bluuebunny/crossref_metadata_2025 huggingface dataset:
Angptl4 links α-cell proliferation following glucagon receptor inhibition with adipose tissue triglyceride metabolism
Authors: Ben-Zvi Danny , Barrandon Ornella , Hadley Stephanie , Blum Barak , Peterson Quinn P. , Melton Douglas A.
Published: December 2015

Significance

Hyperactivity of the hormone glucagon plays an important role in the pathophysiology of type 2 diabetes, but the factors that affect glucagon levels and α-cell proliferation are not entirely understood. This is particularly important for the development diabetes drugs based on glucagon receptor inhibition, which increase glucagon levels in plasma and α-cell mass. Here we show that increased levels of Angiopoietin-like 4 (Angptl4) in adipose tissue and plasma are sufficient to induce α-cell proliferation. Angptl4 is a conserved, secreted lipoprotein lipase inhibitor expressed by many tissues that is regulated by exercise and feeding. Moreover, Angptl4 is required for the compensatory hyperglucagonemia and α-cell proliferation following treatment with glucagon receptor antagonists.
Autotetraploid rice methylome analysis reveals methylation variation of transposable elements and their effects on gene expression
Authors: Zhang Jie , Liu Yuan , Xia En-Hua , Yao Qiu-Yang , Liu Xiang-Dong , Gao Li-Zhi
Published: December 2015

Significance

Whole genome duplication (WGD) has long been recognized as a major force in angiosperm evolution. DNA methylation variation is known to be involved in polyploidization events. We synthesized autotetraploid rice that may rule out disturbances from hybridization and investigated the scope and scale of DNA methylation variation in response to WGD in neopolyploid rice. We found that WGD prompts increased methylation in class II transposable elements, which then suppress the genome-wide expression level of nearby genes. Hypermethylation of these transposable elements inhibits their transposition, stabilizing the integrity of chromosomes, and decreases nearby gene expression, potentially reducing deleterious genome-dosage effects. Our results indicate that DNA methylation plays an important role in assisting plant neopolyploids rapidly adapt to WGD.
Protein-like proton exchange in a synthetic host cavity
Authors: Hart-Cooper William M. , Sgarlata Carmelo , Perrin Charles L. , Toste F. Dean , Bergman Robert G. , Raymond Kenneth N.
Published: December 2015

Significance

Water drives molecular interactions central to the chemistry of life. Critical to life’s metabolic machinery, enzymes catalyze reactions with remarkable selectivities and efficiencies resulting from noncovalent interactions between water, substrate, and the enzyme active site. Here, amide hydrogen–deuterium exchange kinetics provide quantification of the electronic and steric factors that influence exchange between water and a highly charged host molecule whose protective outer shell and hydrophobic cavity allow it to function like an enzyme. Investigations suggest that the host’s interior microenvironment reacts with encapsulated water in a manner that is correlated to the host’s ability to mediate acid catalysis, thereby providing a tool for developing enzyme-like microenvironments to mediate acid- or base catalysis.
Biological soil crusts accelerate the nitrogen cycle through large NO and HONO emissions in drylands
Authors: Weber Bettina , Wu Dianming , Tamm Alexandra , Ruckteschler Nina , Rodríguez-Caballero Emilio , Steinkamp Jörg , Meusel Hannah , Elbert Wolfgang , Behrendt Thomas , Sörgel Matthias , Cheng Yafang , Crutzen Paul J. , Su Hang , Pöschl Ulrich
Published: December 2015

Significance

Biological soil crusts (biocrusts), occurring on ground surfaces in drylands throughout the world, are among the oldest life forms consisting of cyanobacteria, lichens, mosses, and algae plus heterotrophic organisms in varying proportions. They prevent soil erosion and nurture ecosystems by fixing carbon and nitrogen from the atmosphere. Here, we show that the fixed nitrogen is processed within the biocrusts, and during this metabolic activity, nitrogen oxide and nitrous acid are released to the atmosphere. Both of these gases are highly relevant, as they influence the radical formation and oxidizing capacity of the lower atmosphere, also interacting with climate change. In drylands, biocrusts appear to play a key role both in nitrogen fixation and the release of atmospheric reactive nitrogen.
Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel
Authors: Brettmann Joshua B. , Urusova Darya , Tonelli Marco , Silva Jonathan R. , Henzler-Wildman Katherine A.
Published: December 2015

Significance

Pore domains of ion channels form the ion conduction pathway and thus control the identity and flux of ions across the membrane. Flux-dependent inactivation suggests that these two functions are connected, with allosteric linkage between the selectivity filter and inner gate. This study uses solution NMR to investigate structural and dynamic features of ion selectivity and coupling between the gates in the small bacterial channel NaK. NaK is a nonselective cation channel and is homologous to several eukaryotic channels that are not well modeled by KcsA. Our results show a previously unexpected dynamic coupling between the selectivity filter and inner gate in NaK. This suggests that such transmembrane communication is widespread and occurs through distinct mechanisms in diverse channels.
The introduction of RNA-DNA differences underlies interindividual variation in the human
IL12RB1
mRNA repertoire
Authors: Turner Amy J. , Aggarwal Praful , Miller Halli E. , Waukau Jill , Routes John M. , Broeckel Ulrich , Robinson Richard T.
Published: December 2015

