bluuebunny/crossref_metadata_2025 huggingface dataset:
Community Ecology Perspectives on the Structural and Functional Evolution of Consumer Electronics
Authors: Ryen Erinn G. , Babbitt Callie W. , Tyler Anna Christina , Babbitt Gregory A.
Published: April 2014

This article describes how biological ecology models are adapted to analyze the dynamic structure and function of a consumer electronic product “community.” Treating an entire group of interdependent and continually evolving electronic devices as an ecological community provides a basis for more comprehensive analyses of the energy, material, and waste flows associated with household consumption than would be possible using conventional per product approaches. Results show that, similar to a maturing natural community, the average U.S. household electronic product community evolved from a low‐diversity structure dominated by a few products to a highly diverse, evenly distributed community of products between 1990 and 2010. The maturing community of household electronics experienced increased functionality at a community and product level resulting, in part, from introduction of new products, but primarily as a result of increasing ownership of multifunctional products. Multifunctional mobile products are driving increased functionality in a manner similar to a broadly adaptive invasive species, but the community's high functional redundancy, as the result of device convergence, resembles a stable natural community. These results suggest that future strategies to encourage green design, production, and consumption of consumer electronics should focus on minimizing the total number of products owned by maximizing multifunctionality with convergent device design.
Knowledge exchange and integrated services: experiences from an integrated community intellectual (learning) disability service for adults
Authors: Farrington C. , Clare I. C. H. , Holland A. J. , Barrett M. , Oborn E.
Published: April 2014

Background

This paper examines knowledge exchange dynamics in a specialist integrated intellectual (learning) disability service, comprising specialist healthcare provision with social care commissioning and management, and considers their significance in terms of integrated service delivery.

Methods

A qualitative study focusing on knowledge exchange and integrated services. Semi‐structured interviews (n = 25) were conducted with members of an integrated intellectual disability service in England regarding their perceptions of knowledge exchange within the service and the way in which knowledge exchange impinges on the operation of the integrated service.

Results

Exchange of ‘explicit’ (codifiable) knowledge between health and care management components of the service is problematic because of a lack of integrated clinical governance and related factors such as IT and care record systems and office arrangements. Team meetings and workplace interactions allowed for informal exchange of explicit and ‘tacit’ (non‐codifiable) knowledge, but presented challenges in terms of knowledge exchange completeness and sustainability.

Conclusions

Knowledge exchange processes play an important role in the functioning of integrated services incorporating health and care management components. Managers need to ensure that knowledge exchange processes facilitate both explicit and tacit knowledge exchange and do not rely excessively on informal, ‘ad hoc’ interactions. Research on integrated services should take account of micro‐scale knowledge exchange dynamics and relationships between social dynamics and physical factors.
Men with intellectual disabilities with a history of sexual offending: empathy for victims of sexual and non‐sexual crimes
Authors: Hockley O. J. , Langdon P. E.
Published: April 2014

Background

The objectives were (a) to compare the general empathy abilities of men with intellectual disabilities (IDs) who had a history of sexual offending to men withIDswho had no known history of illegal behaviour; and (b) to determine whether men withIDswho had a history of sexual offending had different levels of specific victim empathy towards their own victim, in comparison with an unknown victim of sexual crime, and a victim of non‐sexual crime, and make comparisons with non‐offenders.

Methods

Men with mildIDs(n = 35) were asked to complete a measure of general empathy and a measure of specific victim empathy. All participants completed the victim empathy measure in relation to a hypothetical victim of a sexual offence, and a non‐sexual crime, while additionally, men with a history of sexual offending were asked to complete this measure in relation to their own most recent victim.

Results

Men with a history of sexual offending had significantly lower general empathy, and specific victim empathy towards an unknown sexual offence victim, than men with no known history of illegal behaviour. Men with a history of sexual offending had significantly lower victim empathy for their own victim than for an unknown sexual offence victim. Victim empathy towards an unknown victim of a non‐sexual crime did not differ significantly between the two groups.

Conclusions

The findings suggest that it is important include interventions within treatment programmes that attempt to improve empathy and perspective‐taking.
Peptidylarginine deiminases: novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates
Authors: Lange Sigrun , Rocha‐Ferreira Eridan , Thei Laura , Mawjee Priyanka , Bennett Kate , Thompson Paul R. , Subramanian Venkataraman , Nicholas Anthony P. , Peebles Donald , Hristova Mariya , Raivich Gennadij
Published: April 2014

Neonatal hypoxic ischaemic (HI) injury frequently causes neural impairment in surviving infants. Our knowledge of the underlying molecular mechanisms is still limited. Protein deimination is a post‐translational modification caused by Ca+2‐regulated peptidylarginine deiminases (PADs), a group of five isozymes that display tissue‐specific expression and different preference for target proteins. Protein deimination results in altered protein conformation and function of target proteins, and is associated with neurodegenerative diseases, gene regulation and autoimmunity. In this study, we used the neonatal HI and HI/infection [lipopolysaccharide (LPS) stimulation] murine models to investigate changes in protein deimination. Brains showed increases in deiminated proteins, cell death, activated microglia and neuronal loss in affected brain areas at 48 h after hypoxic ischaemic insult. Upon treatment with the pan‐PAD inhibitor Cl‐amidine, a significant reduction was seen in microglial activation, cell death and infarct size compared with control saline or LPS‐treated animals. Deimination of histone 3, a target protein of the PAD4 isozyme, was increased in hippocampus and cortex specifically upon LPS stimulation and markedly reduced following Cl‐amidine treatment. Here, we demonstrate a novel role for PAD enzymes in neural impairment in neonatal HI Encephalopathy, highlighting their role as promising new candidates for drug‐directed intervention in neurotrauma.

