , Krohn Knut , Hüttelmaier Stefan
Published: October 2015

We demonstrate that the Y3/Y3** noncoding RNAs (ncRNAs) bind to the CPSF (cleavage and polyadenylation specificity factor) and that Y3** associates with the 3′ untranslated region (UTR) of histone pre-mRNAs. The depletion of Y3** impairs the 3′ end processing of histone pre-mRNAs as well as the formation and protein dynamics of histone locus bodies (HLBs), the site of histone mRNA synthesis and processing. HLB morphology is also disturbed by knockdown of the CPSF but not the U7-snRNP components. In conclusion, we propose that the Y3** ncRNA promotes the 3′ end processing of histone pre-mRNAs by enhancing the recruitment of the CPSF to histone pre-mRNAs at HLBs.
Role of the small subunit processome in the maintenance of pluripotent stem cells
Authors: You Kwon Tae , Park Joha , Kim V. Narry
Published: October 2015

RNA-binding proteins (RBPs) play integral roles in gene regulation, yet only a small fraction of RBPs has been studied in the context of stem cells. Here we applied an RNAi screen for RBPs in mouse embryonic stem cells (ESCs) and identified 16 RBPs involved in pluripotency maintenance. Interestingly, six identified RBPs, including Krr1 and Ddx47, are part of a complex called small subunit processome (SSUP) that mediates 18S rRNA biogenesis. The SSUP components are preferentially expressed in stem cells and enhance the global translational rate, which is critical to sustain the protein levels of labile pluripotency factors such as Nanog and Esrrb. Furthermore, the SSUP proteins are required for efficient reprogramming of induced pluripotent stem cells. Our study uncovers the role of the SSUP and the importance of translational control in stem cell fate decision.
The applicability of Grant’s framework in the dynamic digital age
Authors: Rashidirad Mona , Soltani Ebrahim , Salimian Hamid , Liao Yingying
Published: October 2015

Purpose

– This paper aims to investigate the applicability of Grant’s framework in the current changing and dynamic environment.

Design/methodology/approach

– In this paper, a critical review of Grant’s paper was conducted to identify the limitations and weaknesses of the framework, which prevent its effective application in the current digital age.

Findings

– As a result, this paper presented a modified framework and four propositions to consider dynamic capabilities in the new turbulent environment and extend the relationships between a firm’s resources, capabilities, dynamic capabilities, competitive advantage and competitive strategy. Findings tied to this initiative will provide important contributions to research.

Originality/value

– Rooted in resource-based view (RBV), the proposed framework puts forward a valid theoretical foundation on how to create a competitive advantage from a firm’s internal factors, including strategic resources, capabilities and dynamic capabilities. Furthermore, it contributes to RBV literature by considering dynamic capabilities, as the firms’ most crucial factors in the current dynamic digital market.
Advancing tourist gaze research and authenticating the native-visitor: introduction to a special issue honoring work by John Urry
Authors: Woodside Arch G.
Published: October 2015

Purpose

– This introductory paper aims to offer a rudimentary model that describes the antecedent recipes for creating native-visitors. The paper describes what is unique and valuable about the seven articles that follow in their descriptions and explanations of the behavior of native-tourists. This special issue is to honor the originality and value of the contributions of tourism research’s leading critic, John Urry.

Design/methodology/approach

– The paper presents a paradigm that includes eight profiles of tourists identified by low/high conjunctions of knowledge, training and authentication of performances of tourism places. The study calls for a normative stance that tourists should develop a sense of obligation to learn before visiting to enrich understanding of what they are seeing and to reduce the negative outcomes of the tourist gaze. The method includes describing the unique and valuable contributions in each of the seven following articles in the issue.

Findings

– The analysis and outcomes are viewable best as propositions from a thought experiment. The seven articles that follow the introduction are appropriate data for a meta-review of the development of new meanings of tourism generated from the concept of native-tourist.

Research limitations/implications

– This study may spur necessary additional work to confirm that native-tourists do interpret performing tourist places differently and more richly than naïve tourists.

Originality/value

– The article is high in originality in establishing the benefits from studying native-tourists as unique contributors to clarifying and deepening the meanings of tourism drama enactments.
Changing places and identity construction: subjective introspection into researcher’s personal destination experiences
Authors: Batat Wided
Published: October 2015

Purpose

– The purpose of this paper is to draw on a subjective personal introspection (SPI) approach and Breakwell’s identity process theory (IPT) principles to show how elements from different cultures are performed by an individual to form a unique patchwork identity, and how this patchwork identity will contribute to deepen tourist gaze and, thus, achieving and maintaining authentic destination experience.

