bluuebunny/crossref_metadata_2025 huggingface dataset:
Microconnectomics of the pretectum and ventral thalamus in the chicken (Gallus gallus)
Authors: Vega‐Zuniga Tomas , Marín Gonzalo , González‐Cabrera Cristian , Planitscher Eva , Hartmann Anja , Marks Vanessa , Mpodozis Jorge , Luksch Harald
Published: December 2015

The avian pretectal and ventrothalamic nuclei, encompassing the griseum tectale (GT), n. lentiformis mesencephali (LM), and n. geniculatus lateralis pars ventralis (GLv), are prominent retinorecipient structures related to optic flow operations and visuomotor control. Hence, a close coordination of these neural circuits is to be expected. Yet the connectivity among these nuclei is poorly known. Here, using intracellular labeling and in situ hybridization, we investigated the detailed morphology, connectivity, and neurochemical identity of neurons in these nuclei. Two different cell types exist in the GT: one that generates an axonal projection to the optic tectum (TeO), LM, GLv, and n. intercalatus thalami (ICT), and a second population that only projects to the LM and GLv. In situ hybridization revealed that most neurons in the GT express the vesicular glutamate transporter (VGluT2) mRNA, indicating a glutamatergic identity. In the LM, three morphological cell types were defined, two of which project axons towards dorsal targets. The LM neurons showed strong VGluT2 expression. Finally, the cells located in the GLv project to the TeO, LM, GT, n. principalis precommisuralis (PPC), and ICT. All neurons in the GLv showed strong expression of the vesicular inhibitory amino acid transporter (VIAAT) mRNA, suggesting a GABAergic identity. Our results show that the pretectal and ventrothalamic nuclei are highly interconnected, especially by glutamatergic and GABAergic neurons from the GT and GLv, respectively. This complex morphology and connectivity might be required to organize orienting visuomotor behaviors and coordinate the specific optic flow patterns that they induce. J. Comp. Neurol. 524:2208–2229, 2016. © 2015 Wiley Periodicals, Inc.
Arsenic exposure is associated with diminished insulin sensitivity in non‐diabetic Amish adults
Authors: Park Sung Kyun , Peng Qing , Bielak Lawrence F. , Silver Kristi D. , Peyser Patricia A. , Mitchell Braxton D.
Published: December 2015

Background

Substantial evidence supports an association between diabetes and arsenic at high exposure levels, but results are mixed at low exposure levels. The aetiology of diabetes involves insulin resistance and β‐cell dysfunction. However, only a few epidemiologic studies have examined measures of insulin resistance and β‐cell function in relation to arsenic exposure, and no studies have tested for associations with the oral glucose tolerance test (OGTT). We examined the association between urinary total arsenic and OGTT‐based markers of insulin sensitivity and β‐cell function.

Methods

We studied 221 non‐diabetic adults (mean age = 52.5 years) from the Amish Family Diabetes Study. We computed OGTT‐based validated measures of insulin sensitivity and β‐cell function. Generalized estimating equations accounting for sibship were used to estimate associations.

Results

After adjusting for age, sex, waist‐to‐hip ratio and urinary creatinine, an interquartile range increase in urinary total arsenic (6.24 µg/L) was significantly, inversely associated with two insulin sensitivity measures (Stumvoll metabolic clearance rate = −0.23 mg/(kg min), (95% CI: −0.38, −0.089), p = 0.0015; Stumvoll insulin sensitivity index = −0.0029 µmol/(kg min pM), (95% CI: −0.0047, −0.0011), p = 0.0015). Urinary total arsenic was also significantly associated with higher fasting glucose levels (0.57 mg/dL (95% CI: 0.06, 1.09) per interquartile range increase, p = 0.029). No significant associations were found between urinary total arsenic and β‐cell function measures.

Conclusions

This preliminary study found that urinary total arsenic was associated with insulin sensitivity but not β‐cell function measures, suggesting that low‐level arsenic exposure may influence diabetes risk through impairing insulin sensitivity. Copyright © 2015 John Wiley & Sons, Ltd.
Derivation of water quality guidelines for priority pharmaceuticals
Authors: Kumar Anupama , Batley Graeme E. , Nidumolu Bhanu , Hutchinson Thomas H.
Published: December 2015