Significance

The gene interleukin-12 receptor β1 (
IL12RB1
) regulates susceptibility to several human diseases, including mycobacterial disease (e.g., tuberculosis). Here, we demonstrate that many of the mRNAs transcribed from
IL12RB1
in primary immune cells contain RNA-DNA differences (RDDs). RDDs are nucleotide differences between RNA and its encoding DNA and are introduced posttranscriptionally; in the case of
IL12RB1
, RDDs are concentrated in cytokine-binding regions that are important for
IL12RB1
function. This observation is significant, as it is the first demonstration to our knowledge that a mechanism of sequence diversification exists for a human cytokine receptor. Given
IL12RB1
’s importance to mycobacterial disease resistance, our data raise the intriguing possibility that individual differences in
IL12RB1
RDD introduction contribute to differences in mycobacterial disease susceptibility.
Genomic data do not support comb jellies as the sister group to all other animals
Authors: Pisani Davide , Pett Walker , Dohrmann Martin , Feuda Roberto , Rota-Stabelli Omar , Philippe Hervé , Lartillot Nicolas , Wörheide Gert
Published: December 2015

Significance

Clarifying the phylogeny of animals is fundamental to understanding their evolution. Traditionally, sponges have been considered the sister group of all other extant animals, but recent genomic studies have suggested comb jellies occupy that position instead. Here, we analyzed the current genomic evidence from comb jellies and found no convincing support for this hypothesis. Instead, when analyzed with appropriate methods, recent genomic data support the traditional hypothesis. We conclude that the alternative scenario of animal evolution according to which ctenophores evolved morphological complexity independently from cnidarians and bilaterians or, alternatively, sponges secondarily lost a nervous system, muscles, and other characters, is not supported by the available evidence.
Translational profiling identifies a cascade of damage initiated in motor neurons and spreading to glia in mutant SOD1-mediated ALS
Authors: Sun Shuying , Sun Ying , Ling Shuo-Chien , Ferraiuolo Laura , McAlonis-Downes Melissa , Zou Yiyang , Drenner Kevin , Wang Yin , Ditsworth Dara , Tokunaga Seiya , Kopelevich Alex , Kaspar Brian K. , Lagier-Tourenne Clotilde , Cleveland Don W.
Published: December 2015

Significance

Amyotrophic lateral sclerosis can be caused by a mutation in superoxide dismutase. Ubiquitously expressed, disease mechanism involves damage within motor neurons (whose degeneration is responsible for progressive paralysis) and glia. By combining ribosome affinity purification from each of three cell types, a temporal cascade of damage is identified that initiates within motor neurons, with subsequent damage within glia driving disease propagation. Mutant-dependent damage to motor neurons, which are shown to express very low levels of endoplasmic reticulum chaperones, includes synapse and metabolic abnormalities and selective activation of the PERK arm of the unfolded protein response. Early changes in astrocytes are to genes involved in inflammation and metabolism, while dysregulation of myelination and lipid signaling pathways in oligodendrocytes occurs only after disease initiation.
Human autoreactive T cells recognize CD1b and phospholipids
Authors: Van Rhijn Ildiko , van Berlo Twan , Hilmenyuk Tamara , Cheng Tan-Yun , Wolf Benjamin J. , Tatituri Raju V. V. , Uldrich Adam P. , Napolitani Giorgio , Cerundolo Vincenzo , Altman John D. , Willemsen Peter , Huang Shouxiong , Rossjohn Jamie , Besra Gurdyal S. , Brenner Michael B. , Godfrey Dale I. , Moody D. Branch
Published: December 2015

Significance

Peptides are known to be targets of autoreactive T cells that can cause autoimmune diseases. Here we show that human T cells recognize self-lipids displayed on the surface of cells by CD1b proteins. A particular lipid that is recognized by CD1b autoreactive cells, phosphatidylglycerol, is present in mammalian mitochondria and in bacteria. Therefore, these data define a phospholipid autoantigen that is released during mitochondrial stress and bacterial infection.
Amyloid fibrils activate B-1a lymphocytes to ameliorate inflammatory brain disease
Authors: Kurnellas Michael Phillip , Ghosn Eliver Eid Bou , Schartner Jill M. , Baker Jeanette , Rothbard Jesse J. , Negrin Robert S. , Herzenberg Leonore A. , Fathman C. Garrison , Steinman Lawrence , Rothbard Jonathan B.
Published: December 2015

Significance

IL-10–secreting B lymphocytes and peritoneal macrophages are activated by immunization with amyloid fibrils composed of short peptides resulting in reduction of paralysis and inflammation in mice with experimental autoimmune encephalomyelitis. B-cell–deficient μMT mice and IL-10 knockout animals were used to establish the critical role of regulatory B cells in the therapeutic mode of action. Reintroduction of B-1a lymphocytes into the μMT animals reconstituted the ability of the fibrils to ameliorate the paralytic signs, leading to the trafficking of both populations of cells from the peritoneum to secondary lymph organs and not to the CNS. The reduction in CNS inflammation, combined with successful intranasal administration, provides support that this strategy could be translated into an effective human therapeutic.
Functional screen identifies kinases driving prostate cancer visceral and bone metastasis
Authors: Faltermeier Claire M. , Drake Justin M. , Clark Peter M. , Smith Bryan A. , Zong Yang , Volpe Carmen , Mathis Colleen , Morrissey Colm , Castor Brandon , Huang Jiaoti , Witte Owen N.
Published: December 2015