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Hypoxic Ischaemic Insult (HI) results in activation of peptidylarginine deiminases (PADs) because of calcium dysregulation. Target proteins undergo irreversible changes of protein bound arginine to citrulline, resulting in protein misfolding. Infection in synergy with HI causes up‐regulation of TNFα, nuclear translocation of PAD4 and change in gene regulation as a result of histone deimination. Pharmacological PAD inhibition significantly reduced HI brain damage.
The effect of Cyclin‐dependent kinase 5 on voltage‐dependent calcium channels in PC12 cells varies according to channel type and cell differentiation state
Authors: Furusawa Kotaro , Asada Akiko , Saito Taro , Hisanaga Shin‐ichi
Published: April 2014

Cyclin‐dependent kinase 5 (Cdk5) is a Ser/Thr kinase that plays an important role in the release of neurotransmitter from pre‐synaptic terminals triggered by Ca2+ influx into the pre‐synaptic cytoplasm through voltage‐dependent Ca2+ channels (VDCCs). It is reported that Cdk5 regulates L‐, P/Q‐, or N‐type VDCC, but there is conflicting data as to the effect of Cdk5 on VDCC activity. To clarify the mechanisms involved, we examined the role of Cdk5 in regulating the Ca2+‐channel property of VDCCs, using PC12 cells expressing endogenous, functional L‐, P/Q‐, and N‐type VDCCs. The Ca2+ influx, induced by membrane depolarization with high K+, was monitored with a fluorescent Ca2+ indicator protein in both undifferentiated and nerve growth factor (NGF)‐differentiated PC12 cells. Overall, Ca2+ influx was increased by expression of Cdk5‐p35 in undifferentiated PC12 cells but suppressed in differentiated PC12 cells. Moreover, we found that different VDCCs are distinctly regulated by Cdk5‐p35 depending on the differentiation states of PC12 cells. These results indicate that Cdk5‐p35 regulates L‐, P/Q‐, or N‐type VDCCs in a cellular context‐dependent manner.

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Calcium (Ca2+) influx through voltage‐dependent Ca2+ channels (VDCCs) triggers neurotransmitter release from pre‐synaptic terminal of neurons. The channel activity of VDCCs is regulated by Cdk5‐p35, a neuronal Ser/Thr kinase. However, there have been debates about the regulation of VDCCs by Cdk5. Using PC12 cells, we show that Cdk5‐p35 regulates VDCCs in a type (L, P/Q, and N) and differentiation‐dependent manner. NGF = nerve growth factor.
Pre‐treatment with the synthetic antioxidant T‐butyl bisphenol protects cerebral tissues from experimental ischemia reperfusion injury
Authors: Duong Thi Thuy Hong , Chami Belal , McMahon Aisling C. , Fong Genevieve M. , Dennis Joanne M. , Freedman Saul B. , Witting Paul K.
Published: April 2014

Treatments to inhibit or repair neuronal cell damage sustained during focal ischemia/reperfusion injury in stroke are largely unavailable. We demonstrate that dietary supplementation with the antioxidant di‐tert‐butyl‐bisphenol (BP) before injury decreases infarction and vascular complications in experimental stroke in an animal model. We confirm that BP, a synthetic polyphenol with superior radical‐scavenging activity than vitamin E, crosses the blood–brain barrier and accumulates in rat brain. Supplementation with BP did not affect blood pressure or endogenous vitamin E levels in plasma or cerebral tissue. Pre‐treatment with BP significantly lowered lipid, protein and thiol oxidation and decreased infarct size in animals subjected to middle cerebral artery occlusion (2 h) and reperfusion (24 h) injury. This neuroprotective action was accompanied by down‐regulation of hypoxia inducible factor‐1α and glucose transporter‐1 mRNA levels, maintenance of neuronal tissue ATP concentration and inhibition of pro‐apoptotic factors that together enhanced cerebral tissue viability after injury. That pre‐treatment with BP ameliorates oxidative damage and preserves cerebral tissue during focal ischemic insult indicates that oxidative stress plays at least some causal role in promoting tissue damage in experimental stroke. The data strongly suggest that inhibition of oxidative stress through BP scavenging free radicals in vivo contributes significantly to neuroprotection.

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We demonstrate that pre‐treatment with ditert‐butyl bisphenol(Di‐t‐Bu‐BP) inhibits lipid, protein, and total thiol oxidation and decreases caspase activation and infarct size in rats subjected to middle cerebral artery occlusion (2 h) and reperfusion (24 h) injury. These data suggest that inhibition of oxidative stress contributes significantly to neuroprotection.
Microglia are Selectively Activated in Endocrine and Cardiovascular Control Centres in Streptozotocin‐Induced Diabetic Rats
Authors: Rana I. , Badoer E. , Alahmadi E. , Leo C. H. , Woodman O. L. , Stebbing M. J.
Published: April 2014