Pharmaceuticals can enter freshwater and affect aquatic ecosystem health. Although toxicity tests have been carried out for the commonly used pharmaceuticals, evidence-based water quality guidelines have not been derived. High-reliability water quality guideline values have been derived for 4 pharmaceuticals—carbamazepine, diclofenac, fluoxetine, and propranolol—in freshwaters using a Burr type III distribution applied to species sensitivity distributions of chronic toxicity data. Data were quality-assured and had to meet acceptability criteria for “chronic” no-observed-effect concentrations or concentrations affecting 10% of species, endpoints of population relevance (namely, effect endpoints based on development, growth, reproduction, and survival). Biomarker response data (e.g., biochemical, histological, or molecular responses) were excluded from the derivation because they are typically not directly relevant to wildlife population-related impacts. The derived guideline values for 95% species protection were 9.2 μg/L, 770 μg/L, 1.6 μg/L, and 14 μg/L for carbamazepine, diclofenac, fluoxetine, and propranolol, respectively. These values are significantly higher than the unknown reliability values derived for the European Commission, Switzerland, or Germany that are based on the application of assessment factors to the most sensitive experimental endpoint (which may include biochemical, histological, or molecular biomarker responses) of a limited data set. The guideline values derived in the present study were not exceeded in recent data for Australian rivers and streams receiving pharmaceutical-containing effluents from wastewater-treatment plants. Environ Toxicol Chem 2016;35:1815–1824. © 2015 SETAC
Diet, weight loss, and liver health in nonalcoholic fatty liver disease: Pathophysiology, evidence, and practice
Authors: Marchesini Giulio , Petta Salvatore , Dalle Grave Riccardo
Published: December 2015

Fatty liver accumulation results from an imbalance between lipid deposition and removal, driven by the hepatic synthesis of triglycerides and de novo lipogenesis. The habitual diet plays a relevant role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), and both risky (e.g., fructose) and protective foods (Mediterranean diet) have been described, but the contribution of excess calories remains pivotal. Accordingly, weight loss is the most effective way to promote liver fat removal. Several controlled studies have confirmed that an intense approach to lifestyle changes, carried on along the lines of cognitive‐behavior treatment, is able to attain the desired 7%‐10% weight loss, associated with reduced liver fat, nonalcoholic steatohepatitis (NASH) remission, and also reduction of fibrosis. Even larger effects are reported after bariatric surgery‐induced weight loss in NAFLD, where 80% of subjects achieve NASH resolution at 1‐year follow‐up. These results provide solid data to evaluate the safety and effectiveness of the pharmacological treatment of NASH. The battle against metabolic diseases, largely fueled by increased liver fat, needs a comprehensive approach to be successful in an obesiogenic environment. In this review, we will discuss the role of hepatic lipid metabolism, genetic background, diet, and physical activity on fatty liver. They are the basis for a lifestyle approach to NAFLD treatment. (Hepatology 2016;63:2032‐2043)
Translanguaging Practices and Perspectives of Four Multilingual Teens
Authors: Daniel Shannon M. , Pacheco Mark B.
Published: December 2015

Increasingly, educational research suggests that translanguaging pedagogies can provide meaningful supports for English language learners. Yet, few studies examine how multilingual teens in English‐dominant settings independently translanguage to make sense of school and achieve their goals. In this study, we review definitions of translanguaging and shed light on the rich translanguaging practices of four transnational, multilingual teens in high school and middle school. Holding the view that pedagogical moves should be developed in response to particular groups of learners, we show teens' agentive use of translanguaging and connect these to implications for practice in secondary schools.
Combinatorial PX‐866 and Raloxifene Decrease Rb Phosphorylation, Cyclin E2 Transcription, and Proliferation of MCF‐7 Breast Cancer Cells
Authors: Peek Gregory W. , Tollefsbol Trygve O.
Published: December 2015

As a potential means to reduce proliferation of breast cancer cells, a multiple‐pathway approach with no effect on control cells was explored. The human interactome being constructed by the Center for Cancer Systems Biology will prove indispensable to understanding composite effects of multiple pathways, but its discovered protein–protein interactions require characterization. Accordingly, we explored the effects of regulators of one protein on downstream targets of the other protein. MCF‐7 estrogen receptor‐positive (ER+) breast cancer cells were treated with raloxifene to upregulate the TGF‐β pathway and PX‐866 to down‐regulate the PI3K/Akt pathway. This resulted in highly significant downstream reduction of cell cycle proliferation in breast cancer cells with no significant proliferation reduction following similar treatment of noncancerous MCF10A breast epithelial cells. Reduced phosphorylation of p107 and substantial reduction of Rb phosphorylation were observed in response. The effects of reduced Rb and p107 phosphorylation were reflected in significant decline in E2F‐1 transcriptional activity, which is dependent on pocket protein phosphorylation status. The reduced proliferation was related to decreased expression of cyclins, including E2F‐1‐regulated Cyclin E2, which was also in response to raloxifene and PX‐866. All combinations of raloxifene and PX‐866 produced significant or highly significant results for reduced MCF‐7 cell proliferation, reduced Cyclin E2 transcription, and reduced Rb phosphorylation. These studies demonstrated that uncontrolled proliferation of ER+ breast cancer cells can be significantly reduced by combinational targeting of two relevant pathways. J. Cell. Biochem. 117: 1688–1696, 2016. © 2015 Wiley Periodicals, Inc.
Geomorphological and Hydrological Effects of Subsidence and Land use Change in Industrial and Urban Areas
Authors: Machowski Robert , Rzetala Martyna A. , Rzetala Mariusz , Solarski Maksymilian
Published: December 2015