Significance

Therapies are urgently needed to treat metastatic prostate cancer. Mutationally activated and wild-type kinases such as BCR-ABL and BTK are effective therapeutic targets in multiple cancers. Genetically altered kinases are rare in prostate cancer. Wild-type kinases may be implicated in prostate cancer progression, but their therapeutic potential in metastatic prostate cancer remains unknown. Using phosphoproteomics and gene expression datasets, we selected 125 wild-type kinases implicated in human prostate cancer metastasis to screen for metastatic ability in vivo. The RAF family, MERTK, and NTRK2 drove prostate cancer bone and visceral metastasis and were highly expressed in human metastatic prostate cancer tissues. These studies reveal that wild-type kinases can drive metastasis and that the RAF family, MERTK, and NTRK2 may represent important therapeutic targets.
Reversible ubiquitination shapes NLRC5 function and modulates NF-κB activation switch
Authors: Meng Qingcai , Cai Chunmei , Sun Tingzhe , Wang Qianliang , Xie Weihong , Wang Rongfu , Cui Jun
Published: December 2015

NLRC5 is an important regulator in innate immune responses. However, the ability of NLRC5 to inhibit NF-κB activation is controversial in different cell types. How dynamic modification of NLRC5 shapes NF-κB signaling remains unknown. We demonstrated that NLRC5 undergoes robust ubiquitination by TRAF2/6 after lipopolysaccharide treatment, which leads to dissociation of the NLRC5–IκB kinase complex. Experimental and mathematical analyses revealed that the K63-linked ubiquitination of NLRC5 at lysine 1,178 generates a coherent feedforward loop to further sensitize NF-κB activation. Meanwhile, we found USP14 specifically removes the polyubiquitin chains from NLRC5 to enhance NLRC5-mediated inhibition of NF-κB signaling. Furthermore, we found that different cell types may exhibit different sensitivities to NF-κB activation in response to NLRC5 ablation, possibly as a result of the various intrinsic levels of deubiquitinases and NLRC5. This might partially reconcile controversial studies and explain why NLRC5 exhibits diverse inhibitory efficiencies. Collectively, our results provide the regulatory mechanisms of reversible NLRC5 ubiquitination and its role in the dynamic control of innate immunity.
A feedforward loop of NLRC5 (de)ubiquitination keeps IKK–NF-κB in check
Authors: Hu Yinling
Published: December 2015

Many receptors signal via adaptors to the IKK–NF-κB axis, transducing extracellular cues to transcriptional regulation. In this issue, Meng et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505091) reveal that the IKK regulator NLRC5 shapes NF-κB activity through a feedforward loop of NLRC5 ubiquitination and deubiquitination, highlighting a new pathway modulating IKK–NF-κB activity.
Why should cell biologists study microbial pathogens?
Authors: Welch Matthew D.
Published: December 2015

One quarter of all deaths worldwide each year result from infectious diseases caused by microbial pathogens. Pathogens infect and cause disease by producing virulence factors that target host cell molecules. Studying how virulence factors target host cells has revealed fundamental principles of cell biology. These include important advances in our understanding of the cytoskeleton, organelles and membrane-trafficking intermediates, signal transduction pathways, cell cycle regulators, the organelle/protein recycling machinery, and cell-death pathways. Such studies have also revealed cellular pathways crucial for the immune response. Discoveries from basic research on the cell biology of pathogenesis are actively being translated into the development of host-targeted therapies to treat infectious diseases. Thus there are many reasons for cell biologists to incorporate the study of microbial pathogens into their research programs.
Novel insights into mammalian embryonic neural stem cell division: focus on microtubules
Authors: Mora-Bermúdez Felipe , Huttner Wieland B.
Published: December 2015

During stem cell divisions, mitotic microtubules do more than just segregate the chromosomes. They also determine whether a cell divides virtually symmetrically or asymmetrically by establishing spindle orientation and the plane of cell division. This can be decisive for the fate of the stem cell progeny. Spindle defects have been linked to neurodevelopmental disorders, yet the role of spindle orientation for mammalian neurogenesis has remained controversial. Here we explore recent advances in understanding how the microtubule cytoskeleton influences mammalian neural stem cell division. Our focus is primarily on the role of spindle microtubules in the development of the cerebral cortex. We also highlight unique characteristics in the architecture and dynamics of cortical stem cells that are tightly linked to their mode of division. These features contribute to setting these cells apart as mitotic “rule breakers,” control how asymmetric a division is, and, we argue, are sufficient to determine the fate of the neural stem cell progeny in mammals.
‘Social Laser’: action amplification by stimulated emission of social energy
Authors: Khrennikov Andrei
Published: December 2015

The problem of the ‘explanation’ of recent social explosions, especially in the Middle East, but also in Southern Europe and the USA, has been debated actively in the social and political literature. We can mention the contributions of P. Mason, F. Fukuyama, E. Schmidt, J. Cohen and I. Krastev to this debate. We point out that the diversity of opinions and conclusions is really amazing. At the moment, there is no consistent and commonly acceptable theory of these phenomena. We present a model of social explosions based on a novel approach for the description of social processes, namely the quantum-like approach. Here quantum theory is treated simply as an operational formalism—without any direct relation to physics. We explore the quantum-like laser model to describe the possibility of action amplification by stimulated emission of social energy.
Comparing quantum versus Markov random walk models of judgements measured by rating scales
Authors: Wang Z. , Busemeyer J. R.
Published: December 2015