Type 1 and 2 diabetes are associated with dysfunction in multiple hormone systems, as well as increased sympathetic nerve activity, which may contribute to the development of diabetic complications. In other pathologies, such as myocardial infarction, increased sympathetic drive is associated with neuroinflammation and microglial activation in the hypothalamic paraventricular nucleus (PVN), a brain region that regulates sympathetic drive and multiple endocrine responses. In the present study, we used immunohistochemistry to study microglial and neuronal activation in the PVN and related brain regions in streptozotocin (STZ)‐induced diabetic rats. As expected, STZ treatment was associated with elevated blood glucose within 1 week. STZ injections also caused neuronal activation in the PVN and superoptic nucleus (SON) but not in the nucleus tractus solitarius (NTS), which was evident by 6 weeks. STZ‐treated rats showed increased plasma osmolarity, which would be expected to activate PVN and SON neurones. There was no apparent increase in histochemical markers of microglial activation, including phospho‐p38, phospho‐extracellular signal regulated kinase, P2X4 receptor or interleukin 1‐β even at 10 weeks after STZ‐treatment. However, we did see a significant increase in the percentage of microglia with an activated morphology in the PVN, SON and NTS, although not in surrounding hypothalamic, brainstem or cortical regions. These morphological changes included a significant reduction in microglial process length and were evident by 8 weeks but not 6 weeks. The delayed onset of microglial changes compared to neuronal activation in the PVN and SON suggests the over‐excitation of neurones as a mechanism of microglial activation. This delayed microglial activation may, in turn, contribute to the endocrine dysregulation and the elevated sympathetic nerve activity reported in STZ‐treated rats.
Periosteal PTHrP regulates cortical bone modeling during linear growth in mice
Authors: Wang Meina , VanHouten Joshua N. , Nasiri Ali R. , Tommasini Steven M. , Broadus Arthur E.
Published: April 2014

The modeling of long bone surfaces during linear growth is a key developmental process, but its regulation is poorly understood. We report here that parathyroid hormone‐related peptide (PTHrP) expressed in the fibrous layer of the periosteum (PO) drives the osteoclastic (OC) resorption that models the metaphyseal–diaphyseal junction (MDJ) in the proximal tibia and fibula during linear growth. PTHrP was conditionally deleted (cKO) in the PO via Scleraxis gene targeting (Scx‐Cre). In the lateral tibia, cKO of PTHrP led to a failure of modeling, such that the normal concave MDJ was replaced by a mound‐like deformity. This was accompanied by a failure to induce receptor activator of NF‐kB ligand (RANKL) and a 75% reduction in OC number (P ≤ 0.001) on the cortical surface. The MDJ also displayed a curious threefold increase in endocortical osteoblast mineral apposition rate (P ≤ 0.001) and a thickened cortex, suggesting some form of coupling of endocortical bone formation to events on the PO surface. Because it fuses distally, the fibula is modeled only proximally and does so at an extraordinary rate, with an anteromedial cortex in CD‐1 mice that was so moth‐eaten that a clear PO surface could not be identified. The cKO fibula displayed a remarkable phenotype, with a misshapen club‐like metaphysis and an enlargement in the 3D size of the entire bone, manifest as a 40–45% increase in the PO circumference at the MDJ (P ≤ 0.001) as well as the mid‐diaphysis (P ≤ 0.001). These tibial and fibular phenotypes were reproduced in a Scx‐Cre‐driven RANKL cKO mouse. We conclude that PTHrP in the fibrous PO mediates the modeling of the MDJ of long bones during linear growth, and that in a highly susceptible system such as the fibula this surface modeling defines the size and shape of the entire bone.
Soft tissue influence onex vivomobility in the hip ofIguana: comparison within vivomovement and its bearing on joint motion of fossil sprawling tetrapods
Authors: Arnold Patrick , Fischer Martin S. , Nyakatura John A.
Published: April 2014

The reconstruction of a joint's maximum range of mobility (ROM) often is a first step when trying to understand the locomotion of fossil tetrapods. But previous studies suggest that theROMof a joint is restricted by soft tissues surrounding the joint. To expand the limited informative value ofROMstudies for the reconstruction of a fossil species’ locomotor characteristics, it is moreover necessary to better understand the relationship ofex vivoROMwith the actualin vivojoint movement. To gain insight into the relationship betweenex vivomobility andin vivomovement, we systematically tested for the influence of soft tissues on jointROMin the hip of the modern lizardIguana iguana. Then, we compared theex vivomobility toin vivokinematics of the hip joint in the same specimens using X‐ray sequences of steady‐state treadmill locomotion previously recorded. With stepwise removal of soft tissues and a repeated‐measurement protocol, we show that soft tissues surrounding the hip joint considerably limitROM, highlighting the problems when jointROMis deduced from bare bones only. We found the integument to have the largest effect on the range of long‐axis rotation, pro‐ and retraction. Importantly, during locomotion the iguana used only a fragment of theROMthat was measured in our least restrictive dissection situation (i.e. pelvis and femur only conjoined by ligaments), demonstrating the discrepancy between hip jointROMand actualin vivomovement. Our study emphasizes the necessity for caution when attempting to reconstruct jointROMor even locomotor kinematics from fossil bones only, as actualin vivomovement cannot be deduced directly from any condition of cadaver mobility inIguanaand likely in other tetrapods.
Influence of fossoriality on inner ear morphology: insights from caecilian amphibians
Authors: Maddin Hillary C. , Sherratt Emma
Published: April 2014