Land subsidence caused by mining activities is an example of human transformation of the natural environment and leads to changes in land use. The study covers an area of 958 ha in the Silesian Upland, southern Poland. Records from the period 1890–1990 document the presence of subsidence effects in 82.9% of the study area and the maximum displacement figure is more than 30 m which translates to an average rate of 0.3 m per year. It was found that subsidence basins serve as the new local erosion base and new sedimentation basins. They are filled with sediments whose level of pollution ranges from moderate to heavy and extremely heavy. Subsidence has caused a dramatic change in the local hydrology, including the quality and quantity of the water. The specifics involve: the emergence of new closed drainage catchments with a total area of 651.1 ha; an increase in the total watercourse length (from 0.9 to 5.7 km); an increase in the river network density (from 0.09 to 0.56 km km−2); a decrease in the number (from 81 to 48) and an increase in the area (from 23.8 to 58.4 ha) of lakes and ponds; an increase in the lake coverage ratio (from 2.5% to 6.1%) and in water pollution. Subsidence has limited the potential land uses, which led to a decrease in arable land from 619.0 to 122.5 ha that gave way to other land uses, including those equivalent to wasteland. Copyright © 2016 John Wiley & Sons, Ltd.
The finite element square reduced (FE2R) method with GPU acceleration: towards three‐dimensional two‐scale simulations
Authors: Fritzen Felix , Hodapp Max
Published: December 2015

The FE2 method is a renown computational multiscale simulation technique for solid materials with fine‐scale microstructure. It allows for the accurate prediction of the mechanical behavior of structures made of heterogeneous materials with nonlinear material behavior. However, the FE2 method leads to excessive CPU time and storage requirements, even for academic two‐dimensional problems. In order to allow for realistic three‐dimensional two‐scale simulations, a significant reduction of the CPU and memory usage is required. For this purpose, the authors have recently proposed a reduced basis homogenization scheme based on a mixed incremental variational principle. The approach exploits the potential structure of generalized standard materials. Thereby, important speed‐ups and memory savings can be achieved. Using high‐performance GPUs, the reduced‐basis method can be further accelerated. In the present contribution, our previous works are combined and extended to form the FE2‐reduced method: the FE2R. The FE2R can be used to simulate three‐dimensional structural problems with consideration of the nonlinearity and microstructure of the underlying material at acceptable computational cost. Thereby, it allows for a new level of complexity in nonlinear multiscale simulations. Numerical examples illustrate the capabilities of the chosen approach. Copyright © 2016 John Wiley & Sons, Ltd.
The use of proteases complementary to trypsin to probe isoforms and modifications
Authors: Trevisiol Stéphane , Ayoub Daniel , Lesur Antoine , Ancheva Lina , Gallien Sébastien , Domon Bruno
Published: December 2015

The wide diversity of proteins expressed in a cell or a tissue as a result of gene variants, RNA editing or PTMs results in several hundred thousand distinct functional proteins called proteoforms. The large‐scale analysis of proteomes has been driven by bottom‐up MS approaches. This allowed to identify and quantify large numbers of gene products and perform PTM profiling which yielded a significant number of biological discoveries. Trypsin is the gold standard enzyme for the production of peptides in bottom‐up approaches. Several investigators argued recently that the near exclusive use of trypsin provided only a partial view of the proteome and hampered the discovery of new isoforms. The use of multiple proteases in a complementary fashion can increase sequence coverage providing more extensive PTM and sequence variant profiling. Here the various approaches to characterize proteoforms are discussed, including the use of alternative enzymes to trypsin in shotgun approaches to expand the observable sequence space by LC‐MS/MS. The technical considerations associated with the use of alternative enzymes are discussed.
Performance of Multivariate Process Capability Indices Under Normal and Non‐Normal Distributions
Authors: Dianda Daniela F. , Quaglino Marta B. , Pagura José A.
Published: December 2015

In the context of process capability analysis, the results of most processes are dominated by two or even more quality characteristics, so that the assessment of process capability requires that all of them are considered simultaneously. In recent years, many researchers have developed different alternatives of multivariate capability indices using different approaches of construction.