Quantum and Markov random walk models are proposed for describing how people evaluate stimuli using rating scales. To empirically test these competing models, we conducted an experiment in which participants judged the effectiveness of public health service announcements from either their own personal perspective or from the perspective of another person. The order of the self versus other judgements was manipulated, which produced significant sequential effects. The quantum and Markov models were fitted to the data using the same number of parameters, and the model comparison strongly supported the quantum over the Markov model.
Instability of political preferences and the role of mass media: a dynamical representation in a quantum framework
Authors: Khrennikova Polina , Haven Emmanuel
Published: December 2015

We search to devise a new paradigm borrowed from concepts and mathematical tools of quantum physics, to model the decision-making process of the US electorate. The statistical data of the election outcomes in the period between 2008 and 2014 is analysed, in order to explore in more depth the emergence of the so-called divided government. There is an increasing urge in the political literature which indicates that preference reversal (strictly speaking the violation of the transitivity axiom) is a consequence of the so-callednon-separabilityphenomenon (i.e. a strong interrelation of choices). In the political science literature, non-separable behaviour is characterized by a conditioning of decisions on the outcomes of some issues of interest. An additional source of preference reversal is ascribed to the time dynamics of the voters’ cognitive states, in the context of new upcoming political information. As we discuss in this paper, the primary source of political information can be attributed to the mass media. In order to shed more light on the phenomenon of preference reversal among the US electorate, we accommodate the obtained statistical data in a classical probabilistic (Kolmogorovian) scheme. Based on the obtained results, we attribute the strong ties between the voters non-separable decisions that cannot be explained by conditioning with the Bayes scheme, to the quantum phenomenon ofentanglement. Second, we compute the degree of interference of voters’ belief states with the aid of the quantum analogue of the formula of total probability. Lastly, a model, based on the quantum master equation, to incorporate the impact of the mass media bath is proposed.
Paediatric meningococcaemia in northwestern Ontario, Canada: a case for publicly funded meningococcal B vaccination
Authors: Eton Vic , Tsang Raymond S. W. , Ulanova Marina
Published: December 2015

Introduction:

Neisseria meningitidis serogroup B is an important infectious agent in developed countries, including Canada. Infants are particularly susceptible to infection with serogroup B because of immature immune systems, pathogen virulence factors and changing serogroup dynamics in the post-vaccination era. Currently, the Ontario provincial government does not include serogroup B in its routine publicly funded meningococcal vaccination program.

Case Presentation:

A formerly well 14-month-old male presented to a tertiary hospital emergency department with fever, minor respiratory problems, diffuse purpuric rash, distended abdomen, tachycardia, and history of one episode of vomiting and melena each. Meningococcaemia was immediately suspected, and he was treated with ceftriaxone, cefotaxime and vancomycin before transfer to a different acute care facility within 12 h. N. meningitidis serogroup B, sensitive to ceftriaxone and penicillin, was identified in his blood. The patient developed gangrene of the lower legs and underwent bilateral below-knee amputation 8 days post-admission.

Conclusion:

This instance of meningococcaemia with extensive sequelae is an example of the various serious outcomes of meningococcal infection. It provides persuasive reason for routine publicly funded vaccination against N. meningitidis serogroup B in Ontario.
Efficient sequence-specific isolation of DNA fragments and chromatin byin vitroenChIP technology using recombinant CRISPR ribonucleoproteins
Authors: Fujita Toshitsugu , Yuno Miyuki , Fujii Hodaka
Published: December 2015

The clustered regularly interspaced short palindromic repeat (CRISPR) system is widely used for various biological applications, including genome editing. We developed engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR to isolate target genomic regions from cells for their biochemical characterization. In this study, we developed“in vitroenChIP” using recombinant CRISPR ribonucleoproteins (RNPs) to isolate target genomic regions.in vitroenChIP has the great advantage over conventional enChIP of not requiring expression of CRISPR complexes in cells. We first demonstrate thatin vitroenChIP using recombinant CRISPR RNPs can be used to isolate target DNA from mixtures of purified DNA in a sequence-specific manner. In addition, we show that this technology can be employed to efficiently isolate target genomic regions, while retaining their intracellular molecular interactions, with negligible contamination from irrelevant genomic regions. Thus,in vitroenChIP technology is of potential use for sequence-specific isolation of DNA, as well as for identification of molecules interacting with genomic regions of interestin vivoin combination with downstream analysis.
Crystal structure ofcatena-poly[N,N,N′,N′-tetramethylguanidinium [(chloridocadmate)-di-μ-chlorido]]
Authors: Ndiaye Mamadou , Samb Abdoulaye , Diop Libasse , Maris Thierry
Published: December 2015

