bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of incretin‐based therapies and sodium‐glucose co‐transporter‐2 inhibitors as adjuncts to insulin therapy in Type 2 diabetes, with special reference to IDegLira
Authors: Wilding J. P. H. , Bain S. C.
Published: November 2015

The progressive nature of Type 2 diabetes necessitates treatment intensification over time in order to maintain glycaemic control, with many patients ultimately requiring insulin therapy. While insulin has unlimited potential efficacy, its initiation is often delayed and improvements in glycaemic control are typically accompanied by weight gain and an increased risk of hypoglycaemia, particularly as HbA1c approaches and falls below target levels. This may account for the sub‐optimal control often achieved after insulin initiation. Combining insulin with antihyperglycaemic therapies that have a low risk of hypoglycaemia and are weight‐neutral or result in weight loss is a therapeutic strategy with the potential to improve Type 2 diabetes management. Although the effects differ with each individual class of therapy, clinical trials have shown that adding a glucagon‐like peptide‐1 receptor agonist, dipeptidyl peptidase‐4 inhibitor or sodium‐glucose co‐transporter‐2 inhibitor to insulin regimens can offer a significant reduction in HbA1c without substantially increasing hypoglycaemia risk, or weight. The evidence and merit of each approach are reviewed in this paper. Once‐daily co‐formulations of a basal insulin and a glucagon‐like peptide‐1 receptor agonist have been developed (insulin degludec/liraglutide) or are under development (lixisenatide/insulin glargine). Insulin degludec/liraglutide phase III trials and a lixisenatide/insulin glargine phase II trial have shown robust HbA1c reductions, with weight loss and a low risk of hypoglycaemia. With insulin degludec/liraglutide now approved in Europe, an important consideration will be the types of patients who may benefit most from a fixed‐ratio combination; this is discussed in the present review, and we also take a look toward future developments in the field.
Archeological Echocardiography: Digitization and Speckle Tracking Analysis of Archival Echocardiograms in the HyperGEN Study
Authors: Aguilar Frank G. , Selvaraj Senthil , Martinez Eva E. , Katz Daniel H. , Beussink Lauren , Kim Kwang‐Youn A. , Ping Jie , Rasmussen‐Torvik Laura , Goyal Amita , Sha Jin , Irvin Marguerite R. , Arnett Donna K. , Shah Sanjiv J.
Published: November 2015

Background

Several large epidemiologic studies and clinical trials have included echocardiography, but images were stored in analog format and these studies predated tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE). We hypothesized that digitization of analog echocardiograms, with subsequent quantification of cardiac mechanics using STE, is feasible, reproducible, accurate, and produces clinically valid results.

Methods

In the NHLBI HyperGEN study (N = 2234), archived analog echocardiograms were digitized and subsequently analyzed using STE to obtain tissue velocities/strain. Echocardiograms were assigned quality scores and inter‐/intra‐observer agreement was calculated. Accuracy was evaluated in: (1) a separate second study (N = 50) comparing prospective digital strain versus post hoc analog‐to‐digital strain, and (2) in a third study (N = 95) comparing prospectively obtained TDI e’ velocities with post hoc STE e’ velocities. Finally, we replicated previously known associations between tissue velocities/strain, conventional echocardiographic measurements, and clinical data.

Results

Of the 2234 HyperGEN echocardiograms, 2150 (96.2%) underwent successful digitization and STE analysis. Inter/intra‐observer agreement was high for all STE parameters, especially longitudinal strain (LS). In accuracy studies, LS performed best when comparing post hoc STE to prospective digital STE for strain analysis. STE‐derived e’ velocities correlated with, but systematically underestimated, TDI e’ velocity. Several known associations between clinical variables and cardiac mechanics were replicated in HyperGEN. We also found a novel independent inverse association between fasting glucose and LS (adjusted β = −2.4 [95% CI −3.6, −1.2]% per 1‐SD increase in fasting glucose; P < 0.001).

Conclusions

Archeological echocardiography, the digitization and speckle tracking analysis of archival echocardiograms, is feasible and generates indices of cardiac mechanics similar to contemporary studies.
Various aspects of barefoot methodology relevant to farriery in equine veterinary practice
Authors: O'Grady S. E.
Published: November 2015

The structures of the equine foot have the unique ability to adapt, change shape and restore. There are multiple benefits in shod vs. barefoot or in allowing the horse to be without shoes for a given time period to improve the palmar section of the foot. However, it requires a transition period, a change in the manner in which the foot is trimmed, a commitment from the owner/trainer and, in the case of leaving the horse without shoes permanently, it depends whether the horse can perform the desired function without shoes.
Severe eosinophilic cholangiohepatitis due to fluke infestation in a pony in Scotland
Authors: Raftery A. G. , Berman K. G. , Sutton D. G. M.
Published: November 2015

