bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical transitions in disturbance‐driven ecosystems: identifying Windows of Opportunity for recovery
Authors: Balke Thorsten , Herman Peter M. J. , Bouma Tjeerd J.
Published: February 2014

Vegetation recovery in disturbance‐driven ecosystems is difficult to predict. We demonstrate a concept to analyse time series for short‐term variability in external forcing that can identify potential events for sudden vegetation recovery in biogeomorphic ecosystems such as saltmarshes, mangroves, dunes or floodplains.

Time series of external forcing (i.e. water level and wind speed) were analysed for ‘Windows of Opportunity’ (WoO), defined as disturbance‐free periods of a critical minimal duration directly following potential diaspore dispersal, which allow seedling establishment and can induce a sudden shift to a new persistent vegetation cover.

Across different ecosystems, the minimal required WoO duration determines how many WoO events are available for seedling establishment. The distribution of WoO along an elevation gradient on riverbanks and in tidal systems, for example, is defined by the combination of the overall disturbance regime (e.g. seasonal vs. tidal flooding cycles) and the stochastic deviations from that regime (e.g. changes in weather conditions). Standardizing the WoO for the frequency of the regular disturbance regime shows that tidal and river systems have a similar relation between the required WoO length and the elevation suitable for establishment. WoO analysis correctly predicted a sudden vegetation recovery event in a saltmarsh case study.

Synthesis. Time‐series analysis for ‘WoO’ offers an important tool towards predicting the establishment of vegetation cover in disturbance‐driven ecosystems and may have broader implications for understanding critical transitions in general. Quantifying the effects of stochastic external forcing on critical transitions in ecosystems is crucial for restoration efforts and to assess the effects of anthropogenic and global change.
Importance of amoebae as a tool to isolate amoeba‐resisting microorganisms and for their ecology and evolution: the Chlamydia paradigm
Authors: Kebbi‐Beghdadi Carole , Greub Gilbert
Published: February 2014

Free‐living amoebae are distributed worldwide and are frequently in contact with humans and animals. As cysts, they can survive in very harsh conditions and resist biocides and most disinfection procedures. Several microorganisms, called amoeba‐resisting microorganisms (ARMs), have evolved to survive and multiply within these protozoa. Among them are many important pathogens, such as Legionella and Mycobacteria, and also several newly discovered Chlamydia‐related bacteria, such as Parachlamydia acanthamoebae, Estrella lausannensis, Simkania negevensis or Waddlia chondrophila whose pathogenic role towards human or animal is strongly suspected.

Amoebae represent an evolutionary crib for their resistant microorganisms since they can exchange genetic material with other ARMs and develop virulence traits that will be further used to infect other professional phagocytes. Moreover, amoebae constitute an ideal tool to isolate strict intracellular microorganisms from complex microbiota, since they will feed on other fast‐growing bacteria, such as coliforms potentially present in the investigated samples. The paradigm that ARMs are likely resistant to macrophages, another phagocytic cell, and that they are likely virulent towards humans and animals is only partially true. Indeed, we provide examples of the Chlamydiales order that challenge this assumption and suggest that the ability to multiply in protozoa does not strictly correlate with pathogenicity and that we should rather use the ability to replicate in multiple and diverse eukaryotic cells as an indirect marker of virulence towards mammals. Thus, cell‐culture‐based microbial culturomics should be used in the future to try to discover new pathogenic bacterial species.
Analysis of clinicopathological features of the echinoderm microtubule‐associated protein‐like‐4‐anaplastic lymphoma kinase fusion gene in Chinese patients with advanced non‐small‐cell lung cancer
Authors: Liu Yu‐Tao , Shi Yuan‐Kai , Hao Xue‐Zhi , Wang Lin , Li Jun‐Ling , Han Xiao‐Hong , Li Dan , Zhou Yu‐Jie , Tang Le
Published: February 2014

Background

The echinoderm microtubule‐associated protein‐like‐4‐anaplastic lymphoma kinase (EML4‐ALK) fusion gene defines a novel molecular subset of non‐small‐cell lung cancer (NSCLC). However, the clinicopathological features of patients with the EML4‐ALK fusion gene have not been defined completely.

Methods

Clinicopathological data of 200 Chinese patients with advanced NSCLC were analyzed retrospectively to explore their possible correlations with EML4‐ALK fusions.

Results

The EML4‐ALK fusion gene was detected in 56 (28.0%) of the 200 NSCLC patients, and undetected in 22 (11.0%) patients because of an insufficient amount of pathological tissue. The median age of the patients with positive and negative EML4‐ALK was 48 and 55 years, respectively. Patients with the EML4‐ALK fusion gene were significantly younger (P < 0.001). The detection rate of the EML4‐ALK fusion gene in patients who received primary tumor or metastatic lymph node resection was significantly higher than in patients who received fine‐needle biopsy (P = 0.003). The detection rate of the EML4‐ALK fusion gene in patients with a time lag from obtainment of the pathological tissue to EML4‐ALK fusion gene detection ≤48 months was significantly higher than in patients >48 months (P = 0.020). The occurrence of the EML4‐ALK fusion gene in patients with wild‐type epidermal growth factor receptor (EGFR) was significantly higher than in patients with mutant‐type EGFR (42.5% [37/87] vs. 6.3% [1/16], P = 0.005).