In this paper, four of them are compared through the study of their ability to correctly distinguish capable processes from incapable processes under a diversity of simulated scenarios, defining suitable minimum desirable values that allow to decide whether the process meets or does not meet specifications. In this sense, properties analyzed can be seen as sensitivity and specificity, assuming that a measure is sensitive if it can detect the lack of capability when it actually exists and specific if it correctly identifies capable processes. Two indices based on ratios of regions and two based on the principal component analysis have been selected for the study. The scenarios take into account several joint distributions for the quality variables, normal and non‐normal, several numbers of variables, and different levels of correlation between them, covering a wide range of possible situations.

The results showed that one of the indices has better properties across most scenarios, leading to right conclusions about the state of capability of processes and making it a recommendable option for its use in real‐world practice. Copyright © 2015 John Wiley & Sons, Ltd.
Use of nanoparticles to deliver immunomodulatory oligonucleotides
Authors: Klinman Dennis M. , Sato Takashi , Shimosato Takeshi
Published: December 2015

Synthetic oligonucleotides (ODNs) containing unmethylated ‘CpG motifs’ stimulate the innate immune system to produce cytokines, chemokines, and polyreactive antibodies. CpG ODNs have shown promise as vaccine adjuvants and for the treatment of infectious diseases and cancer. The immunostimulatory activity of CpG ODNs is inhibited by DNA‐containing ‘suppressive’ motifs. ODNs expressing suppressive motifs (Sup ODNs) reduce ongoing immune reactions and show promise in the treatment of autoimmune and inflammatory diseases. This work reviews recent progress in the use of nanoparticles as carriers of CpG and Sup ODNs to target their delivery to the GI tract and lungs. WIREs Nanomed Nanobiotechnol 2016, 8:631–637. doi: 10.1002/wnan.1382

This article is categorized under:

Implantable Materials and Surgical Technologies > Nanomaterials and Implants

Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
The Production of Commodities
Authors: Woods John E.
Published: December 2015

The purpose of this book is to provide an elementary account of Sraffa’s Production of Commodities by means of Commodities. Operating with a two-sector model in order to minimise the mathematical demands on the reader, the author is nonetheless able to analyse all the essential questions arising from Sraffa’s book-prices of production, choice of technique, fixed capital, land and joint production – as well as discuss micro- and macro-economic implications of this theory.
Impaired Health‐Related Quality of Life in Children and Families Affected by Methylmalonic Acidemia
Authors: Splinter Kimberly , Niemi Anna‐Kaisa , Cox Rachel , Platt Julia , Shah Monisha , Enns Gregory M. , Kasahara Mureo , Bernstein Jonathan A.
Published: December 2015

An understanding of health related quality of life (HRQoL) in children and families affected by methylmalonic acidemia (MMA) is important in planning counseling and therapeutic intervention. Liver transplantation (LT) is used as a treatment for MMA; however, its risks and benefits continue to be investigated. The purpose of this study was twofold: (1) to measure HRQoL in children and families affected by MMA using the Pediatric Quality of Life Inventory (PedsQL™) parent version, and (2) to assess the impact of LT on HRQoL by comparing LT and non‐LT patient scores and free responses. Parents/caregivers reported lower scores on the majority of the PedsQL™ scales as compared to samples of healthy children, children with solid organ transplants for indications other than MMA, and families affected by chronic conditions. Scores for children with MMA were lowest in school and social functioning and scores for families were lowest in worry and activity impairment. There were no significant differences in LT and non‐LT patient scores on the PedsQL™ scales. Our results document the negative impact of MMA on HRQoL.
Vetch aphid, Megoura crassicauda (Hemiptera: Aphididae), parasitism does not reduce the bean production of narrow‐leaved vetch, Vicia sativa subsp. nigra (Fabaceae)
Authors: Kasai Atsushi
Published: December 2015

Megoura crassicauda Mordvilko (Hemiptera: Aphididae) is a dominant aphid species found on Vicia sativa subsp. nigra (L.) Ehrh. (Fabaceae) in the spring. Worker ants of Formica japonica, the dominant ant species attracted to the extrafloral nectaries of V. s. nigra, often attack ladybirds (Coccinella septempunctata), which are aphid enemies. However, the workers of F. japonica do not attack or exclude M. crassicauda, the non‐myrmecophilous aphid. It appears that the “bodyguard” retained by the plant guards the plant's herbivore by attacking the herbivores’ enemies, rather than guarding the plant itself. The relationship between V. s. nigra and M. crassicauda was observed in the field to examine and evaluate the cost of parasitism. Parasitism by M. crassicauda delayed flower bud formation markedly in V. s. nigra but did not kill the plants. V. s. nigra plants that were parasitized showed a net bean production similar to that of the non‐parasitized controls. The parasitism rate of M. crassicauda increased when extrafloral nectaries were used by F. japonica. These results may indicate that M. crassicauda provides V. s. nigra with benefits by preventing other serious disadvantages.
Evidence for historical human-induced extinctions of vertebrate species on La DÉsirade (French West Indies)
Authors: Boudadi-Maligne Myriam , Bailon Salvador , Bochaton Corentin , Casagrande Fabrice , Grouard Sandrine , Serrand Nathalie , Lenoble Arnaud
Published: December 2015