Fasciola hepatica infestation is reported as a cause of severe eosinophilic cholangiohepatitis in a 28‐year‐old Warmblood cross pony gelding. The gelding presented initially for investigation of acute laminitis found to be secondary to pars pituitary intermedia dysfunction (PPID). Six weeks of treatment including administration of pergolide achieved good control of the laminitis but there was a marked general clinical deterioration over this period with notable weight loss, tachycardia, anorexia and ventral oedema. Hepatobiliary enzymes were increased significantly and there was mild elevation of plasma bile acid concentration. An eosinophilia in both blood and peritoneal fluid specimens and histopathological confirmation of an eosinophilic cholangiohepatitis on examination of liver biopsies supported a primary parasitic aetiology. The pony was treated for Fasciola hepatica with triclabendazole 12 mg/kg bwt but clinical signs continued to progress. Due to poor clinical response the pony was subjected to euthanasia and post mortem examination revealed an overwhelming infestation of the biliary tracts with Fasciola hepatica and a secondary chronic and severe cholangiohepatitis with marked fibrosis. To the authors' knowledge this is the first equine report demonstrating the relationship between the clinical disease syndrome, eosinophilic cholangiohepatitis and hepatic fluke infestation. Depending on geographical location, fasciolosis should be considered as a differential diagnosis for equine hepatopathies and can result in severe disease.
Equine orbital disease: A review
Authors: Pucket J. D.
Published: November 2015

The purpose of this review is to discuss orbital disease in horses and how it pertains to the unique anatomy as well as the clinical presentation, diagnostics and aetiologies of orbital disease in this species.
Agronomic improvements can make future cereal systems in South Asia far more productive and result in a lower environmental footprint
Authors: Ladha Jagdish Kumar , Rao Adusumilli Narayana , Raman Anitha K. , Padre Agnes Tirol , Dobermann Achim , Gathala Mahesh , Kumar Virender , Saharawat Yashpal , Sharma Sheetal , Piepho Hans Peter , Alam Md Mursedul , Liak Ranjan , Rajendran Ramasamy , Reddy Chinnagangannagari Kesava , Parsad Rajender , Sharma Parbodh C. , Singh Sati shankar , Saha Abhijit , Noor Shamsoon
Published: November 2015

South Asian countries will have to double their food production by 2050 while using resources more efficiently and minimizing environmental problems. Transformative management approaches and technology solutions will be required in the major grain‐producing areas that provide the basis for future food and nutrition security. This study was conducted in four locations representing major food production systems of densely populated regions of South Asia. Novel production‐scale research platforms were established to assess and optimize three futuristic cropping systems and management scenarios (S2, S3, S4) in comparison with current management (S1). With best agronomic management practices (BMPs), including conservation agriculture (CA) and cropping system diversification, the productivity of rice‐ and wheat‐based cropping systems of South Asia increased substantially, whereas the global warming potential intensity (GWPi) decreased. Positive economic returns and less use of water, labor, nitrogen, and fossil fuel energy per unit food produced were achieved. In comparison with S1, S4, in which BMPs, CA and crop diversification were implemented in the most integrated manner, achieved 54% higher grain energy yield with a 104% increase in economic returns, 35% lower total water input, and a 43% lower GWPi. Conservation agriculture practices were most suitable for intensifying as well as diversifying wheat–rice rotations, but less so for rice–rice systems. This finding also highlights the need for characterizing areas suitable for CA and subsequent technology targeting. A comprehensive baseline dataset generated in this study will allow the prediction of extending benefits to a larger scale.
Relative contribution of four nucleases, CtIP, Dna2, Exo1 and Mre11, to the initial step of DNA double‐strand break repair by homologous recombination in both the chicken DT40 and human TK6 cell lines
Authors: Hoa Nguyen Ngoc , Akagawa Remi , Yamasaki Tomomi , Hirota Kouji , Sasa Kentaro , Natsume Toyoaki , Kobayashi Junya , Sakuma Tetsushi , Yamamoto Takashi , Komatsu Kenshi , Kanemaki Masato T. , Pommier Yves , Takeda Shunichi , Sasanuma Hiroyuki
Published: November 2015

Homologous recombination (HR) is initiated by double‐strand break (DSB) resection, during which DSBs are processed by nucleases to generate 3′ single‐strand DNA. DSB resection is initiated by CtIP and Mre11 followed by long‐range resection by Dna2 and Exo1 in Saccharomyces cerevisiae. To analyze the relative contribution of four nucleases, CtIP, Mre11, Dna2 and Exo1, to DSB resection, we disrupted genes encoding these nucleases in chicken DT40 cells. CtIP and Dna2 are required for DSB resection, whereas Exo1 is dispensable even in the absence of Dna2, which observation agrees with no developmental defect in Exo1‐deficient mice. Despite the critical role of Mre11 in DSB resection in S. cerevisiae, loss of Mre11 only modestly impairs DSB resection in DT40 cells. To further test the role of CtIP and Mre11 in other species, we conditionally disrupted CtIP and MRE11 genes in the human TK6 B cell line. As with DT40 cells, CtIP contributes to DSB resection considerably more significantly than Mre11 in TK6 cells. Considering the critical role of Mre11 in HR, this study suggests that Mre11 is involved in a mechanism other than DSB resection. In summary, CtIP and Dna2 are sufficient for DSB resection to ensure efficient DSB repair by HR.
A feasibility study of Lactobacillus plantarum in fruit powders after processing and storage
Authors: Borges Sandra , Barbosa Joana , Silva Joana , Gomes Ana M. , Pintado Manuela , Silva Cristina L. M. , Morais Alcina M. M. B. , Teixeira Paula
Published: November 2015