Conclusions

Younger age and wild‐type EGFR were identified as clinicopathological characteristics of patients with advanced NSCLC who harbored the EML4‐ALK fusion gene. The optimal time lag from the obtainment of the pathological tissue to the time of EML4‐ALK fusion gene detection is ≤48 months.
Genetic dissection of marbling trait through integration of mapping and expression profiling
Authors: Yamada Takahisa
Published: February 2014

Marbling traits, defined by the amount of intramuscular fat, has a heritable component and are quantitative in nature, being influenced by many genes of variable individual effects. The identification of the genetic variation associated with marbling is an important step toward the improvement of beef quality through breeding programs and the understanding of the biological network of marbling. A lot of genomic studies based on functional candidate gene approach and quantitative trait locus (QTL) mapping and many transcriptome studies based on expression profiling, respectively, provide information on variation in genomic regions and individual genes associated with marbling and of genes with marbling‐associated expression changes. Further, the integrative approach combining mapping and expression profiling data is proving useful for identifying the causal genes for marbling QTLs. Application of this integrative approach to our marbling study using a rat model, Otsuka Long‐Evans Tokushima Fatty (OLETF) rat and Japanese Black beef cattle is introduced finally in this review.
Effects of a breeding scheme combined by genomic pre‐selection and progeny testing on annual genetic gain in a dairy cattle population
Authors: Yamazaki Takeshi , Togashi Kenji , Iwama Satoru , Matsumoto Shigeo , Moribe Kimihiro , Nakanishi Takatoshi , Hagiya Koichi , Hayasaka Kiyoshi
Published: February 2014

The effectiveness of the incorporation of genomic pre‐selection into dairy cattle progeny testing (GS‐PT) was compared with that of progeny testing (PT) where the fraction of dam to breed bull (DB) selected was 0.01. When the fraction of sires to breed bulls (SB) selected without being progeny tested to produce young bulls (YB) in the next generation was 0.2, the annual genetic gain fromGS‐PTwas 13% to 43% greater when h2 = 0.3 and 16% to 53% greater when h2 = 0.1 compared with that fromPT. Given h2 = 0.3, a selection accuracy of 0.8 for bothYBandDB, and selected fractions of 0.117 forYBand 0.04 forDB,GS‐PTproduced 40% to 43% greater annual genetic gain thanPT. Given h2 = 0.1, a selection accuracy of 0.6 for bothYBandDB, and selected fractions of 0.117 forYBand 0.04 forDB, annual genetic gain fromGS‐PTwas 48% to 53% greater than that fromPT. When h2 = 0.3, progeny testing capacity had little effect on annual genetic gain fromGS‐PT. However, when h2 = 0.1, annual genetic gain fromGS‐PTincreased with increasing progeny testing capacity.
Changes in the composition of the extracellular matrix accumulated by mesenchymal stem cells duringin vitroexpansion
Authors: Nakamura Ryosuke , Nakamura Fumio , Fukunaga Shigeharu
Published: February 2014

One of the approaches to preserve the properties of mesenchymal stem cells (MSCs) duringin vitroexpansion is to use cell culture substrates.MSCsare known to generate the extracellular matrix (ECM) proper to preserve their proliferative capacityin vitro, but extensive expansion is considered to depriveMSCsof the capacity to prepare suchECM. In order to examine the features ofECMproper that is required to preserve the proliferative capacity ofMSCs, we analyzed the changes in the composition ofECMaccumulated byMSCsduringin vitroexpansion. Biochemical and immunological analysis showed that collagen and laminin content decreased during expansion. Immunofluorescence and ultrastructural analyses showed that theECMstructure changed from a dynamic fibrous, porous and steric structure to a static, crammed, and planar one. The results ofWestern blotting analysis suggested loose intermolecular association inECMmolecules accumulated by extensively proliferatedMSCs. TheECMprepared by extensively proliferatedMSCswas less effective to recover their proliferative capacity than that prepared by less proliferated cells. Our results suggest that a cell culture substrate to expandMSCsrequires abundance in collagen and basement membrane components, and steric, porous and fibrous structure in whichECMmolecules are tightly associated.
Effect of feeding garlic leaf on microbial nitrogen supply, kinetics of plasma phenylalanine, tyrosine and protein synthesis in sheep
Authors: Kamruzzaman Md. , Liang Xi , Sekiguchi Natsumi , Sano Hiroaki
Published: February 2014

The objective of the present study was to assess the feeding effects of garlic leaf on microbial N supply (MNS), turnover rates of plasma phenylalanine (PheTR) and tyrosine (TyrTR) and whole body protein synthesis (WBPS) in sheep. The sheep were fed either mixed hay (Hay‐diet, as control) or hay plus garlic leaf diet (GL‐diet, at a ratio of 9:1) in a crossover design each for a 21 day period. The isotope dilution method using [2H5]Phe and [2H2]Tyr was performed on the 21st day of each dietary treatment. Nitrogen intake remained similar between the diets and N absorption and N digestibility were higher (P < 0.05) in the GL‐diet than Hay‐diet. Total purine derivatives excretion and MNS were greater (P < 0.05) in the GL‐diet than the Hay‐diet. Plasma PheTR tended to be higher (P = 0.06) during GL feeding and TyrTR did not differ between the diets. Further, WBPS tended to be greater (P = 0.05) for the GL‐diet compared with the Hay‐diet. Hence, the present results suggest that garlic leaf may have positive effects on N metabolism by influencing MNS in sheep and could be used as a potential ruminant feed in the future.
Aggregates of Small Nuclear Ribonucleic Acids (snRNAs) in Alzheimer's Disease
Authors: Hales Chadwick M. , Dammer Eric B. , Diner Ian , Yi Hong , Seyfried Nicholas T. , Gearing Marla , Glass Jonathan D. , Montine Thomas J. , Levey Allan I. , Lah James J.
Published: February 2014

