bluuebunny/crossref_metadata_2025 huggingface dataset:
Density-dependent selection closes an eco-evolutionary feedback loop in the stick insect
Timema cristinae
Authors: Farkas Timothy E. , Montejo-Kovacevich Gabriela
Published: December 2014

Empirical demonstrations of feedbacks between ecology and evolution are rare. Here, we used a field experiment to test the hypothesis that avian predators impose density-dependent selection (DDS) on
Timema cristinae
stick insects. We transplanted wild-caught
T. cristinae
to wild bushes at 50 : 50 cryptic : conspicuous morph ratio and manipulated density by transplanting either 24 or 48 individuals. The frequency of the conspicuous morph was reduced by 73% in the low-density treatment, but only by 50% in the high-density treatment, supporting a hypothesis of negative DDS. Coupled with previous studies on
T. cristinae
, which demonstrate that maladaptive gene flow reduces population density, we support an eco-evolutionary feedback loop in this system. Furthermore, our results support the hypothesis that predator satiation is the mechanism driving DDS. We found no effects of
T. cristinae
density on the abundance or species richness of other arthropods. Eco-evolutionary feedbacks, driven by processes like DDS, can have implications for adaptive divergence and speciation.
Patterns of functional vision loss in glaucoma determined with archetypal analysis
Authors: Elze Tobias , Pasquale Louis R. , Shen Lucy Q. , Chen Teresa C. , Wiggs Janey L. , Bex Peter J.
Published: December 2014

Glaucoma is an optic neuropathy accompanied by vision loss which can be mapped by visual field (VF) testing revealing characteristic patterns related to the retinal nerve fibre layer anatomy. While detailed knowledge about these patterns is important to understand the anatomic and genetic aspects of glaucoma, current classification schemes are typically predominantly derived qualitatively. Here, we classify glaucomatous vision loss quantitatively by statistically learning prototypical patterns on the convex hull of the data space. In contrast to component-based approaches, this method emphasizes distinct aspects of the data and provides patterns that are easier to interpret for clinicians. Based on 13 231 reliable Humphrey VFs from a large clinical glaucoma practice, we identify an optimal solution with 17 glaucomatous vision loss prototypes which fit well with previously described qualitative patterns from a large clinical study. We illustrate relations of our patterns to retinal structure by a previously developed mathematical model. In contrast to the qualitative clinical approaches, our results can serve as a framework to quantify the various subtypes of glaucomatous visual field loss.
Boxfish swimming paradox resolved: forces by the flow of water around the body promote manoeuvrability
Authors: Van Wassenbergh S. , van Manen K. , Marcroft T. A. , Alfaro M. E. , Stamhuis E. J.
Published: December 2014

The shape of the carapace protecting the body of boxfishes has been attributed an important hydrodynamic role in drag reduction and in providing automatic, flow-direction realignment and is therefore used in bioinspired design of cars. However, tight swimming-course stabilization is paradoxical given the frequent, high-performance manoeuvring that boxfishes display in their spatially complex, coral reef territories. Here, by performing flow-tank measurements of hydrodynamic drag and yaw moments together with computational fluid dynamics simulations, we reverse several assumptions about the hydrodynamic role of the boxfish carapace. Firstly, despite serving as a model system in aerodynamic design, drag-reduction performance was relatively low compared with more generalized fish morphologies. Secondly, the current theory of course stabilization owing to flow over the boxfish carapace was rejected, as destabilizing moments were found consistently. This solves the boxfish swimming paradox: destabilizing moments enhance manoeuvrability, which is in accordance with the ecological demands for efficient turning and tilting.
High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts
Authors: Kang Bong Jin , Park Jinhyoung , Kim Jieun , Kim Hyung Ham , Lee Changyang , Hwang Jae Youn , Lien Ching-Ling , Shung K. Kirk
Published: December 2014

Adult zebrafish is a well-known small animal model for studying heart regeneration. Although the regeneration of scars made by resecting the ventricular apex has been visualized with histological methods, there is no adequate imaging tool for tracking the functional recovery of the damaged heart. For this reason, high-frequency Doppler echocardiography using dual mode pulsed wave Doppler, which provides both tissue Doppler (TD) and Doppler flow in a same cardiac cycle, is developed with a 30 MHz high-frequency array ultrasound imaging system. Phantom studies show that the Doppler flow mode of the dual mode is capable of measuring the flow velocity from 0.1 to 15 cm s
−1
with high accuracy (
p
-value = 0.974 > 0.05). In the
in vivo
study of zebrafish, both TD and Doppler flow signals were simultaneously obtained from the zebrafish heart for the first time, and the synchronized valve motions with the blood flow signals were identified. In the longitudinal study on the zebrafish heart regeneration, the parameters for diagnosing the diastolic dysfunction, for example,
E
/
E
m < 10,
E
/
A
< 0.14 for wild-type zebrafish, were measured, and the type of diastolic dysfunction caused by the amputation was found to be similar to the restrictive filling. The diastolic function was fully recovered within four weeks post-amputation.
The virtue of innovation: innovation through the lenses of biological evolution
Authors: Kell Douglas B. , Lurie-Luke Elena
Published: December 2014