Design/methodology/approach

– The use of SPI gives the researcher an easy access to data collection of his personal, daily experiences related to changing destinations and consuming different places in Europe (France, UK and Italy), North America (USA and Canada) and North Africa (Algeria, Morocco and Egypt) for unlimited 24-hour access from an insider’s ongoing lived experiences.

Findings

– The results show that Breakwell’s IPT four principles are an integral part of patchwork identity construction when living and experiencing several places. Patchwork identity encompasses the individual’s ability to cross different social and symbolic boundaries when experiencing different destination. Each cultural context contributes to the bricolage and the assemblage of individual patchwork identity revealing one or more IPT dimensions.

Practical implications

– This paper serves to emphasize the importance of SPI-based research to patchwork identity construction in understanding the impact of cultural identity on tourist gaze. This approach can help marketers and tourism professionals to understand how consumers select the cultural elements that fit their identity and how the patchwork identity formed will contribute to deepen tourist gaze and destination experience of authenticity.

Originality/value

– The use of IPT and SPI-based research to explore tourist gaze offers a comprehensive framework based on a personal introspective approach where the starting point is the meaning individual provides to his hyphenated identity as coping mechanism to respond to social, psychological, ideological, cultural, symbolic, functional, structural, etc., aspirations.
Subjective and confirmatory personal introspections of cultural city holidays
Authors: Gountas John , Gountas Sandra
Published: October 2015

Purpose

– This paper aims to explore tourism consumer’s perceptions of cultural, emotional and behavioural differences. The subjective personal introspection (SPI) approach is used to investigate specific cultural differences which impact tourism satisfaction. It aims to identify the key attributes of cultural tourism satisfaction by comparing three European cities. The cultural attributes are synthesised into a confirmatory personal introspection (CPI), and a provisional research model is proposed.

Design/methodology/approach

– The research data of the cultural experiences are based on SPI data of “native-visitors” to London and ordinary visitors to Venice and Barcelona. The duration and the travel arrangements are the same for all three cultural experiences. The CPI uses thought experiments to formulate new research propositions.

Findings

– The SPI results show that the tourism gaze focus can be the cognitive-affective experiences of cultural holidays. Tourism consumer satisfaction is dependent on the quality of natural and man-made attractions and the social-emotional interactions between the hosts and guests in a destination. The three cities in our research, London, Venice and Barcelona, have different micro-cultures and levels of social-emotional interactions vary considerably between them. Overall tourism satisfaction is hypothesised to be influenced by the degree of social interaction and micro-cultural differences.

Practical implications

– The findings support the usefulness of SPI in tourism consumer research. SPI research findings produce in-depth understandings of the cultural tourism product attributes which cannot be captured in any other way. The personal insights are valuable to marketing professionals because they provide first-hand feedback of consumer’s perceptions over a longer period than a focus group session. The confirmatory introspections are valuable hypotheses to be tested empirically with specific tourism segments to identify product strengths and weaknesses as well as opportunities and threats.

Originality/value

– The use of SPI and CPI produces original hypotheses of the cultural tourism attributes which influence tourism satisfaction. The paper demonstrates that the tourism gaze can be expanded to investigate the cognitive-affective observations which have a direct effect on tourism satisfaction and decision-making.
Do clinical incidents, complaints and medicolegal claims overlap?
Authors: Goldsmith Paul , Moon Jackie , Anderson Paul , Kirkup Steve , Williams Susan , Gray Margaret
Published: October 2015

Purpose

– Error reporting by healthcare staff, patient-derived complaints and patient-derived medico-legal claims are three separate processes present in most healthcare systems. It is generally assumed that all relate to the same cases. Given the high costs associated with these processes and strong desire to maximise quality and standards, the purpose of this paper is to see whether it was indeed the case that most complaints and claims related to medical errors and the relative resource allocation to each group.

Design/methodology/approach

– Electronic databases for clinical error recording, patient complaints and medico-legal claims in a large NHS healthcare provider organisation were reviewed and case overlap analysed.

Findings

– Most complaints and medico-legal claims do not associate with a prior clinical error. Disproportionate resource is required for a small number of complaints and the medico-legal claims process. Most complaints and claims are not upheld.

Research limitations/implications

– The authors have only looked at data from one healthcare provider and for one period. It would be useful to analyse other healthcare organisations over a longer time period. The authors were unable to access data on secondary staffing costs, which would have been informative. As the medico-legal process can go on for many years, the authors do not know the ultimate outcomes for all cases. The authors also do not know how many medico-legal cases were settled out of court pragmatically to minimise costs.

Practical implications

– Staff error reporting systems and patient advisory services seem to be efficient and working well. However, the broader complaints and claims process is costing considerable time and money, yet may not be useful in driving up standards. System changes to maximise helpful complaints and claims, from a quality and standards perspective, and minimise unhelpful ones are recommended.

