bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance
Authors: Ferrando Carlos , Suárez-Sipmann Fernando , Gutierrez Andrea , Tusman Gerardo , Carbonell Jose , García Marisa , Piqueras Laura , Compañ Desamparados , Flores Susanie , Soro Marina , Llombart Alicia , Belda Francisco Javier
Published: January 2015

Introduction

The stress index (SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw).

Methods

Lung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a ‘normal’ PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals.

Results

PaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg,P = 0.01), with a resulting lower pH (7.19 versus 7.34,P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg−1,P = 0.002) and Pplat values (30 versus 35 cmH2O,P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99,P = 0.42) and end-inspiratory transpulmonary pressure (PTP) (17 versus 18 cmH2O,P = 0.42) were similar in the Pplat- and SI-groups respectively, without differences in overinflated lung areas at end- inspiration in both groups. Cytokines and histopathology showed no differences.

Conclusions

Setting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance.
Preoperative intra-aortic balloon pump to reduce mortality in coronary artery bypass graft: a meta-analysis of randomized controlled trials
Authors: Zangrillo Alberto , Pappalardo Federico , Dossi Roberto , Di Prima Ambra Licia , Sassone Marta Eugenia , Greco Teresa , Monaco Fabrizio , Musu Mario , Finco Gabriele , Landoni Giovanni
Published: January 2015

Introduction

The intra-aortic balloon pump is routinely used in cardiac surgery; however, its impact on outcome is still a matter of debate and several randomized trials have been published recently. We perform an updated meta-analysis of randomized controlled trials that investigated the use of preoperative intra-aortic balloon pump in adult patients undergoing coronary artery bypass grafting.

Methods

Potentially eligible trials were identified by searching the Medline, Embase, Scopus, ISI Web of Knowledge and The Cochrane Library. Searches were not restricted by language or publication status and were updated in August 2014. Randomized controlled trials on preoperative intra-aortic balloon pump in patients undergoing coronary artery bypass grafting either with or without cardiopulmonary bypass were identified. The primary end point was mortality at the longest follow-up available and the secondary end point was 30-day mortality.

Results

The eight included randomized clinical trials enrolled 625 patients (312 to the intra-aortic balloon pump group and 313 to control). The use of intra-aortic balloon pump was associated with a significant reduction in the risk of mortality (11 of 312 (3.5%) versus 33 of 313 (11%), risk ratio = 0.38 (0.20 to 0.73), P for effect = 0.004, P for heterogeneity = 0.7, I-square = 0%, with eight studies included). The benefit on mortality reduction was confirmed restricting the analysis to trials with low risk of bias, to those reporting 30-day follow-up and to patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass.

Conclusions

Preoperative intra-aortic balloon pump reduces perioperative and 30-day mortality in high-risk patients undergoing elective coronary artery bypass grafting.
Reintubation in critically ill patients: procedural complications and implications for care
Authors: Elmer Jonathan , Lee Sean , Rittenberger Jon C , Dargin James , Winger Daniel , Emlet Lillian
Published: January 2015

Introduction

In critically ill patients, re-intubation is common and may be a high-risk procedure. Anticipating a difficult airway and identifying high-risk patients can allow time for life-saving preparation. Unfortunately, prospective studies have not compared the difficulty or complication rates associated with reintubation in this population.

Methods

We performed a secondary analysis of a prospective registry of in-hospital emergency airway management, focusing on patients that underwent multiple out-of-operating room intubations during a single hospitalization. Our main outcomes of interest were technical difficulty of intubation (number of attempts, need for adjuncts to direct laryngoscopy, best Cormack-Lehane grade and training level of final intubator) and the frequency of procedural complications (aspiration, arrhythmia, airway trauma, new hypotension, new hypoxia, esophageal intubation and cardiac arrest). We compared the cohort of reintubated patients to a matched cohort of singly intubated patients and compared each repeatedly intubated patient’s first and last intubation.

Results

Our registry included 1053 patients, of which 151 patients (14%) were repeatedly intubated (median two per patient). Complications were significantly more common during last intubation compared to first (13% versus 5%, P = 0.02). The most common complications were hypotension (41%) and hypoxia (35%). These occurred despite no difference in any measure of technical difficultly across intubations.

Conclusion

In this cohort of reintubated patients, clinically important procedural complications were significantly more common on last intubation compared to first.
The association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study
Authors: Salciccioli Justin D , Marshall Dominic C , Pimentel Marco AF , Santos Mauro D , Pollard Tom , Celi Leo Anthony , Shalhoub Joseph
Published: January 2015

Introduction

The neutrophil-to-lymphocyte ratio (NLR) is a biological marker that has been shown to be associated with outcomes in patients with a number of different malignancies. The objective of this study was to assess the relationship between NLR and mortality in a population of adult critically ill patients.

Methods

We performed an observational cohort study of unselected intensive care unit (ICU) patients based on records in a large clinical database. We computed individual patient NLR and categorized patients by quartile of this ratio. The association of NLR quartiles and 28-day mortality was assessed using multivariable logistic regression. Secondary outcomes included mortality in the ICU, in-hospital mortality and 1-year mortality. An a priori subgroup analysis of patients with versus without sepsis was performed to assess any differences in the relationship between the NLR and outcomes in these cohorts.