We recently discovered that protein components of the ribonucleic acid (RNA) spliceosome form cytoplasmic aggregates in Alzheimer's disease (AD) brain, resulting in widespread changes in RNA splicing. However, the involvement of small nuclear RNAs (snRNAs), also key components of the spliceosome complex, in the pathology of AD remains unknown. Using immunohistochemical staining of post‐mortem human brain and spinal cord, we identified cytoplasmic tangle‐shaped aggregates of snRNA in both sporadic and familial AD cases but not in aged controls or other neurodegenerative disorders. Immunofluorescence using antibodies reactive with the 2,2,7‐trimethylguanosine cap of snRNAs and transmission electron microscopy demonstrated snRNA localization with tau and paired helical filaments, the main component of neurofibrillary tangles. Quantitative real‐time polymerase chain reaction (PCR) showed U1 snRNA accumulation in the insoluble fraction of AD brains whereas other U snRNAs were not enriched. In combination with our previous results, these findings demonstrate that aggregates of U1 snRNA and U1 small nuclear ribonucleoproteins represent a new pathological hallmark of AD.
Different Dynamics of Aquaporin 4 and Glutamate Transporter‐1 Distribution in the Perineuronal and Perivascular Compartments during Ischemic Stroke
Authors: Mogoanta Laurentiu , Ciurea Marius , Pirici Ionica , Margaritescu Claudiu , Simionescu Cristiana , Ion Daniela A. , Pirici Daniel
Published: February 2014

Aquaporin‐4 (AQP4) and glutamate transporter‐1 (GLT‐1) represent the major water and glutamate astrocyte buffering gateways in the brain. Utilizing perilesional ischemic human cortices, we have performed here for the first time an integrative assessment on both AQP4 and GLT‐1, and on their proximity to blood vessels and neurons. Counting the relative number of AQP4±/GLT‐1±/glial fibrillary acidic protein± cells showed that double‐positive variants were overall most frequent, and their number tended to decrease from organized and recent perilesional cortices to controls. AQP4/GLT‐1 colocalization showed higher coefficients for the perilesional cortices compared with controls, suggesting an increased water/glutamate‐buffering capability. Distance frequency analysis of AQP4/GLT‐1 in relationship to neurons showed that both markers were concentrated at 20–40 μm around the perikarya; with AQP4 being more abundant in close proximity, these differences were not being driven by changes in neuropil density alone. Our study suggests a dual, simultaneous astrocytic function depending on the relative distance to neurons and vessels, with increased water and glutamate‐buffering capability in the mid perineuronal space, and an increased water‐buffering capability in the immediate perineuronal space, even higher than around vessels. Thus, adding specific AQP4/GLT‐1 modulator agents selectively depending on the acute/chronic phase of stroke might increase the efficacy of existing treatments.
Opioid receptor trafficking and interaction in nociceptors
Authors: Zhang X , Bao L , Li S
Published: February 2014

Opiate analgesics such as morphine are often used for pain therapy. However, antinociceptive tolerance and dependence may develop with long‐term use of these drugs. It was found that μ‐opioid receptors can interact with δ‐opioid receptors, and morphine antinociceptive tolerance can be reduced by blocking δ‐opioid receptors. Recent studies have shown that μ‐ and δ‐opioid receptors are co‐expressed in a considerable number of small neurons in the dorsal root ganglion. The interaction of μ‐opioid receptors with δ‐opioid receptors in the nociceptive afferents is facilitated by the stimulus‐induced cell‐surface expression of δ‐opioid receptors, and contributes to morphine tolerance. Further analysis of the molecular, cellular and neural circuit mechanisms that regulate the trafficking and interaction of opioid receptors and related signalling molecules in the pain pathway would help to elucidate the mechanism of opiate analgesia and improve pain therapy.

Linked Articles

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Acute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre‐activation of AMPK‐dependent autophagy
Authors: Jiang Teng , Yu Jin‐Tai , Zhu Xi‐Chen , Wang Hui‐Fu , Tan Meng‐Shan , Cao Lei , Zhang Qiao‐Quan , Gao Li , Shi Jian‐Quan , Zhang Ying‐Dong , Tan Lan
Published: February 2014

Background and Purpose

Recent clinical trials report that metformin, an activator of AMP‐activated protein kinase (AMPK) used to treat type 2 diabetes, significantly reduces the risk of stroke by actions that are independent of its glucose‐lowering effects. However, the underlying molecular mechanisms are not known. Here, we tested the possibility that acute metformin preconditioning confers neuroprotection by pre‐activation of AMPK‐dependent autophagy in a rat model of permanent middle cerebral artery occlusion (pMCAO).

Experimental Approach

Male Sprague‐Dawley rats were pretreated with either vehicle, an AMPK inhibitor, Compound C, or an autophagy inhibitor, 3‐methyladenine, and were injected with a single dose of metformin (10 mg kg−1, i.p.). Then, AMPK activity and autophagy biomarkers in the brain were assessed. At 24 h after metformin treatment, rats were subjected to pMCAO; infarct volume, neurological deficits and cell apoptosis were evaluated 24 and 96 h later.

Key Results

A single dose of metformin significantly activated AMPK and induced autophagy in the brain. The enhanced autophagic activity was inhibited by Compound C pretreatment. Furthermore, acute metformin preconditioning significantly reduced infarct volume, neurological deficits and cell apoptosis during a subsequent focal cerebral ischaemia. The neuroprotection mediated by metformin preconditioning was fully abolished by Compound C and partially inhibited by 3‐methyladenine.