It is widely accepted that a relationship exists between inner ear morphology and functional aspects of an animal's biology, such as locomotor behaviour. Animals that engage in agile and spatially complex behaviours possess semicircular canals that morphologically maximise sensitivity to correspondingly complex physical stimuli. Stemming from the prediction that fossorial tetrapods require a well‐developed sense of spatial awareness, we investigate the hypothesis that fossoriality leads to inner ear morphology that is convergent with other spatially adept tetrapods. We apply morphometrics to otic capsule endocasts of 26 caecilian species to quantify aspects of inner ear shape, and compare these with a sample of frog and salamander species. Our results reveal caecilians (and also frogs) possess strongly curved canals, a feature in common with spatially adept species. However, significantly shorter canals in caecilians suggest reduced sensitivity, possibly associated with reduced reliance on vestibulo‐ocular reflexes in this group of visually degenerate tetrapods. An elaboration of the sacculus of caecilians is interpreted as a unique adaptation among amphibians to increase sensitivity to substrate‐borne vibrations transmitted through the head. This study represents the first quantitative analyses of inner ear morphology of limbless fossorial tetrapods, and identifies features within a new behavioural context that will contribute to our understanding of the biological consequences of physical stimuli on sensory function and associated morphological evolution.
Bruxism and genetics: a review of the literature
Authors: Lobbezoo F. , Visscher C. M. , Ahlberg J. , Manfredini D.
Published: April 2014

People who suffer from bruxism (teeth‐grinding) often ask their dentists whether their condition is hereditary. The purpose of this study is to enable dentists to provide an ‘evidence‐based’ answer to this question. The biomedical literature was searched using PubMed, and 32 publications were identified, of which nine proved relevant to the research question. The references cited by the publications identified yielded one further publication, bringing the total number of publications included in the analysis to 10. Four publications related to family studies, five related to twin studies and one related to a DNA analysis. With the exception of one of the twin studies, all the included studies concluded that bruxism appears to be (in part) genetically determined. Dentists whose patients ask them about bruxism can therefore tell them that teeth‐grinding does indeed ‘run in families’.
Immunohistochemical assessment of ATG7, LC3, and p62 in ameloblastomas
Authors: Okada Miwa , Oikawa Mariko , Miki Yasuhiro , Shimizu Yoshinaka , Echigo Seishi , Takahashi Tetsu , Kumamoto Hiroyuki
Published: April 2014

Background

To investigate the roles of autophagy in tumorigenesis, cytodifferentiation, and prognosis of odontogenic tumors, we analyzed the immunohistochemical expression of ATG7, LC3, and p62 in odontogenic tissues.

Methods

Tissue specimens of nine dental follicles and 69 ameloblastomas were immunohistochemically examined with antibodies against ATG7, LC3, and p62.

Results

Immunohistochemical reactivity for ATG7, LC3, and p62 was detected in many odontogenic epithelial cells and several endothelial cells and fibroblasts in dental follicles and ameloblastomas. ATG7 reactivity in ameloblatomas was significantly higher than that in dental follicles. Expression of ATG7, LC3, and p62 was found markedly in neoplastic cells near the basement membrane rather than central polyhedral cells in ameloblastomas. Reactivity for these molecules was significantly higher in unicystic ameloblastomas than in solid ameloblastomas. Granular cells in granular cell ameloblastomas showed obvious reactivity for the autophagy‐ related molecules, and LC3 reactivity in granular cell ameloblastomas was significantly higher than in other ameloblastoma variations. Recurrent ameloblastomas showed significantly lower reactivity of LC3 and p62 than primary ameloblastomas.

Conclusions

Expression of ATG7, LC3, and p62 in dental follicles and ameloblastomas suggests that autophagy regulation might be affected by microenvironment alterations during tumorigenesis. The molecular machinery for autophagy is possibly involved in tissue architecture, neoplastic cell differentiation, and prognosis of the benign epithelial odontogenic tumor.
Frequent hypermethylation of WNT pathway genes in laryngeal squamous cell carcinomas
Authors: Paluszczak Jarosław , Hemmerling Dawid , Kostrzewska‐Poczekaj Magdalena , Jarmuż‐Szymczak Małgorzata , Grenman Reidar , Wierzbicka Małgorzata , Baer‐Dubowska Wanda
Published: April 2014

Background

Aberrations in the function of the WNT signaling pathway have been recently implicated in the pathogenesis of head and neck cancer, and the hypermethylation of several WNT cascade inhibitors were shown to be useful in disease prognosis. However, the extent of deregulation of WNT pathway by DNA hypermethylation has not been studied in detail in laryngeal cancer so far. The aim of this study was to establish the frequency of methylation of WNT pathway negative regulators in laryngeal squamous cell carcinomas and evaluate its prognostic significance.

Methods

Twenty‐six laryngeal squamous cell carcinoma cell lines and samples obtained from twenty‐eight primary laryngeal carcinoma patients were analyzed. The methylation status of DKK1, LKB1, PPP2R2B, RUNX3, SFRP1, SFRP2, and WIF‐1 was assessed using the methylation‐specific polymerase chain reaction.

Results

Frequent hypermethylation of DKK1, PPP2R2B, SFRP1, SFRP2, and WIF‐1 was detected, and a high methylation index was usually observed. Half of the cell lines analyzed and seventy percent of primary laryngeal carcinoma cases were characterized by the methylation of at least four genes. The hypermethylation of PPP2R2B or WIF‐1 was associated with longer survival in laryngeal carcinoma cell lines. Moreover, the concurrent methylation of PPP2R2B and SFRP1 differentiated primary from recurrent laryngeal carcinoma cell lines.