The aim of this study was to develop fruit powders (apple, banana and strawberry) enriched with a probiotic strain (Lactobacillus plantarum 299v). Two methodologies were proposed: (i) drying of the fruit with probiotic culture incorporated (by convection) or (ii) drying of fruit (by convection) and addition of spray‐dried probiotic culture. In the first methodology, processing caused a notable reduction in probiotic viable counts in apple, but this reduction was lower during drying of banana and strawberry. A large reduction in viable cells was also recorded during storage. In the second methodology, the survival of L. plantarum 299v was considerably higher during spray‐drying, and fruit powders with a microbial content suitable for a probiotic food (108–109 cfu g−1) were obtained. The fruit powders incorporating L. plantarum 299v can be stored at 4 °C or at room temperature, for at least 3 months. This preliminary study demonstrated that fruit powders are good carriers of probiotic cultures, but the techniques used to produce them should be carefully considered.
Has Migration Been Beneficial for Migrants and Their Children?
Authors: Zuccotti Carolina V. , Ganzeboom Harry B. G. , Guveli Ayse
Published: November 2015

The study compares the social mobility and status attainment of first-and second-generation Turks in nine Western European countries with those of Western European natives and with those of Turks in Turkey. It shows that the children of low-class migrants are more likely to acquire a higher education than their counterparts in Turkey, making them more educationally mobile. Moreover, they successfully convert this education in the Western European labor market, and are upwardly mobile relative to the first generation. When comparing labor market outcomes of second generations relative to Turks in Turkey, however, the results show that the same level of education leads to a higher occupation in Turkey. The implications of these findings are discussed.
EU, US and ASEAN Actorness in G20 Financial Policy‐Making: Bridging the EU Studies–New Regionalism Divide
Authors: Murau Steffen , Spandler Kilian
Published: November 2015

This article compares the European Union's (EU) actorness in foreign financial policy to that of the US and ASEAN. It thus contributes to the dialogue between EU studies and the New Regionalism by putting it into practice through comparative research. It argues that a process‐oriented interpretation of the actorness concept can be used to compare the EU to both nation‐states and international organizations at the same time. This makes it possible to examine the ‘nature of the beast’ in specific foreign policy contexts on empirical grounds. The case study analyses EU, US and ASEAN actorness in the IMF reform negotiations within the G20 framework. The findings suggest that a ‘two‐way comparison’ of the EU is not only possible but also provides valuable empirical insights into the role of informal politics in the EU and other regions.
It Takes Two? An Exploration of Processes and Outcomes in a Two‐Session Couple Intervention
Authors: Bradford Kay , Mock D. Jim , Stewart J. Wade
Published: November 2015

Although relationship distress is common, couples often forego professional help due to concerns such as time constraints, financial costs, and stigma. The two‐session relationship checkup is an alternative format of couple intervention developed to address these concerns. In this qualitative study, we interviewed 20 coupled participants and six clinicians to examine the checkup's processes and outcomes. The phenomenological themes that emerged revealed sequential processes by which this format works. Couple themes included client motivation, the therapeutic relationship, and therapeutic change in terms of perceptions and behaviors—particularly with regard to communication. Clinician data largely mirrored these themes. The results suggest the intervention addressed barriers to help‐seeking and may be a viable selective option for at‐risk couples.
Remarkable impairment of Wnt/β‐catenin signaling in the brains of the mice infected with scrapie agents
Authors: Sun Jing , Wang Hui , Chen Li‐Na , Wang Jing , Lv Yan , Yang Xiao‐Dong , Zhang Bao‐Yun , Tian Chan , Shi Qi , Dong Xiao‐Ping
Published: November 2015

Prion diseases are a group of neurodegenerative diseases characterized by neuronal loss and spongiform degeneration, astrogliosis and aggregation of scrapie prion protein (PrPSc) in the central nervous system (CNS). The Wnt signaling pathway is a highly evolutionarily conserved pathway in eukaryotes that regulates cell proliferation, differentiation and survival. Impairment of Wnt/β‐catenin signaling has been reported in the CNS of various neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. To investigate the functional state of Wnt/β‐catenin signaling in the CNS tissues during the progression of prion disease, the components of Wnt/β‐catenin signaling in the brains of the scrapie agents 139A‐ and ME7‐infected mice were evaluated. Compared with the normal controls, the brain levels of phosphor‐β‐catenin (Ser33,37 and Thr41) in 139A‐ and ME7‐infected mice were significantly increased, while those of cyclin D1, which is one of the target genes of Wnt signaling, were decreased. The levels of phosphor‐glycogen synthase kinase‐3β (GSK‐3β) Ser9 were markedly reduced, representing an enhanced GSK‐3β activity in scrapie‐infected mice. Both western blot and immunohistochemical assays revealed a remarkable increase of Dickkopf‐1, the antagonist of Wnt/β‐catenin signaling, in the brains of scrapie‐infected anim‐als, which co‐localized well with the remaining neurons in the immunofluorescent tests. We also observed slightly decreased Wnt‐3 and unchanged disheveled‐3 (Dvl‐3) in the brains of the infected mice. Our data, here, strongly indicate an impairment of Wnt/β‐catenin pathway in the brains of prion disease, which shows a time‐dependent progression along with the incubation period.