In the structure of the title salt, {(C5H14N3)[CdCl3]}n, the CdIIatom of the complex anion is five-coordinated by one terminal and four bridging Cl atoms. The corresponding coordination polyhedron is a distorted trigonal bipyramid, with Cd—Cl distances in the range 2.4829 (4)–2.6402 (4) Å. The bipyramids are condensed into a polyanionic zigzag chain extending parallel to [101]. The tetramethylguanidinium cations are situated between the polyanionic chains and are linked to them through N—H...Cl hydrogen bonds, forming a layered network parallel to (010).
Fieldnotes as a Social Practice: Elevating and Innovating Fieldnotes in Applied Ethnography, Using a Collaborative Online Tool as a Case Study
Authors: CURY MARIA
Published: December 2015

In this paper I propose that applied ethnographers should think critically and innovatively about the practice of producing fieldnotes in ethnographic research. Critical thought on ethnographic fieldnotes has been relatively underdeveloped, both in applied and academic anthropology. Moreover, as applied ethnographers our projects have particular opportunities and constraints that are unique from academic anthropology. I make a case for elevating fieldnotes as a topic of more critical discussion in applied ethnography, and for moving fieldnotes from a private practice to a social practice. I use a collaborative online tool as a case example for possible innovation. Collaborative practices present certain vulnerabilities and challenges to creating fieldnotes, but I argue that the benefits of innovating fieldnotes help to build bridges both between researchers, and between researchers and stakeholders in a project. Innovative fieldnote practices can: deepen the thinking in our research; increase our impact; help ensure that our practices are credible as applied ethnography; and make contributions to the practice of ethnography more broadly.
How to Create Value via Object Circulation in Gift‐Systems
Authors: SCARABOTO DAIANE , FIGUEIREDO BERNARDO
Published: December 2015

Gift‐systems build relationships and create various types of value for the individuals who participate in them. Organizations may also reap the benefits of gift‐systems when they understand, support, and foster practices of object circulation within these systems. We adopt a theoretical framework based on anthropological approaches to value‐in‐action to explain value creation for individuals in contemporary gift systems. We mobilize ethnographic and netnographic data on the circulation of small wooden chapels containing a statue of the Virgin Mary among Catholic households to develop a conceptual framework that illuminates value creation in gift systems and demonstrates how practices of circulation (setting, protecting, registering, retrieving, keeping, passing on, monitoring, interacting, and storytelling) can be used to generate value for organizations.
Building Bridges between Management and the Workforce
Authors: CIRIA‐SUÁREZ LAURA , BELL ROBERT ANDREW
Published: December 2015

This paper examines the sales force in a retail setting, considering how Business Anthropology can enlighten managerial practices as a means to defining organisational strategy. Specifically, we look at sales force engagement, motivation and reward – considering how to build bridges in the management‐employee relationship and shed light on the sales force culture. We will look at anthropology's position in relation to key business activities using the service‐dominant logic to understand how individual sensemaking and perception of power can influence internal and external relationships in the value creation and realisation process, examining engrained paradigms and using Corporate Ethnography to offer new insights and perceptions on organisational culture, power and hierarchies.
Knowing That and Knowing How: Towards Embodied Strategy
Authors: ROBERTS SIMON , HOY TOM
Published: December 2015

This paper explores two different forms of knowledge. We compare embodied understanding with propositional or abstract knowledge. Ethnographic research, with its commitment to understanding through immersion and engagement in social fields produces dexterous, intuitive and practical cultural knowledge, which is highly suited towards culturally attuned activity. We argue that ethnography can often be reduced to propositional knowledge as a result of the lack of team participation in research and how we communicate insight. Ideas of professional expertise sit behind the division of labour that characterises client‐researcher relationships. Accompanying that division of labour is a need for the communication of ethnographic research to bridge the gap between client and external worlds – the world we as researchers explore and that our clients needs to act in. By engaging our clients in shared, immersive experiences we can create the conditions for them to develop ‘know how’ about relevant social fields. The shared nature of this understanding forms the basis for the development of ‘embodied strategy’ – collective action based on shared, deep, first‐hand understanding of a world.
“Right in the Middle”: An Experience of Women Reconciliation within the D.I.Y. Movement
Authors: MORENO ANDREA MORALES
Published: December 2015

A very personal view of how a Mexican teenager finds empowerment in the D.I.Y. punk culture and how she manages to reinterpret her feminity in a patriarchal country by making meaningful creations for her and other girls.
Myths and Facts about the Sharing Economy Promise in Emergent Countries
Authors: MORALES NORA
Published: December 2015

A question about how taxicabs look alike in different countries started a visual dialogue between two friends living in India and Mexico. Through their conversation, they discovered similar patterns on how each country is adapting to the promise of sharing economies. How are those systems based on information technology are really empowering individuals, corporations and governments? Are they really delivering value and bringing opportunities to transact and collaborate? The author might not have an answer, but her narrative is challenging the way we think about local human and physical resources and their changing role in the emergent economy stage.
MARDI GRAS: A GIFT ECONOMY
Authors: PHILLIPS HAL , KINNEY MEG
Published: December 2015

To residents of New Orleans, there is a special brand of pageantry and community surrounding the Mardi Gras ritual. At the center of it all are Parades – the heartbeat of Mardi Gras. Each Krewe (social club) puts on a huge parade sometime during Carnivale Season. They each have their own personality, costumes and “throws”. Throws can be as simple as the iconic beads we all know, or elaborate handcrafted items that are highly sought after prizes.