Results

A total of 5,056 patients were included. Their 28-day mortality rate was 19%. The median age of the cohort was 65 years, and 47% were female. The median NLR for the entire cohort was 8.9 (interquartile range, 4.99 to 16.21). Following multivariable adjustments, there was a stepwise increase in mortality with increasing quartiles of NLR (first quartile: reference category; second quartile odds ratio (OR) = 1.32; 95% confidence interval (CI), 1.03 to 1.71; third quartile OR = 1.43; 95% CI, 1.12 to 1.83; 4th quartile OR = 1.71; 95% CI, 1.35 to 2.16). A similar stepwise relationship was identified in the subgroup of patients who presented without sepsis. The NLR was not associated with 28-day mortality in patients with sepsis. Increasing quartile of NLR was statistically significantly associated with secondary outcome.

Conclusion

The NLR is associated with outcomes in unselected critically ill patients. In patients with sepsis, there was no statistically significant relationship between NLR and mortality. Further investigation is required to increase understanding of the pathophysiology of this relationship and to validate these findings with data collected prospectively.
Dynamic arterial elastance predicts mean arterial pressure decrease associated with decreasing norepinephrine dosage in septic shock
Authors: Guinot Pierre-Grégoire , Bernard Eugénie , Levrard Mélanie , Dupont Hervé , Lorne Emmanuel
Published: January 2015

Introduction

Gradual reduction of the dosage of norepinephrine (NE) in patients with septic shock is usually left to the physician’s discretion. No hemodynamic indicator predictive of the possibility of decreasing the NE dosage is currently available at the bedside. The respiratory pulse pressure variation/respiratory stroke volume variation (dynamic arterial elastance (Eadyn)) ratio has been proposed as an indicator of vascular tone. The purpose of this study was to determine whether Eadyn can be used to predict the decrease in arterial pressure when decreasing the NE dosage in resuscitated sepsis patients.

Methods

A prospective study was carried out in a university hospital intensive care unit. All consecutive patients with septic shock monitored by PICCO2 for whom the intensive care physician planned to decrease the NE dosage were enrolled. Measurements of hemodynamic and PICCO2 variables were obtained before/after decreasing the NE dosage. Responders were defined by a >15% decrease in mean arterial pressure (MAP).

Results

In total, 35 patients were included. MAP decreased by >15% after decreasing the NE dosage in 37% of patients (n = 13). Clinical characteristics appeared to be similar between responders and nonresponders. Eadyn was lower in responders than in nonresponders (0.75 (0.69 to 0.85) versus 1 (0. 83 to 1.22), P <0.05). Baseline Eadyn was correlated with NE-induced MAP variations (r = 0.47, P = 0.005). An Eadyn less than 0.94 predicted a decrease in arterial pressure, with an area under the receiver-operating characteristic curve of 0.87 (95% confidence interval (95% CI): 0.72 to 0.96; P <0.0001), 100% sensitivity, and 68% specificity.

Conclusions

In sepsis patients treated with NE, Eadyn may predict the decrease in arterial pressure in response to NE dose reduction. Eadyn may constitute an easy-to-use functional approach to arterial-tone assessment, which may be helpful to identify patients likely to benefit from NE dose reduction.
Application of the 2012 Systemic Lupus International Collaborating Clinics classification criteria to patients in a regional Swedish systemic lupus erythematosus register
Authors: Ighe Anna , Dahlström Örjan , Skogh Thomas , Sjöwall Christopher
Published: January 2015

Introduction

In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) network presented a new set of criteria (SLICC-12) to classify systemic lupus erythematosus (SLE). The present study is the first to evaluate the performance of SLICC-12 in an adult European study population. Thus, SLICC-12 criteria were applied to confirmed SLE cases in our regional SLE register as well as to individuals with a fair suspicion of systemic autoimmune disease who were referred to rheumatology specialists at our unit.

Methods

We included 243 confirmed SLE patients who met the 1982 American College of Rheumatology (ACR-82) classification criteria and/or the Fries ‘diagnostic principle’ (presence of antinuclear antibodies on at least one occasion plus involvement of at least two defined organ systems) and 55 controls with possible systemic autoimmune disease, including the presence of any SLE-related autoantibody.

Results

SLICC-12 showed a diagnostic sensitivity of 94% (95% confidence interval (CI), 0.90 to 0.96) compared with 90% (95% CI, 0.85 to 0.93) for the updated set of ACR criteria from 1997 (ACR-97), whereas ACR-82 failed to identify every fifth true SLE case. However, the disease specificity of SLICC-12 reached only 74% (95% CI, 0.60 to 0.84) and did not change much when involvement of at least two different organs was required as an indicator of systemic disease. In addition, SLICC-12 misclassified more of the controls compared to ACR-82, ACR-97 and Fries.

