bluuebunny/crossref_metadata_2025 huggingface dataset:
Subsurface evidence for late Mesozoic extension in western Mongolia: tectonic and petroleum systems implications
Authors: Johnson C. L. , Constenius K. C. , Graham S. A. , Mackey G. , Menotti T. , Payton A. , Tully J.
Published: April 2014

New seismic reflection profiles from the Tugrug basin in the Gobi‐Altai region of western Mongolia demonstrate the existence of preserved Mesozoic extensional basins by imaging listric normal faults, extensional growth strata, and partially inverted grabens. A core hole from this region recovered ca. 1600 continuous meters of Upper Jurassic – Lower Cretaceous (Kimmeridgian–Berriasian) strata overlying Late Triassic volcanic basement. The cored succession is dominated by lacustrine and marginal lacustrine deposits ranging from stratified lacustrine, to subaqueous fan and delta, to subaerial alluvial‐fluvial environments. Multiple unconformities are encountered, and these represent distinct phases in basin evolution including syn‐extensional deposition and basin inversion. Prospective petroleum source and reservoir intervals occur, and both fluid inclusions and oil staining in the core provide evidence of hydrocarbon migration. Ties to correlative outcrop sections underscore that, in general, this basin appears to share a similar tectono‐stratigraphic evolution with petroliferous rift basins in eastern Mongolia and China. Nevertheless, some interesting contrasts to these other basins are noted, including distinct sandstone provenance, less overburden, and younger (Neogene) inversion structures. The Tugrug basin occupies an important but perplexing paleogeographic position between late Mesozoic contractile and extensional provinces. Its formation may record a rapid temporal shift from orogenic crustal thickening to extensional collapse in the Late Jurassic, and/or an accommodation zone with a Mesozoic strike‐slip component.
Molecular pathways linking non‐shivering thermogenesis and obesity: focusing on brown adipose tissue development
Authors: Valente Angelica , Jamurtas Athanasios Z. , Koutedakis Yiannis , Flouris Andreas D.
Published: April 2014

An increase in energy intake and/or a decrease in energy expenditure lead to fat storage, causing overweight and obesity phenotypes. The objective of this review was to analyse, for the first time using a systematic approach, all published evidence from the past 8 years regarding the molecular pathways linking non‐shivering thermogenesis and obesity in mammals, focusing on mechanisms involved in brown adipose tissue development. Two major databases were scanned from 2006 to 2013 using ‘brown adipose tissue’ AND ‘uncoupling protein‐1’ AND ‘mammalian thermoregulation’ AND ‘obesity’ as key words. A total of 61 articles were retrieved using the search criteria. The available research used knockout methodologies, various substances, molecules and agonist treatments, or different temperature and diet conditions, to assess the molecular pathways linking non‐shivering thermogenesis and obesity. By integrating the results of the evaluated animal and human studies, our analysis identified specific molecules that enhance non‐shivering thermogenesis and metabolism by: (i) stimulating ‘brite’ (brown‐like) cell development in white adipose tissue; (ii) increasing uncoupling protein‐1 expression in brite adipocytes; and (iii) augmenting brown and/or brite adipose tissue mass. The latter can be also increased through low temperature, hibernation and/or molecules involved in brown adipocyte differentiation. Cold stimuli and/or certain molecules activate uncoupling protein‐1 in the existing brown adipocytes, thus increasing total energy expenditure by a magnitude proportional to the number of available brown adipocytes. Future research should address the interplay between body mass, brown adipose tissue mass, as well as the main molecules involved in brite cell development.
MGr1‐Ag/37LRP induces cell adhesion‐mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer
Authors: Sun Li , Liu Lili , Liu Xiangqiang , Wang Yafang , Li Mengbin , Yao Liping , Yang Jianjun , Ji Genlin , Guo Changcun , Pan Yanglin , Liang Shuhui , Wang Biaoluo , Ding Jie , Zhang Hongwei , Shi Yongquan
Published: April 2014

It is well known that tumor microenvironment plays a vital role in drug resistance and cell adhesion‐mediated drug resistance (CAM‐DR), a form of de novo drug resistance. In our previous study, we reported that MGr1‐Ag/37LRP ligation‐induced adhesion participated in protecting gastric cancer cells from a number of apoptotic stimuli caused by chemotherapeutic drugs. Further study suggested that MGr1‐Ag could prompt CAM‐DR through interaction with laminin. However, the MGr1‐Ag‐initiated intracellular signal transduction pathway is still unknown. In this study, our experimental results showed that gastric cancer MDR cell lines mediated CAM‐DR through upregulation of Bcl‐2 by MGr1‐Ag interaction with laminin. Further study found that, as a receptor of ECM components, MGr1‐Ag/37LRP may activate the downstream signal pathway PI3K/AKT and MAPK/ERK through interaction with phosphorylated FAK. Moreover, the sensitivity to chemotherapeutic drugs could be significantly enhanced by inhibiting MGr1‐Ag/37LRP expression through mAbs, siRNA, and antisense oligonucleotide. According to these results, we concluded that the FAK/PI3K and MAPK signal pathway plays an important role in MGr1‐Ag‐mediated CAM‐DR in gastric cancer. MGr1‐Ag/37LRP might be a potential effective reversal target to MDR in gastric cancer.
Impact of epidermal growth factor single‐nucleotide polymorphism on recurrence of hepatocellular carcinoma after hepatectomy in patients with chronic hepatitis C virus infection
Authors: Yoshiya Shohei , Fujimoto Yukiko , Bekki Yuki , Konishi Hideyuki , Yamashita Yo‐ichi , Ikegami Toru , Yoshizumi Tomoharu , Shirabe Ken , Oda Yoshinao , Maehara Yoshihiko
Published: April 2014