During parades, a strange thing happens – objects that have little commercial value become incredibly valuable, even for a few moments. People jockey for position to catch beads, toys, custom medallions, and above all the prized throws of each Krewe. There is a whole system of value attached to each parade, which the city celebrates. We will explore how the gift economy of the Mardi Gras parade unites old and young, and bridges racial boundaries in a shared ritual.
DataTaxi: Applied Ethnography for Connecting the Feeling of the Streets and Communication Messages
Authors: SILVA SERGIO
Published: December 2015

The urban environment has created a multiplication of stimulus that causes people to pay less attention to message content. In an attempt to understand what really interests them, the author found the taxi cab –a traditional mobile scenario– as way to explore aspects and encounter feelings of the population. By applying ethnographic approach and training taxi drivers this tool collects information from participant and consumers while traveling through São Paulo streets.

Ethnography, methodology development, research innovation, marketing research.
TEST performance of a myositis panel in a clinical immunology laboratory in New South Wales, Australia
Authors: Tan Teck Choon , Wienholt Louise , Adelstein Stephen
Published: December 2015

Background

There is increasing recognition of a clinico‐serological correlation between the idiopathic inflammatory myopathies and myositis‐specific autoantibodies (MSA). We review the use of a line immunoassay‐based myositis panel incorporating both MSA and myositis‐associated autoantibodies (MAA) in a selected population of patients.

Methods

A retrospective analysis of patients with myositis panel assays performed in 2013 were reviewed and compared against clinical diagnoses.

Results

A total of 96 patient samples were evaluated, the clinical indications include 60 patients with suspected idiopathic inflammatory myositis (IIM), 24 patients with suspected interstitial lung disease (ILD) and 12 patients with suspected systemic autoimmune disease (SAD). In the myositis group, there were 21 patients diagnosed with IIM and 18 patients diagnosed with IIM had a positive myositis panel. Of the 39 patients without IIM, nine of these patients had a positive myositis panel. In the ILD group, 10 of 24 patients had a positive myositis panel; of these, two were diagnosed anti‐synthetase syndrome (ASS) and five patients with ILD. In the suspected SAD group, three had positive myositis panel and all did not appear associated with their final diagnoses. In patients with a clinical diagnosis of IIM or ILD‐associated SAD, four patients with anti‐PL‐12 were detected, three patients with anti‐signal recognition protein, two patients with anti‐Jo‐1, and two patients with anti‐Mi2.

Conclusions

The myositis panel is an objective investigative modality with a sensitivity of 80.00% and a specificity of 75.76% in a setting of high pretest clinical suspicion.
Pulmonary IgG4‐related disease and colon adenocarcinoma: possible paraneoplastic syndrome
Authors: Krause Megan L. , Yi Eunhee S. , Warrington Kenneth J.
Published: December 2015

Malignancy has a complicated association with immunoglobulin G4‐related disease (IgG4‐RD) both being an item in the differential diagnosis as well as malignancy occurring in the background of IgG4‐RD in the same organ. However, recently there is evidence of higher rates of distant malignancy in patients with IgG4‐RD. Here we report a case of pulmonary IgG4‐RD potentially consistent with a paraneoplastic phenomenon which improved with treatment of the underlying colon adenocarcinoma.
Synergistic antitumor activity of pro‐apoptotic agent PAC‐1 with cisplatinum by the activation of CASP3 in pulmonary adenocarcinoma cell line H1299
Authors: Huang Jian‐qing , Liang Hong‐ling , Zhang Xu‐chao , Xie Zhi , Jin Tian‐en
Published: December 2015

Aim

Evasion of apoptosis is a hallmark of human cancer cells. We sought to explore the potential synergistic antitumor activity and underlying mechanisms of the pro‐apoptotic agent PAC‐1 plus cisplatinum (Cis) in non‐small cell lung cancer (NSCLC) cell lines.

Methods

The adenocarcinoma cell lines H1299, A549, PC9, H1650 and H1975 were used as in vitro models. Colorimetric MTT assays, Western blotting and flow cytometry were used to evaluate the anti‐growth effects of PAC‐1 and/or Cis and apoptosis status. The activated form of CASP3 (C‐CASP3) was assessed by immunofluorescent staining.

Results

Single‐agent Cis and PAC‐1 were able to inhibit the cancer cell growth in certain dose ranges, with IC50 values of 1.9–11.7 and 5.6–14.8 μM, respectively. Sequential Cis→PAC‐1 or concurrent Cis + PAC‐1, but not PAC‐1→Cis combinations showed synergistic effects on cell growth inhibition in H1299 cells (combination index, CI ≤ 0.6). In contrast, other combination modes mostly showed seemingly antagonistic effects (CI > 1.0). Flow cytometric analysis showed that Cis→PAC‐1 sequential combination showed strong pro‐apoptotic effects in H1299 cells. Western blots showed that in H1299, PC9 and H1975 cells, PAC‐1 promoted the C‐CASP3, but only in H1299 cells was there a synergistic effect with Cis on the CASP3 activation.