Pit cave 6 on Pointe Gros Rempart (Baie-Mahault, La Désirade, French West Indies) is a stratified fossil-bearing site. While the archaeological material and faunal remains from the oldest assemblage demonstrate it to have formed during the Amerindian period, the second assemblage dates to the first one-hundred years of the island's colonial period (mid-18th to mid-19th centuries). Faunal analysis revealed the presence of 4 now locally extinct or extinct species, three of which have never before been documented on La Désirade (Ameivasp.,Leiocephaluscf.cuneusandAlsophissp.). Changing faunal spectrums (invertebrates and vertebrates) due to environmental destabilisation combined with aspects of the island's colonial economy demonstrate habitat degradation and over-grazing to be the principal causes of extinctions and or extirpations.
Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s disease
Authors: Goozee K. G. , Shah T. M. , Sohrabi H. R. , Rainey-Smith S. R. , Brown B. , Verdile G. , Martins R. N.
Published: December 2015

Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer’s disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellularβamyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβmetabolism/clearance contribute to AD pathogenesis.In vitrostudies have shown that Aβmetabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aβmetabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin’s relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, includingin vitroandin vivostudies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.
Responses in whole-body amino acid kinetics to an acute, sub-clinical endotoxin challenge in lambs
Authors: Hoskin S. O. , Bremner D. M. , Holtrop G. , Lobley G. E.
Published: December 2015

Some effects of parasitism, endotoxaemia or sepsis can be mitigated by provision of extra protein. Supplemented protein may encompass a metabolic requirement for specific amino acids (AA). The current study investigates a method to identify and quantify the amounts of AA required during inflammation induced by an endotoxin challenge. One of each pair of six twin sheep was infused in the jugular vein for 20 h with either saline (control) or lipopolysaccharide (LPS, 2 ng/kg body weight per min) fromEscherichia coli. Between 12 and 20 h a mixture of stable isotope-labelled AA was infused to measure irreversible loss rates. From 16 to 20 h all sheep were supplemented with a mixture of unlabelled AA infused intravenously. Blood samples were taken before the start of infusions, and then continuously over intervals between 14 and 20 h. At 20 h the sheep were euthanised, and liver and kidney samples were taken for measurement of serine-threonine dehydratase (SDH) activity. LPS infusion decreased plasma concentrations of most AA (P<0·05;P<0·10 for leucine and tryptophan), except for phenylalanine (which increasedP=0·022) and tyrosine. On the basis of the incremental response to the supplemental AA, arginine, aspartate, cysteine, glutamate, lysine (tendency only), glycine, methionine, proline, serine and threonine were important in the metabolic response to the endotoxaemia. The AA infusion between 16 and 20 h restored the plasma concentrations in the LPS-treated sheep for the majority of AA, except for glutamine, isoleucine, methionine, serine and valine. LPS treatment increased (P<0·02) SDH activity in both liver and kidney. The approach allows quantification of key AA required during challenge situations.
Acute unilateral sensorineural hearing loss associated with anabolic steroids and polycythaemia: case report
Authors: Tikka T , Mistry N , Janjua A
Published: December 2015

Background:

Unilateral sudden sensorineural hearing loss due to an infarct in the vertebrobasilar system has been widely reported. Most patients have a background of traditional coronary risk factors related to these cerebrovascular episodes.

Case report:

A 32-year-old male, a regular user of anabolic steroids, presented to the emergency department with unilateral sensorineural hearing loss and symptoms suggestive of an infarct of the anterior inferior cerebellar artery but in the absence of risk factors for ischaemic stroke.

Results:

Magnetic resonance imaging confirmed the presence of infarction in the region supplied by the anterior inferior cerebellar artery. Polycythaemia was found on haematological analysis, which we believe was secondary to the use of anabolic steroids. The patient was commenced on aspirin as per the stroke management protocol. There was resolution of neurological symptomatology six weeks after the episode, but no improvement in hearing.