Conclusions and Implications

These results provide the first evidence that acute metformin preconditioning induces autophagy by activation of brain AMPK, which confers neuroprotection against subsequent cerebral ischaemia. This suggests that metformin, a well‐known hypoglycaemic drug, may have a practical clinical use for stroke prevention.
Impaired neurogenesis by HIV‐1‐Gp120 is rescued by genetic deletion of fatty acid amide hydrolase enzyme
Authors: Avraham H K , Jiang S , Fu Y , Rockenstein E , Makriyannis A , Wood J , Wang L , Masliah E , Avraham S
Published: February 2014

Background and Purpose

The HIV‐envelope glycoprotein Gp120 is involved in neuronal injury and is associated with neuro‐AIDS pathogenesis in the brain. Endocannabinoids are important lipid ligands in the CNS regulating neural functions, and their degeneration is controlled by hydrolysing enzymes such as the fatty acid amide hydrolase (FAAH). Here, we examined whether in vivo genetic deletion of Faah gene prevents HIV‐1 Gp120‐mediated effects on neurogenesis.

Experimental Approach

We generated new GFAP/Gp120 transgenic (Tg) mice that have genetic deletion of Faah gene by mating glial fribillary acidic protein (GFAP)/Gp120 Tg mice with Faah−/− mice. Neurogenesis and cell death were assessed by immunocytochemical analysis.

Key Results

Endocannabinoid levels in the brain of the double GFAP/Gp120//Faah−/− mice were similar to those observed in Faah−/− mice. However, unlike the impaired neurogenesis observed in GFAP/Gp120 Tg mice and Faah−/− mice, these GFAP/Gp120//Faah‐/ mice showed significantly improved neurogenesis in the hippocampus, indicated by a significant increase in neuroblasts and neuronal cells, an increase in BrdU+ cells and doublecortin positive cells (DCX+), and an increase in the number of PCNA. Furthermore, a significant decrease in astrogliosis and gliogenesis was observed in GFAP/Gp120//Faah−/−mice and neurogenesis was stimulated by neural progenitor cells (NPCs) and/or the newly formed NPC niches characterized by increased COX‐2 expression and elevated levels of PGE2.

Conclusions and Implications

In vivo genetic ablation of Faah, resulted in enhanced neurogenesis through modulation of the newly generated NPC niches in GFAP/Gp120//Faah−/− mice. This suggests a novel approach of using FAAH inhibitors to enhance neurogenesis in HIV‐1 infected brain.
Targeting Rho‐GTPases in immune cell migration and inflammation
Authors: Biro Maté , Munoz Marcia A , Weninger Wolfgang
Published: February 2014

Leukocytes are unmatched migrators capable of traversing barriers and tissues of remarkably varied structural composition. An effective immune response relies on the ability of its constituent cells to infiltrate target sites. Yet, unwarranted mobilization of immune cells can lead to inflammatory diseases and tissue damage ranging in severity from mild to life‐threatening. The efficacy and plasticity of leukocyte migration is driven by the precise spatiotemporal regulation of the actin cytoskeleton. The small GTPases of the Rho family (Rho‐GTPases), and their immediate downstream effector kinases, are key regulators of cellular actomyosin dynamics and are therefore considered prime pharmacological targets for stemming leukocyte motility in inflammatory disorders. This review describes advances in the development of small‐molecule inhibitors aimed at modulating the Rho‐GTPase‐centric regulatory pathways governing motility, many of which stem from studies of cancer invasiveness. These inhibitors promise the advent of novel treatment options with high selectivity and potency against immune‐mediated pathologies.

Linked Articles

This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐24
ABT‐263 enhances sorafenib‐induced apoptosis associated with Akt activity and the expression of Bax and p21(CIP1/WAF1) in human cancer cells
Authors: Li Jingru , Chen Yicheng , Wan Jiali , Liu Xin , Yu Chunrong , Li Wenhua
Published: February 2014

Background and purpose

Sorafenib, a potent inhibitor that targets several kinases associated with tumourigenesis and cell survival, has been approved for clinical treatment as a single agent. However, combining sorafenib with other agents improves its anti‐tumour efficacy in various preclinical tumour models. ABT‐263, a second‐generation BH3 mimic, binds to the anti‐apoptotic family members Bcl‐2, Bcl‐xL and Bcl‐w, and has been demonstrated to enhance TNFSF10 (TRAIL)‐induced apoptosis in human hepatocarcinoma cells. Hence, we investigated the effects of ABT‐263 treatment combined with sorafenib.

Experimental Approach

The effects of ABT‐263 combined with sorafenib were investigated in vitro, on cell viability, clone formation and apoptosis, and the mechanism examined using western blot and flow cytometry. This combination was also evaluated in vivo, in a mouse xenograft model; tumour growth, volume and weights were measured and a TUNEL assay performed.

Key Results

ABT‐263 enhanced sorafenib‐induced apoptosis while sparing non‐tumourigenic cells. Although ABT‐263 plus sorafenib significantly stimulated intracellular reactive oxygen species production and subsequent mitochondrial depolarization, this was not sufficient to trigger cell apoptosis. ABT‐263 plus sorafenib significantly decreased Akt activity, which was, at least partly, involved in its effect on apoptosis. Bax and p21 (CIP1/WAF1) were shown to play a critical role in ABT‐263 plus sorafenib‐induced apoptosis. Combining sorafenib with ABT‐263 dramatically increased its efficacy in vivo.