Conclusions

Establishing a standard definition of SLE continues to challenge lupus researchers and clinicians. We confirm that SLICC-12 has advantages with regard to diagnostic sensitivity, whereas we found the diagnostic specificity to be surprisingly low. To accomplish increased sensitivity and specificity figures, a combination of criteria sets for clinical SLE studies should be considered.
Gluing Silting Objects
Authors: Liu Qunhua , Vitória Jorge , Yang Dong
Published: January 2015

Recent results by Keller and Nicolás and by Koenig and Yang have shown bijective correspondences between suitable classes of t-structures and cot-structures with certain objects of the derived category: silting objects. On the other hand, the techniques of gluing (co-)t-structures along a recollement play an important role in the understanding of derived module categories. Using the above correspondence with silting objects, we present explicit constructions of gluing of silting objects, and, furthermore, we answer the question of when the glued silting is tilting.
Chemotactic response with a constant delay-time mechanism in Ciona spermatozoa revealed by a high time resolution analysis of flagellar motility
Authors: Miyashiro Daisuke , Shiba Kogiku , Miyashita Tahahiro , Baba Shoji A. , Yoshida Manabu , Kamimura Shinji
Published: January 2015

During their chemotactic swimming toward eggs, sperm cells detect their species-specific chemoattractant and sense concentration gradients by unknown mechanisms. After sensing the attractant, sperm cells commonly demonstrate a series of responses involving different swimming patterns by changing flagellar beats, gradually approaching a swimming path toward the eggs, which is the source of chemoattractants. Shiba et al. observed a rapid increase in intracellular Ca2+ concentrations in Ciona spermatozoa after sensing chemoattractants; however, the biochemical processes occurring inside the sperm cells are unclear. In the present study, we focused on the timing and sensing mechanism of chemical signal detection in Ciona. One of the most crucial problems to be solved is defining the initial epoch of chemotactic responses. We adopted a high rate of video recording (600 Hz) for detailed analysis of sperm motion and a novel method for detecting subtle signs of beat forms and moving paths of sperm heads. From these analyses, we estimated a virtual sensing point of the attractant before initiation of motility responses and found that the time delay from sensing to motility responses was almost constant. To evaluate the efficiency of this constant delay model, we performed computer simulation of chemotactic behaviors of Ciona spermatozoa.
ICAM-5 affects spine maturation by regulation of NMDA receptor binding to α-actinin
Authors: Ning Lin , Paetau Sonja , Nyman-Huttunen Henrietta , Tian Li , Gahmberg Carl G.
Published: January 2015

ICAM-5 is a negative regulator of dendritic spine maturation and facilitates the formation of filopodia. Its absence results in improved memory functions, but the mechanisms have remained poorly understood. Activation of NMDA receptors induces ICAM-5 ectodomain cleavage through a matrix metalloproteinase (MMP)-dependent pathway, which promotes spine maturation and synapse formation. Here, we report a novel, ICAM-5-dependent mechanism underlying spine maturation by regulating the dynamics and synaptic distribution of α-actinin. We found that GluN1 and ICAM-5 partially compete for the binding to α-actinin; deletion of the cytoplasmic tail of ICAM-5 or ablation of the gene resulted in increased association of GluN1 with α-actinin, whereas internalization of ICAM-5 peptide perturbed the GluN1/α-actinin interaction. NMDA treatment decreased α-actinin binding to ICAM-5, and increased the binding to GluN1. Proper synaptic distribution of α-actinin requires the ICAM-5 cytoplasmic domain, without which α-actinin tended to accumulate in filopodia, leading to F-actin reorganization. The results indicate that ICAM-5 retards spine maturation by preventing reorganization of the actin cytoskeleton, but NMDA receptor activation is sufficient to relieve the brake and promote the maturation of spines.
Establishing neural crest identity: a gene regulatory recipe
Authors: Simões-Costa Marcos , Bronner Marianne E.
Published: January 2015

The neural crest is a stem/progenitor cell population that contributes to a wide variety of derivatives, including sensory and autonomic ganglia, cartilage and bone of the face and pigment cells of the skin. Unique to vertebrate embryos, it has served as an excellent model system for the study of cell behavior and identity owing to its multipotency, motility and ability to form a broad array of cell types. Neural crest development is thought to be controlled by a suite of transcriptional and epigenetic inputs arranged hierarchically in a gene regulatory network. Here, we examine neural crest development from a gene regulatory perspective and discuss how the underlying genetic circuitry results in the features that define this unique cell population.
The CXCR3-CXCL11 signaling axis mediates macrophage recruitment and dissemination of mycobacterial infection
Authors: Torraca Vincenzo , Cui Chao , Boland Ralf , Bebelman Jan-Paul , van der Sar Astrid M. , Smit Martine J. , Siderius Marco , Spaink Herman P. , Meijer Annemarie H.
Published: January 2015