Conclusion:

To our knowledge, this is the first case report of unilateral sensorineural hearing loss secondary to the use of anabolic steroids causing polycythaemia. This cause should be considered in the differential diagnosis of patients presenting with sensorineural hearing loss, especially in young males, when no other risk factors can be identified.
The work of the British School at Athens, 2014–2015
Authors: Morgan Catherine
Published: December 2015

Over the past year the School has delivered a rich and varied research programme combining a range of projects in antiquity, spanning the Palaeolithic to Byzantine periods, science-based archaeology to epigraphy (including the work of the Fitch Laboratory and the Knossos Research Centre), with research in sectors from the fine arts to history and the social sciences (see Map 2).

At Knossos, new investigation in the suburb of Gypsadhes, directed by Ioanna Serpetsedaki (23rd EPCA), Eleni Hatzaki (Cincinnati), Amy Bogaard (Oxford) and Gianna Ayala (Sheffield), forms part of Oxford University's ERC-funded project Agricultural Origins of Urban Civilisation. The Gypsadhes excavation features large-scale bioarchaeological research, aimed at providing the fine-grained information necessary to reconstruct the Knossian economy through time.
Recent discoveries & resources in Athenian epigraphy
Authors: Pitt Robert K.
Published: December 2015

Archaeology in Greece has a long history of reporting epigraphic discoveries, and in recent years the print versions have highlighted a number of finds which have added little by little to our understanding of the history and topography of ancient Athens, including many of the reports now available online (see, for example, inscriptions helping to identify the Sanctuary of Apollo Pythios [ID4053] and of Zeus Meilichios [Map 3, no. 1; ID4557], or new voting sherds from the Athenian procedure of ostracism [Map 3, no. 5; ID1877]). Archaeology in Greece Online tags epigraphic material within its reports, allowing the reader to search for inscriptions as a keyword and also by region (such as Attica). This review of recent Athenian epigraphic developments focuses on major finds of the last decade, in particular focusing on discoveries reported in periodicals and publications from Greece, which some may find difficult to access, and is of course a personal and only a small selection of the voluminous literature on the subject (for more thorough coverage readers are pointed to SEG, the superb annual review of all epigraphy-related publications).
Governing Body of the Church in Wales
Authors: Morris Philip
Published: December 2015

The Church in Wales Review had recommended that the Diocese of Llandaff be designated the permanent archiepiscopal see and that the diocese should have an area bishop with a legally designated area of pastoral responsibility. In his presidential address in September, the archbishop recognised that it was a difficult question but one that needed to be faced because of the dual role of archbishop and diocesan bishop, the relentless workload and the need for the archbishop to be located in Cardiff. It had been the subject of several reports and Governing Body motions in the past but with no change to the present situation.
A dual role for Caspase8 and NF-κB interactions in regulating apoptosis and necroptosis of ovarian cancer, with correlation to patient survival
Authors: Hernandez L , Kim M K , Noonan A M , Sagher E , Kohlhammer H , Wright G , Lyle L T , Steeg P S , Anver M , Bowtell D D ,   on behalf of the Australian Ovarian Cancer Study Group, Annunziata C M
Published: December 2015

Ovarian cancer is a deadly disease characterized by primary and acquired resistance to chemotherapy. We previously associated NF-κB signaling with poor survival in ovarian cancer, and functionally demonstrated this pathway as mediating proliferation, invasion and metastasis. We aimed to identify cooperating pathways in NF-κB-dependent ovarian cancer cells, using genome-wide RNA interference as a loss-of-function screen for key regulators of cell survival with IKKβ inhibition. Functional genomic screen for interactions with NF-κB in ovarian cancer showed that cells depleted of Caspase8 died better with IKKβ inhibition. Overall, low Caspase8 was associated with shorter overall survival in three independent gene expression data sets of ovarian cancers. Conversely, Caspase8 expression was markedly highest in ovarian cancer subtypes characterized by strong T-cell infiltration and better overall prognosis, suggesting that Caspase8 expression increased chemotherapy-induced cell death. We investigated the effects of Caspase8 depletion on apoptosis and necroptosis of TNFα-stimulated ovarian cancer cell lines. Inhibition of NF-κB in ovarian cancer cells switched the effects of TNFα signaling from proliferation to death. Although Caspase8-high cancer cells died by apoptosis, Caspase8 depletion downregulated NF-κB signaling, stabilized RIPK1 and promoted necroptotic cell death. Blockage of NF-κB signaling and depletion of cIAP with SMAC-mimetic further rendered these cells susceptible to killing by necroptosis. These findings have implications for anticancer strategies to improve outcome for women with low Caspase8-expressing ovarian cancer.
Erratum: Lateral forces on circularly polarizable particles near a surface
Authors: Rodríguez-Fortuño Francisco J. , Engheta Nader , Martínez Alejandro , Zayats Anatoly V.
Published: December 2015