Conclusions

PAC‐1 showed anti‐tumor activity in NSCLCs in vitro and a synergistic effect with cisplatin in EGFRwtKRASwt H1299 cells. Our data suggest a potential treatment approach using cisplatin plus a pro‐apoptotic agent acting via CASP3 activation for this subgroup of pulmonary adenocarcinomas.
Peri‐operative cardiac protection for non‐cardiac surgery
Authors: Wong S. S. C. , Irwin M. G.
Published: December 2015

Cardiovascular complications are an important cause of morbidity and mortality after non‐cardiac surgery. Pre‐operative identification of high‐risk individuals and appropriate peri‐operative management can reduce cardiovascular risk. It is important to continue chronic beta‐blocker and statin therapy. Statins are relatively safe and peri‐operative initiation may be beneficial in high‐risk patients and those scheduled for vascular surgery. The pre‐operative introduction of beta‐blockers reduces myocardial injury but increases rates of stroke and mortality, possibly due to hypotension. They should only be considered in high‐risk patients and the dose should be titrated to heart rate. Alpha‐2 agonists may also contribute to hypotension. Aspirin continuation can increase the risk of major bleeding and offset the benefit of reduced myocardial risk. Contrary to the initial ENIGMA study, nitrous oxide does not seem to increase the risk of myocardial injury. Volatile anaesthetic agents and opioids have been shown to be cardioprotective in animal laboratory studies but these effects have, so far, not been conclusively reproduced clinically.
Peri‐operative pulmonary dysfunction and protection
Authors: Marseu K. , Slinger P.
Published: December 2015

Pulmonary complications are a major cause of peri‐operative morbidity and mortality, but have been researched less thoroughly than cardiac complications. It is important to try and predict which patients are at risk of peri‐operative pulmonary complications and to intervene to reduce this risk. Anaesthetists are in a unique position to do this during the whole peri‐operative period. Pre‐operative training, smoking cessation and lung ventilation with tidal volumes of 6–8 ml.kg−1 and low positive end‐expiratory pressure probably reduce postoperative pulmonary complications.
Twenty‐Year Outcome After Right Ventricular Outflow Tract Repair Using Heterotopic Pulmonary Conduits in Infants and Children
Authors: Hoxha Stiljan , Torre Salvatore , Rungatscher Alessio , Sandrini Camilla , Rossetti Lucia , Barozzi Luca , Faggian Giuseppe , Luciani Giovanni Battista
Published: December 2015

Durability of pulmonary conduits (PCs) used for reconstruction of the right ventricular outflow tract (RVOT) may be affected by a variety of factors. Among these, the technique used for PC implantation, whether in orthotopic or heterotopic position, strictly dependent upon the underlying anatomy, has been suggested to influence long‐term outcome after RVOT repair. To determine the outcome of heterotopic implantation in infants and children treated at our institution, late results of heterotopic PC in non‐Ross patients were analyzed and compared with data of orthotopic PC in age‐matched pediatric Ross patients operated during the same time period. Between November 1991 and January 2015, 58 infants and children, 32 male and 26 female, with a median age of 9.4 years (range 1 day–18 years) underwent implantation of heterotopic PC (31 homografts [HG] and 27 xenografts [XG]) for reconstruction of RVOT. Median age in the XG group was significantly lower than in the HG group (0.9 vs. 13.4 years, P = 0.01), while male/female ratio was similar. Fifty (86%) patients had undergone one or more prior cardiac operations, while 32 (55%) required associated procedures during PC implantation. Comparison with data in 305 children and with a median age of 9.4 years, receiving orthotopic PC between 1990 and 2012 (Italian Pediatric Ross Registry), was undertaken. Descriptive, univariate, and Kaplan–Meier analysis defined outcome. There were three (5.2%) early and five (9.0%) late deaths, during a median follow‐up of 7.6 years (range 2 months–23 years). Patients having XG had trend toward higher hospital mortality (2/27 vs. 1/31, P = 0.2), but similar late mortality (2/24 vs. 3/30, P = 0.3). Overall survival was 88 and 62%, while freedom from PC replacement was 49 and 21%, at 10 and 20 years, respectively. The latter proved significantly worse than freedom from orthotopic PC replacement, which was 94 ± 2 and 70 ± 9% at 10 and 20 years (P = 0.02). When stratified for type of heterotopic PC, late survival proved comparable (81 and 81% for XG vs. 92 and 60% for HG, at 10 and 20 years, respectively, P = 0.7). However, freedom from PC replacement was significantly higher in patients with heterotopic HG (21 and 5% for XG vs. 63 and 48% for HG, at 10 and 20 years, respectively, P = 0.001). RVOT repair using either XG or HG in heterotopic position is a safe procedure associated with low hospital mortality and satisfactory late survival. Freedom from reoperation is significantly lower than that observed in age‐matched children having orthotopic HG. Freedom from reoperation in heterotopic XG is poorer than in HG, although different baseline demography may have influenced this finding.
Vascular and ductal elastotic changes in pancreatic cancer
Authors: Lakiotaki Eleftheria , Sakellariou Stratigoula , Evangelou Kostantinos , Liapis George , Patsouris Efstratios , Delladetsima Ioanna
Published: December 2015