Originality/value

– This study provides important data on the lack of overlap between errors, complaints and claims cases.
Building national initiatives of compulsory licences
Authors: Manu Thaddeus
Published: October 2015

Purpose

– The purpose of this paper is to examine the extent to which developing countries could build national initiatives of compulsory licences.

Design/methodology/approach

– The focus of this article is only on developing countries. The author reflects on the Indian patent jurisprudence regarding the operational relationship between the general principles applicable to working of patented inventions locally and the grant of compulsory licences. The discussion that follows is based on a review of the case: Bayer Corporation versus Natco Pharma with a view to presenting a model for developing countries to maintain that the public interest principle of patent law is well-founded in their domestic patent regimes.

Findings

– The analysis confirms that failure to work locally continues to be abusive of the patent right under the Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement, and remains a valid condition on which to grant a compulsory licence. Thus, this reverses the often-contrary misconception that has become almost a unanimous assumption that failure to work basis for granting compulsory licensing would violate Article 27(1) of TRIPS and its enforcement provisions on patent.

Originality/value

– The author argues that as no member state has challenged the legality of Indian’s decision in the World Trade Organisation, under the dispute settlement understanding (DSU) system is more supportive of the contention that failure to work locally continues to be permissible under TRIPS and remains valid conditions on which member states can grant compulsory licences. This further adds weight to the understanding that nothing in the light of TRIPS would, in fact, preclude any possibility of developing countries amending their patent laws accordingly to maintain that the public interest principle underlining patent law is well-founded in their domestic patent regimes.
Temperate phages promote colicin‐dependent fitness of Salmonella enterica serovar Typhimurium
Authors: Nedialkova Lubov P. , Sidstedt Maja , Koeppel Martin B. , Spriewald Stefanie , Ring Diana , Gerlach Roman G. , Bossi Lionello , Stecher Bärbel
Published: October 2015

Bacteria employ bacteriocins for interference competition in microbial ecosystems. Colicin Ib (ColIb), a pore‐forming bacteriocin, confers a significant fitness benefit to Salmonella enterica serovar Typhimurium (S. Tm) in competition against commensal Escherichia coli in the gut. ColIb is released from S. Tm into the environment, where it kills susceptible competitors. However, colicin‐specific release proteins, as they are known for other colicins, have not been identified in case of ColIb. Thus, its release mechanism has remained unclear. In the current study, we have established a new link between ColIb release and lysis activity of temperate, lambdoid phages. By the use of phage‐cured S. Tm mutant strains, we show that the presence of temperate phages and their lysis genes is necessary and sufficient for release of active ColIb into the culture supernatant. Furthermore, phage‐mediated lysis significantly enhanced S. Tm fitness in competition against a ColIb‐susceptible competitor. Finally, transduction with the lambdoid phage 933W rescued the defect of E. coli strain MG1655 with respect to ColIb release. In conclusion, ColIb is released from bacteria in the course of phage lysis. Our data reveal a new mechanism for colicin release and point out a novel function of temperate phages in enhancing colicin‐dependent bacterial fitness.
Aid, Employment and Poverty Reduction in Africa
Authors: Page John , Shimeles Abebe
Published: October 2015

Growth in Africa is weakly linked to poverty reduction. The reason is that Africa has failed to create enough good jobs. Structural transformation—the relative growth of employment in high productivity sectors—has not featured in Africa's post‐1995 growth story. As a result, the region's fastest growing economies have the least responsiveness of employment and poverty to growth. Development aid is partly responsible. Across Africa more aid went to countries with a low employment intensity of growth. The study proposes a new approach to aid and poverty in Africa, one that focuses on supporting structural change for job creation.
Is Small Beautiful? Small Enterprise, Aid and Employment in Africa
Authors: Page John , Söderbom Måns
Published: October 2015

Aid providers often describe small firms as ‘job creators’. But what types of jobs do they create? Drawing on enterprise survey data for nine African countries and panel data for Ethiopia we find that small and large formal sector firms create similar numbers of net jobs. Small firms, however, have much higher turnover of employment and pay persistently lower wages. To create more ‘good’ jobs aid should target the constraints to the growth of firms of all sizes. Improving the ‘investment climate’ and new programs to increase firms' capabilities—through, for example, management training—offer greater prospects for employment creation.
Priorities for Boosting Employment in Sub‐Saharan Africa: Evidence for Mozambique
Authors: Jones Sam , Tarp Finn
Published: October 2015