Nature Communications 6: Article number: 8799 (2015); Published 19 November 2015; Updated 14 December 2015 Due to errors in the production process data were missing in the original version of Fig. 4b. The correct version of this figure appears below. Figure 4
Correction: Corrigendum: Reducing the stress of drug administration: implications for the 3Rs
Authors: Stuart Sarah A. , Robinson Emma S.J.
Published: December 2015

Restraint in animals is known to cause stress but is used during almost all scientific procedures in rodents, representing a major welfare and scientific issue. Administration of substances, a key part of most scientific procedures, almost always involves physical restraint of the animal. In this study, we developed a method to inject substances to rats using a non-restrained technique. We then compared the physiological, behavioral and emotional impacts of restrained versus non-restrained injection procedures. Our results highlight the negative welfare implications associated with physical restraint and demonstrate a method which can be used to avoid this. Our work shows how adopting strategies that avoid restraint can minimize a widespread source of stress in laboratory animals and improve welfare through refinement.
Erratum: Auxenochlorella protothecoides and Prototheca wickerhamii plastid genome sequences give insight into the origins of non-photosynthetic algae
Authors: Yan Dong , Wang Yun , Murakami Tatsuya , Shen Yue , Gong Jianhui , Jiang Huifeng , Smith David R. , Pombert Jean-Francois , Dai Junbiao , Wu Qingyu
Published: December 2015

The forfeiting of photosynthetic capabilities has occurred independently many times throughout eukaryotic evolution. But almost all non-photosynthetic plants and algae still retain a colorless plastid and an associated genome, which performs fundamental processes apart from photosynthesis. Unfortunately, little is known about the forces leading to photosynthetic loss; this is largely because there is a lack of data from transitional species. Here, we compare the plastid genomes of two “transitional” green algae: the photosynthetic, mixotrophic Auxenochlorella protothecoides and the non-photosynthetic, obligate heterotroph Prototheca wickerhamii. Remarkably, the plastid genome of A. protothecoides is only slightly larger than that of P. wickerhamii, making it among the smallest plastid genomes yet observed from photosynthetic green algae. Even more surprising, both algae have almost identical plastid genomic architectures and gene compositions (with the exception of genes involved in photosynthesis), implying that they are closely related. This close relationship was further supported by phylogenetic and substitution rate analyses, which suggest that the lineages giving rise to A. protothecoides and P. wickerhamii diverged from one another around six million years ago.
Erratum: Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3
Authors: Li-Sha Ge , Jing-Lin Zhao , Guang-Yi Chen , Li Liu , De-Pu Zhou , Yue-Chun Li
Published: December 2015

The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis. BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine was administered at doses of 0.1, 0.2 or 0.4 mg/kg three times per day for 7 or 14 consecutive days. The effects of nicotine on survival, myocardial histopathological changes, cardiac function, and cytokine levels were studied. The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group. Treatment with high-dose nicotine reduced the myocardial inflammation and improved the impaired left ventricular function in infected mice. The mRNA expressions and protein levels of TNF-α, IL-1β, IL-6, and IL-17A were significantly downregulated in dose-dependent manners in the nicotine treatment groups compared to the infected untreated group. Nicotine dose-dependently reduced the severity of viral myocarditis through inhibiting the production of proinflammatory cytokines. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis.
Resistance Mechanisms and Molecular Docking Studies of Four Novel QoI Fungicides in Peronophythora litchii
Authors: Zhou Yuxin , Chen Lei , Hu Jian , Duan Hongxia , Lin Dong , Liu Pengfei , Meng Qingxiao , Li Bin , Si Naiguo , Liu Changling , Liu Xili
Published: December 2015

Peronophythora litchii is the causal agent of litchi downy blight. Enestroburin, SYP-1620, SYP-2815 and ZJ0712 are four novel QoI fungicides developed by China. Eight mutants of P. litchii resistant to these QoI fungicides and azoxystrobin (as a known QoI fungicide) were obtained in our preliminary work. In this study, the full length of the cytochrome b gene in P. litchii, which has a full length of 382 amino acids, was cloned from both sensitive isolates and resistant mutants and single-site mutations G142A, G142S, Y131C, or F128S were found in resistant mutants. Molecular docking was used to predict how the mutations alter the binding of the five QoI fungicides to the Qo-binding pockets. The results have increased our understanding of QoI fungicide-resistance mechanisms and may help in the development of more potent inhibitors against plant diseases in the fields.
Gene silencing of TACE enhances plaque stability and improves vascular remodeling in a rabbit model of atherosclerosis
Authors: Zhao Xueqiang , Kong Jing , Zhao Yuxia , Wang Xuping , Bu Peili , Zhang Cheng , Zhang Yun
Published: December 2015