The recruitment of leukocytes to infectious foci depends strongly on the local release of chemoattractant mediators. The human CXC chemokine receptor 3 (CXCR3) is an important node in the chemokine signaling network and is expressed by multiple leukocyte lineages, including T cells and macrophages. The ligands of this receptor originate from an ancestral CXCL11 gene in early vertebrates. Here, we used the optically accessible zebrafish embryo model to explore the function of the CXCR3-CXCL11 axis in macrophage recruitment and show that disruption of this axis increases the resistance to mycobacterial infection. In a mutant of the zebrafish ortholog of CXCR3 (cxcr3.2), macrophage chemotaxis to bacterial infections was attenuated, although migration to infection-independent stimuli was unaffected. Additionally, attenuation of macrophage recruitment to infection could be mimicked by treatment with NBI74330, a high-affinity antagonist of CXCR3. We identified two infection-inducible CXCL11-like chemokines as the functional ligands of Cxcr3.2, showing that the recombinant proteins exerted a Cxcr3.2-dependent chemoattraction when locally administrated in vivo. During infection of zebrafish embryos with Mycobacterium marinum, a well-established model for tuberculosis, we found that Cxcr3.2 deficiency limited the macrophage-mediated dissemination of mycobacteria. Furthermore, the loss of Cxcr3.2 function attenuated the formation of granulomatous lesions, the typical histopathological features of tuberculosis, and led to a reduction in the total bacterial burden. Prevention of mycobacterial dissemination by targeting the CXCR3 pathway, therefore, might represent a host-directed therapeutic strategy for treatment of tuberculosis. The demonstration of a conserved CXCR3-CXCL11 signaling axis in zebrafish extends the translational applicability of this model for studying diseases involving the innate immune system.
Adding ‘epi-’ to behaviour genetics: implications for animal domestication
Authors: Jensen Per
Published: January 2015

In this review, it is argued that greatly improved understanding of domestication may be gained from extending the field of behaviour genetics to also include epigenetics. Domestication offers an interesting framework of rapid evolutionary changes caused by well-defined selection pressures. Behaviour is an important phenotype in this context, as it represents the primary means of response to environmental challenges. An overview is provided of the evidence for genetic involvement in behavioural control and the presently used methods for finding so-called behaviour genes. This shows that evolutionary changes in behaviour are to a large extent correlated to changes in patterns of gene expression, which brings epigenetics into the focus. This area is concerned with the mechanisms controlling the timing and extent of gene expression, and a lot of focus has been placed on methylation of cytosine in promoter regions, usually associated with genetic downregulation. The review considers the available evidence that environmental input, for example stress, can modify methylation and other epigenetic marks and subsequently affect behaviour. Furthermore, several studies are reviewed, demonstrating that acquired epigenetic modifications can be inherited and cause trans-generational behaviour changes. In conclusion, epigenetics may signify a new paradigm in this respect, as it shows that genomic modifications can be caused by environmental signals, and random mutations in DNA sequence are therefore not the only sources of heritable genetic variation.
Influence of environmental exposure on human epigenetic regulation
Authors: Marsit Carmen J.
Published: January 2015

Environmental toxicants can alter epigenetic regulatory features such as DNA methylation and microRNA expression. As the sensitivity of epigenomic regulatory features may be greatest during the in utero period, when critical windows are narrow, and when epigenomic profiles are being set, this review will highlight research focused on that period. I will focus on work in human populations, where the impact of environmental toxicants in utero, including cigarette smoke and toxic trace metals such as arsenic, mercury and manganese, on genome-wide, gene-specific DNA methylation has been assessed. In particular, arsenic is highlighted, as this metalloid has been the focus of a number of studies and its detoxification mechanisms are well understood. Importantly, the tissues and cells being examined must be considered in context in order to interpret the findings of these studies. For example, by studying the placenta, it is possible to identify potential epigenetic adaptations of key genes and pathways that may alter the developmental course in line with the developmental origins of health and disease paradigm. Alternatively, studies of newborn cord blood can be used to examine how environmental exposure in utero can impact the composition of cells within the peripheral blood, leading to immunological effects of exposure. The results suggest that in humans, like other vertebrates, there is a susceptibility for epigenomic alteration by the environment during intrauterine development, and this may represent a mechanism of plasticity of the organism in response to its environment as well as a mechanism through which long-term health consequences can be shaped.
Neurogenomic mechanisms of social plasticity
Authors: Cardoso Sara D. , Teles Magda C. , Oliveira Rui F.
Published: January 2015

Group-living animals must adjust the expression of their social behaviour to changes in their social environment and to transitions between life-history stages, and this social plasticity can be seen as an adaptive trait that can be under positive selection when changes in the environment outpace the rate of genetic evolutionary change. Here, we propose a conceptual framework for understanding the neuromolecular mechanisms of social plasticity. According to this framework, social plasticity is achieved by rewiring or by biochemically switching nodes of a neural network underlying social behaviour in response to perceived social information. Therefore, at the molecular level, it depends on the social regulation of gene expression, so that different genomic and epigenetic states of this brain network correspond to different behavioural states, and the switches between states are orchestrated by signalling pathways that interface the social environment and the genotype. Different types of social plasticity can be recognized based on the observed patterns of inter- versus intra-individual occurrence, time scale and reversibility. It is proposed that these different types of social plasticity rely on different proximate mechanisms at the physiological, neural and genomic level.
Natural epigenetic variation in bats and its role in evolution
Authors: Liu Sen , Sun Keping , Jiang Tinglei , Feng Jiang
Published: January 2015