Should policy‐makers, including foreign donors, focus employment strategies in sub‐Saharan Africa on strengthening access to formal wage employment or on raising productivity in the informal sector? We examine the evidence in Mozambique and show that crude distinctions between formality and informality are not illuminating. The observed welfare advantage of formal sector workers essentially derives from differences in endowments and local conditions. Non‐agricultural informal work can yield higher returns than formal work. The implication is that the informal sector must not be marginalized; and raising productivity in agriculture must be accorded a central place in boosting employment.
Italo‐Romance Metaphony and the Tuscan Diphthongs
Authors: Maiden Martin
Published: October 2015

The historical causes of general so‐called ‘opening’ diphthongization of proto‐Romance low mid vowels in stressed open syllables are an enduring matter of dispute in historical Romance phonology, the two principal positions being that the diphthongs originate in the assimilatory process of metaphony conditioned by following unstressed vowels, or that they are a matter of ‘spontaneous’ diphthongization associated with lengthening of the vowels. Most recent scholarship on the subject has tended to favour the latter view. This study, focusing on Tuscan (and thereby on Italian), reasserts the case for the former interpretation, critically reviewing older arguments and adducing new ones to show that the details of Tuscan open syllable diphtongization are significantly correlated with a metaphonic origin, despite claims to the contrary. In particular, I argue that the restriction of the generalized diphthongs to open syllables reflects the early conditions of metaphony, and that the occasional absence of the diphthongs in Tuscan systematically presupposes the historical absence of a metaphonizing environment. In conclusion, I reflect on the significance of my claims both for general Romance historical morphology and, particularly, for the place of Tuscan among the Italo‐Romance dialects. The data also show how morphological analogy may play a significant role in the diffusion of the effects of sound change.
Property and place attachment: a legal geographical analysis of biodiversity law reform in New South Wales
Authors: Bartel Robyn , Graham Nicole
Published: October 2015

Environmental indicators suggest that the legislation regulating land clearing inNSWshould be strengthened. However, reform has moved in the opposite direction, continuously weakening the law in response to the marginal but politically significant argument that the Act undermined sacrosanct private property rights. The cultural mythology around property and the legal discourse of property dephysicalise relations between people and place, transforming them into categories of abstract and predominantly commercial rights, and foster a vocabulary of entitlement to land as a civil and political right. Opponents to the existing legislation have also argued that it insufficiently accommodates vernacular knowledge regarding locally specific conditions and variations, and creates disrespect and mistrust between government and landholders. This paper interrogates the relationships between the key arguments of opponents to the existing legislation with place attachment. Place attachment describes the bond between people and place and is usually regarded as being positive for environmental protection. However, it may also underpin reactionary place‐protective behaviours includingNIMBYism, the preservation of degraded landscapes and inappropriate place management practices, including the institution of private property itself. Paradoxically, while place‐protective resistance may appear to conflict with conservation, potential for resolution to this ongoing legal and geographical crisis in biodiversity conservation may be found through highlighting the common ground of place connection and inter‐dependence, and by rephysicalising law to better articulate shared interests in healthy environments beyond the narrow prism of individual property rights. This endeavour may be best achieved through a multi‐scalar and poly‐vocal participatory process, to ensure such narrow and monological interests do not hold disproportionate sway and address path dependency and legacy issues.
Assessment of gene expression levels of proopiomelanocortin (POMC) and melanocortin‐1 receptor (MC1R) in vitiligo
Authors: Nagui Noha A , Mahmoud Sara B , Abdel Hay Rania M , Hassieb May M , Rashed Laila A
Published: October 2015

Proopiomelanocortin (POMC) and melanocortin 1 receptor (MC1R) are regulators of melanogenesis and pigmentation. Our objective was to estimate their levels, searching for a possible role of the melanocortin system in vitiligo. This study included 40 vitiligo patients and 40 controls. Skin biopsies were taken from lesional and non‐lesional skin of patients and from the non‐sun exposed skin of controls to detect the expression of POMC and MC1R using quantitative real‐time polymerase chain reaction. Both factors were significantly lower in lesional than non‐lesional skin and controls, while they were significantly higher in non‐lesional skin than in controls. There was a statistically significant positive correlation between lesional levels of POMC and MC1R, as well as between non‐lesional levels of POMC and MC1R in the patients. On the other hand, we found a statistically significant negative correlation between the lesional and non‐lesional levels of POMC, as well as between the lesional and non‐lesional levels of MC1R in the patients. As a conclusion, the melanocortin system could play a role in the pathogenesis of vitiligo or could be affected as the end result of the disease.
Screening for Down syndrome in the second trimester of pregnancy
Authors: O'Leary Peter , Maxwell Susannah , Sinosich Michael , DeVoss Kerry , Fletcher Janice , Ranieri Enzo , Metz Michael P.
Published: October 2015