We rehearse the processes of innovation and discovery in general terms, using as our main metaphor the biological concept of an evolutionary fitness landscape. Incremental and disruptive innovations are seen, respectively, as successful searches carried out locally or more widely. They may also be understood as reflecting evolution by mutation (incremental) versus recombination (disruptive). We also bring a platonic view, focusing on virtue and memory. We use ‘virtue’ as a measure of efforts, including the knowledge required to come up with disruptive and incremental innovations, and ‘memory’ as a measure of their lifespan, i.e. how long they are remembered. Fostering innovation, in the evolutionary metaphor, means providing the wherewithal to promote novelty, good objective functions that one is trying to optimize, and means to improve one's knowledge of, and ability to navigate, the landscape one is searching. Recombination necessarily implies multi- or inter-disciplinarity. These principles are generic to all kinds of creativity, novel ideas formation and the development of new products and technologies.
Exploitation and recovery of a sea urchin predator has implications for the resilience of southern California kelp forests
Authors: Hamilton Scott L. , Caselle Jennifer E.
Published: December 2014

Size-structured predator–prey interactions can be altered by the history of exploitation, if that exploitation is itself size-selective. For example, selective harvesting of larger sized predators can release prey populations in cases where only large individuals are capable of consuming a particular prey species. In this study, we examined how the history of exploitation and recovery (inside marine reserves and due to fisheries management) of California sheephead (Semicossyphus pulcher) has affected size-structured interactions with sea urchin prey in southern California. We show that fishing changes size structure by reducing sizes and alters life histories of sheephead, while management measures that lessen or remove fishing impacts (e.g. marine reserves, effort restrictions) reverse these effects and result in increases in density, size and biomass. We show that predation on sea urchins is size-dependent, such that the diet of larger sheephead is composed of more and larger sized urchins than the diet of smaller fish. These results have implications for kelp forest resilience, because urchins can overgraze kelp in the absence of top-down control. From surveys in a network of marine reserves, we report negative relationships between the abundance of sheephead and urchins and the abundance of urchins and fleshy macroalgae (including giant kelp), indicating the potential for cascading indirect positive effects of top predators on the abundance of primary producers. Management measures such as increased minimum size limits and marine reserves may serve to restore historical trophic roles of key predators and thereby enhance the resilience of marine ecosystems.
Phase 2a, randomized, double‐blind, placebo‐controlled, multicenter, parallel‐group study of a H4R‐antagonist (JNJ‐39758979) in Japanese adults with moderate atopic dermatitis
Authors: Murata Yoko , Song Michael , Kikuchi Hisayuki , Hisamichi Katsuya , Xu Xie L. , Greenspan Andrew , Kato Mai , Chiou Chiun‐Fang , Kato Takeshi , Guzzo Cynthia , Thurmond Robin L. , Ohtsuki Mamitaro , Furue Masutaka
Published: December 2014

This trial was conducted to evaluate the safety and efficacy of the H4R‐antagonist JNJ‐39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ‐39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double‐blind, multicenter, placebo‐controlled study. Primary efficacy was assessed via week‐6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient‐reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty‐eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end‐point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ‐39758979 100 mg (−3.7) and 300 mg (−3.0) versus placebo (−1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ‐39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ‐39758979 and placebo with the exception of two patients (both receiving JNJ‐39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H4R‐antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ‐39758979 appears to be associated with drug‐induced agranulocytosis, likely an off‐target effect.
Hair shaft miRNA‐221 levels as a new tumor marker of malignant melanoma
Authors: Inada Taisuke , Fukushima Satoshi , Murai Masayuki , Jinnin Masatoshi , Miyashita Azusa , Nakahara Satoshi , Yamashita Junji , Aoi Jun , Masuguchi Shinichi , Ihn Hironobu
Published: December 2014

miRNA‐221 (miR‐221) is known to be abnormally expressed in many human cancers. The serum levels of miR‐221 have been reported as a tumor marker for malignant melanoma (MM). We hypothesized that the hair shaft miR‐221 levels may be increased in patients with MM. We therefore assessed the possibility that hair shaft miR‐221 levels could be a marker for MM. The hair shaft miR‐221 levels were significantly higher in patients with MM than controls. The rates of increased hair shaft miR‐221 levels above the cut‐off value were comparable to those of serum 5‐S‐CD, which is a tumor marker commonly used for MM. Measurements of the hair shaft miR‐221 levels could have potential clinical value in the detection of MM. This is the first report investigating the hair shaft levels of an miRNA in patients with MM. Our investigations offer new insight into the relationship between miR‐221 and MM, and may provide a new, non‐invasive way to screen for melanoma.
Effect of micro‐inhomogeneity on the effective stress coefficients and undrained bulk modulus of a poroelastic medium: a double spherical shell model
Authors: Glubokovskikh Stanislav , Gurevich Boris
Published: December 2014