image

Schematic for the impairment of canonical Wnt signaling during prion infection. The left and right parts represent the normal and prion‐infected situations, respectively. Prion infection or PrPSc accumulation triggers the over‐expression of Dickkopf WNT signaling pathway inhibitor 1 (DKK‐1) and the enhancement of glycogen synthase kinase 3β (GSK‐3β) activity, which subsequently promotes the phosphorylation and degradation of β‐catenin. As a result, the impairment of β‐catenin signaling leads to the down‐regulation of Wnt target genes.
No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic‐ischemic brain injury in the neonatal rat
Authors: Berger Hester R. , Morken Tora Sund , Vettukattil Riyas , Brubakk Ann‐Mari , Sonnewald Ursula , Widerøe Marius
Published: November 2015

Mitochondrial impairment is a key feature underlying neonatal hypoxic‐ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used 1H and 13C NMR spectroscopy after injection of [1‐13C]glucose and [1,2‐13C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7‐day‐old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia‐ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism.

image

Neuronal and astrocytic metabolism was examined by 13C and 1H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic‐ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia‐ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism.
Striatal adenosine–cannabinoid receptor interactions in rats over‐expressing adenosine A2A receptors
Authors: Chiodi Valentina , Ferrante Antonella , Ferraro Luca , Potenza Rosa Luisa , Armida Monica , Beggiato Sarah , Pèzzola Antonella , Bader Michael , Fuxe Kjell , Popoli Patrizia , Domenici Maria Rosaria
Published: November 2015

Adenosine A2A receptors (A2ARs) and cannabinoid CB1 receptors (CB1Rs) are highly expressed in the striatum, where they functionally interact and form A2A/CB1 heteroreceptor complexes. We investigated the effects of CB1R stimulation in a transgenic rat strain over‐expressing A2ARs under the control of the neural‐specific enolase promoter (NSEA2A rats) and in age‐matched wild‐type (WT) animals. The effects of the CB1R agonist WIN 55,212‐2 (WIN) were significantly lower in NSEA2A rats than in WT animals, as demonstrated by i) electrophysiological recordings of synaptic transmission in corticostriatal slices; ii) the measurement of glutamate outflow from striatal synaptosomes and iii) in vivo experiments on locomotor activity. Moreover, while the effects of WIN were modulated by both A2AR agonist (CGS 21680) and antagonists (ZM 241385, KW‐6002 and SCH‐442416) in WT animals, the A2AR antagonists failed to influence WIN‐mediated effects in NSEA2A rats. The present results demonstrate that in rats with genetic neuronal over‐expression of A2ARs, the effects mediated by CB1R activation in the striatum are significantly reduced, suggesting a change in the stoichiometry of A2A and CB1 receptors and providing a strategy to dissect the involvement of A2AR forming or not forming heteromers in the modulation of striatal functions. These findings add additional evidence for the existence of an interaction between striatal A2ARs and CB1Rs, playing a fundamental role in the regulation of striatal functions.

image

We studied A2A‐CB1 receptor interaction in transgenic rats over‐expressing adenosine A2A receptors under the control of the neuron‐specific enolase promoter (NSEA2A). In these rats, we demonstrated a reduced effect of the CB1 receptor agonist WIN 55,212‐2 in the modulation of corticostriatal synaptic transmission and locomotor activity, while CB1 receptor expression level did not change with respect to WT rats. A reduction in the expression of A2A‐CB1 receptor heteromers is postulated.

Read the Editorial Highlight for this article on page 897.
The development of a questionnaire to evaluate rheumatoid arthritis patient's knowledge about methotrexate
Authors: Fayet Françoise , Savel Carine , Rodere Malory , Pereira Bruno , Abdi Dihya , Mathieu Sylvain , Tournadre Anne , Soubrier Martin , Dubost Jean‐Jacques
Published: November 2015

Aims and objectives

Assess knowledge concerning methotrexate in rheumatoid arthritis patients by means of a questionnaire.

Background

Methotrexate is the standard drug for rheumatoid arthritis treatment. It has potentially serious side effects that can be largely prevented by making sure that patients are well informed and comply with prescription guidelines.

Design

Cross‐sectional survey.

Methods

A questionnaire on methotrexate (mode of action, administration, drug interactions), side effects, monitoring and lifestyle implications was offered to all the rheumatoid arthritis patients treated with the drug seen between March and September 2013 in a large hospital in France.

Results

One hundred and eighty‐three patients (143 women), mean age 60 (13·5) years, with a median disease duration of 12 years [7–20] and treated with methotrexate for eight years [5–13] took part. Methotrexate was identified as a disease‐modifying antirheumatic drug by 78% of the patients. The weekly administration method was well assimilated (97%); 67% indicated that the rationale for folic acid was to reduce treatment toxicity. Only 21% knew that trimethoprim was contraindicated. Half were aware of the haematologic risk and 36% were aware of the risk of hypersensitivity pneumonitis. There was knowledge concerning laboratory testing (80%), but 54% thought they were only being monitored for rheumatoid arthritis activity. Only 13% of the men, but 90% of the women, of childbearing age knew that contraception was essential, and 75% indicated that alcohol consumption should be limited. A low knowledge score correlated significantly with age and low educational level. It was independent of sex, duration of treatment for rheumatoid arthritis.