Antenatal screening for fetal anomalies has provided women and their partners with information to make reproductive choices based on the risk of serious chromosomal or structural defects since the 1990s. Alternative tests include first‐trimester screening (combined ultrasound and maternal serum markers), second‐trimester maternal serum markers and noninvasive cell‐free DNA testing. The recent recommendations by the Royal Australian and New Zealand College of Obstetrics and Gynaecology and the Human Genetics Society of Australasia against second‐trimester triple testing are based on unsound performance criteria, raise several contestable issues around access and equity and challenge the principles of governments providing affordable options.
The effects of metformin treatment of gestational diabetes on maternal weight and glucose tolerance postpartum – a prospective follow‐up study
Authors: Pellonperä Outi , Rönnemaa Tapani , Ekblad Ulla , Vahlberg Tero , Tertti Kristiina
Published: October 2015

Introduction

Metformin seems to reduce gestational weight gain compared with insulin in women with gestational diabetes (GDM). Women with GDM requiring insulin are more likely to develop abnormal glucose tolerance postpartum than women treated with diet only. In this prospective follow‐up study of a randomized clinical trial, we investigated the effect of metformin treatment in women with GDM on weight gain and glucose tolerance postpartum.

Materials and Methods

Women with GDM with two or more pathologic glucose values at 2‐h 75‐g oral glucose tolerance test (OGTT) were recruited. Those needing medication to achieve sufficient glycemic control were randomized at 22–34 weeks of gestation to either metformin (n = 110) or insulin (n = 107) treatment until delivery. A third GDM group (n = 128) requiring no medication had only diet treatment. Weight, OGTT and glycosylated hemoglobin (HbA1c) were determined at 6–8 weeks and 1 year postpartum.

Results

At least one postpartum visit was attended by 104, 101 and 120 women in the metformin, insulin and diet‐only groups, respectively. No significant differences were found in the change of weight, HbA1c or OGTT glucose values between the groups during the study (p ≥ 0.121 in all comparisons). One year postpartum the diet‐only group had less impaired glucose tolerance compared with the metformin and insulin groups (7.1%, 19.1% and 15.6%, respectively; overall p = 0.039) and a lower incidence of diabetes (p = 0.027).

Conclusions

Short‐term metformin therapy does not affect weight, HbA1c or OGTT glucose values postpartum compared with insulin or diet‐only treatments. Women with GDM requiring no medication are least likely to develop impaired glucose tolerance or diabetes postpartum.
Augmentation of Voluntary Locomotor Activity by Transcutaneous Spinal Cord Stimulation in Motor‐Incomplete Spinal Cord‐Injured Individuals
Authors: Hofstoetter Ursula S. , Krenn Matthias , Danner Simon M. , Hofer Christian , Kern Helmut , McKay William B. , Mayr Winfried , Minassian Karen
Published: October 2015

The level of sustainable excitability within lumbar spinal cord circuitries is one of the factors determining the functional outcome of locomotor therapy after motor‐incomplete spinal cord injury. Here, we present initial data using noninvasive transcutaneous lumbar spinal cord stimulation (tSCS) to modulate this central state of excitability during voluntary treadmill stepping in three motor‐incomplete spinal cord‐injured individuals. Stimulation was applied at 30 Hz with an intensity that generated tingling sensations in the lower limb dermatomes, yet without producing muscle reflex activity. This stimulation changed muscle activation, gait kinematics, and the amount of manual assistance required from the therapists to maintain stepping with some interindividual differences. The effect on motor outputs during treadmill‐stepping was essentially augmentative and step‐phase dependent despite the invariant tonic stimulation. The most consistent modification was found in the gait kinematics, with the hip flexion during swing increased by 11.3° ± 5.6° across all subjects. This preliminary work suggests that tSCS provides for a background increase in activation of the lumbar spinal locomotor circuitry that has partially lost its descending drive. Voluntary inputs and step‐related feedback build upon the stimulation‐induced increased state of excitability in the generation of locomotor activity. Thus, tSCS essentially works as an electrical neuroprosthesis augmenting remaining motor control.
Respiratory syncytial virus induces phosphorylation of mTOR at ser2448 in CD8 T cells from nasal washes of infected infants
Authors: de Souza A P Duarte , de Freitas D Nascimento , Antuntes Fernandes K E , D'Avila da Cunha M , Antunes Fernandes J L , Benetti Gassen R , Fazolo T , Pinto L A , Scotta M , Mattiello R , Pitrez P M , Bonorino C , Stein R T
Published: October 2015