When facing the challenges of environmental change, such as habitat fragmentation, organisms have to adjust their phenotype to adapt to various environmental stresses. Recent studies show that epigenetic modifications could mediate environmentally induced phenotypic variation, and this epigenetic variance could be inherited by future generations, indicating that epigenetic processes have potential evolutionary effects. Bats living in diverse environments show geographic variations in phenotype, and the females usually have natal philopatry, presenting an opportunity to explore how environments shape epigenetic marks on the genome and the evolutionary potential of epigenetic variance in bat populations for adaptation. We have explored the natural epigenetic diversity and structure of female populations of the great roundleaf bat (Hipposideros armiger), the least horseshoe bat (Rhinolophus pusillus) and the eastern bent-winged bat (Miniopterus fuliginosus) using a methylation-sensitive amplified polymorphism technique. We have also estimated the effects of genetic variance and ecological variables on epigenetic diversification. All three bat species have a low level of genomic DNA methylation and extensive epigenetic diversity that exceeds the corresponding genetic variance. DNA sequence divergence, epigenetic drift and environmental variables contribute to the epigenetic diversities of each species. Environment-induced epigenetic variation may be inherited as a result of both mitosis and meiosis, and their potential roles in evolution for bat populations are also discussed in this review.
Erection pattern and section-wise wettability of honeybee glossal hairs in nectar feeding
Authors: Wu Jianing , Zhu Rengao , Yan Shaoze , Yang Yunqiang
Published: January 2015

The honeybee's tongue (glossa) is covered with bushy hairs and resembles a mop or a brush. We examined the dimensions of glossal hairs of the Italian honeybee (Apis mellifera ligustica) and found that the average length of hairs increased from the proximal segment to the distal end. The glossal dynamic surface of a honeybee in drinking cycles was captured by a specially designed high-speed camera system, and we discovered that the glossal hairs erected rhythmically when drinking nectar; specifically, hairs on the proximal segment erected earlier than those on the distal end of a honeybee's tongue, which was identified as the phenomenon of asynchronous hair erection. Moreover, by measuring the wettability of the tongue, we found that the flabellum was the most hydrophilic and the root of the tongue was hardest to be wetted. According to our observations, we suggest that the honeybee has an optimal hair-erection pattern that could balance nectar intake and viscous drag. These results will be helpful to understand the liquid-feeding mechanism of honeybees, especially the role of erectable glossal hairs.
Vasotocin and isotocin regulate aquaporin 1 function in the sea bream
Authors: Martos-Sitcha Juan Antonio , Campinho Marco Antonio , Mancera Juan Miguel , Martínez-Rodríguez Gonzalo , Fuentes Juan
Published: January 2015

Aquaporins (AQPs) are specific transmembrane water channels with an important function in water homeostasis. In terrestrial vertebrates, AQP2 function is regulated by vasopressin (AVP) to accomplish key functions in osmoregulation. The endocrine control of aquaporin function in teleosts remains little studied. Therefore, in this study we investigated the regulatory role of vasotocin (AVTR) and isotocin (ITR) receptors in Aqp1 paralog gene function in the teleost gilthead sea bream (Sparus aurata). The complete coding regions of Aqp1a, Aqp1b, AVTR V1a2-type, AVTR V2-type and ITR from sea bream were isolated. A Xenopus oocyte-swelling assay was used to functionally characterize AQP1 function and regulation by AVT and IT through their cognate receptors. Microinjection of oocytes with Aqp1b mRNA revealed regulation of water transport via PKA (IBMX+forskolin sensitive), whereas Aqp1a mRNA injection had the same effect via PKC signaling (PDBU sensitive). In the absence of expressed receptors, AVT and IT (10−8 mol l−1) were unable to modify AQP1 function. AVT regulated AQP1a and AQP1b function only when the AVTR V2-type was co-expressed. IT regulated AQP1a function, but not AQP1b, only when ITR was present. Considering that Aqp1a and Aqp1b gene expression in the sea bream intestine is highly salinity dependent in vivo, our results in ovo demonstrate a regulatory role for AVT and IT in AQP1 function in the sea bream in the processing of intestinal fluid to achieve osmoregulation.
Mechanical challenges to freshwater residency in sharks and rays
Authors: Gleiss Adrian C. , Potvin Jean , Keleher James J. , Whitty Jeff M. , Morgan David L. , Goldbogen Jeremy A.
Published: January 2015