Conclusion and Implications

The anti‐tumour activity of ABT‐263 plus sorafenib may involve the induction of intrinsic cell apoptosis via inhibition of Akt, and reduced Bax and p21 expression. Our findings offer a novel effective therapeutic strategy for tumour treatment.
Using viruses as nanomedicines
Authors: van Kan‐Davelaar H E , van Hest J C M , Cornelissen J J L M , Koay M S T
Published: February 2014

The field of nanomedicine involves the design and fabrication of novel nanocarriers for the intracellular delivery of therapeutic cargo or for use in molecular diagnostics. Although traditionally recognized for their ability to invade and infect host cells, viruses and bacteriophages have been engineered over the past decade as highly promising molecular platforms for the targeted delivery and treatment of many human diseases. Inherently biodegradable, the outer capsids of viruses are composed entirely of protein building blocks, which can be genetically or chemically engineered with molecular imaging reagents, targeting ligands and therapeutic molecules. While there are several examples of viruses as in vitro molecular cargo carriers, their potential for applications in nanomedicine has only recently emerged. Here we highlight recent developments towards the design and engineering of viruses for the treatment of cancer, bacterial infections and immune system‐related diseases.

Linked Articles

This article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐17
High‐resolution genomic copy number profiling of primary intraocular lymphoma by single nucleotide polymorphism microarrays
Authors: Wang Ludan , Sato‐Otsubo Aiko , Sugita Sunao , Takase Hiroshi , Mochizuki Manabu , Usui Yoshihiko , Goto Hiroshi , Koyama Takatoshi , Akiyama Hiroki , Miura Osamu , Ogawa Seishi , Arai Ayako
Published: February 2014

Primary intraocular lymphoma (PIOL) is a rare lymphoma. Because of difficulties in obtaining tissue samples, little is known about the disease's genetic features. In order to clarify these features, we carried out single nucleotide polymorphism array karyotyping of IOL using genomic DNA extracted from vitreous fluid. We analyzed 33 samples of IOLs consisting of 16 PIOLs, 12 IOLs with a central nervous system (CNS) lesion at diagnosis (IOCNSL), and five secondary IOLs following systemic lymphoma. All were B‐cell type. We identified recurrent copy number (CN) gain regions in PIOLs, most frequently on chromosome 1q followed by 18q and 19q. Chromosome 6q was the most frequent loss region. Although these CN gain regions of PIOL were in common with those of IOCNSL, loss of 6q22.33 containing PTPRK and 9p21.3 containing CDKN2A were more frequently deleted in IOCNSL. Large CN loss in 6q was detected in three of four PIOL patients who had early CNS development and short survival periods, whereas long‐term survivors did not have such deletions. There was a correlation between gain of the IL‐10 gene located on 1q and intravitreal interleukin‐10 concentration, which was higher in IOL than in benign uveitis. The results suggest that IOCNSL is a highly malignant form of PIOL that infiltrates into the CNS at an early stage. They also indicate that genetic differences between PIOL and primary CNS lymphoma need to be clarified.
Peptide Inhibitors Against Dengue Virus Infection
Authors: Panya Aussara , Bangphoomi Kunan , Choowongkomon Kiattawee , Yenchitsomanus Pa‐thai
Published: February 2014

Dengue virus (DENV) infection has become a public health problem worldwide. The development of anti‐DENV drug is urgently needed because neither licensed vaccine nor specific drug is currently available. Inhibition of DENV attachment and entry to host cells by blocking DENV envelope (E) protein is an attractive strategy for anti‐DENV drug development. A hydrophobic pocket on the DENV E protein is essential for structural transition in the membrane fusion, and inhibition of this process is able to inhibit DENV infection. To search for a safe anti‐DENV drug, we identified short peptides targeting the hydrophobic pocket by molecular docking. In addition, the information of predicted ligand‐binding site of reported active compounds of DENV2 hydrophobic pocket was also used for peptide inhibitors selection. The di‐peptide, EF, was the most effective on DENV2 infection inhibition in vitro with a half maximal inhibition concentration (IC50) of 96 μm. Treatment of DENV2 with EF at the concentration of 200 μm resulted in 83.47% and 84.15% reduction in viral genome and intracellular E protein, respectively. Among four DENV serotypes, DENV2 was the most effective for the inhibition. Our results provide the proof of concept for the development of therapeutic peptide inhibitors against DENV infection by the computer‐aided molecular design.
Synthesis and Anticonvulsant Activity of Ethyl 2,2‐dimethyl‐1‐(2‐substitutedhydrazinecarboxamido) Cyclopropanecarboxylate Derivatives
Authors: Zhong Min , Zhang Yongmin , He Xianran
Published: February 2014

In this study on the development of new anticonvulsants, fourteen ethyl 2,2‐dimethyl‐1‐(2‐substitutedhydrazinecarboxamido) cyclopropanecarboxylate derivatives were synthesized and tested for anticonvulsant activity using the maximal electroshock, subcutaneous pentylenetetrazole screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotorod test. Two compounds 6f and 6k showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 6k showed the maximal electroshock‐induced seizures with ED50 value of 9.2 mg/kg and TD50 value of 387.5 mg/kg after intraperitoneally injection to mice, which provided compound 6k with a protective index (TD50/ED50) of 42.1 in the maximal electroshock test.
Prevalence and risk factors of tinnitus: the Korean National Health and Nutrition Examination Survey 2010–2011, a cross‐sectional study
Authors: Park R.J. , Moon J.D.
Published: February 2014

Objectives

The aim of this study was to examine the association between tinnitus and several potential risk factors in Korean population.