Although most rocks are complex multi‐mineralic aggregates, quantitative interpretation workflows usually ignore this complexity and employ Gassmann equation and effective stress laws that assume a micro‐homogeneous (mono‐mineralic) rock. Even though the Gassmann theory and effective stress concepts have been generalized to micro‐inhomogeneous rocks, they are seldom if at all used in practice because they require a greater number of parameters, which are difficult to measure or infer from data. Furthermore, the magnitude of the effect of micro‐heterogeneity on fluid substitution and on effective stress coefficients is poorly understood. In particular, it is an open question whether deviations of the experimentally measurements of the effective stress coefficients for drained and undrained elastic moduli from theoretical predictions can be explained by the effect of micro‐heterogeneity. In an attempt to bridge this gap, we consider an idealized model of a micro‐inhomogeneous medium: a Hashin assemblage of double spherical shells. Each shell consists of a spherical pore surrounded by two concentric spherical layers of two different isotropic minerals. By analyzing the exact solution of this problem, we show that the results are exactly consistent with the equations of Brown and Korringa (which represent an extension of Gassmann's equation to micro‐inhomogeneous media). We also show that the effective stress coefficients for bulk volume α, for porosity nϕ and for drained and undrained moduli are quite sensitive to the degree of heterogeneity (contrast between the moduli of the two mineral components). For instance, while for micro‐homogeneous rocks the theory gives nϕ = 1, for strongly micro‐inhomogenous rocks, nϕ may span a range of values from –∞ to ∞ (depending on the contrast between moduli of inner and outer shells). Furthermore, the effective stress coefficient for pore volume (Biot–Willis coefficient) α can be smaller than the porosity ϕ. Further studies are required to understand the applicability of the results to realistic rock geometries.
Bryophyte communities in the Amazon forest are regulated by height on the host tree and site elevation
Authors: de Oliveira Sylvia Mota , ter Steege Hans
Published: December 2014

Community composition of epiphytic bryophyte communities, sampled systematically in nine localities across 2800 km from east to west of the Amazon forest, was mostly explained by their height zone along the vertical microenvironmental gradient from the base to the top of the host tree.

Despite the lack of correlation between geographical distance and dissimilarity in species composition, communities within the same locality were significantly more similar than communities from different localities in all height zones, with the highest values of similarity found between outer canopy communities.

While height zone on the host tree explained most of the variation in species composition at local scale, elevation and temperature were the variables most strongly related to species composition at a geographical scale.

Using the concepts of meta/local community of the Neutral Theory of Biodiversity and Biogeography, we showed that establishment limitation was strongest at the extremes of the vertical gradient. We estimated that communities of the tree base and the outer canopy drew individuals from outside the habitat species pool at a rate of 0.28 and 0.22, respectively, in contrast with values between 0.55 and 0.76 of other height zones.

Our results offered contrasting evidence for the hypothesis that species inhabiting the canopy have higher chances of engaging in long‐distance dispersal events. If the stronger establishment limitation at the extremes of the gradient is not compensated by facilitated dispersal compared to other zones, as our results suggest, communities on the base and on the outer canopy might be, through time, subjected to stronger selection.

Synthesis. This study indicated that the community composition of epiphytic bryophytes in the Amazon is mainly regulated by environmental conditions, both at local and at geographical scales. Dispersal, although predominantly local, did not show geographical structure across the area.
The Production of Place: Perception, Reality and the Politics of Becoming
Authors: Willett Joanie
Published: December 2014

This article uses critical political theories to engage with regional economic development as a site of exclusion, inequality and interwoven power relationships, which would benefit from theoretical analysis. It does this through the concept of lifestyle from regional development creative industries discourses and regional branding, considering how time operates in the narratives of place used to represent and promote a region to the outside world. Using Cornwall as a case study and an analysis informed by complexity theory, the article claims that regional narratives need to be understood not just for how they are produced and what they say, but also for the futures that they imply. It argues that while strategic development narratives need to be situated within an affective assemblage that resonates with popular perceptions of place, they also need to have a narrative that opens up spaces of possibility for future action and facilitates adaptation.
Equal Partners in Dialogue? Participation Equality in a Transnational Deliberative Poll (Europolis)
Authors: Gerber Marlène
Published: December 2014

By gathering a representative sample of citizens from all 27 EU Member States, the deliberative poll Europolis created the opportunity for the inclusion of a wide variety of European voices. Taking up claims of difference democrats who argue that informal hurdles to participation can endure even after individuals gain formal access to the floor, this article argues for an extended approach to evaluate equality in deliberative minipublics. Specifically, it assesses whether participants contributed in roughly equal measures to the discussion and whether their discussion partners considered their contributions on equal merits. In doing so, the article adds to the small but growing literature on deliberation that expresses reservations about taking the willingness to engage with others' claims for granted. In order to account for the intrinsically relational aspect of interpersonal communication, measures of social network analysis are introduced as possible tools to evaluate participation equality in deliberative encounters.
A toxicology study to evaluate the embryotoxicity of metformin compared with the hypoglycemic drugs, the anticancer drug, the anti‐epileptic drug, the antibiotic, and the cyclo‐oxygenase (COX)‐2 inhibitor
Authors: Li Li , Zhang Xing , Wang Lei , Chai Zhenhai , Shen Xiuping , Zhang Zongpeng , Liu Changxiao
Published: December 2014

Background

The safe use of medications in pregnant females, their embryos and in offspring is important. The aim of the present study was to evaluate embryotoxicity of metformin (MET) compared with other hypoglycemic drugs (rosiglitazone [RSG] and glimepiride [GLIM]), the anticancer drug 5‐fluorouracil (5‐FU), the anti‐epileptic drug diphenylhydantoin (DPH), the antibiotic penicillin G (PenG), and the cyclo‐oxygenase (COX)‐2 inhibitor nimesulide (NIM) in an embryonic stem cell test (EST).