Epidermal growth factor (EGF) gene single‐nucleotide polymorphism (SNP) is associated with an increased risk of hepatic tumors. The study aimed to elucidate the impact of EGF SNP and EGF receptor (EGFR) expression on the recurrence of hepatocellular carcinoma (HCC) after hepatectomy. To examine the impact of EGF SNP and EGFR on recurrent HCC, we retrospectively analyzed 141 HCC patients with chronic hepatitis C virus infection who underwent curative hepatectomy. The EGF *61 GG allele was present in 69 patients (48.9%), AG in 56 (39.7%) and AA in 16 (11.4%). The AA group had a significantly lower rate of intrahepatic metastasis (0% vs 16.5%, P = 0.02), lower serum EGF concentration (26.3 ± 15.9 pg/mL vs 43.4 ± 30.5 pg/mL, P = 0.02) and lower proportion of early recurrence (≤2 years; 28.6% vs 71.2%, P = 0.03) than the AG/GG group. The AA group had significantly higher recurrence‐free survival than the AG/GG group (P = 0.04), but there was no significant difference in overall survival between these two groups (P = 0.97). High versus low EGFR expression analyzed by immunohistochemical staining in cancer cells was not significantly associated with overall survival (P = 0.37) or recurrence‐free survival (P = 0.39). Therefore, EGF *61 AA was associated with a lower risk of recurrence after curative hepatectomy for HCC in patients with hepatitis C virus infection than other genotypes, but EGFR expression in cancer cells was not significantly associated with prognosis.
RETRACTED: Capn4 is a marker of poor clinical outcomes and promotes nasopharyngeal carcinoma metastasis via nuclear factor‐κB‐induced matrix metalloproteinase 2 expression
Authors: Zheng Pei‐Chan , Chen Xiong , Zhu Hong‐Wu , Zheng Wei , Mao Li‐Hua , Lin Cheng , Liu Jing‐Nan , Zheng Ming
Published: April 2014

Calpain small subunit 1 (Capn4) plays a key role in tumor migration or invasion. In this study, expression and function of Capn4 was investigated in human nasopharyngeal carcinoma (NPC). Here we report that both mRNA and protein levels of Capn4 were elevated in NPC tissues when compared to normal NP tissues. Similarly, Capn4 was also highly expressed in multiple NPC cell lines, compared to immortalized human nasopharyngeal epithelial cell line NP69. Moreover, expression of Capn4 was significantly correlated with Epstein‐Barr virus infection, advanced stages, and lymph node or distant metastasis (P < 0.001). The patients with NPC displaying higher Capn4 had a significantly shorter overall survival (P = 0.002) and progression‐free survival (P = 0.003). Furthermore, siRNA knockdown of Capn4 suppressed cell migration and invasion in vitro and in vivo. These events resulted from Capn4 downregulation were associated with reduced expression of matrix metalloproteinase 2 (MMP2), Snail, and Vimentin. Finally, we demonstrated that Capn4 upregulated MMP2 via nuclear factor‐κB (NF‐κB) activation, manifested by increased phosphorylation of p65, a subunit of NF‐κB. Together, these findings argue a novel function of Capn4 in invasion and metastasis of NPC, and thereby suggest that Capn4 may represent an independent prognostic factor and a potential therapeutic target in NPC.
Identification of Novel Inhibitors of Daboia russelli Phospholipase A2 Using the Combined Pharmacophore Modeling Approach
Authors: Ramakrishnan Chandrasekaran , Joshi Vikram , Joseph Joseph Mavelithuruthel , Vishwanath Bannikuppe S. , Velmurugan Devadasan
Published: April 2014

Crystal structures available for Daboia russelli venom PLA2 confirm that it undergoes dimerization with asymmetry and hence difference in the conformation of active site of the two subunits. The active site of subunit A is open and that of subunit B is closed. Pharmacophore models were generated based on the interaction of different types of inhibitors with their preferred subsites in the active site of subunit A. Particularly, the features responsible for recognizing subsites 1–3 and those of subsites 4–6 were combined as these two are involving in inflammation and anticoagulation processes, respectively. Pharmacophore model was edited to make the geometry suitable for the active site of both the subunits A and B. Final model is validated and subjected for screening a library of druglike compounds. Eight compounds were shortlisted and subjected for molecular docking and dynamics simulation to assess their binding mode with both the subunits. Based on the hydrophobic interactions and binding free energy, four compounds were selected for further biochemical assay. The overall results suggest that two compounds can bind both the subunits of PLA2 of Daboia russelli venom in spite of its aggregated form and other two inhibit structurally very similar Naja naja PLA2.
Tissue response of selective retina therapy by means of a feedback‐controlled energy ramping mode
Authors: Park Young‐Gun , Seifert Eric , Roh Young J , Theisen‐Kunde Dirk , Kang Seungbum , Brinkmann Ralf
Published: April 2014

Background

The purpose of the study was to evaluate the safety and selectivity of the retinal pigment epithelium lesions by using automatic energy ramping and dosimetry technique for selective retina therapy and to investigate the healing response.