Design

A cross‐sectional study.

Setting

Based on data from the fifth Korean National Health and Nutrition Examination Survey.

Participants

The study included 10 061 Korean individuals.

Main outcome measures

Tinnitus was assessed by using a questionnaire, and otorhinolaryngologic examination was conducted. Risk factors associated with tinnitus were evaluated using a multiple logistic regression analysis.

Results

Of the 10 061 participants ranging from 20 to 97 years old, the overall prevalence of any tinnitus was 21.4% and annoying tinnitus was 7.3%. In a multivariable logistic regression model, the following factors were associated with having tinnitus: occupational noise exposure [any tinnitus, odd ratio (OR) = 1.34; annoying tinnitus, OR = 1.47], non‐occupational noise exposure (any tinnitus, OR = 1.48; annoying tinnitus, OR = 2.02), hearing impairment (any tinnitus, OR = 2.27; annoying tinnitus, OR = 3.61), chronic otitis media (any tinnitus, OR = 1.53; annoying tinnitus, OR = 1.36), chronic rhinosinusitis (any tinnitus, OR = 1.38; annoying tinnitus, OR = 1.38), temporomandibular disorder (any tinnitus, OR = 1.69; annoying tinnitus, OR = 1.90), depression (any tinnitus, OR = 1.44; annoying tinnitus, OR = 1.70), and higher stress level (any tinnitus, OR = 1.28; annoying tinnitus, OR = 1.76).

Conclusions

These results suggest that tinnitus is common in Korea and may be associated with some avoidable risk factors.
Limonene hydroperoxide analogues show specific patch test reactions
Authors: Bråred Christensson Johanna , Hellsén Staffan , Börje Anna , Karlberg Ann‐Therese
Published: February 2014

Background

The fragrance terpene R‐limonene is a very weak sensitizer, but forms allergenic oxidation products upon contact with air. The primary oxidation products of oxidized limonene, the hydroperoxides, have an important impact on the sensitizing potency of the oxidation mixture. One analogue, limonene‐1‐hydroperoxide, was experimentally shown to be a significantly more potent sensitizer than limonene‐2‐hydroperoxide in the local lymph node assay with non‐pooled lymph nodes.

Objectives

To investigate the pattern of reactivity among consecutive dermatitis patients to two structurally closely related limonene hydroperoxides, limonene‐1‐hydroperoxide and limonene‐2‐hydroperoxide.

Methods

Limonene‐1‐hydroperoxide, limonene‐2‐hydroperoxide, at 0.5% in petrolatum, and oxidized limonene 3.0% pet. were tested in 763 consecutive dermatitis patients.

Results

Of the tested materials, limonene‐1‐hydroperoxide gave most reactions, with 2.4% of the patients showing positive patch test reactions. Limonene‐2‐hydroperoxide and oxidized R‐limonene gave 1.7% and 1.2% positive patch test reactions, respectively. Concomitant positive patch test reactions to other fragrance markers in the baseline series were frequently noted.

Conclusions

The results are in accordance with the experimental studies, as limonene‐1‐hydroperoxide gave more positive patch test reactions in the tested patients than limonene‐2‐hydroperoxide. Furthermore, the results support the specificity of the allergenic activity of the limonene hydroperoxide analogues and the importance of oxidized limonene as a cause of contact allergy.
Expression of HMGA2 in bladder cancer and its association with epithelial‐to‐mesenchymal transition
Authors: Ding X. , Wang Y. , Ma X. , Guo H. , Yan X. , Chi Q. , Li J. , Hou Y. , Wang C.
Published: February 2014

Objectives

High mobility group protein2 (HMGA2) and epithelial‐to‐mesenchymal transition are both related to progress of bladder cancer, however, the relationship between HMGA2, E‐cadherin and vimentin in bladder cancer is not yet known. Thus, this study has examined expression of HMGA2, E‐cadherin and vimentin in bladder cancer and investigated their relationship.

Materials and methods

The 5637 bladder cancer cell line and SV‐HUC‐1 normal uroepithelial cells were used to study expression of HMGA2, E‐cadherin and vimentin using RT‐PCR and western blotting. Paraffin wax‐embedded bladder cancer tissues were used to study protein expression using immunohistochemistry and χ2 analysis and Kendall's correlation were utilized statistical methods.

Results

Overexpression of HMGA2 was associated with down‐regulation of E‐cadherin and up‐regulation of vimentin in the 5637 bladder cancer line. A total of 49 paraffin wax‐embedded tissues of transitional cell bladder cancer were used. Positive expression levels of HMGA2 protein and vimentin were 41 and 43% in bladder tissues, respectively. No expression of E‐cadherin was found in 43%. Expression of HMGA2, loss of E‐cadherin and expression of vimentin are all significantly correlated with bladder cancer grade and stage. Loss of E‐cadherin and expression of vimentin both correlated with recurrence of the bladder cancer.

Conclusions

Expression of HMGA2 was closely associated with occurrence of epithelial‐to‐mesenchymal transition. Expression of HMGA2, loss of E‐cadherin and expression of vimentin may indicate high degree malignancy of bladder cancer. Loss of E‐cadherin expression and positive expression of vimentin may predict recurrence of bladder cancer.
Myasthenia and risk of cancer: a population‐based case–control study
Authors: Pedersen E. G. , Pottegård A. , Hallas J. , Friis S. , Hansen K. , Jensen P. E. H. , Gaist D.
Published: February 2014

Background and purpose

To evaluate the association between having non‐thymoma myasthenia and the risk of extra‐thymic cancer in a population‐based setting.