This study aims to identify and define the type and frequency of elastotic alterations of vessels and ducts in pancreatic ductal carcinoma (PDAC) and evaluate its diagnostic significance. Representative tissue from 36 Whipple specimens, stained with Verhoeff's Van‐Gieson, was studied focusing on the density and distribution of elastic fibers in walls of vessels and ducts, in perivascular and periductal tissue and in tumor stroma. Vessels and ducts within the carcinoma, at tumor periphery and in non‐tumoral pancreas were grouped and examined separately. Vimentin and α‐SMA immunostains were used for the depiction of fibroblasts and myofibroblasts. Histochemistry revealed mild to severe elastotic changes of vessels and ducts in all examined cases. Vascular and ductal elastosis was more prominent within the tumor and diminished at tumor periphery. In tumor stroma and non‐tumoral pancreatic tissue mild or no elastosis was identified. α‐SMA+ cells were observed in large numbers in tumor stroma and as a ring around carcinomatous structures. There were scant α‐SMA+ cells around elastotic and non‐elastotic vessels. Conclusively, vascular and ductal elastosis is a tumor‐associated phenomenon in PDAC. Its presence is indicative of benignity acquiring a possible diagnostic role.
Chronic mucocutaneous candidiasis: characterization of a family with STAT-1 gain-of-function and development of an ex-vivo assay for Th17 deficiency of diagnostic utility
Authors: Dhalla F , Fox H , Davenport E E , Sadler R , Anzilotti C , van Schouwenburg P A , Ferry B , Chapel H , Knight J C , Patel S Y
Published: December 2015

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent and persistent superficial infections, with Candida albicans affecting the mucous membranes, skin and nails. It can be acquired or caused by primary immune deficiencies, particularly those that impair interleukin (IL)−17 and IL-22 immunity. We describe a single kindred with CMC and the identification of a STAT1 GOF mutation by whole exome sequencing (WES). We show how detailed clinical and immunological phenotyping of this family in the context of WES has enabled revision of disease status and clinical management. Together with analysis of other CMC cases within our cohort of patients, we used knowledge arising from the characterization of this family to develop a rapid ex-vivo screening assay for the detection of T helper type 17 (Th17) deficiency better suited to the routine diagnostic setting than established in-vitro techniques, such as intracellular cytokine staining and enzyme-linked immunosorbent assay (ELISA) using cell culture supernatants. We demonstrate that cell surface staining of unstimulated whole blood for CCR6+CXCR3–CCR4+CD161+ T helper cells generates results that correlate with intracellular cytokine staining for IL-17A, and is able to discriminate between patients with molecularly defined CMC and healthy controls with 100% sensitivity and specificity within the cohort tested. Furthermore, removal of CCR4 and CD161 from the antibody staining panel did not affect assay performance, suggesting that the enumeration of CCR6+CXCR3–CD4+ T cells is sufficient for screening for Th17 deficiency in patients with CMC and could be used to guide further investigation aimed at identifying the underlying molecular cause.
Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes
Authors: Adikari T N , Gomes L , Wickramasinghe N , Salimi M , Wijesiriwardana N , Kamaladasa A , Shyamali N L A , Ogg G S , Malavige G N
Published: December 2015

Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P < 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes.
The pathogenesis of multiple sclerosis
Authors: Goodin Douglas S.
Published: December 2015

The pathogenesis of multiple sclerosis (MS) involves both genetic‐susceptibility and, at least, three sequential environmental‐events. The first environmental‐event is a maternal‐factor, which acts near birth. The second acts subsequently but prior to approximately age 15 years and the third acts long after these first two events have already taken place. Two environmental‐events strongly implicated in MS‐pathogenesis are vitamin D deficiency and Epstein‐Barr viral (EBV) infection. These factors seem well‐suited to the first two environmental‐events in this causal chain. If this notion is correct, it is likely that interrupting either of these factors (e.g. the timely supplementation of Vitamin D or the development of an EBV vaccine might be simple and effective methods for achieving primary disease prevention. In addition to these environmental‐events, genetic factors are both crucial and complex. More than 110 genomic‐regions have now been associated with MS‐susceptibility and only a very small fraction of the population is genetically‐susceptible. However, the actual genes involved are much more poorly defined than is often thought. For example, it turns out that the well‐established association with the DRB1*1501 allele on chromosome 6, is, likely, not due to this allele itself but, rather, to something else that resides on the SNP‐haplotype, which usually harbors this allele. Also, despite women being the large majority of MS patients, men are more likely to be genetically‐susceptible. Nevertheless, women are more responsive to the changing environmental‐exposures, which have occurred recently; thereby accounting for the changes in sex‐ratio and MS‐prevalence in women, which have been found in many regions.
Anti‐myelin oligodendrocyte glycoprotein antibody in demyelinating diseases
Authors: Nakashima Ichiro
Published: December 2015

Anti‐myelin oligodendrocyte glycoprotein (MOG) antibody, which is specifically detected using a cell‐based assay (CBA), has been identified in various demyelinating diseases, including neuromyelitis optica spectrum disorders (NMOSD), acute idiopathic optic neuritis (ON), and pediatric multiphasic disseminated encephalomyelitis. Although its pathogenic role has not been established, antibody seropositive cases appear to share several characteristic features, such as a preferable response to steroid therapy and a good prognosis. Antibody detection at the onset of a demyelinating disease is important to predict the prognosis. Further analysis of the clinical features and investigation of the pathogenic roles of the antibody are required to establish the disease spectrum associated with the antibody. Although the associated diseases appear to have a relatively good prognosis, treatment recommendations are offered for patients with severe symptoms or frequent relapses.