Methods

Ten eyes of Chinchilla Bastard rabbits were treated with an automatic dosage controlled selective retina therapy laser (frequency doubled Q‐switched Nd:YLF, wavelength: 527 nm, pulse duration: 1.7 μs, repetition rate: 100 Hz, pulse energy: linear increasing from pulse to pulse up to shut down – maximal 110 μJ, max. number of pulses in a burst: 30, retinal spot diameter: 133 μm). After treatment, fundus photography, optical coherence tomography and fluorescein angiography were performed at three time points from 1 h to 3 weeks. Histological analysis was performed.

Results

A total of 381 selective retina therapy laser spots were tested (range 13–104 μJ).Typical fundus photographs obtained at 1 h after irradiation showed that 379 out of 381 lesions produced by selective retina therapy were not visible ophthalmoscopically and the lesions could be detected by angiography only. Optical coherence tomography images revealed that the structure of photoreceptors was preserved, but a disrupted retinal pigment epithelium layer was observed as was expected. By 3 weeks, histology showed selective retinal pigment epithelium damage without any effect on the inner retina and focal proliferation of the retinal pigment epithelium layer.

Conclusions

Automatically controlled selective retina therapy is a significant improvement in this innovative treatment. It could be demonstrated that the non‐contact, reflectometric technique with a controlled pulse energy ramp is safe and selective.
Collaborating with families in differential responses: practitioners' views
Authors: Healy Karen , Harrison Gai , Venables Jemma , Bosly Fiona
Published: April 2014

Child protection authorities in many countries are concerned with reducing the rates of investigations and with diverting at‐risk families from the child protection service system. In several countries, differential responses have been introduced into child protection law providing service providers with some choice between investigative or family support pathways, depending upon the level of risk posed in the circumstance. In this paper, we report on a study into a form of differential response known as Intervention with Parents' Agreement introduced in Queensland, Australia, in 2005. A unique feature of this differential response is that it occurs after an initial child protection investigation, although it does provide child protection services with options for providing supportive interventions to at‐risk families to prevent the further escalation of concerns. In this paper, we analyse practitioners' perceptions of factors that inhibit and promote implementation of the Intervention with Parents' Agreement. Drawing upon interviews with 25 practitioners, we identify factors that become important for securing participation after an initial investigation has occurred. We discuss the implications for the development of differential responses in child protection service systems.
Clinical application of genetics to guide prevention and treatment of oral diseases
Authors: Kornman K.S. , Polverini P.J.
Published: April 2014

Dental care costs in the United States exceed $100 billion annually. Personalized medicine efforts in dentistry are driven by potentially compelling clinical utility and cost‐effectiveness prospects in the major diseases of periodontitis, caries, and oral cancers. This review discusses progress and challenges identifying genetic markers and showing clinical utility in dentistry. Genome‐wide association studies (GWAS) of chronic periodontitis (CP) identified no significant variants, but CDKN2BAS variants on chromosome 9 were significantly associated with aggressive periodontitis. Stratifying patients by interleukin (IL)‐1 gene variants, smoking and diabetes differentiated CP prevention outcomes. Dental caries' GWAS identified significant signals in LYZL2, AJAp1, and KPNA4; and efforts are ongoing to identify genetic factors for multiple caries phenotypes. Trials of molecularly targeted therapies are in progress for oral, head, and neck squamous cell carcinomas (OHNSCC) and results have been promising but limited in their effectiveness. Current opportunities and challenges for molecular targeting for OHNSCC are discussed.
Does Agriculture Really Matter for Economic Growth in Developing Countries?
Authors: Awokuse Titus O. , Xie Ruizhi
Published: April 2014

This paper revisits the debate on the role of agriculture in promoting economic growth in a selection of nine developing countries. We investigated the causal linkages between agriculture and gross domestic product growth with the aid of directed acyclic graphs, a recently developed algorithm of inductive causation. The results suggest that while agriculture could be an engine of economic growth, the impact varies across countries. In some cases, we found strong evidence in support of the agriculture‐led growth hypothesis. In contrast, the results for some other countries indicate that having a vibrant aggregate economy is a prerequisite for agricultural development.
Positive Allosteric Modulation of GABAB Receptors Ameliorates Sensorimotor Gating in Rodent Models
Authors: Frau Roberto , Bini Valentina , Pillolla Giuliano , Malherbe Pari , Pardu Alessandra , Thomas Andrew W. , Devoto Paola , Bortolato Marco
Published: April 2014

Background

Converging evidence points to the involvement of γ‐amino‐butyric acid B receptors (GABABRs) in the regulation of information processing. We previously showed that GABABR agonists exhibit antipsychotic‐like properties in rodent models of sensorimotor gating deficits, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. The therapeutic potential of these agents, however, is limited by their neuromuscular side effects; thus, in this study, we analyzed whether rac‐BHFF, a potent GABABR‐positive allosteric modulator (PAM), could counter spontaneous and pharmacologically induced PPI deficits across various rodent models.