Respiratory syncytial virus (RSV)-specific CD8+ T cell responses do not protect against reinfection. Activation of mammalian target of rapamycin (mTOR) impairs memory CD8+ T cell differentiation. Our hypothesis was that RSV inhibits the formation of CD8+ T cells memory responses through mTOR activation. To explore this, human and mouse T cells were used. RSV induced mTOR phosphorylation at Ser2448 in CD8 T cells. mTOR activation by RSV was completely inhibited using rapamycin. RSV-infected children presented higher mTOR gene expression on nasal washes comparing to children infected with metapneumovirus and rhinovirus. In addition, RSV-infected infants presented a higher frequency of CD8+ pmTORser2448+ T cells in nasal washes compared to RSV-negative infants. Rapamycin treatment increased the frequency of mouse CD8 RSV-M282–90 pentamer-positive T cells and the frequency of RSV-specific memory T cells precursors. These data demonstrate that RSV is activating mTOR directly in CD8 T cells, indicating a role for mTOR during the course of RSV infection.
Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells
Authors: Townsley E , O'Connor G , Cosgrove C , Woda M , Co M , Thomas S J , Kalayanarooj S , Yoon I-K , Nisalak A , Srikiatkhachorn A , Green S , Stephens H A F , Gostick E , Price D A , Carrington M , Alter G , McVicar D W , Rothman A L , Mathew A
Published: October 2015

Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR–HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self-limited viral infections. During our investigation of CD8+ T cell responses to a conserved HLA-B57-restricted epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long-standing clinical cohort in Thailand. We confirmed binding of the NS1 tetramer to CD56dim NK cells, which are known to express KIRs. Using depletion studies and KIR-transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1. Phenotypical analysis of PBMC from HLA-B57+ subjects with acute DENV infection revealed marked activation of NS1 tetramer-binding natural killer (NK) cells around the time of defervescence in subjects with severe dengue disease. Collectively, our findings indicate that subsets of NK cells are activated relatively late in the course of acute DENV illness and reveal a possible role for specific KIR–HLA interactions in the modulation of disease outcomes.
Temperature and time variations during osteotomies performed with different piezosurgical devices: an in vitro study
Authors: Delgado‐Ruiz R. A. , Sacks D. , Palermo A. , Calvo‐Guirado J. L. , Perez‐Albacete C. , Romanos G. E.
Published: October 2015

Aim

The aim of this experimental in vitro study was to evaluate the effects of the piezoelectric device in temperature and time variations in standardized osteotomies performed with similar tip inserts in bovine bone blocks.

Methods

Two different piezosurgical devices were used the OE‐F15® (Osada Inc., Los Angeles, California, USA) and the Surgybone® (Silfradent Inc., Sofia, Forli Cesena, Italy). Serrated inserts with similar geometry were coupled with each device (ST94 insert/test A and P0700 insert/test B). Osteotomies 10 mm long and 3 mm deep were performed in bone blocks resembling type II (dense) and type IV (soft) bone densities with and without irrigation. Thermal changes and time variations were recorded. The effects of bone density, irrigation, and device on temperature changes and time necessary to accomplish the osteotomies were analyzed.

Results

Thermal analysis showed significant higher temperatures during piezosurgery osteotomies in hard bone without irrigation (P < 0.05). The type of piezosurgical device did not influence thermal variations (P > 0.05). Time analysis showed that the mean time values necessary to perform osteotomies were shorter in soft bone than in dense bone (P < 0.05).

Conclusions

Within the limitations of this in vitro study, it may be concluded that the temperature increases more in piezosurgery osteotomies in dense bone without irrigation; the time to perform the osteotomy with piezosurgery is shorter in soft bone compared to hard bone; and the piezosurgical device have a minimal influence in the temperature and time variations when a similar tip design is used during piezosurgery osteotomies.
From species distributions to meta‐communities
Authors: Thuiller Wilfried , Pollock Laura J. , Gueguen Maya , Münkemüller Tamara
Published: October 2015

The extent that biotic interactions and dispersal influence species ranges and diversity patterns across scales remains an open question. Answering this question requires framing an analysis on the frontier between species distribution modelling (SDM), which ignores biotic interactions and dispersal limitation, and community ecology, which provides specific predictions on community and meta‐community structure and resulting diversity patterns such as species richness and functional diversity. Using both empirical and simulated datasets, we tested whether predicted occurrences from fine‐resolution SDMs provide good estimates of community structure and diversity patterns at resolutions ranging from a resolution typical of studies within reserves (250 m) to that typical of a regional biodiversity study (5 km). For both datasets, we show that the imprint of biotic interactions and dispersal limitation quickly vanishes when spatial resolution is reduced, which demonstrates the value of SDMs for tracking the imprint of community assembly processes across scales.
Functional trait diversity across trophic levels determines herbivore impact on plant community biomass
Authors: Deraison Hélène , Badenhausser Isabelle , Loeuille Nicolas , Scherber Christoph , Gross Nicolas
Published: October 2015