Methods

Differences in the expression of developmental marker genes following treatment with the test compounds during the course of differentiation (from embryonic stem cellD3 (D3 cells) to myocardial cells) were determined using real‐time quantitative polymerase chain reaction. In these studies, 5‐FUwas used as a positive control andPenGwas used as a negative control. The cytotoxicity of these drugs againstD3 cells and 3T3 fibroblasts was determined by the 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay. Embryotoxicity was classified according to the prediction model ofEST.

Results

At concentrations >800 μg/mLMEThad a greater cytotoxic effect onD3 cells than 3T3 fibroblasts. At the highest concentration ofMET(5 mg/mL), the cell viability ofD3 cells and 3T3 fibroblasts was <10% and >30%, respectively. The size of the embryonic body (EB) differentiation area was almost the same over the concentration range 50–200 μg/mLMET, and there was no significant difference inEBdifferentiation area until a concentration of 400 μg/mLMET. At a concentration of 800 μg/mLMET, the size ofEBoutgrowth was significantly reduced. The same assays revealedGLIM,RSG, andNIMto be weakly embryotoxic substances.

Conclusions

Based on theEST,METcan be classified as a weakly embryotoxic substance, which suggests that it should be prescribed with caution to pregnant women with gestational diabetes.
Carbon Price versus Subsidies to Reduce Greenhouse Gas Emissions
Authors: Freebairn John
Published: December 2014

This paper describes the operation of a price and a subsidy to reduce greenhouse gas emissions (GHG), and it compares and contrasts efficiency, redistribution and transactions costs of the two options. An initial comparison assumes comprehensive bases and negligible transaction costs. Then, actual examples for Australia are assessed, namely the carbon tax of 2012–2014 and the proposed Direct Action plan under consideration for 2015. It is argued that the price intervention option will be more cost effective per unit of GHG reduction, that it will be simpler and easier to operate, and that as part of a budget package it can provide at least as good a net distribution outcome.
Foreign Investment and Vertical Specialisation: Emerging Trends in Chinese Exports
Authors: Sharma Kishor , Wei Wang
Published: December 2014

This paper contributes to the debate about the role of foreign direct investment (FDI) in vertical specialisation inChinese exports. Globalisation of the world economy, together with well‐developed physical infrastructure, and falling costs of transport and communications, has led to a significant increase in foreign investment intoChina to take advantage of its comparative advantage in labour‐intensive activities. Initially, foreign investment came to simple assembly line (such as textile, clothing, electronic goods), but gradually,China attractedFDIto sophisticated manufacturing industries (such as, information and communications technology products, office and medical equipments etc.). AsChina became increasingly open following its accession to the World Trade Organisation, the share of vertical specialisation in its exports appears to have increased. Over one‐quarter ofChinese exports appears to be due to the expansion of back‐and‐forth transactions in vertically fragmented cross‐border production process, which has significant implications for policy formulation.
Purchasing Power Parity in African Countries: Evidence from the Sequential Panel Selection Method
Authors: Bahmani‐Oskooee Mohsen , Kones Alice , Chang Tsangyao
Published: December 2014

Application of new methodological advances to Africa either does not exist or is always with substantial delay, mostly due to lack of data. In this paper, we use the newly constructed real effective exchange rates of twenty African countries over the current floating rate period of 1971Q1–2012Q4 and test the well‐known Purchasing Power Parity (PPP) theory by applying Panel Kapitanios‐Shin‐Snell unit root test through the sequential panel selection method. This method classifies the whole panel into a group of stationary and non‐stationary series and hence identifies how many and which series in the panel are stationary processes. Our empirical results indicate that PPP holds only in three of twenty African countries under study.
Not so far away: a collaborative model of engaging refugee youth in the outreach of their digital stories
Authors: Luchs Michele , Miller Elizabeth
Published: December 2014