Methods

We tested the antipsychotic effects of rac‐BHFF on the PPI deficits caused by the N‐methyl‐D‐aspartate glutamate receptor antagonist dizocilpine, in Sprague‐Dawley rats and C57BL/6 mice. Furthermore, we verified whether rac‐BHFF ameliorated the spontaneous PPI impairments in DBA/2J mice.

Results

rac‐BHFF dose‐dependently countered the PPI deficits across all three models, in a fashion akin to the GABABR agonist baclofen and the atypical antipsychotic clozapine; in contrast with these compounds, however, rac‐BHFF did not affect startle magnitude.

Conclusions

The present data further support the implication of GABABRs in the modulation of sensorimotor gating and point to their PAMs as a novel promising tool for antipsychotic treatment, with fewer side effects than GABABR agonists.
MICROECONOMIC REFORM AND INCOME DISTRIBUTION: THE CASE OF AUSTRALIAN PORTS AND RAIL FREIGHT
Authors: Verikios George , Zhang Xiao‐Guang
Published: April 2014

We analyze structural changes in the Australian ports and rail freight industries that were driven by microeconomic reform; we find such reforms may generate welfare gains with reduced inequality. We estimate the effects on household income groups of these industry changes by applying a computable general equilibrium model incorporating microsimulation behavior. The structural changes lead to a small increase in household welfare in most regions, with an overall increase of 0.18%, and a small decrease in inequality. Our analysis suggests that policy makers in Australia and other high‐income nations should give serious consideration to microeconomic reform of infrastructure industries. (JEL C68, C69, D31, L92)
Egocentric and allocentric navigation strategies in Williams syndrome and typical development
Authors: Broadbent Hannah J. , Farran Emily K. , Tolmie Andy
Published: April 2014

Recent findings suggest that difficulties on small‐scale visuospatial tasks documented in Williams syndrome (WS) also extend to large‐scale space. In particular, individuals with WS often present with difficulties in allocentric spatial coding (encoding relationships between items within an environment or array). This study examined the effect of atypical spatial processing in WS on large‐scale navigational strategies, using a novel 3D virtual environment. During navigation of recently learnt large‐scale space, typically developing (TD) children predominantly rely on the use of a sequential egocentric strategy (recalling the sequence of left–right body turns throughout a route), but become more able to use an allocentric strategy between 5 and 10 years of age. The navigation strategies spontaneously employed by TD children between 5 and 10 years of age and individuals with WS were analysed. The ability to use an allocentric strategy on trials where spatial relational knowledge was required to find the shortest route was also examined. Results showed that, unlike TD children, during spontaneous navigation the WS group did not predominantly employ a sequential egocentric strategy. Instead, individuals with WS followed the path until the correct environmental landmarks were found, suggesting the use of a time‐consuming and inefficient view‐matching strategy for wayfinding. Individuals with WS also presented with deficits in allocentric spatial coding, demonstrated by difficulties in determining short‐cuts when required and difficulties developing a mental representation of the environment layout. This was found even following extensive experience in an environment, suggesting that – unlike in typical development – experience cannot contribute to the development of spatial relational processing in WS. This atypical presentation of both egocentric and allocentric spatial encoding is discussed in relation to specific difficulties on small‐scale spatial tasks and known atypical cortical development in WS.
Serious harm from inpatient hypoglycaemia: a survey of hospitals in the UK
Authors: Rajendran R. , Rayman G.
Published: April 2014

Aim

To estimate the incidence of serious harm to inpatients with diabetes from hypoglycaemia.

Method

An anonymised questionnaire was e‐mailed to lead organisers at the 142 acute NHS Trusts that contributed to the National Diabetes Inpatient Audit 2012. Each diabetes team was asked collectively to recall and report any serious adverse events from inpatient hypoglycaemia in the previous year. A total of 83 Trusts agreed to participate. Serious harm was defined as death, a cardiac or cerebral event or a fall resulting in permanent physical injury or fracture.

Results

A total of 41 Trusts returned the survey. Of these, only 28 (68.3%) were confident that robust methods existed in their Trust to ensure all such events were reported, and only 23 (56.1%) were confident that all such events were reported to the diabetes team. Despite these reporting concerns, the retrospective nature of the survey and the reliance on recall, 12 serious adverse events were reported from nine trusts: three deaths; two cases of permanent cerebral damage; two successfully resuscitated cardiac arrests; three seizures; and two undefined events. Insulin therapy was implicated in 10 events. Importantly, three events with two deaths occurred in patients who had received insulin/dextrose to correct hyperkalaemia; only one of whom had diabetes.

Conclusions

An alarming number of serious adverse events was reported: 12 serious adverse events with three deaths over a 1‐year period in 41 Trusts. This may be the tip of the iceberg, considering the potential under‐reporting. Robust reporting mechanisms are required to determine the full extent of this serious preventable harm.
Brazil's International Development Co‐operation: Old and New Motivations
Authors: Burges Sean
Published: April 2014

Brazil has entered the world of development assistance, but with its own twist. This article argues that Brazil is taking a cross‐government policy approach to the provision of development assistance, and which includes recruitment of business interests. There is a genuine concern with global poverty alleviation in Brazil, but this does not preclude policy‐makers from using aid and development‐related activities to advance national interests. The added quirk that sets Brazil apart from Northern counterparts is that the provision of development assistance offers significant benefits in terms of building up international bureaucratic experience inside the country and helping national firms internationalise their market activities.
Role of Echocardiography in the Treatment of Cardiac Tamponade
Authors: Chandraratna P. A. N. , Mohar Dilbahar S. , Sidarous Peter F.
Published: April 2014