Major transitions between marine and freshwater habitats are relatively infrequent, primarily as a result of major physiological and ecological challenges. Few species of cartilaginous fish have evolved to occupy freshwater habitats. Current thought suggests that the metabolic physiology of sharks has remained a barrier to the diversification of this taxon in freshwater ecosystems. Here, we demonstrate that the physical properties of water provide an additional constraint for this species-rich group to occupy freshwater systems. Using hydromechanical modeling, we show that occurrence in fresh water results in a two- to three-fold increase in negative buoyancy for sharks and rays. This carries the energetic cost of lift production and results in increased buoyancy-dependent mechanical power requirements for swimming and increased optimal swim speeds. The primary source of buoyancy, the lipid-rich liver, offers only limited compensation for increased negative buoyancy as a result of decreasing water density; maintaining the same submerged weight would involve increasing the liver volume by very large amounts: 3- to 4-fold in scenarios where liver density is also reduced to currently observed minimal levels and 8-fold without any changes in liver density. The first data on body density from two species of elasmobranch occurring in freshwater (the bull shark Carcharhinus leucas, Müller and Henle 1839, and the largetooth sawfish Pristis pristis, Linnaeus 1758) support this hypothesis, showing similar liver sizes as marine forms but lower liver densities, but the greatest negative buoyancies of any elasmobranch studied to date. Our data suggest that the mechanical challenges associated with buoyancy control may have hampered the invasion of freshwater habitats in elasmobranchs, highlighting an additional key factor that may govern the predisposition of marine organisms to successfully establish in freshwater habitats.
Shaping the Future of Research: a perspective from junior scientists
Authors: McDowell Gary S. , Gunsalus Kearney T. W. , MacKellar Drew C. , Mazzilli Sarah A. , Pai Vaibhav P. , Goodwin Patricia R. , Walsh Erica M. , Robinson-Mosher Avi , Bowman Thomas A. , Kraemer James , Erb Marcella L. , Schoenfeld Eldi , Shokri Leila , Jackson Jonathan D. , Islam Ayesha , Mattozzi Matthew D. , Krukenberg Kristin A. , Polka Jessica K.
Published: January 2015

The landscape of scientific research and funding is in flux as a result of tight budgets, evolving models of both publishing and evaluation, and questions about training and workforce stability. As future leaders, junior scientists are uniquely poised to shape the culture and practice of science in response to these challenges. A group of postdocs in the Boston area who are invested in improving the scientific endeavor, planned a symposium held on October 2nd and 3rd, 2014, as a way to join the discussion about the future of US biomedical research. Here we present a report of the proceedings of participant-driven workshops and the organizers’ synthesis of the outcomes.
Binding of a fluorescence reporter and a ligand to an odorant-binding protein of the yellow fever mosquito, Aedes aegypti
Authors: Leal Gabriel M. , Leal Walter S.
Published: January 2015

Odorant-binding proteins (OBPs), also named pheromone-binding proteins when the odorant is a pheromone, are essential for insect olfaction. They solubilize odorants that reach the port of entry of the olfactory system, the pore tubules in antennae and other olfactory appendages. Then, OBPs transport these hydrophobic compounds through an aqueous sensillar lymph to receptors embedded on dendritic membranes of olfactory receptor neurons. Structures of OBPs from mosquito species have shed new light on the mechanism of transport, although there is considerable debate on how they deliver odorant to receptors. An OBP from the southern house mosquito, Culex quinquefasciatus, binds the hydrophobic moiety of a mosquito oviposition pheromone (MOP) on the edge of its binding cavity. Likewise, it has been demonstrated that the orthologous protein from the malaria mosquito binds the insect repellent DEET on a similar edge of its binding pocket. A high school research project was aimed at testing whether the orthologous protein from the yellow fever mosquito, AaegOBP1, binds DEET and other insect repellents, and MOP was used as a positive control. Binding assays using the fluorescence reporter N-phenyl-1-naphtylamine (NPN) were inconclusive. However, titration of NPN fluorescence emission in AaegOBP1 solution with MOP led to unexpected and intriguing results. Quenching was observed in the initial phase of titration, but addition of higher doses of MOP led to a stepwise increase in fluorescence emission coupled with a blue shift, which can be explained at least in part by formation of MOP micelles to house stray NPN molecules.
Association between obesity and depression in patients with diabetes mellitus type 2; a study protocol
Authors: De la Cruz-Cano Eduardo , Tovilla-Zarate Carlos Alfonso , Reyes-Ramos Emilio , Gonzalez-Castro Thelma Beatriz , Juarez-Castro Isela , López-Narváez Maria Lilia , Fresan Ana
Published: January 2015

Background: Diabetes mellitus and depression are highly prevalent conditions throughout the world and have significant impact on health outcomes. It has been estimated that diabetes mellitus type 2 affects about 246 million people in the world; nevertheless, incidence varies among countries. There is evidence that depression is associated with a poor metabolic control in patients with type 2 diabetes mellitus that present other health problems (such as hypertension and obesity). The aim of this study protocol is to determine if obesity increases the risk for depression in patient with diabetes type 2.