A majority of literature on participatory visual methodologies focuses on the creation stage of a project, but less is written about involving participants in the outreach phase. Drawing on the experience of collaborating with three refugee youth on a city‐wide school tour of their digital stories, this article explores the benefits and challenges of extending participatory processes beyond process and into outreach. ‘On Tour’ was the last phase of Mapping Memories, a five‐year Montreal‐based participatory media project with refugee youth. Through ten media workshops, the project reached out to over 150 youth, and offered them the chance to learn new media skills, reflect on their past experiences, work in collaborative contexts, strengthen their networks and express themselves creatively as they shaped their experiences into compelling digital stories, photo‐essays, mixed media collages, and even bus and walking tours. ‘On Tour’ was developed in the last year of the project to explore the impact of combining live presentations with digital stories to instigate peer‐to‐peer dialogue about stereotypes that frame refugees as victims, outsiders or ‘burdens to the system’. The outreach initiative permitted us to explore ethical and critical pedagogical frameworks when bringing digital stories into classrooms. We also had a chance to confront our assumptions regarding youth involvement in outreach and to explore the following questions: What ethical considerations need to be taken into account when bringing youth participants and their sensitive digital stories beyond process and into the realm of outreach? And what methods should be used to ensure that everyone involved benefits?
Trust, authentic pride, and moral reasoning: a unified framework of relational governance and emotional self‐regulation
Authors: Spraggon Martin , Bodolica Virginia
Published: December 2014

This conceptual article introduces behavioral perspectives into the governance arena and undertakes a psychological assessment of managerial decision making in organizations by elaborating on the treatment of trust and (authentic and hubristic) pride in the extant literature. While trust is conceived by governance scholars as a device for monitoring relationships with others, we argue that authentic pride, contrary to hubris, could operate as an attribute of emotional self‐regulation allowing corporate leaders to govern the social behavior of their own self. Contrasting the features of trust and authentic pride, we advance several propositions to capture their relevance and simultaneous importance as viable governance mechanisms in light of a manager's level of cognitive moral reasoning. Our study builds a unified theoretical framework of governance which integrates human agency, psychological states, and moral judgment to foster a deeper understanding of complex self‐regulatory processes that are activated by decision makers in the execution of their roles.
Biochemical, biological and structural properties of romidepsin (FK228) and its analogs as novel HDAC/PI3K dual inhibitors
Authors: Saijo Ken , Imamura Jin , Narita Koichi , Oda Akifumi , Shimodaira Hideki , Katoh Tadashi , Ishioka Chikashi
Published: December 2014

Romidepsin (FK228, depsipeptide) is a potent histone deacetylase (HDAC) inhibitor that has FDA approval for the treatment of cutaneous and peripheral T‐cell lymphomas. We have previously reported that FK228 and its analogs have an additional activity as phosphatidylinositol 3‐kinase (PI3K) inhibitors, and are defined as HDAC/PI3K dual inhibitors. Because a combination of an HDAC inhibitor and a PI3K inhibitor induces apoptosis in human cancer cells in a synergistic manner, development of an HDAC/PI3K dual inhibitor will provide an attractive novel drug for cancer therapy. Using structure‐based optimization of the analogs, FK‐A11 was identified as the most potent analog. FK‐A11 inhibited phosphorylation of AKT and accelerated histone acetylation at lower concentrations, resulting in stronger cytotoxic effects than FK228 and the other analogs in human cancer cells. In this study, we have characterized the biochemical, biological and structural properties of FK228 analogs as PI3K inhibitors. First, FK‐A11 is an ATP competitive PI3K inhibitor. Second, FK‐A11 is a pan‐p110 isoform inhibitor. Third, FK‐A11 selectively inhibits PI3K among 22 common cellular kinases. Fourth, conformational changes of FK228 analogs by reduction of an internal disulfide bond have no effect on PI3K inhibitory activity, unlike HDAC inhibitory activity. Finally, molecular modeling of PI3K‐FK228 analogs and analyses of the binding affinities identified the structure that defines potency for PI3K inhibitory activity. These results prove our concept that a series of FK228 analogs are HDAC/PI3K dual inhibitors. These findings should help in the development of FK228 analogs as novel HDAC/PI3K dual inhibitors.
Immunologically augmented skin flap as a novel dendritic cell vaccine against head and neck cancer in a rat model
Authors: Inoue Keita , Saegusa Noriko , Omiya Maho , Ashizawa Tadashi , Miyata Haruo , Komiyama Masaru , Iizuka Akira , Kume Akiko , Sugino Takashi , Yamaguchi Ken , Kiyohara Yoshio , Nakagawa Masahiro , Akiyama Yasuto
Published: December 2014

Local recurrence is a major clinical issue following surgical resection in head and neck cancer, and the dissemination and lymph node metastasis of minimal residual disease is relatively difficult to treat due to the lack of suitable therapeutic approaches. In the present study, we developed and evaluated a novel immunotherapy using a skin flap transfer treated with sensitized dendritic cells (DC), termed the “immuno‐flap,” in a rat tumor model. After the local round area of skin was resected, SCC‐158 cells (a rat head and neck cancer cell line) were inoculated into the muscle surface; lastly, the groin skin flap injected with mature DC was overlaid. Two weeks after the second DC injection, systemic immunological reactions and tumor size were measured. The DC‐treated group showed a significant reduction in tumor size compared with the control. Although the induction of CTL activity in spleen cells was marginal, Th1 cytokines such as interleukin‐2 and interferon‐γ were elevated in the DC‐treated group. These results suggest that a novel immunotherapy based on the immuno‐flap method has the potential for clinical application to prevent the local recurrence of head and neck cancer patients.
Disclosure of incidental findings in cancer genomic research: investigators' perceptions on obligations and barriers
Authors: Kleiderman E. , Avard D. , Besso A. , Ali‐Khan S. , Sauvageau G. , Hébert J.
Published: December 2014