Accumulation of fluid within the pericardial sac results in elevation of intrapericardial pressure with consequent cardiac compression or tamponade. Cardiac tamponade is a life‐threatening condition which requires urgent evacuation of pericardial effusion (PE). Current pericardial evacuation techniques and approaches are varied. Echocardiography provides valuable insights into identifying patients who are suitable candidates and further facilitates pericardiocentesis by improving guidance techniques. Several previous publications have provided excellent reviews of the pathophysiology of cardiac tamponade. We review the clinical presentation and role of echocardiography for diagnosis of tamponade. We focus on medical and surgical approaches for the removal of PE. Moreover, as the clinical and hemodynamic consequences of PE depend on the volume and the rate of accumulation of PE, we review the various scenarios of “small” PE resulting in cardiac tamponade.
Rearing history affects behaviour and performance of two virulent Nasonovia ribisnigri populations on two lettuce cultivars
Authors: ten Broeke Cindy J.M. , Dicke Marcel , van Loon Joop J.A.
Published: April 2014

Many aphid species have become virulent to host‐plant resistance, which limits the sustainability of insect resistance breeding. However, when this adaptation to resistant plants is associated with fitness costs for the aphids, virulence can be lost in the absence of resistant plants. For two populations of the lettuce aphid, Nasonovia ribisnigri (Mosely) (Hemiptera: Aphididae), we evaluated whether virulence to Nr‐gene‐based resistance was lost on a susceptible lettuce, Lactuca sativa L. (Asteraceae), and assessed possible costs of virulence. The feeding behaviour and performance of these aphids, reared and tested on susceptible and resistant lettuce, were investigated. The rearing plant affected feeding behaviour and performance of the aphids. Temporary reduction and long‐term loss of virulence were found. The total duration of phloem intake was shorter after being reared on susceptible lettuce and tested on resistant lettuce. In addition, one population had a lower survival on resistant lettuce after being reared on susceptible lettuce. There were also indications of fitness costs of the virulence in both populations.
Natural soil microbes alter flowering phenology and the intensity of selection on flowering time in a wild Arabidopsis relative
Authors: Wagner Maggie R. , Lundberg Derek S. , Coleman‐Derr Devin , Tringe Susannah G. , Dangl Jeffery L. , Mitchell‐Olds Thomas
Published: April 2014

Plant phenology is known to depend on many different environmental variables, but soil microbial communities have rarely been acknowledged as possible drivers of flowering time. Here, we tested separately the effects of four naturally occurring soil microbiomes and their constituent soil chemistries on flowering phenology and reproductive fitness ofBoechera stricta, a wild relative of Arabidopsis. Flowering time was sensitive to both microbes and the abiotic properties of different soils; varying soil microbiota also altered patterns of selection on flowering time. Thus, soil microbes potentially contribute to phenotypic plasticity of flowering time and to differential selection observed between habitats. We also describe a method to dissect the microbiome into single axes of variation that can help identify candidate organisms whose abundance in soil correlates with flowering time. This approach is broadly applicable to search for microbial community members that alter biological characteristics of interest.
Long‐term outcome after limited cortical resections in two cases of adult‐onset Rasmussen encephalitis
Authors: Villani Flavio , Didato Giuseppe , Deleo Francesco , Tringali Giovanni , Garbelli Rita , Granata Tiziana , Marras Carlo Efisio , Cordella Roberto , Spreafico Roberto
Published: April 2014

Rasmussen encephalitis (RE) is a progressive inflammatory disorder characterized by brain hemiatrophy, unilateral focal deficits, and drug‐refractory focal epilepsy. Epilepsia partialis continua (EPC) is a hallmark of the disease. Several immunomodulatory treatments may slow but not halt the disease progression. The treatment of choice still relies on surgical hemispheric disconnection, which is burdened by heavy neurologic morbidity. More limited cortical resections, although more tolerable, are usually considered to be, at best, only transiently effective in RE. Hemispheric disconnections may be not feasible when neurologic functions are preserved and the dominant hemisphere is affected. Adult patients with a milder RE course that preserves neurologic function for a long period are particularly at risk of developing severe deficits after surgery. In this study we present the histories of two patients with adult‐onset RE who have undergone selective cortical resections to control EPC, avoiding, at the same time, the severe postsurgical deficits that may be induced by hemispheric disconnective surgery. The good result obtained on EPC has been stable over a prolonged period; however, this result was not paralleled by the stop of neurologic progression in one of the two cases.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Heart rate variability analysis indicates preictal parasympathetic overdrive preceding seizure‐induced cardiac dysrhythmias leading to sudden unexpected death in a patient with epilepsy
Authors: Jeppesen Jesper , Fuglsang‐Frederiksen Anders , Brugada Ramon , Pedersen Birthe , Rubboli Guido , Johansen Peter , Beniczky Sándor
Published: April 2014