Methods

A nationwide case–control study was conducted in Denmark based on medical registries. The study included all cases with a first time diagnosis of cancer during 2000–2009. Each case was matched by birth year and gender with eight population controls using risk set sampling. Subjects with myasthenia were identified through a validated register‐based algorithm. Conditional logistic regression was used to compute crude and adjusted odds ratios (ORs), with 95% confidence intervals (CIs), for cancer associated with a prior diagnosis of myasthenia.

Results

In all, 233 437 cases and 1 867 009 controls were identified. A total of 80 cases and 518 controls had a prior diagnosis of myasthenia. Myasthenia was not associated with an increased risk of overall cancer (OR 1.1; 95% CI 0.9–1.4). Adjusted ORs for major cancer sites were also close to unity, whereas an elevated risk of lymphomas was observed (OR 2.0; 95% CI 0.8–5.5). Early‐onset myasthenia was associated with a slightly increased OR for overall cancer (1.5; 95% CI 1.0–2.3); however, this estimate was based on small numbers.

Conclusions

Non‐thymoma myasthenia was not associated with an increased risk of overall cancer. Larger studies are necessary to evaluate the association between myasthenia and risk of lymphoma and the potential effect modification by age of myasthenia onset in relation to cancer risk.
Role of GAD2 and HTR1B genes in early‐onset obsessive‐compulsive disorder: results from transmission disequilibrium study
Authors: Mas S. , Pagerols M. , Gassó P. , Ortiz A. , Rodriguez N. , Morer A. , Plana M. T. , Lafuente A. , Lazaro L.
Published: February 2014

One of the leading biological models of obsessive‐compulsive disorder (OCD) is the frontal‐striatal‐thalamic model. This study undertakes an extensive exploration of the variability in genes related to the regulation of the frontal‐striatal‐thalamic system in a sample of early‐onset OCD trios. To this end, we genotyped 266 single nucleotide polymorphisms (SNPs) in 35 genes in 84 OCD probands and their parents. Finally, 75 complete trios were included in the analysis. Twenty SNPs were overtransmitted from parents to early‐onset OCD probands and presented nominal pointwise P < 0.05 values. Three of these polymorphisms achieved P < 2 × 10−4, the significant P‐value after Bonferroni corrections: rs8190748 and rs992990 localized in GAD2 and rs2000292 in HTR1B. When we stratified our sample according to gender, different trends were observed between males and females. In males, SNP rs2000292 (HTR1B) showed the lowest P‐value (P = 0.0006), whereas the SNPs in GAD2 were only marginally significant (P = 0.01). In contrast, in females HTR1B polymorphisms were not significant, whereas rs8190748 (GAD2) showed the lowest P‐value (P = 0.0006). These results are in agreement with several lines of evidence that indicate a role for the serotonin and γ‐Aminobutyric acid (GABA) pathways in the risk of early‐onset OCD and with the gender differences in OCD pathophysiology reported elsewhere. However, our results need to be replicated in studies with larger cohorts in order to confirm these associations.
Dental care utilization among older adults with cognitive impairment in the USA
Authors: Lee Kyung Hee , Wu Bei , Plassman Brenda L
Published: February 2014

Aim

We examined the relationship between cognitive impairment and dental care utilization among older adults in the USA.

Methods

A total of 329 older adults aged 70 years and older in West Virginia, USA, were included in the present analyses. We carried out multivariate ordinal regression analyses.

Results

Individuals with dementia were less likely to visit a dentist regularly, and more time had passed since their last dental visit compared with individuals with normal cognitive function. However, the pattern of dental care utilization for those with cognitive impairment, not dementia did not differ from individuals with normal cognition. A perceived greater social network and having dental insurance were associated with increased dental care utilization.

Conclusions

Less dental care utilization might contribute to the oral health problems often observed among individuals with dementia. Efforts to increase the use of dental care should include cost‐effective options for dental insurance. In addition, educating formal and informal caregivers on the importance of dental care might be beneficial, as these individuals are in the best position to facilitate dental care for individuals with dementia. Geriatr Gerontol Int 2015; 15: 255–260.
Varying Costs to Change? Institutional Change in the Public Sector
Authors: Gingrich Jane
Published: February 2014

Many scholars have argued that social programs are marked by a logic of “increasing returns” that makes change difficult. Yet over the past decades, reformers across industrialized countries have introduced substantial administrative reforms in these services, even as entitlement reform remains politically difficult. This paper explains these shifts by breaking apart the logic of “increasing returns” into three distinct “costs to change”: technical, political, and expectations. Decreases in a particular type of costs produce different logics of institutional change—back end, informal, and front end—that privilege the state, professionals or private, or political actors in distinct ways. I support these claims by reexamining three cases that were considered exemplars of stability but that ultimately had major entitlement reform: health care in theUnitedKingdom andUnitedStates and welfare programs in theUnitedStates. I show that even before radical reforms occurred, reformers introduced distinct logics of administrative change that underpinned later changes.
Preservation of Fusobacterium nucleatum and Peptostreptococcus anaerobius DNA after loss of cell viability
Authors: Brundin M. , Figdor D. , Sundqvist G. , Sjögren U.
Published: February 2014

Aim

To investigate whether DNA from two obligate anaerobes, Fusobacterium nucleatum and Peptostreptococcus anaerobius, is recoverable after loss of cell viability induced by air exposure.