Conclusions

Frequent hypermethylation of WNT pathway negative regulators is observed in laryngeal squamous cell carcinomas. The possible prognostic significance of the methylation of DKK1, PPP2R2B, and SFRP1 needs to be evaluated in further prospective studies.
Zoledronic acid and geranylgeraniol regulate cellular behaviour and angiogenic gene expression in human gingival fibroblasts
Authors: Zafar S. , Coates D. E. , Cullinan M. P. , Drummond B. K. , Milne T. , Seymour G. J.
Published: April 2014

The mevalonate pathway (MVP) and the anti‐angiogenic effect of bisphosphonates have been shown to play a role in the pathogenesis of bisphosphonate‐related osteonecrosis of the jaw (BRONJ). This study determined the effect of the bisphosphonate, zoledronic acid and the replenishment of the MVP by geranylgeraniol on human gingival fibroblasts. Cell viability, apoptosis, morphological analysis using transmission electron microscopy, and gene expression for vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B, epiregulin and interferon‐alpha were conducted. Results showed cellular viability was decreased in the presence of zoledronic acid and the co‐addition of zoledronic acid with geranylgeraniol restored cell viability to control levels. Caspase 3/7 was detected in zoledronic‐acid‐treated cells indicating apoptosis. Transmission electron microscopy revealed dilation of the rough endoplasmic reticulum with zoledronic acid and the appearance of multiple lipid‐like vesicles following the addition of geranylgeraniol. Zoledronic acid significantly (P < 0.05, FR > ±2) up‐regulated vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B and epiregulin at one or more time points but not interferon‐alpha. Addition of geranylgeraniol resulted in a reduction in the expression of all five genes compared with zoledronic‐acid‐treated human gingival fibroblasts. The study concluded geranylgeraniol partially reversed the effects of zoledronic acid in human gingival fibroblasts both at the cellular and genetic levels, suggesting the regulation of these genes is mediated via the mevalonate pathway.
Arecoline is cytotoxic for human endothelial cells
Authors: Ullah Mafaz , Cox Stephen , Kelly Elizabeth , Boadle Ross , Zoellner Hans
Published: April 2014

Background

Oral submucous fibrosis is a pre‐malignant fibrotic condition caused by areca nut use and involves reduced mucosal vascularity. Arecoline is the principal areca nut alkaloid and is cytotoxic for epithelium and fibroblasts. Endothelial cell cycle arrest is reported on exposure to arecoline, as is cytotoxicity for endothelial–lung carcinoma hybrid cells. We here describe cytotoxicity for primary human endothelial cultures from seven separate donors.

Materials and methods

Human umbilical vein endothelial cells were exposed to increasing concentrations of arecoline and examined by: phase‐contrast microscopy, haemocytometer counts, transmission electron microscopy, lactate dehydrogenase release and the methyl‐thiazol‐tetrazolium assay.

Results

Vacuolation and detachment of endothelium were observed at and above arecoline concentrations of 333 μg/ml or more. Ultrastructural features of cellular stress were seen after 24‐h treatment with 111 μg/ml arecoline and included reduced ribosomal studding of endoplasmic reticulum, increased autophagolysosomal structures, increased vacuolation and reduced mitochondrial cristae with slight swelling. Similar changes were seen at 4 h with arecoline at 333 μg/ml or above, but with more severe mitochondrial changes including increased electron density of mitochondrial matrix and greater cristal swelling, while by 24 h, these cells were frankly necrotic. Haemocytometer counts were paralleled by both lactate dehydrogenase release and the methyl‐thiazol‐tetrazolium assays.

Conclusions

Arecoline is cytotoxic via necrosis for endothelium, while biochemical assays indicate no appreciable cellular leakage before death and detachment, as well as no clear effect on mitochondrial function in viable cells. Arecoline toxicity may thus contribute to reduced vascularity in oral submucous fibrosis.
Alcohol withdrawal alleviates adipose tissue inflammation in patients with alcoholic liver disease
Authors: Voican Cosmin S. , Njiké‐Nakseu Micheline , Boujedidi Hédia , Barri‐Ova Nadège , Bouchet‐Delbos Laurence , Agostini Hélène , Maitre Sophie , Prévot Sophie , Cassard‐Doulcier Anne‐Marie , Naveau Sylvie , Perlemuter Gabriel
Published: April 2014

Background & Aims

Patients with alcoholic liver disease (ALD) display inflammation of the subcutaneous adipose tissue (SAT) which correlates with liver lesions. We examined macrophage markers and polarization in the SAT of alcoholic patients and adipokine expression according to liver inflammation; we studied the consequences of alcohol withdrawal.

Patients and methods

Forty‐seven patients with ALD were prospectively included. SAT and blood samples were collected at inclusion and after 1 week of alcohol withdrawal. Pro‐inflammatory cytokines/chemokines, inflammasome components and products, adipokine expression levels, macrophage markers and polarization in liver and SAT samples were assessed by RT‐PCR arrays.

Results

mRNA expression level of chemokines (IL8, semaphorin 7A) correlated with hepatic steatosis in both liver and SAT. Liver expression of inflammasome components (IL1β, IL18, caspase‐1) and SAT IL6 and CCL2 correlated with liver damage. In patients with mild ALD, 1 week of alcohol withdrawal was sufficient to decrease expression level of total macrophage markers in the adipose tissue, to orient adipose tissue macrophages (ATM) towards an anti‐inflammatory M2 phenotype and to decrease the mRNA expression of cytokines/chemokines (IL18, CCL2, osteopontin, semaphorin 7A). In patients with severe ALD, 1 week of abstinence was also associated with an increase in CCL18 expression.