Conclusions

Rheumatoid arthritis patient's knowledge concerning methotrexate is poor, particularly for the most serious side effects (haematologic and hypersensitivity pneumonitis), interactions with trimethoprim, and in men, the need for contraception.

Relevance to clinical practice

Patient knowledge concerning methotrexate should be regularly checked and supported using the different therapeutic education tools available, especially when patients are older people and have had limited schooling.
Global DNA hypomethylation is associated with the development and poor prognosis of tongue squamous cell carcinoma
Authors: Chen Hung‐Chih , Yang Cheng‐Mei , Cheng Jiin‐Tsuey , Tsai Kuo‐Wang , Fu Ting‐Ying , Liou Huei‐Han , Tseng Hui‐Hwa , Lee Jang‐Hwa , Li Guan‐Cheng , Wang Jyh‐Seng , Hou Yu‐Yi , Weng Ta‐Jung , Ger Luo‐Ping
Published: November 2015

Backgrounds

Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well‐known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC.

Methods

The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues.

Results

We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease‐specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I‐II, P = 0.046), small tumor size (T1–T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009).

Conclusions

Global hypomethylation was an independent biomarker for the development and poor prognosis of TSCC.
E‐cadherin regulators are differentially expressed in the epithelium and stroma of keratocystic odontogenic tumors
Authors: Porto Lia Pontes Arruda , dos Santos Jean Nunes , Ramalho Luciana Maria Pedreira , Figueiredo Andreia Leal , Carneiro Júnior Bráulio , Gurgel Clarissa Araújo , Paiva Katiúcia Batista Silva , Xavier Flávia Caló Aquino
Published: November 2015

Background

The epithelial–mesenchymal transition (EMT) is the process where cells lose their epithelial features and acquire properties of typical mesenchymal cells. The dissociation of tumor cells due to changes in cell–cell adhesion is one of the key principles of tumor invasion and EMT. Thus, the knowledge of the molecular features of EMT in keratocyst odontogenic tumor (KOT) can provide useful markers to aid in the diagnosis and prognosis and perhaps contribute to an alternative therapeutic approach as it shows an aggressive clinical behavior and high recurrence rates. This study aimed to evaluate the EMT in KOT by the immunoexpression of E‐cadherin, N‐cadherin, Snail, and Slug and comparing to radicular cysts and dental follicles.

Methods

Thirty‐two KOTs, 15 radicular cysts, and 08 dental follicles were used for immunohistochemistry, evaluating the extent, intensity, labeling pattern, cellular compartment in the epithelium and stroma, and the presence of inflammation.

Results

E‐cadherin was preserved in most cases of keratocystic odontogenic tumor. N‐cadherin was increased in the tumor epithelium, a result that was positively correlated with the heterogeneous and nuclear immunoexpression of Slug in the epithelium; Slug also correlated with high Snail immunoexpression. N‐cadherin was positively correlated with Slug in the stroma of keratocystic odontogenic tumors.

Conclusions

The high immunoexpression of Snail and nuclear Slug in keratocystic odontogenic tumors suggests these proteins as transcription factors without necessarily participating in ‘cadherin switching’. However, the knowledge of their induction of the epithelial–mesenchymal transition in odontogenic tumors is still limited.
New Host Record of Myrothecium roridum Causing Leaf Spot on Abutilon megapotamicum from China
Authors: Ben Hai‐Yan , Gao Wei , Qu Hong‐Yun , Chai A‐Li , Shi Yan‐Xia , Xie Xue‐Wen , Li Bao‐Ju
Published: November 2015

During September 2010, Abutilon megapotamicum plants with dark‐brown concentric spots on leaves were observed in a commercial glasshouse located in Beijing, China. This study was carried out to identify the causal agent of this disease based on Koch's postulates and morphological characteristics. Pathogenicity tests in the glasshouse showed that Myrothecium roridum Tode ex Fr. caused the leaf spot on A. megapotamicum plants, which were the same as those observed in naturally infected plants in the field. Moreover, to confirm the pathogen to species, the rDNA internal transcribed spacer (ITS) of isolate was PCR‐amplified using ITS1 and ITS4 primer pairs and sequenced. DNA analysis revealed a 100% species identity index for M. roridum. To the best of our knowledge, this is the first report of M. roridum on A. megapotamicum in China.
Differentiation and Classification of Phytoplasmas Associated with Almond and GF‐677 Witches'‐Broom Diseases using rRNA and rp Genes
Authors: Motamedi Ehsan , Salehi Mohammad , Sabbagh Seyed Kazem , Salari Mohammad
Published: November 2015