Understanding the consequences of trophic interactions for ecosystem functioning is challenging, as contrasting effects of species and functional diversity can be expected across trophic levels. We experimentally manipulated functional identity and diversity of grassland insect herbivores and tested their impact on plant community biomass. Herbivore resource acquisition traits, i.e. mandible strength and the diversity of mandibular traits, had more important effects on plant biomass than body size. Higher herbivore functional diversity increased overall impact on plant biomass due to feeding niche complementarity. Higher plant functional diversity limited biomass pre‐emption by herbivores. The functional diversity within and across trophic levels therefore regulates the impact of functionally contrasting consumers on primary producers. By experimentally manipulating the functional diversity across trophic levels, our study illustrates how trait‐based approaches constitute a promising way to tackle existing links between trophic interactions and ecosystem functioning.
Evolutionary mechanisms of habitat invasions, using the copepodEurytemora affinisas a model system
Authors: Lee Carol Eunmi
Published: October 2015

The study of the copepodEurytemora affinishas provided unprecedented insights into mechanisms of invasive success. In this invited review, I summarize a subset of work from my laboratory to highlight key insights gained from studyingE. affinisas a model system. Invasive species with brackish origins are overrepresented in freshwater habitats. The copepodE. affinisis an example of such a brackish invader, and has invaded freshwater habitats multiple times independently in recent years. These invasions were accompanied by the evolution of physiological tolerance and plasticity, increased body fluid regulation, and evolutionary shifts in ion transporter (V‐type H+ATPase, Na+, K+‐ATPase) activity and expression. These evolutionary changes occurred in parallel across independent invasions in nature and in laboratory selection experiments. Selection appears to act on standing genetic variation during invasions, and maintenance of this variation is likely facilitated through ‘beneficial reversal of dominance’ in salinity tolerance across habitats. Expression of critical ion transporters is localized in newly discovered Crusalis leg organs. Increased freshwater tolerance is accompanied by costs to development time and greater requirements for food. High‐food concentration increases low‐salinity tolerance, allowing saline populations to invade freshwater habitats. Mechanisms observed here likely have relevance for other taxa undergoing fundamental niche expansions.
Liquidity Constraints, Competition, and Markup Cyclicality
Authors: Braun Matías , Raddatz Claudio
Published: October 2015

This article provides evidence on the relation among financial constraints, competition, and the cyclicality of markups. Based on a long series of industry data from a large number of countries, we find that markups increase in conjunction with the business cycle in environments with higher short‐term financial constraints (liquidity constraints) and more competition. The evidence also suggests that these two elements complement each other: the procyclicality of markups in firms facing both high competition and high liquidity constraints is higher than that explained by each determinant independently.
What factors are influencing tea consumption among Chinese urban residents? An empirical study
Authors: Chen Fuqiao , Li Shujie , Jiang Renhua , Jiang Aiqin
Published: October 2015

Using primary data collected from a questionnaire survey in 12 cities in China, we set up a model to analyze the influencing factors of Chinese urban residents' tea consumption. Three groups of factors are considered in the model, i.e., demographic and personal characteristics, economic factors and consumption habits. Research findings indicate that tea consumption is significantly impacted by gender difference, personal income, consumption atmosphere and habitual factors. This has important policy implications for tea marketing. First of all, it is essential to develop more tea products that cater to the needs of urban females while at the meantime securing the steady growth of tea consumption among males. Second, in light of the consumption discrepancies between families, areas and occupations, differentiated marketing strategies should be created with an emphasis on cultivating and taking advantage of consumption atmosphere in the society. In addition, income disparities call for diversified tea products with affordable prices. It is also suggested that educational programs on tea consumption be advocated to promote the consumption frequency and quantity of tea both in China and in other countries.
Molecular characterization of T‐cell immunoglobulin mucin domain‐3 and Galectin‐9 genes of swamp‐ and riverine‐type water buffaloes
Authors: Duran P. L. H. , Padiernos R. B. C. , Abella E. A. , Konnai S. , Mingala C. N.
Published: October 2015

Molecular characterization of T‐cell immunoglobulin mucin domain‐3 (TIM‐3) and Galectin‐9 (GAL‐9) genes of swamp‐ and riverine‐type water buffaloes was conducted to compare these genes with other species; determine the unique characteristic specific in water buffalo; and provide baseline information for the assessment of disease progression in buffalo species. TIM‐3 and GAL‐9 genes were amplified, purified, sequenced and characterized. The sequence result of TIM‐3 in both types of water buffaloes contained 843 nucleotides encoding to 280 amino acids while GAL‐9 of swamp‐type and riverine‐type water buffaloes contained 1023 and 972 nucleotides encoding to 340 and 323 amino acids, respectively. Meanwhile, the nucleotide and amino sequence of TIM‐3 in water buffalo were 83–98% and 94–97% identical with other artiodactyl species, respectively. On the other hand, GAL‐9 nucleotide and amino acid sequence in water buffalo were 85–98% and 76–96% identical with other artiodactyl species. The tyrosine‐kinase phosphorylation motif and potential glycosylation sites were conserved within the tribe Bovinae. It is imperative to have further studies in the assessment of the role of these genes in disease progression in water buffalo during chronic infection. The study is the first report that describes the genetic characteristic of TIM‐3 and GAL‐9 genes in water buffalo.
Improving discharge planning communication between hospitals and patients
Authors: New P. W. , McDougall K. E. , Scroggie C. P. R.
Published: October 2015