Evidence for seizure‐induced cardiac dysrhythmia leading to sudden unexpected death in epilepsy (SUDEP) has been elusive. We present a patient with focal cortical dysplasia who has had epilepsy for 19 years and was undergoing presurgical evaluation. The patient did not have any cardiologic antecedents. During long‐term video–electroencephalography (EEG) monitoring, following a cluster of secondarily generalized tonic–clonic seizures (GTCS), the patient had prolonged postictal generalized EEG suppression, asystole, followed by arrhythmia, and the patient died despite cardiopulmonary resuscitation. Analysis of heart rate variability showed a marked increase in the parasympathetic activity during the period preceding the fatal seizures, compared with values measured 1 day and 7 months before, and also higher than the preictal values in a group of 10 patients with GTCS without SUDEP. The duration of the QTc interval was short (335–358 msec). This unfortunate case documented during video‐EEG monitoring indicates that autonomic imbalance and seizure‐induced cardiac dysrhythmias contribute to the pathomechanisms leading to SUDEP in patients at risk (short QT interval).

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Revisiting the metabolic syndrome and paving the way for microRNAs in non‐alcoholic fatty liver disease
Authors: Ferreira Duarte M. S. , Simão André L. , Rodrigues Cecília M. P. , Castro Rui E.
Published: April 2014

Non‐alcoholic fatty liver disease (NAFLD) comprises a spectrum of stages from simple steatosis to non‐alcoholic steatohepatitis, which can progress to fibrosis, cirrhosis and, ultimately, hepatocellular carcinoma. Despite being one of the most common chronic liver diseases, NAFLD pathogenesis remains largely unknown. In this review, we discuss the key molecular mechanisms involved in NAFLD development and progression, focusing on the emerging role of microRNAs. NAFLD is intrinsically related to obesity and the metabolic syndrome. Changes in lipid metabolism increase free fatty acids in blood, which in turn induces peripheral insulin resistance and increases oxidative and endoplasmic reticulum stress. Although not yet considered in the diagnosis of NAFLD, recent reports also reinforce the crucial role of apoptosis in disease progression via activation of either death receptor or mitochondrial pathways and p53. In addition, the role of gut microbiota and the gut–liver axis has been recently associated with NAFLD. Finally, there is an accumulating and growing body of evidence supporting the role of microRNAs in NAFLD pathogenesis and progression, as well as hinting at their use as biomarkers or therapeutic tools. The ultimate goal is to review different molecular pathways that may underlie NAFLD pathogenesis in the hope of finding targets for new and efficient therapeutic interventions.
Clustering of Trade Prices by High‐Frequency and Non–High‐Frequency Trading Firms
Authors: Davis Ryan L. , Van Ness Bonnie F. , Van Ness Robert A.
Published: April 2014

We examine clustering of transaction prices in a sample that contains high‐frequency trading firms’ transactions. We separate our sample into four categories: transactions with a high‐frequency trading firm on both sides of the transaction, on only one side of the transaction (either liquidity provider or liquidity demander), or on neither side of the transaction. We find that transaction price clustering is less frequent when a high‐frequency trading firm is on both sides of the transaction than when a high‐frequency trading firm is on only one side of the transaction or if a high‐frequency trading firm is not involved in the transaction. Further, we find that transactions where the liquidity providing order, which more likely dictates the price, is submitted by a high‐frequency trading firm cluster less than when the liquidity providing order is submitted by a non–high‐frequency trader. We thus conclude that the tendency of prices to cluster appears to be driven by a distinctly human bias.
Co‐benefits, trade‐offs, barriers and policies for greenhouse gas mitigation in the agriculture, forestry and other land use (AFOLU) sector
Authors: Bustamante Mercedes , Robledo‐Abad Carmenza , Harper Richard , Mbow Cheikh , Ravindranat Nijavalli H. , Sperling Frank , Haberl Helmut , de Siqueira Pinto Alexandre , Smith Pete
Published: April 2014

The agriculture, forestry and other land use (AFOLU) sector is responsible for approximately 25% of anthropogenic GHG emissions mainly from deforestation and agricultural emissions from livestock, soil and nutrient management. Mitigation from the sector is thus extremely important in meeting emission reduction targets. The sector offers a variety of cost‐competitive mitigation options with most analyses indicating a decline in emissions largely due to decreasing deforestation rates. Sustainability criteria are needed to guide development and implementation of AFOLU mitigation measures with particular focus on multifunctional systems that allow the delivery of multiple services from land. It is striking that almost all of the positive and negative impacts, opportunities and barriers are context specific, precluding generic statements about which AFOLU mitigation measures have the greatest promise at a global scale. This finding underlines the importance of considering each mitigation strategy on a case‐by‐case basis, systemic effects when implementing mitigation options on the national scale, and suggests that policies need to be flexible enough to allow such assessments. National and international agricultural and forest (climate) policies have the potential to alter the opportunity costs of specific land uses in ways that increase opportunities or barriers for attaining climate change mitigation goals. Policies governing practices in agriculture and in forest conservation and management need to account for both effective mitigation and adaptation and can help to orient practices in agriculture and in forestry towards global sharing of innovative technologies for the efficient use of land resources. Different policy instruments, especially economic incentives and regulatory approaches, are currently being applied however, for its successful implementation it is critical to understand how land‐use decisions are made and how new social, political and economic forces in the future will influence this process.
Interannual variation in nitrous oxide emissions from perennial ryegrass/white clover grassland used for dairy production
Authors: Burchill William , Li Dejun , Lanigan Gary J. , Williams Micheal , Humphreys James
Published: April 2014