Stone fruits are affected by several diseases associated with plant pathogenic phytoplasmas. Previous studies have been shown that phytoplasma agents of almond and GF‐677 witches'‐broom (AlmWB and GWB, respectively) diseases belong to pigeon pea witches'‐broom (16SrIX) phytoplasma group. In this study, partial biological and molecular characterization was used to compare and classify phytoplasma agents of Khafr AlmWB (KAlmWB) and Estahban GWB (EGWB) diseases. Production of different symptoms in periwinkle indicated that agents of KAlmWB and EGWB are differentiable. Expected fragments were amplified from diseased almond and GF‐677 trees in direct PCR using phytoplasma universal primer pairs P1/P7 and rpF1/rpR1 and nested PCR using P1/P7 followed by R16F2n/ R16R2 primer pair. 16S‐rDNA Restriction fragment length polymorphism (RFLP) as well as phylogenetic analysis of rplV‐rpsC and 16S–23S rRNA spacer region sequences classified KAlmWB and EGWB phytoplasmas within 16SrIX‐C (rpIX‐C) and 16SrIX‐B (rpIX‐B) subgroups, respectively.
Contrasting lineage‐specific patterns conceal community phylogenetic structure in larger clades
Authors: Elliott Tammy L. , Waterway Marcia J. , Davies T. Jonathan
Published: November 2015

Question

Community phylogenetic approaches can provide information on the ecological forces structuring plant community composition. For example, assuming evolutionary conservatism of ecological traits, environmental filtering has been suggested to result in phylogenetic clustering, whereas competition has been suggested to lead to phylogenetic over‐dispersion. However, current approaches report aggregate community‐wide metrics and typically assume that all lineages respond similarly. Here, we question this assumption and evaluate evidence for lineage‐specific patterns of co‐occurrence.

Location

Eastern Canadian subarctic.

Methods

We use a novel individual‐based, neighbourhood approach to evaluate lineage‐specific co‐occurrence patterns among 35 focal species of Cyperaceae (sedges). Cyperaceae is a species‐rich clade, with many species sharing similar niche preferences and environmental tolerances, making this a model clade for evaluating interspecific interaction strengths.

Results

We reveal striking differences in co‐occurrence patterns between clades. Within the Cyperaceae, the two species of the genus Trichophorum tended to cluster with each other, whereas species within Eriophorum co‐occurred more often with less closely related neighbours. These contrasting patterns repeated themselves within Carex, with species in the Core Carex clade more often co‐occurring with close relatives, while phylogenetic over‐dispersion was more prominent in the Vignea clade. As a consequence of these opposing lineage‐specific relationships, the overall phylogenetic structure of sedge communities appears random.

Conclusions

We show opposing lineage‐specific patterns in phylogenetic structure that are obscured when species are aggregated into larger clades. Our results reveal cryptic complexities in plant community assembly across taxonomic scales, and indicate that different plant lineages may vary in their response to community‐level processes. We suggest that the processes underlying community composition can be better understood by using alternative sampling and analytical approaches combined with thoughtfully‐created null models.
Bringing CLARITY to the human brain: visualization of Lewy pathology in three dimensions
Authors: Liu A. K. L. , Hurry M. E. D. , Ng O.T. W. , DeFelice J. , Lai H. M. , Pearce R. K. B. , Wong G. T‐C. , Chang R. C‐C. , Gentleman S. M.
Published: November 2015

Aims

CLARITY is a novel technique which enables three‐dimensional visualization of immunostained tissue for the study of circuitry and spatial interactions between cells and molecules in the brain. In this study, we aimed to compare methodological differences in the application of CLARITY between rodent and large human post mortem brain samples. In addition, we aimed to investigate if this technique could be used to visualize Lewy pathology in a post mortem Parkinson's brain.

Methods

Rodent and human brain samples were clarified and immunostained using the passive version of the CLARITY technique. Samples were then immersed in different refractive index matching media before mounting and visualizing under a confocal microscope.

Results

We found that tissue clearing speed using passive CLARITY differs according to species (human vs. rodents), brain region and degree of fixation (fresh vs. formalin‐fixed tissues). Furthermore, there were advantages to using specific refractive index matching media. We have applied this technique and have successfully visualized Lewy body inclusions in three dimensions within the nucleus basalis of Meynert, and the spatial relationship between monoaminergic fibres and Lewy pathologies among nigrostriatal fibres in the midbrain without the need for physical serial sectioning of brain tissue.

Conclusions

The effective use of CLARITY on large samples of human tissue opens up many potential avenues for detailed pathological and morphological studies.
Drought × CO2interactions in trees: a test of the low‐intercellularCO2concentration (Ci) mechanism
Authors: Kelly Jeff W. G. , Duursma Remko A. , Atwell Brian J. , Tissue David T. , Medlyn Belinda E.
Published: November 2015

Models of tree responses to climate typically project that elevated atmosphericCO2concentration (eCa) will reduce drought impacts on forests. We tested one of the mechanisms underlying this interaction, the ‘lowCieffect’, in which stomatal closure in drought conditions reduces the intercellularCO2concentration (Ci), resulting in a larger relative enhancement of photosynthesis witheCa, and, consequently, a larger relative biomass response.

We grew twoEucalyptusspecies of contrasting drought tolerance at ambient and elevatedCafor 6–9 months in large pots maintained at 50% (drought) and 100% field capacity.

Droughted plants did not have significantly lowerCithan well‐watered plants, which we attributed to long‐term changes in leaf area. Hence, there should not have been an interaction between eCaand water availability on biomass, and we did not detect one. The xeric species did have higherCithan the mesic species, indicating lower water‐use efficiency, but both species exhibited similar responses of photosynthesis and biomass toeCa, owing to compensatory differences in the photosynthetic response toCi.