Methods: The analysis will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).The studies suitable for inclusion will be assessed by the Newcastle-Ottawa Scale (NOS) to determine their methodological quality. To identify the studies of interest, we will search on PubMed and EBSCO databases. We will use the following keyword combinations: "Diabetes Mellitus type 2 AND obesity AND depression", "depression AND Diabetes Mellitus type 2", "Diabetes Mellitus type 2 AND body mass index cross sectional study", "depression AND obesity cross-sectional study". Causes for exclusion will be publications that studied patients diagnosed with diabetes mellitus type 1; articles that focused on the treatment and complications of diabetes mellitus type 2; publications that have studied other clinical or psychiatric conditions (for instance, seizure disorder or history of schizophrenia, bipolar disorder, psychotic symptoms or dementia).

Conclusion: The results of this study will form the basis for a better understanding of the association between obesity and depression in patients with diabetes mellitus type 2, and will allow development of prediction tools and better interventions. It is evident that several modifiable and non-modifiable risk factors play an important role in the pathogenesis of diabetes among population. Currently, evidence for the deleterious effects of diabetes mellitus type 2 are based on cross-sectional or other observational designs. Therefore, this study will have important implications for future research and public health guidance.
Open peer review at four STEM journals: an observational overview
Authors: Ford Emily
Published: January 2015

Open peer review, peer review where authors' and reviewers' identities are disclosed to one another, is a growing trend in scholarly publishing. Through observation of four journals in STEM disciplines,PLoS One,Atmospheric Chemistry & Physics,PeerJ, andF1000Research, an observational overview is conducted. The overview relies on defined characteristics of open peer review. Results show that despite differing open peer review implementations, each journal retains editorial involvement in scholarly publishing. Further, the analysis shows that only one of these implementations is fully transparent in its peer review and decision making process. Finally, the overview contends that journals should clearly outline peer review and editorial processes in order to allow for open peer review to be better understood and adopted by authors, reviewers, editors, and readers of science communications.
Oxygen-binding and sensing proteins
Authors: Poole Robert K.
Published: January 2015

This collection of papers is a snapshot of topics presented at the international conference on Oxygen-Binding and Sensing Proteins (O2BiP) held in Sheffield, UK, on 6th-10th July 2014. The collection will grow over time as new papers relating to O2BiP topics are completed and published.
Using Single-Neuron Recording in Marketing: Opportunities, Challenges, and an Application to Fear Enhancement in Communications
Authors: Cerf Moran , Greenleaf Eric , Meyvis Tom , Morwitz Vicki G.
Published: January 2015

This article introduces the method of single-neuron recording in humans to marketing and consumer researchers. First, the authors provide a general description of this methodology, discuss its advantages and disadvantages, and describe findings from previous single-neuron human research. Second, they discuss the relevance of this method for marketing and consumer behavior and, more specifically, how it can be used to gain insights into the areas of categorization, sensory discrimination, reactions to novel versus familiar stimuli, and recall of experiences. Third, they present a study designed to illustrate how single-neuron studies are conducted and how data from them are processed and analyzed. This study examines people's ability to up-regulate (i.e., enhance) the emotion of fear, which has implications for designing effective fear appeals. The study shows that the firing rates of neurons previously shown to respond selectively to fearful content increased with emotion enhancement instructions, but only for a video that did not automatically evoke substantial fear. The authors discuss how the findings help illustrate which conclusions can and cannot be drawn from single-neuron research.
Consumer Neuroscience: Applications, Challenges, and Possible Solutions
Authors: Plassmann Hilke , Venkatraman Vinod , Huettel Scott , Yoon Carolyn
Published: January 2015

The first decade of consumer neuroscience research has produced groundbreaking work in identifying the basic neural processes underlying human judgment and decision making, with the majority of such studies published in neuroscience journals and influencing models of brain function. Yet for the field of consumer neuroscience to thrive in the next decade, the current emphasis on basic science research must be extended into marketing theory and practice. The authors suggest five concrete ways that neuroscientific methods can be fruitfully applied to marketing. They then outline three fundamental challenges facing consumer neuroscientists and offer potential solutions for addressing them. The authors conclude by describing how consumer neuroscience can become an important complement to research and practice in marketing.
Materials Specification Needs for Future Development of Ultra High Performance Concrete
Authors: Allena Srinivas , Newtson Craig M.
Published: January 2015

Over the next several years, new mixtures for ultra high performance concrete (UHPC) products are expected to move from prepackaged mixtures toward the use of locally available materials to make UHPC economically viable for future projects. Because a wider variety of materials will be used in UHPC, it will be necessary to develop or modify material specifications to ensure high quality UHPC mixtures are produced that provide strength and durability properties consistent with designers’ expectations. New or modified specifications will be needed for chemical requirements on the cement and supplementary cementitious materials considered for use in UHPC as well as to guide producers in the selection of aggregates for use in UHPC. This paper discusses these material issues along with issues related to admixture and fiber selection that are important to the future development of UHPC. Suggestions for development or modification of specifications that will ensure selection of high quality materials and potential performance based specifications that may evolve in the future are also provided.
Pluralism Unleashed
Authors: Thiêm Bùi Hải
Published: January 2015