Conclusions

In alcoholic patients, upregulation of chemotactic factors in the liver and SAT is an early event that begins as early as the steatosis stage. The inflammasome pathway is upregulated in the liver of patients with ALD. One week of alcohol withdrawal alleviates macrophage infiltration in SAT and orients ATM towards a M2 anti‐inflammatory phenotype; this implicates alcohol in adipose tissue inflammation (ClinicalTrials.gov NCT00388323).
Cirrhosis regression in hepatitis C patients with sustained virological response after antiviral therapy: a meta‐analysis
Authors: Akhtar Ehsaan , Manne Vignan , Saab Sammy
Published: April 2014

Background & Aims

Chronic hepatitis C may be associated with cirrhosis, liver failure and hepatocellular carcinoma. Studies have demonstrated improved clinical outcome in patients who achieved a sustained viral response (SVR).

Methods

A systematic literature search was performed to identify studies that assessed the association between SVR and cirrhosis regression. The main outcome studied was cirrhosis regression in patients with a SVR as compared with patients without a SVR. Six studies totalling 443 patients were included. Dichotomous outcomes were reported as risk ratios (RR) with 95% confidence intervals (CI).

Results

Of the 443 patients with cirrhosis, 137 achieved a SVR. Of these 137 patients who achieved an SVR, 73 (53%) patients had regression of cirrhosis. The risk ratio of cirrhosis regression was 2.69 [Confidence Interval (CI) 1.45–4.97, P < 0.01] in patients who achieved a SVR. The risk of cirrhosis regression was consistently in favour of patients who achieved a SVR regardless of the length of the biopsy or whether the biopsy was reviewed by a single or multiple pathologists. The risk ratio of cirrhosis regression was related to the duration of follow‐up between biopsies. The relative risk for regression of cirrhosis in studies in which the mean or median time for the follow‐up liver biopsy was greater than 36‐month was 4.33 (CI 1.1–17.0, P = 0.04) as compared to a relative risk of 1.79 (CI 1.26–2.29, P < 0.01) in studies with a mean or median time between the follow‐up biopsy of less than 36‐month.

Conclusions

Our results suggest that the majority of patients with cirrhosis who achieve a SVR develop cirrhosis regression. Time between biopsies appears to be an important determinant of the likelihood of cirrhosis regression.
Molecular mechanisms controlling the phenotype and the EMT/MET dynamics of hepatocyte
Authors: Cicchini Carla , Amicone Laura , Alonzi Tonino , Marchetti Alessandra , Mancone Carmine , Tripodi Marco
Published: April 2014

The complex spatial and paracrine relationships between the various liver histotypes are essential for proper functioning of the hepatic parenchymal cells. Only within a correct tissue organization, in fact, they stably maintain their identity and differentiated phenotype. The loss of histotype identity, which invariably occurs in the primary hepatocytes in culture, or in vivo in particular pathological conditions (fibrosis and tumours), is mainly because of the phenomenon of epithelial‐to‐mesenchymal transition (EMT). The EMT process, that occurs in the many epithelial cells, appears to be driven by a number of general, non‐tissue‐specific, master transcriptional regulators. The reverse process, the mesenchymal‐to‐epithelial transition (MET), as yet much less characterized at a molecular level, restores specific epithelial identities, and thus must include tissue‐specific master elements. In this review, we will summarize the so far unveiled events of EMT/MET occurring in liver cells. In particular, we will focus on hepatocyte and describe the pivotal role in the control of EMT/MET dynamics exerted by a tissue‐specific molecular mini‐circuitry. Recent evidence, indeed, highlighted as two transcriptional factors, the master gene of EMT Snail, and the master gene of hepatocyte differentiation HNF4α, exhorting a direct reciprocal repression, act as pivotal elements in determining opposite cellular outcomes. The different balances between these two master regulators, further integrated by specific microRNAs, in fact, were found responsible for the EMT/METs dynamics as well as for the preservation of both hepatocyte and stem/precursor cells identity and differentiation. Overall, these findings impact the maintenance of stem cells and differentiated cells both in in vivo EMT/MET physio‐pathological processes as well as in culture.
Divergent transcriptional responses to low temperature among populations of alpine and lowland species of New Zealand stick insects (Micrarchus)
Authors: Dunning Luke T. , Dennis Alice B. , Sinclair Brent J. , Newcomb Richard D. , Buckley Thomas R.
Published: April 2014