Our results demonstrate that long‐term acclimation to drought, and coordination among species traits may be important for predicting plant responses toeCaunder low water availability.
Aquaporin8 regulates cellular development and reactive oxygen species production, a critical component of virulence in Botrytis cinerea
Authors: An Bang , Li Boqiang , Li Hua , Zhang Zhanquan , Qin Guozheng , Tian Shiping
Published: November 2015

Aquaporins (AQPs) are ubiquitous in nearly all organisms, mediating selective and rapid flux of water across biological membranes. The role of AQPs in phytopathogenic fungi is poorly understood.

Orthologs of AQP genes in Botrytis cinerea were identified and knocked out. The effects of AQPs on hyphal growth and conidiation, formation of infection structures and virulence on plant hosts were examined. The role of AQP8 in reactive oxygen species (ROS) production, distribution and transport were further determined.

Among eight AQPs, only AQP8 was essential for the ability of B. cinerea to infect plants. AQP8 was demonstrated to be an intrinsic plasma membrane protein, which may function as a channel and mediate hydrogen peroxide uptake. Deletion of AQP8 in B. cinerea completely inhibited the development of conidia and infection structures, and significantly affected noxR expression. Further observations revealed that both AQP8 and noxR impacted ROS distribution in the hyphal tips of B. cinerea. Moreover, AQP8 affected the expression of a mitochondrial protein, NQO1. A knockout mutant of NQO1 was observed to display reduced virulence.

These data lead to a better understanding of the important role of AQP8 in the development and pathogenesis of plant pathogens.
The nature of the CO2‐concentrating mechanisms in a marine diatom, Thalassiosira pseudonana
Authors: Clement Romain , Dimnet Laura , Maberly Stephen C. , Gontero Brigitte
Published: November 2015

Diatoms are widespread in aquatic ecosystems where they may be limited by the supply of inorganic carbon. Their carbon dioxide‐concentrating mechanisms (CCMs) involving transporters and carbonic anhydrases (CAs) are well known, but the contribution of a biochemical CCM involving C4 metabolism is contentious.

The CCM(s) present in the marine‐centric diatom, Thalassiosira pseudonana, were studied in cells exposed to high or low concentrations of CO2, using a range of approaches.

At low CO2, cells possessed a CCM based on active uptake of CO2 (70% contribution) and bicarbonate, while at high CO2, cells were restricted to CO2. CA was highly and rapidly activated on transfer to low CO2 and played a key role because inhibition of external CA produced uptake kinetics similar to cells grown at high CO2. The activities of phosphoenolpyruvate (PEP) carboxylase (PEPC) and the PEP‐regenerating enzyme, pyruvate phosphate dikinase (PPDK), were lower in cells grown at low than at high CO2. The ratios of PEPC and PPDK to ribulose bisphosphate carboxylase were substantially lower than 1, even at low CO2.

Our data suggest that the kinetic properties of this species results from a biophysical CCM and not from C4 type metabolism.
Functional ratios among leaf, xylem and phloem areas in branches change with shade tolerance, but not with local light conditions, across temperate tree species
Authors: Zhang Lan , Copini Paul , Weemstra Monique , Sterck Frank
Published: November 2015

Leaf, xylem and phloem areas drive the water and carbon fluxes within branches and trees, but their mutual coordination is poorly understood. We test the hypothesis that xylem and phloem areas increase relative to leaf area when species are selected for, or branches are exposed to, higher levels of light intensity.

Trees of 10 temperate, broadleaved and deciduous, tree species were selected. Fifty‐centimetre‐long branches were collected from shaded and exposed conditions at a height of 3–4 m. We measured the total leaf area, xylem area, phloem area and leaf traits, as well as the area of the constituent cell types, for a stem section at the branch base.

Xylem area : leaf area and phloem area : leaf area ratios did not differ consistently between sun and shade branches, but, as expected, they decreased with species' shade tolerance. Similar trends were observed for conductive cell areas in xylem and phloem.

Trees of light‐demanding species maintain higher water loss and carbon gain rates per leaf area by producing more xylem area and phloem area than shade‐tolerant species. We call for more comparative branch studies as they provide an integrated biological perspective on functional traits and their role in the ecology of tree species.
Recent assembly of the global herbaceous flora: evidence from the paper daisies (Asteraceae: Gnaphalieae)
Authors: Nie Ze‐Long , Funk Vicki A. , Meng Ying , Deng Tao , Sun Hang , Wen Jun
Published: November 2015

The global flora is thought to contain a large proportion of herbs, and understanding the general spatiotemporal processes that shaped the global distribution of these communities is one of the most difficult issues in biogeography.

We explored patterns of world‐wide biogeography in a species‐rich herbaceous group, the paper daisy tribe Gnaphalieae (Asteraceae), based on the hitherto largest taxon sampling, a total of 835 terminal accessions representing 80% of the genera, and encompassing the global geographic range of the tribe, with nuclear internal transcribed spacer (ITS) and external transcribed spacer (ETS) sequences.

Biogeographic analyses indicate that Gnaphalieae originated in southern Africa during the Oligocene, followed by repeated migrations into the rest of Africa and the Mediterranean region, with subsequent entries into other continents during various periods starting in the Miocene.