Although there has been significant research surrounding incidental findings (IFs), the guidelines and information provided to investigators remain unspecific, unclear, and often generalize the course of action to everyone in the field. We explored the perceptions and experiences of investigators regarding the return of IFs in genetic research. Researchers and clinician‐researchers were invited to participate in semi‐structured telephone interviews in Quebec and Ontario. Twenty professionals participated, and thematic analysis was used to analyze the transcriptions. Four contextual elements emerged: (i) degree of significance of results, (ii) respect for persons, (iii) infrastructure implications, and (iv) professional responsibilities. Our findings demonstrate that all investigators raised similar contextual elements surrounding the return of IFs. However, some nuances in participants' experiences of the understanding of professional responsibilities also emerged. Because of the existing nuances, a one‐size‐fits‐all approach is inappropriate, suggesting that context ought to be considered in decisions about IFs.
Clinical predictors and time course of the improvement in β–cell function with short‐term intensive insulin therapy in patients with Type 2 diabetes
Authors: Stein C. M. , Kramer C. K. , Zinman B. , Choi H. , Opsteen C. , Retnakaran R.
Published: December 2014

Aims

In patients with Type 2 diabetes, a short course of intensive insulin therapy can improve β–cell function and even induce transient remission of diabetes. However, not all patients respond to this therapy. Although the achievement of fasting glucose  < 7.0 mmol/l one day after stopping intensive insulin therapy can identify patients in whom β–cell function has improved, we sought to determine clinical predictors for the early identification of such responders and the time course of response.

Methods

We pooled data from two studies in which 97 patients with Type 2 diabetes mellitus (median 3 years duration) and HbA1c 51 ± 8.7 mmol/mol (6.8 ± 0.8%) underwent 4–8 weeks of intensive insulin therapy, consisting of basal detemir and pre‐meal insulin aspart. They were classified as responders (n = 74) or non‐responders (n = 23), defined by the achievement of fasting glucose  < 7.0 mmol/l after stopping intensive insulin therapy.

Results

On logistic regression analyses, duration of diabetes (odds ratio [OR] = 0.72, 95% confidence interval [CI] 0.56–0.92, P = 0.009) and baseline fasting glucose (OR = 0.40, 95% CI 0.24–0.68, P = 0.001) emerged as predictors of the likelihood of responding. Ninety per cent of patients with duration ≤ 4 years and fasting glucose ≤ 8.0 mmol/l responded to intensive insulin therapy. Despite having lower glucose levels during intensive insulin therapy, responders had less hypoglycaemia than non‐responders (median 0.3 vs. 1.6 episodes/week, P < 0.0001), with rates of hypoglycaemia diverging sharply from the third week onwards.

Conclusion

At baseline, shorter duration of diabetes and lower fasting glucose can identify patients most likely to benefit from short‐term intensive insulin therapy. Most importantly, during therapy, responders had less hypoglycaemia from the third week onwards, despite lower glycaemia, suggesting that 2 weeks of intensive insulin therapy may be needed to improve endogenous islet function.
Necrostatin‐1 alleviates reperfusion injury following acute myocardial infarction in pigs
Authors: Koudstaal Stefan , Oerlemans Martinus I. F. J. , Van der Spoel Tycho I. G. , Janssen Aafke W. F. , Hoefer Imo E. , Doevendans Pieter A. , Sluijter Joost P. G. , Chamuleau Steven A. J.
Published: December 2014

Background

In rodents, it has previously been shown that necrostatin‐1 (Nec‐1) inhibits RIP1, a central regulator of programmed necrosis, thereby decreasing cell death and reducing infarct size (IS) after ischaemia/reperfusion (I/R) injury. To address unanswered questions on feasibility and efficacy of Nec‐1 in a large animal model, we assessed the effects of Nec‐1 in a porcine I/R model, relevant to human disease.

Materials and methods

In Dalland landrace pigs (69 ± 3 kg), I/R injury was induced by a 75‐min surgical ligation of the left circumflex coronary artery (LCx). Ten minutes prior to reperfusion, pigs were randomly allocated to different Nec‐1 doses (1·0 mg/kg or 3·3 mg/kg) or vehicle treatment (control, CTRL). Functional endpoints and immunohistological analyses were performed 24 h after reperfusion.

Results

Nec‐1 3·3 mg/kg significantly reduced IS (n = 6; 24·4 ± 15·6%) compared to Nec‐1 1·0 mg/kg (n = 5; 54·8 ± 16·9%) or CTRLs (n = 6; 62·1 ± 26·6%; P = 0·016). In line, LV ejection fraction (LVEF) was significantly higher in Nec‐1 3·3 mg/kg, compared to Nec‐1 1·0 mg/kg or CTRL treated animals (50·0 ± 12·0% vs. 32·5 ± 12·9% vs. 31·9 ± 6·6%, respectively, P = 0·015). Hemodynamically, a preserved contractility was observed [end‐systolic volume at 100 mmHg (ESV100)] at 24‐h follow‐up (87·6 ± 17·3 mL vs. 74·5 ± 41·1 mL vs. 56·8 ± 11·8 mL, respectively, P = 0·032), reflecting improved cardiac function.