Background

A potential barrier to patient discharge from hospital is communication problems between the treating team and the patient or family regarding discharge planning.

Aim

To determine if a bedside ‘Leaving Hospital Information Sheet’ increases patient and family's knowledge of discharge date and destination and the name of the key clinician primarily responsible for team–patient communication.

Methods

This article is a ‘before‐after’ study of patients, their families and the interdisciplinary ward‐based clinical team. Outcomes assessed pre‐implementation and post‐implementation of a bedside ‘Leaving Hospital Information Sheet’ containing discharge information for patients and families. Patients and families were asked if they knew the key clinician for team–patient communication and the proposed discharge date and discharge destination. Responses were compared with those set by the team. Staff were surveyed regarding their perceptions of patient awareness of discharge plans and the benefit of the ‘Leaving Hospital Information Sheet’.

Results

Significant improvement occurred regarding patients' knowledge of their key clinician for team–patient communication (31% vs 75%; P = 0.0001), correctly identifying who they were (47% vs 79%; P = 0.02), and correctly reporting their anticipated discharge date (54% vs 86%; P = 0.004). There was significant improvement in the family's knowledge of the anticipated discharge date (78% vs 96%; P = 0.04). Staff reported the ‘Leaving Hospital Information Sheet’ assisted with communication regarding anticipated discharge date and destination (very helpful n = 11, 39%; a little bit helpful n = 11, 39%).

Conclusions

A bedside ‘Leaving Hospital Information Sheet’ can potentially improve communication between patients, families and their treating team.
Microbiota and host immune responses: a love–hate relationship
Authors: Tomkovich Sarah , Jobin Christian
Published: October 2015

A complex relationship between the microbiota and the host emerges early at birth and continues throughout life. The microbiota includes the prokaryotes, viruses and eukaryotes living among us, all of which interact to different extents with various organs and tissues in the body, including the immune system. Although the microbiota is most dense in the lower intestine, its influence on host immunity extends beyond the gastrointestinal tract. These interactions with the immune system operate through the actions of various microbial structures and metabolites, with outcomes ranging from beneficial to deleterious for the host. These differential outcomes are dictated by host factors, environment, and the type of microbes or products present in a specific ecosystem. It is also becoming clear that the microbes are in turn affected and respond to the host immune system. Disruption of this complex dialogue between host and microbiota can lead to immune pathologies such as inflammatory bowel diseases, diabetes and obesity. This review will discuss recent advances regarding the ways in which the host immune system and microbiota interact and communicate with one another.
Altered transcription of inflammation‐related genes in dental pulp of coeliac children
Authors: Bossù Maurizio , Montuori Monica , Casani Daniela , Di Giorgio Gianni , Pacifici Andrea , Ladniak Barbara , Polimeni Antonella
Published: October 2015

Background

Coeliac disease is a chronic small intestinal immune‐mediated enteropathy precipitated by exposure to dietary gluten, and possible relationships between coeliac disease and dental pathogenic conditions during childhood have been poorly investigated.

Aim

The dental pulp plays a pivotal role in the immune defence against possible entry of pathogens from teeth, and the aim of this work was to investigate quantitative transcription levels of selected genes (IL‐9, IL‐11, IL‐15, IL‐18, IL‐21, IL‐27, MICA, IFN‐γ) coding for pro‐inflammatory immune innate activities in the pulp of primary teeth from healthy children and children with coeliac disease.

Design

The pulp from primary teeth of 10 healthy children and 10 children with coeliac disease was used to extract RNA and prepare cDNA for quantitative PCR transcription analysis employing commercial nucleotide probes for selected genes.

Results

In children with coeliac disease, the genes coding for pro‐inflammatory cytokines IFN‐γ, IL‐11, IL‐18, and IL‐21 were significantly overexpressed, suggesting the possible importance of these cytokines in the relationships between coeliac disease and dental disorders.

Conclusion

For the first time, we reported in dental pulp of children possible relationships between coeliac disease and modulation in transcription of cytokine‐dependent inflammatory activities.