Expansions in the late Miocene to Pliocene appear to have been the driving force that shaped the global distribution of the tribe as forests were progressively broken up by the mid‐continent aridification and savannas and grasslands expanded into the interior of the major continents. This pattern of recent colonizations may explain the world‐wide distribution of many other organisms in open ecosystems and it is highlighted here as an emerging pattern in the evolution of the global flora.
Farewell to Political Obligation: In Defense of a Permissive Conception of Legitimacy
Authors: Zhu Jiafeng
Published: November 2015

In the recent debate on political legitimacy, we have seen the emergence of a revisionist camp, advocating the idea of ‘legitimacy without political obligation,’ as opposed to the traditional view that political obligation is necessary for state legitimacy. The revisionist idea of legitimacy is appealing because if it stands, the widespread skepticism about the existence of political obligation will not lead us to conclude that the state is illegitimate. Unfortunately, existing conceptions of ‘legitimacy without political obligation’ are subject to serious objections. In this article, I propose a new conception of ‘legitimacy without political obligation,’ and defend it against various objections that the revisionist idea of legitimacy is either conceptually or morally mistaken. This new conception of legitimacy promises to advance the debates between anarchists and statists by making the task of philosophical anarchists significantly more difficult.
Rab9A is required for delivery of cargo from recycling endosomes to melanosomes
Authors: Mahanty Sarmistha , Ravichandran Keerthana , Chitirala Praneeth , Prabha Jyothi , Jani Riddhi Atul , Setty Subba Rao gangi
Published: November 2015

Melanosomes are a type of lysosome‐related organelle that is commonly defective in Hermansky–Pudlak syndrome. Biogenesis of melanosomes is regulated by BLOC‐1, ‐2, ‐3, or AP‐1, ‐3 complexes, which mediate cargo transport from recycling endosomes to melanosomes. Although several Rab GTPases have been shown to regulate these trafficking steps, the precise role of Rab9A remains unknown. Here, we found that a cohort of Rab9A associates with the melanosomes and its knockdown in melanocytes results in hypopigmented melanosomes due to mistargeting of melanosomal proteins to lysosomes. In addition, the Rab9A‐depletion phenotype resembles Rab38/32‐inactivated or BLOC‐3‐deficient melanocytes, suggesting that Rab9A works in line with BLOC‐3 and Rab38/32 during melanosome cargo transport. Furthermore, silencing of Rab9A, Rab38/32 or its effector VARP, or BLOC‐3‐deficiency in melanocytes decreased the length of STX13‐positive recycling endosomal tubules and targeted the SNARE to lysosomes. This result indicates a defect in directing recycling endosomal tubules to melanosomes. Thus, Rab9A and its co‐regulatory GTPases control STX13‐mediated cargo delivery to maturing melanosomes.
Evolutionary history of Apocheima cinerarius (Lepidoptera: Geometridae), a female flightless moth in northern China
Authors: Liu Shuxian , Jiang Nan , Xue Dayong , Cheng Rui , Qu Yanhua , Li Xinxin , Lei Fumin , Han Hongxiang
Published: November 2015

The alterations in the phylogeographical structures of insects in response to the uplift of the Qinghai–Tibet Plateau and the Quaternary glaciations in eastern Asia, particularly in northern China, remain largely unknown. In this study, we selected Apocheima cinerarius, a moth with flightless females, using molecular data (complete mitochondrial genomes and nuclear data) and ecological niche modelling (ENM) to investigate the effects of paleoclimatic changes on the evolutionary history of insects in the area of northern China. The phylogenetic tree of complete mitochondrial genomes indicated that there were two lineages, the western and eastern lineages. The nuclear gene analyses also detected unique haplotypes in each lineage. Time of the most recent common ancestor (TMRCA) of the two lineages was approximately in Early–Middle Pleistocene. Bayesian skyline plots revealed that the western lineage underwent a population expansion event after the Last Glacial Maximum, whereas the eastern lineage underwent expansion between the Last Interglacial and the Last Glacial Maximum. Our results suggest that A. cinerarius expanded eastward from western sites until the moth was distributed across the entire region of northern China. Then, A. cinerarius underwent contraction into isolated glacial refugia followed by subsequent expansion driven by Pleistocene climate changes, which established a narrow sympatric area. Our results indicate that the Quaternary environmental fluctuations had profound influences on the diversification and demography of an insect in northern China, and the same species in north‐western China and north‐eastern China have different demographic histories.
Sub-Weyl subconvexity for Dirichlet -functions to prime power moduli
Authors: Milićević Djordje
Published: November 2015

We prove a subconvexity bound for the central value $L(\frac{1}{2},{\it\chi})$ of a Dirichlet $L$-function of a character ${\it\chi}$ to a prime power modulus $q=p^{n}$ of the form $L(\frac{1}{2},{\it\chi})\ll p^{r}q^{{\it\theta}+{\it\epsilon}}$ with a fixed $r$ and ${\it\theta}\approx 0.1645<\frac{1}{6}$, breaking the long-standing Weyl exponent barrier. In fact, we develop a general new theory of estimation of short exponential sums involving $p$-adically analytic phases, which can be naturally seen as a $p$-adic analogue of the method of exponent pairs. This new method is presented in a ready-to-use form and applies to a wide class of well-behaved phases including many that arise from a stationary phase analysis of hyper-Kloosterman and other complete exponential sums.