The paper explores contestations playing out in constitutional debates around the 1992 constitutional amendments with a focal point in the exercise of discursive power and struggles for change. The paper discusses the significance of conflict in the constitutional reform process re-initiated in 2011. It demonstrates how the emphasis on stability and harmonious integration in initial constitutional amendment proposals has been compromised and renegotiated in the face of sustained criticisms of the constitution that draw on non-orthodox ideological foundations. The contestations that characterize constitutional reform discourse reveals how conflict is a significant driver of the changes presently underway in Vietnam.
The Party v. the People
Authors: Vu Tuong
Published: January 2015

The South China Sea conflict is spurring a popular nationalist movement in Vietnam that challenges the ruling communist Party by demanding Hà Nội to sever relations with its patron in Beijing. This paper examines this movement by connecting it to the often misunderstood historical relationship between the ruling Party and modern Vietnamese nationalism. This historical relationship explains why the Party has tried to suppress the movement and why movement discourse strives to debunk national myths and reconstruct national history. Linking national interests to democracy and human rights, the currently fragile movement is creating dissent within the Party and damaging its legitimacy.
THERAPY OF ENDOCRINE DISEASE: Response and toxicity of small-molecule tyrosine kinase inhibitors in patients with thyroid carcinoma: a systematic review and meta-analysis
Authors: Klein Hesselink E N , Steenvoorden D , Kapiteijn E , Corssmit E P , van der Horst-Schrivers A N A , Lefrandt J D , Links T P , Dekkers O M
Published: January 2015

Context

Many tyrosine kinase inhibitors (TKIs) have been studied in patients with thyroid carcinoma (TC). However, the effect and toxicity of various TKIs in differentiated TC (DTC) and medullary TC (MTC) patients have not been directly compared. The aim of the present systematic review and meta-analysis was to systematically summarize response and toxicity of TKIs in TC patients.

Methods

All major databases were systematically searched for publications on TKIs in TC. Primary endpoint was objective response; secondary endpoints were clinical benefit, percentage TKI dose reduction/discontinuation, hand–foot syndrome, diarrhea, and nausea/vomiting. Meta-analysis was performed using an exact likelihood approach and a logistic regression. Pooled percentages and 95% CIs were reported.

Results

In total, 22 publications were included. For DTC patients, gefitinib induced no objective responses. Pooled percentage was highest for pazopanib, 49 (95% CI 33–64)%, and was 17 (95% CI 12–24)% for sorafenib. For MTC, gefitinib and imatinib induced no objective responses, whereas sunitinib induced objective response in 43 (95% CI 14–77)%. For vandetanib and cabozantinib, these numbers were 40 (95% CI 34–46)% and 27 (95% CI 22–32)% respectively. Clinical benefit was found in 53 (95% CI 48–59)% of DTC patients on sorafenib, and in 84 (95% CI 79–88)% and 55 (95% CI 49–61)% of MTC patients on vandetanib and cabozantinib respectively. All TKIs were associated with considerable toxicity.

Conclusion

The currently studied TKIs show a modest response, while side effects are not negligible. Therefore, we suggest to solely consider TKIs in TC patients with rapid progressive disease, for whom the benefits of treatment outweigh toxicity.
Thyroid incidentalomas in patients with multiple endocrine neoplasia type 1
Authors: Lodewijk Lutske , Bongers Pim J , Kist Jakob W , Conemans Elfi B , de Laat Joanne M , Pieterman Carla R C , van der Horst-Schrivers Anouk N A , Jorna Ciska , Hermus Ad R , Dekkers Olaf M , de Herder Wouter W , Drent Madeleine L , Bisschop Peter H , Havekes Bas , Rinkes Inne H M Borel , Vriens Menno R , Valk Gerlof D
Published: January 2015

Objective

Currently, little is known about the prevalence of thyroid tumors in multiple endocrine neoplasia type 1 (MEN1) patients and it is unclear whether tumorigenesis of these thyroid tumors is MEN1-related. The aim of the study was to assess the prevalence of thyroid incidentalomas in MEN1 patients compared with nonMEN1 patients and to verify whether thyroid tumorigenesis is MEN1-related.

Design

A cross-sectional study.

Methods

The study included two groups: patients with MEN1 and a matched non-MEN1 control group without known thyroid disease, who underwent an ultrasound of the neck for the localization of parathyroid adenoma. Ninety-five MEN1 patients underwent ultrasound of the neck and were matched on gender and age with non-MEN1 patients. The prevalence of thyroid incidentalomas described in the ultrasound report was scored. Multinodular goiters, solitary nodes, and cysts were scored as incidentalomas. Presence of nuclear menin expression was evaluated by menin immunostaining of the thyroid tumors.

Results

In the MEN1 group, 43 (45%) patients had a thyroid incidentaloma compared with 48 (51%) in the non-MEN1 group, of which 14 (15%) and 16 (17%), respectively, were solitary nodes. Menin was expressed in the nuclei of all evaluated thyroid tumors.

Conclusions

MEN1 patients do not have a higher prevalence of thyroid incidentalomas compared with primary hyperparathyroidism patients without the diagnosis of MEN1. Menin was expressed in the thyroid tumors of MEN1 patients.