Conclusions

In the pig model of I/R injury, intravenous administration of Nec‐1 prior to reperfusion was an effective and above all practical therapeutic strategy that significantly reduced IS and preserved left ventricular function. These data highlight the potential of cardioprotection as a promising adjuvant therapy in the setting of early reperfusion following I/R injury.
The confidence of undergraduate dental students when performing root canal treatment and their perception of the quality of endodontic education
Authors: Davey J. , Bryant S. T. , Dummer P. M. H.
Published: December 2014

Aim

This article aims to gain understanding into the perception of undergraduate dental students in terms of their confidence and competence at performing root canal treatment and their perception of the quality of endodontic education.

Methods

An online questionnaire was distributed to all 3rd, 4th and 5th year dental students at Cardiff University via their academic e‐mail addresses. The questionnaire utilised both scaled response and open questions to gain an insight into undergraduate opinion.

Results

Out of a possible 208 students, 98 responses were obtained (response rate = 47%). Perception of competence and confidence were significantly greater amongst the more senior year groups (P < 0.01). However, 49% (n = 38) of participants did not feel competent performing root canal treatment on anterior, single‐rooted teeth, whilst 74% (n = 70) did not feel competent performing root canal treatment on posterior, multirooted teeth. Free comments from participants indicated that this was due to a lack of clinical experience. Approximately, 80% of participants ranked education in endodontics at Cardiff University as ≤5 on a Likert scale (1 = inadequate to 10 = good), indicating that improvement was required. Improvements that were suggested by the students included the provision of further information within lectures, a broader range of lecturers, an increased number of shorter, more organised practical sessions, additional training equipment, greater supervision and online reference guides to root canal treatment.

Conclusion

Enhancing undergraduate education in endodontics is necessary to increase students' perception of their confidence and competence when performing root canal treatment.
Visual presentation of a medical physiology seminar modifies dental students' perception of its clinical significance
Authors: Vuletic L. , Spalj S. , Peros K.
Published: December 2014

Introduction

The primary objective of this study was to assess whether exposing dental students to visual stimuli related to dental profession during the medical physiology seminar could affect their perception of the clinical relevance of the topic.

Subjects and methods

A self‐administered questionnaire on attitudes towards medical physiology was conducted amongst 105 students of the School of Dental Medicine in Zagreb, Croatia, aged 19‐24 years (80% females) following a seminar on respiratory system physiology. Power‐point presentation accompanying the seminar for a total of 52 students (study group) was enriched with pictures related to dental practice in order to assess whether these pictures could make the topic appear more clinically relevant for a future dentist.

Results

The results of the survey indicated that dental students in the study group perceived the topic of the seminar as more important for them as future dentists when compared to the perception of the control group (P = 0.025).

Discussion and conclusion

The results of this survey encourage physiology lecturers to present medical physiology as clinically relevant for dental students whenever possible as this could increase students' interest in the subject and their motivation for learning. Such an approach could be particularly beneficial if there is a significant time gap between basic courses and involvement of students into clinical training for it could promote meaningful learning.
Cerebral malacia in a mule with ependymoma
Authors: Mendes de Cordova F. , Vaz Burns L. , Tony Ramos A. , Estevan Moron S. , Silva de Cordova C. A. , da Luz Silva G. M.
Published: December 2014

Ependymoma is a rare tumour of the central nervous system that can vary in anatomical location and produce a broad range of clinical signs. Sporadically described in dogs, cats, cattle and horses, this disease has never previously been reported in a mule. This report describes a case of a 12‐year‐old mule showing neurological signs, including blindness, dysphagia, incoordination, sternal recumbency, depression, apathy and emaciation. Because of the worsening health conditions, the animal was subjected to euthanasia for humane reasons. At necropsy, an area of malacia in the right subcortical region of the frontoparietal area of the cerebrum and an ovoid, firm, grey, 2.4 × 1.0 × 0.7 cm nodule in the right lateral ventricle was observed. Histopathology revealed that the nodule was a densely cellular mass with cells arranged in nests and cords, formations of pseudorosettes with perivascular deposition of fibrillar eosinophilic material and the presence of a few lymphocytes. The cells had rounded and moderately hyperchromatic nuclei, punctate chromatin, distinct nucleoli, and indistinct cytoplasmic margins. Based on the histopathological features, the nodule was diagnosed as an ependymoma, a tumour considered rare, but that may be included in the differential diagnosis for diseases with neurological signs.
Physicochemical and biological responses of streams to wildfire severity in riparian zones
Authors: Cooper Scott D. , Page Henry M. , Wiseman Sheila W. , Klose Kristie , Bennett Danuta , Even Thomas , Sadro Steven , Nelson Craig E. , Dudley Thomas L.
Published: December 2014

We investigated the effects of a wildfire on stream physical, chemical and biological characteristics in a Mediterranean climate, comparing stream community structure and consumer resource use in burned versus unburned catchments in Santa Barbara County, CA, U.S.A.