In widespread and genetically structured populations, temperature variation may lead to among‐population differentiation of thermal biology. The New Zealand stick insect genus Micrarchus contains four species that inhabit different thermal environments, two of which are geographically widespread. RNA‐Seq and quantitative PCR were used to investigate the transcriptional responses to cold shock among lowland and alpine species to identify cold‐responsive transcripts that differ between the species and to determine whether there is intraspecific geographical variation in gene expression. We also used mitochondrial DNA, nuclear 28S ribosomal DNA and transcriptome‐wide SNPs to determine phylogeographic structure and the potential for differences in genetic backgrounds to contribute to variation in gene expression. RNA‐Seq identified 2160 unigenes that were differentially expressed as a result of low‐temperature exposure across three populations from two species (M. hystriculeus and M. nov. sp. 2), with a majority (68% ± 20%) being population specific. This extensive geographical variation is consistent across years and is likely a result of background genetic differences among populations caused by genetic drift and possibly local adaptation. Responses to cold shock shared among alpine M. nov. sp. 2 populations included the enrichment of cuticular structure‐associated transcripts, suggesting that cuticle modification may have accompanied colonization of low‐temperature alpine environments and the development of a more cold‐hardy phenotype.
Disseminated Scedosporium prolificans infection in an ‘extensive metaboliser’: navigating the minefield of drug interactions and pharmacogenomics
Authors: Trubiano J. A. , Paratz E. , Wolf M. , Teh B. W. , Todaro M. , Thursky K. A. , Slavin M. A.
Published: April 2014

We report a case of non‐fatal disseminated Scedosporium prolificans infection, including central nervous system disease and endophthalmitis, in a relapsed acute myeloid leukaemia patient with extensive CYP2C19 metabolism. Successful treatment required aggressive surgical debridement, three times daily voriconazole dosing and cimetidine CYP2C19 inhibition. In addition, the unique use of miltefosine was employed due to azole‐chemotherapeutic drug interactions. Prolonged survival following disseminated S. prolificans, adjunctive miltefosine and augmentation of voriconazole exposure with cimetidine CYP2C19 inhibition has not been reported.
Argumentativeness, Avoidance, Verbal Aggressiveness, and Verbal Benevolence as Predictors of Partner Perceptions of an Individual's Conflict Style
Authors: Guerrero Laura K. , Gross Michael A.
Published: April 2014

This study addressed two main questions. First, are the traits of argumentativeness, verbal aggressiveness, avoidance, and verbal benevolence reflected in conflict styles such that they are perceived by others? Second, how do these traits predict the five conflict styles in the dual concern model? These questions were tested using dyadic data from a simulated downsizing activity. Results showed that participants perceived their partners differently depending on the traits their partners endorsed. For example, people who reported being avoidant or verbally aggressive were less likely to be perceived as using the compromising style. Overall, the results suggested that the four traits investigated in this study are likely to be associated with observable behavior. Findings also demonstrated that these traits help differentiate the five conflict styles in more nuanced ways than predicted by the dual concern model. Finally, the results supported the idea that conflict styles are not only shaped by one's own traits but also by the traits of others and the interaction between two people's traits.
Ways of knowing: realism, non‐realism, nominalism and a typology revisited with a counter perspective for nursing science
Authors: Garrett Bernard M , Cutting Roger L
Published: April 2014

In this paper, we reconsider the context of Barbara Carper'salternative ways of knowing,a prominent discourse in modern nursing theory in North America. We explore this relative to the concepts ofrealism, non‐realismandnominalism, and investigate the philosophical divisions behind the original typology, particularly in relationship to modern scientific enquiry. We examine forms of knowledge relative to realist and nominalist positions and make an argument ad absurdum against relativistic interpretations of knowledge using the example of Borge's Chinese Emporium of Benevolent Knowledge. We propose a contentious postpositivist practical classification for nursing knowledge that demonstrates and supports the idea that knowledge has both individual and subjective components. This classification supports the practical application of nursing knowledge within the paradigm of realist postpositivist science.
A cytotaxonomic analysis of Chinese Polygonatum (Asparagaceae) species
Authors: Zhao Li‐Hua , Zhou Song‐Dong , He Xing‐Jin , Wang Zhi‐Xin , Peng Lu
Published: April 2014

Chromosome numbers and karyotype data of 19 Chinese Polygonatum species generated from 51 populations are presented in this paper. Karyograms of P. cirrhifoliodes, P. gracile, P. hookeri, P. jinzhaiense and P. nodosum are reported for the first time. The chromosome numbers 2n = 28 for P. hookeri and 2n = 60 for P. zanlanscianense are reported for the first time. Satellite chromosomes in the analyzed Polygonatum species can be classified into nine types with respect to the position of secondary constrictions. The occurrence of these types correlates with the infrageneric classification. Karyotypes are bimodal in most Polygonatum species. Polyploidy is common in Polygonatum, and polyploid taxa exhibit higher karyotype asymmetry.
Identification of quantitative trait loci (QTLs) for seed protein concentration in soybean and analysis for additive effects and epistatic effects of QTLs under multiple environments
Authors: Qi Zhaoming , Hou Meng , Han Xue , Liu Chunyan , Jiang Hongwei , Xin Dawei , Hu Guohua , Chen Qingshan
Published: April 2014

Soybean protein concentration is a key trait driver of successful soybean quality. A recombination inbred lines derived from a cross between ‘Charleston’ and ‘Dongnong594’, were planted in three environments across four years in China. Then, the genetic effects were partitioned into additive main effects, epistatic main effects and their environment interaction effects by using composite interval mapping, multiple interval mapping and composite interval mapping in a mixed linear model. Forty‐three quantitative trait loci QTLs were identified on 17 of 20 soybean chromosomes excluding Ch 7, Ch 8 and Ch 17. Two QTLs showed a good stability across multiple environments, qPRO20‐1 was detected under four environments, which explained 4.4–9.95% phenotypic variances and the allele was from ‘Charleston’ among four environments. qPRO7‐5 was detected under three environments, which explained 7.2–14.5% phenotypic variances and the allele was from ‘Dongnong 594’, three pathway genes of protein biosynthesis were detected in the interval of qPRO7‐5. The additive main‐effect QTLs contributed more phenotypic variation than the epistasis and environmental interaction. This indicated that it is feasible by marker‐assisted selection to improve soybean protein concentration.
Chilling to zero degrees disrupts pollen formation but not meiotic microtubule arrays in Triticum aestivum L.
Authors: BARTON DEBORAH A. , CANTRILL LAURENCE C. , LAW ANDREW M. K. , PHILLIPS COLLIN G. , SUTTON BRUCE G. , OVERALL ROBYN L.
Published: April 2014