Nitrous oxide (N2O) emissions are subject to intra‐ and interannual variation due to changes in weather and management. This creates significant uncertainties when quantifying estimates of annual N2O emissions from grazed grasslands. Despite these uncertainties, the majority of studies are short‐term in nature (<1 year) and as a consequence, there is a lack of data on interannual variation in N2O emissions. The objectives of this study were to (i) quantify annual N2O emissions and (ii) assess the causes of interannual variation in emissions from grazed perennial ryegrass/white clover grassland. Nitrous oxide emissions were measured from fertilized and grazed perennial ryegrass/white clover grassland (WC) and from perennial ryegrass plots that were not grazed and did not receive N input (GB), over 4 years from 2008 to 2012 in Ireland (52°51′N, 08°21′W). The annual N2O‐N emissions (kg ha−1; mean ± SE) ranged from 4.4 ± 0.2 to 34.4 ± 5.5 from WC and from 1.7 ± 0.8 to 6.3 ± 1.2 from GB. Interannual variation in N2O emissions was attributed to differences in annual rainfall, monthly (December) soil temperatures and variation in N input. Such substantial interannual variation in N2O emissions highlights the need for long‐term studies of emissions from managed pastoral systems.
Agronomic factors in the establishment of tetraploid seeded Miscanthus × giganteus
Authors: Anderson Eric K. , Lee DoKyoung , Allen Damian J. , Voigt Thomas B.
Published: April 2014

To meet US renewable fuel mandates, perennial grasses have been identified as important potential feedstocks for processing into biofuels. Triploid Miscanthus × giganteus, a sterile, rhizomatous grass, has proven to be a high‐yielding biomass crop over the past few decades in the European Union and, more recently, in the United States. However, high establishment costs from rhizomes are a limitation to more widespread plantings without government subsidies. A recently developed tetraploid cultivar of M. × giganteus producing viable seeds (seeded miscanthus) shows promise in producing high yields with reduced establishment costs. Field experiments were conducted in Urbana, Illinois from 2011 to 2013 to optimize seeded miscanthus establishment by comparing seeding rates (10, 20, and 40 seeds m−2) and planting methods (drilling seeds at 38 and 76 cm row spacing vs. hydroseeding with and without premoistened seeds) under irrigated and rainfed conditions. Drought conditions in 2011 and 2012 coincided with stand establishment failure under rainfed conditions, suggesting that seeded miscanthus may not establish well in water‐stressed environments. In irrigated plots, hydroseeding without premoistening was significantly better than hydroseeding with premoistening, drilling at 38 cm and drilling at 76 cm with respect to plant number (18%, 54%, and 59% higher, respectively), plant frequency (13%, 30%, and 40% better, respectively), and the rate of canopy closure (18%, 33%, and 43% faster, respectively) when averaged across seeding rates. However, differences in second‐year biomass yields among treatments were less pronounced, as plant size partially compensated for plant density. Both hydroseeding and drilling at rates of 20 or 40 seeds m−2 appear to be viable planting options for establishing seeded miscanthus provided sufficient soil moisture, but additional strategies are required for this new biomass production system under rainfed conditions.
Implications of tobacco smoking on the oral health of older adults
Authors: Agnihotri Rupali , Gaur Sumit
Published: April 2014

Cigarette smoking is the foremost health risk issue affecting individuals of all age groups globally. It specifically influences the geriatric population as a result of chronic exposure to toxins. Its role in various systemic and oral diseases including cancer, premalignant lesions, periodontitis, tooth loss, dental caries and implant failures is well established. Smoking causes immuno‐inflammatory imbalances resulting in increased oxidative stress in the body. The latter hastens the immunosenescence and inflammaging process, which increases the susceptibility to infections. Thus, implementation of smoking cessation programs among older adults is imperative to prevent the development and progression of oral and systemic diseases. The present review focuses on smoking‐associated oral health problems in older adults, and the steps required for cessation of the habit. Geriatr Gerontol Int 2014; 14: 526–540..
Role of p53 in the entrainment of mammalian circadian behavior rhythms
Authors: Hamada Toshiyuki , Niki Tomoko , Ishida Norio
Published: April 2014

p53 protein plays a role for control of cell proliferation and the induction of apoptosis in normal cells. However, its role in the circadian rhythms that control many physiological functions including locomotor behavior remains unknown. The present study examined the locomotors activity rhythms of mice which have homozygous mutations of p53 gene. The period of drinking activity rhythms in p53 knockout (p53 KO) mice became unstable under constant dark. Light pulse causes a big phase shifts at CT15.5–17, when p53 mRNA expression peaks in the suprachiasmatic nucleus (SCN). Furthermore, photic entrainment of p53 KO mice is unusual under light–dark conditions. These findings suggest that p53 is involved in entrainment of the circadian behavioral rhythm.
Investigation of Brain‐Derived Neurotrophic Factor (BDNF) Gene Variants in Migraine
Authors: Sutherland Heidi G. , Maher Bridget H. , Rodriguez‐Acevedo Astrid J. , Haupt Larisa M. , Griffiths Lyn R.
Published: April 2014

Objective

A number of observations have suggested that brain‐derived neurotrophic factor (BDNF) plays a role in migraine pathophysiology. This study investigates whether variants in the BDNF gene are associated with migraine in an Australian case‐control population.