Methodology

Harvested cultures of F. nucleatum and P. anaerobius were killed by exposure to air and stored in phosphate‐buffered saline. Dead cells were incubated aerobically for up to 6 months. Every month, the presence of detectable DNA in the cell pellet and supernatant was assessed by conventional and quantitative PCR. Cell staining techniques were used to characterize the cell wall permeability of air‐killed cells. Scanning electron microscopy was used to examine viable, freshly killed and stored cells.

Results

With conventional PCR, amplifiable DNA was detectable over 6 months in all samples. Quantitative PCR showed a progressive fall in DNA concentration in nonviable cell pellets and a concomitant rise in DNA concentration in the supernatant. DNA staining showed that some air‐killed cells retained an intact cell wall. After storage, SEM of both air‐killed species revealed shrivelling of the cells, but some cells of P. anaerobius retained their initial form.

Conclusion

Amplifiable DNA from F. nucleatum and P. anaerobius was detectable 6 months after loss of viability. Air‐killed anaerobes initially retained their cell form, but cells gradually shriveled over time. The morphological changes were more pronounced with the gram‐negative F. nucleatum than the gram‐positive P. anaerobius. Over 6 months, there was a gradual increase in cell wall permeability with progressive leakage of DNA. Bacterial DNA was recoverable long after loss of cell viability.
Absence of interleukin 22 affects the oral microbiota and the progression of induced periapical lesions in murine teeth
Authors: de Oliveira K. M. H. , da Silva R. A. B. , De Rossi A. , Fukada S. Y. , Feres M. , Nelson‐Filho P. , da Silva L. A. B.
Published: February 2014

Aim

To evaluate the absence of IL‐22 on the progression of periapical lesions in wild‐type (WT) and IL‐22 knockout (IL‐22 KO) mice.

Methodology

The evaluation of the oral microbial profile of mice was performed by Checkerboard DNA–DNA hybridization from saliva samples. Periapical lesions were induced in manbibular first molars by pulpal exposure and evaluated after 7, 21 and 42 days (n = 15). Haematoxylin‐eosin‐stained sections were analysed under conventional and fluorescence microscopy to evaluate the tissue features and size of periapical lesions and tartrate‐resistant acid phosphatase histoenzymology (TRAP), Brown & Brenn staining and immunohistochemistry. The scores of the number of bacterial cells present in the oral cavity were analysed by the Mann–Whitney test, and the results and comparisons for periapical lesion size and number of osteoclasts were subjected to one‐way anova and Bonferroni's post‐test (α = 0.05).

Results

Significant differences were observed for bacterial load between the groups of animals for 6 bacterial species (P < 0.05), with five species found in higher levels in the WT group, and one in the IL‐22 KO group. WT mice had significantly larger periapical lesions (P < 0.05) between 7 and 42 days and between 21 and 42 days, with an increase in the mean size and number of osteoclasts. IL‐22 KO mice had an increase in periapical lesion size and number of osteoclasts between 7 and 21 days (P < 0.05). No differences were found between bacteria localization in the root canal system between the experimental groups. Small variations related to the location of immunostaining were found between the groups.

Conclusion

This study revealed differences in the composition of oral microbiota between mice that may be taken into account in the susceptibility to infections and development of periapical lesions. The absence of IL‐22 in mice resulted in smaller periapical lesions with fewer osteoclasts at the final experimental period, suggesting the participation of IL‐22 in the host immune and inflammatory response to a periradicular infection.
Structural and Electrical Properties of Ni‐Substituted Mg‐Mn Nanoferrite by Coprecipitation Route
Authors: Chitra Subbiah Rammohan , Sendhilnathan Sechasalom
Published: February 2014

Ni2+ ions doped on Mg0.40Mn0.60‐xNixFe2O4 compositions with 0.00 ≤ x ≤ 0.60 have been synthesized by coprecipitation method and taken for the present work to study the dielectric properties and impedance characterization using the XRD and electrical measurements. The X‐ray diffraction and FT‐IR revealed that the ferrite has single‐phase cubic spinel structure. The calculated particle size from XRD data verified using SEM as well as AFM. These photographs show that the ferrites have crystalline size in the range of 20–50 nm. It was observed that the particle size decreased and Ni concentration increased. The dielectric constant and dielectric loss decreased with increase in nonmagnetic Ni2+ ions. Electrical properties indicate that synthesized nanoferrite particles have high resistivity.
Production of oligosaccharides from coconut meal by subcritical water treatment
Authors: Khuwijitjaru Pramote , Pokpong Areewan , Klinchongkon Khwanjai , Adachi Shuji
Published: February 2014

Coconut meal, a by‐product from coconut milk production, was hydrolysed via subcritical water treatment at various maximum temperatures in the range of 100–300 °C using a batch‐type vessel under nonisothermal conditions. The effect of the treatment temperature and time was evaluated using the severity factor (R0) as a parameter. The highest yield of mono‐ and oligosaccharides (28.3 g/100 g dry coconut meal) was obtained at lnR0 = 10.4 (maximum temperature of 250 °C within the treatment time of 14 min). At higher temperature, degradation of the saccharides was observed and a large quantity of 5‐hydroxymethyl‐2‐furaldehyde was detected. The hydrolysates contained mannose, glucose and manno‐oligosaccharides with various degrees of polymerisation. The yield and ratio of saccharide components were affected by variation of the ratio of coconut meal to water used in the subcritical water treatment.