Canopy cover was lower and water temperature was higher in streams draining basins where the riparian vegetation burned than in streams in unburned basins or burned basins where riparian vegetation remained intact. Stream flow and suspended sediment concentrations during large post‐fire storms and wet season nutrient levels were higher in burned than unburned catchments, with increased sedimentation after flood peaks.

A year after fires, algal levels were highest in streams where riparian vegetation burned and lowest in streams in burned basins where the riparian canopy remained intact. In contrast, streams in burned basins had lower particulate organic matter, detritivore and predator levels than unburned basins, regardless of whether riparian vegetation burned. Where present, southern California steelhead trout (Oncorhynchus mykiss) were extirpated from burned basins.

Algivore densities were high in streams with burned riparian vegetation for two post‐fire years before declining to unburned stream levels. Shredder densities rebounded in streams in burned basins with intact riparian vegetation, but remained low for 4 years where riparian vegetation burned. Predatory invertebrate densities increased at sites where trout were eliminated by wildfire.

Hydrogen stable isotope analysis indicated that the diets of most invertebrate taxa in streams with burned riparian vegetation a year after fires were comprised of a higher proportion of algal material than riparian detritus relative to invertebrates in streams with intact riparian vegetation.

Wildfire impacts on stream food webs are determined, in part, by fire severity in the riparian zone. Streams with burned riparian canopies supported algal‐based food webs and streams with intact riparian canopies sustained detrital‐based food webs. Fire affected basal resources (nutrients, light, allochthonous inputs) with bottom‐up effects on primary producers and consumers, but top‐down effects were decoupled at the trophic link between invertebrate predators and primary consumers.
Restaging “Degenerate Art”: The Politics of Memory in the Berlin Sculpture Find Exhibit
Authors: Itkin Alan Joshua
Published: December 2014

In January of 2010, excavations near the Rotes Rathaus in Berlin yielded a surprising discovery: workers unearthed a cache of sculptures stored in a forgotten depot of the Nazi Reichspropagandaministerium. Although these sculptures, damaged during the aerial bombardment of Berlin, recalled ancient artifacts, they were actually among those works of modern art censored as “degenerate art” by the Nazis. In this article, I examine the subsequent exhibition of these sculptures in the Neues Museum and explore the place of so‐calledentartete Kunstand the classical collections of Berlin within the cultural landscape of contemporary Germany. Through the juxtaposition ofentartete Kunstwith classical artifacts, the curators of the “Berliner Skupturenfund” exhibit project an art historical narrative that allows visitors to seeentartete Kunstin a new light. At the same time, they obscure the long and troubling history of classical appropriation, which played a large part in the Nazi campaign to censor modern art as “degenerate.”
Humboldt and the Monkeys: On the Friend‐Food Distinction
Authors: Buhanan Kurt
Published: December 2014

In this essay, I argue that the image of cannibalism in Alexander von Humboldt's Personal Narrative operates as a multistable image, an ideologically charged biopicture. The argument proceeds through three stages: first, I contextualize the cannibal as a stock image in Western thought, one that Humboldt inherits even before his journey to South America. Second, I examine this over‐determined image, a veritable fixation in the European imaginary, against the claim advanced in recent Humboldt scholarship that he “took the novel step” of asking the cannibals to speak for themselves. Finally, I propose a reading of Humboldt's image of cannibalism as a politically charged picture of social relations, which simultaneously resists and reproduces the ideologically structured representation of indigenous peoples that Humboldt attempts to subvert.
Importance of the monomer–dimer–tetramer interconversion of the clock protein KaiB in the generation of circadian oscillations in cyanobacteria
Authors: Iida Takahiro , Mutoh Risa , Onai Kiyoshi , Morishita Megumi , Furukawa Yukio , Namba Keiichi , Ishiura Masahiro
Published: December 2014

The molecular machinery of the cyanobacterial circadian clock oscillator consists of three proteins, KaiA, KaiB and KaiC, which interact with each other to generate circadian oscillations in the presence of ATP (the in vitro KaiABC clock oscillator). KaiB comprises four subunits organized as a dimer of dimers. Our previous study suggested that, on interaction with KaiC, the tetrameric KaiB molecule dissociates into two molecules of dimeric KaiB. It is uncertain whether KaiB also exists as a monomer and whether the KaiB monomer can drive normal circadian oscillation. To address these questions, we constructed a new KaiB oligomer mutant with an N‐terminal deletion, KaiB10–108. KaiB10–108 was a monomer at 4 °C but a dimer at 35 °C. KaiB10–108 was able to drive normal clock oscillation in an in vitro reconstituted KaiABC clock oscillator at 25 °C, but it was not able to drive normal circadian gene expression rhythms in cyanobacterial cells at 41 °C. Wild‐type KaiB existed in equilibrium between a dimer and tetramer at lower KaiB concentrations or in the presence of 1 m NaCl. Our findings suggest that KaiB is in equilibrium between a monomer, dimer and tetramer in cyanobacterial cells.