Background

BDNF has an important role in neural growth, development, and survival in the central nervous system and is an important modulator of central and peripheral pain responses. Variants in BDNF, in particular the functional Val66Met polymorphism (rs6265), have been found to be associated with a number of psychiatric disorders, cognitive function, and obesity. As BDNF has been found to be differentially expressed in a number of aspects related to migraine, we tested for association between single nucleotide polymorphisms (SNPs) in BDNF and migraine.

Methods

Five SNPs in the BDNF locus (rs1519480, rs6265, rs712507, rs2049046, and rs12273363) were genotyped initially in a cohort of 277 migraine cases, including 172 diagnosed with migraine with aura (MA) and 105 with migraine without aura (MO), and 277 age‐ and sex‐matched controls. Three of these SNPs (rs6265, rs2049046, and rs12273363) were subsequently genotyped in a second cohort of 580 migraineurs, including 473 diagnosed with MA and 105 with MO, and 580 matched controls.

Results

BDNF SNPs rs1519480, rs6265, rs712507, and rs12273363 were not significantly associated with migraine. However, rs2049046 showed a significant association with migraine, and in particular, MA in the first cohort. In the second cohort, although an increase in the rs2049046 T‐allele frequency was observed in migraine cases, and in both MA and MO subgroups, it was not significantly different from controls. Analysis of data combined from both cohorts for rs2049046 showed significant differences in the genotypic and allelic distributions for this marker in both migraine and the MA subgroup.

Conclusion

This study confirmed previous studies that the functional BDNF SNP rs6265 (Val66Met) is not associated with migraine. However, we found that rs2049046, which resides at the 5' end of one the BDNF transcripts, may be associated with migraine, suggesting that further investigations of this SNP may be warranted.
Impact of non‐alcoholic fatty liver disease on liver volume in humans
Authors: Bian Hua , Hakkarainen Antti , Zhou You , Lundbom Nina , Olkkonen Vesa M , Yki‐Järvinen Hannele
Published: April 2014

Aim

Knowledge of liver volume is needed in the preoperative screening of liver transplant donors and in pharmacokinetic studies. In previous studies, bodyweight, surface area, age and sex have been identified as predictors of total liver volume, but the impact of non‐alcoholic fatty liver disease (NAFLD) independent of body size on liver volume has not been determined. We examined whether and to what extent liver fat due to NAFLD influences liver volume.

Methods

We quantified the percentage of liver fat by proton magnetic resonance spectroscopy (1H‐MRS) and liver total, lean and fat volumes using magnetic resonance imaging (MRI) in 112 subjects (62 women, 50 men), who were characterized with respect to metabolic parameters associated with NAFLD.

Results

Of the subjects, 45% had NAFLD (liver fat 12.5 ± 4.5% vs 1.8 ± 1.6%, NAFLD vs no NAFLD, P < 0.001). Total liver volume was 29% higher in subjects with NAFLD (1.91 ± 0.45 L) than in those with no NAFLD (1.49 ± 0.31 L, P < 0.001). In multiple linear regression analysis, the percentage of liver fat and bodyweight independently explained variation in total liver volume (r2 = 0.42, P < 0.001). The r‐values for the relationship between metabolic parameters and the total liver fat volume were not significantly better than those between metabolic parameters and the percentage of liver fat.

Conclusion

Both bodyweight and NAFLD increase liver volume independent of each other. Measurement of liver fat by 1H‐MRS allows accurate quantification of NAFLD and calculation of total liver volume.
Micronodular thymoma with lymphoid stroma: an immunohistochemical study of the distribution of Langerhans cells and mature dendritic cells in six patients
Authors: Ishikawa Yoshinori , Tateyama Hisashi , Yoshida Megumi , Takami Koji , Matsuguma Haruhisa , Taniguchi Tetsuo , Usami Noriyasu , Kawaguchi Koji , Fukui Takayuki , Ishiguro Futoshi , Nakamura Shota , Yokoi Kohei
Published: April 2014

Aims

Micronodular thymoma with lymphoid stroma (MNT) is an uncommon variant of thymoma, characterized by multiple small nodules consisting of type A thymoma‐like cells, which are separated by abundant B lymphocytes. The aim of the study was to elucidate the pathogenesis of the stromal lymphoid hyperplasia, which is currently unclear.

Methods and results

We retrieved six cases of MNT, and immunohistochemically examined the number and distribution of Langerhans cells (LCs) and mature dendritic cells (DCs), and compared them with those in type A and type AB thymomas. Many LCs were present within the small tumour nests, but LCs were rarely seen in the stroma (75.5/HPF versus 6.1/HPF, P < 0.0001). In contrast, mature DCs were present mainly in the surrounding stroma rather than within the tumour nodules (63.5/HPF versus 6.0/HPF, P < 0.0001), forming clusters with mature T lymphocytes adjacent to lymphoid follicles. In large nodules, as well as in type A and type AB thymomas, a few scattered LCs and DCs were identified. All patients were still alive and well.

Conclusions

Our results suggest that LCs take up tumour antigens and migrate to the stroma, where they mature and form clusters with T lymphocytes to activate them, resulting in lymphoid follicle formation. The favourable clinical behaviour may be attributable to the immune response induced by LCs.