Throughout the wheat‐growing regions of Australia, chilling temperatures below 2 °C occur periodically on consecutive nights during the period of floral development in spring wheat (Triticum aestivum L.). In this study, wheat plants showed significant reductions in fertility when exposed to prolonged chilling temperatures in controlled environment experiments. Among the cultivars tested, the Australian cultivars Kite and Hartog had among the lowest levels of seed set due to chilling and their responses were investigated further. The developmental stage at exposure, the chilling temperature and length of exposure all influenced the level of sterility. The early period of booting, and specifically the +4 cm auricle distance class, was the most sensitive and corresponded to meiosis within the anthers. The response of microtubules to chilling during meiosis in Hartog was monitored, but there was little difference between chilled and control plants. Other abnormalities, such as plasmolysis and cytomixis increased in frequency, were associated with death of developing pollen cells, and could contribute to loss of fertility. The potential for an above‐zero chilling sensitivity in Australian spring wheat varieties could have implications for exploring the tolerance of wheat flower development to chilling and freezing conditions in the field.
Induced carbon reallocation and compensatory growth as root herbivore tolerance mechanisms
Authors: ROBERT CHRISTELLE A. M. , FERRIERI RICHARD A. , SCHIRMER STEFANIE , BABST BENJAMIN A. , SCHUELLER MICHAEL J. , MACHADO RICARDO A. R. , ARCE CARLA C. M. , HIBBARD BRUCE E. , GERSHENZON JONATHAN , TURLINGS TED C. J. , ERB MATTHIAS
Published: April 2014

Upon attack by leaf herbivores, many plants reallocate photoassimilates below ground. However, little is known about how plants respond when the roots themselves come under attack. We investigated induced resource allocation in maize plants that are infested by the larvae Western corn rootworm Diabrotica virgifera virgifera. Using radioactive 11CO2, we demonstrate that root‐attacked maize plants allocate more new 11C carbon from source leaves to stems, but not to roots. Reduced meristematic activity and reduced invertase activity in attacked maize root systems are identified as possible drivers of this shoot reallocation response. The increased allocation of photoassimilates to stems is shown to be associated with a marked thickening of these tissues and increased growth of stem‐borne crown roots. A strong quantitative correlation between stem thickness and root regrowth across different watering levels suggests that retaining photoassimilates in the shoots may help root‐attacked plants to compensate for the loss of belowground tissues. Taken together, our results indicate that induced tolerance may be an important strategy of plants to withstand belowground attack. Furthermore, root herbivore‐induced carbon reallocation needs to be taken into account when studying plant‐mediated interactions between herbivores.
Local Government Responses to Fiscal Stress: Evidence from the Public Education Sector
Authors: Nelson Ashlyn Aiko , Balu Rekha
Published: April 2014

This article investigates local government responses to fiscal stress through the lens of the K–12 public education sector, examining two major policy options available to school districts for managing fiscal hardship: (1) cutting costs, especially through layoffs, and (2) raising revenues locally through voter referenda. The article employs district‐level administrative and survey data from California and Indiana to examine whether school districts exhibit features of a rational or natural system—in which their behaviors largely reflect fiscal pressures only—or whether they exhibit features of an open system in which nonfinancial factors also shape responses. In Indiana, district fiscal characteristics explain differences in cost‐cutting and revenue‐raising behaviors; there is little empirical evidence that school districts exhibit features of an open system. In California, both fiscal and environmental attributes, including poverty characteristics, average student achievement levels, and the enrollment of English learner students, explain school district behaviors.
Fruit‐feeding Butterfly Communities are Influenced by Restoration Age in Tropical Forests
Authors: Sant'Anna Clara L. B. , Ribeiro Danilo B. , Garcia Letícia C. , Freitas André V. L.
Published: April 2014

Currently, a large‐scale restoration project aims to restore around 15 million hectares of Atlantic Forest in Brazil. This will increase forest cover and connectivity among remnant sites as well as restore environmental services. Currently, studies on recovery of fauna in restored areas of the Atlantic Forest are practically nonexistent. To address this knowledge vacuum, our study compares diversity patterns of fruit‐feeding butterflies in three forest areas with different restoration ages (11, 22, and 54 years), and uses a native forest area as reference. Results showed butterfly communities in maturing restored areas becoming more similar to the ones found in the native forest, with an increase in the proportional abundance of forest species, and a decrease of edge and grassland species. Moreover, we found a higher diversity among sites at the intermediate restoration age, with a community composed of both grassland and forest species. Butterfly species composition differed significantly among sites, showing interesting patterns of potential species replacement over time. Our results indicate that, although restored sites were located in a fragmented landscape, they provide suitable habitats for recolonization by fruit‐feeding butterfly assemblages. Hence, restored areas can be considered important habitat for forest animal species, increasing local biodiversity and, possibly, restoring some of the ecosystem services provided by them.