We aimed to test the hypothesis that gene silencing of tumor necrosis factor alpha converting enzyme (TACE) may attenuate lesion inflammation and positive vascular remodeling and enhance plaque stability in a rabbit model of atherosclerosis. Lentivirus-mediated TACE shRNA was injected into the abdominal aortic plaques of rabbits which effectively down-regulated TACE expression and activities from week 8 to week 16. TACE gene silencing reduced remodeling index and plaque burden and diminished the content of macrophages and lipids while increased that of smooth muscle cells and collagen in the aortic plaques. In addition, TACE gene silencing attenuated the local expression of P65, iNOS, ICAM-1, VEGF and Flt-1 and activities of MMP9 and MMP2 while increased the local expression of TGF-β1 together with reduced number of neovessels in the aorta. TACE shRNA treatment resulted in down-regulated expression of TACE in macrophages and blunted ERK-P38 phosphorylation and tube formation of co-cultured mouse vascular smooth muscle cells or human umbilical vein endothelial cells. In conclusion, gene silencing of TACE enhanced plaque stability and improved vascular positive remodeling. The mechanisms may involve attenuated local inflammation, neovascularization and MMP activation, as well as enhanced collagen production probably via down-regulated ERK-NF-κB and up-regulated TGF-β1 signaling pathways.
Stochasticity in economic losses increases the value of reputation in indirect reciprocity
Authors: dos Santos Miguel , Placì Sarah , Wedekind Claus
Published: December 2015

Recent theory predicts harsh and stochastic conditions to generally promote the evolution of cooperation. Here, we test experimentally whether stochasticity in economic losses also affects the value of reputation in indirect reciprocity, a type of cooperation that is very typical for humans. We used a repeated helping game with observers. One subject (the “Unlucky”) lost some money, another one (the “Passer-by”) could reduce this loss by accepting a cost to herself, thereby building up a reputation that could be used by others in later interactions. The losses were either stable or stochastic, but the average loss over time and the average efficiency gains of helping were kept constant in both treatments. We found that players with a reputation of being generous were generally more likely to receive help by others, such that investing into a good reputation generated long-term benefits that compensated for the immediate costs of helping. Helping frequencies were similar in both treatments, but players with a reputation to be selfish lost more resources under stochastic conditions. Hence, returns on investment were steeper when losses varied than when they did not. We conclude that this type of stochasticity increases the value of reputation in indirect reciprocity.
Graphene Based Surface Plasmon Polariton Modulator Controlled by Ferroelectric Domains in Lithium Niobate
Authors: Wang Hao , Zhao Hua , Hu Guangwei , Li Siren , Su Hang , Zhang Jingwen
Published: December 2015

We proposed a ferroelectric domain controlled graphene based surface plasmon polariton modulator. Ferroelectricity-induced electronic and optical property tuning of graphene by domain in lithium niobate was theoretically investigated considering both interband and intraband contributions of surface conductivity. With the corrected Sellmeier equation of lithium niobate, the propagation of transverse magnetic mode surface plasmon polaritons in an air/graphene/lithium niobate structure was studied when monolayer graphene was tuned by down polarization direction ferroelectric domain with different polarization levels. The length of the ferroelectric domain was optimized to be 90 nm for a wavelength of 5.0 μm with signal extinction per unit 14.7 dB/μm, modulation depth 474.1 dB/μm and figure of merit 32.5. This work may promote the study of highly efficient modulators and other ultra-compact nonvolatile electronic and photonic devices in which two-dimensional materials and ferroelectric materials are combined.
Reversible strain-induced magnetization switching in FeGa nanomagnets: Pathway to a rewritable, non-volatile, non-toggle, extremely low energy straintronic memory
Authors: Ahmad Hasnain , Atulasimha Jayasimha , Bandyopadhyay Supriyo
Published: December 2015

We report reversible strain-induced magnetization switching between two stable/metastable states in ~300 nm sized FeGa nanomagnets delineated on a piezoelectric PMN-PT substrate. Voltage of one polarity applied across the substrate generates compressive strain in a nanomagnet and switches its magnetization to one state, while voltage of the opposite polarity generates tensile strain and switches the magnetization back to the original state. The two states can encode the two binary bits, and, using the right voltage polarity, one can write either bit deterministically. This portends an ultra-energy-efficient non-volatile “non-toggle” memory.
Manipulation of magnetization switching and tunnel magnetoresistance via temperature and voltage control
Authors: Liu Houfang , Wang Ran , Guo Peng , Wen Zhenchao , Feng Jiafeng , Wei Hongxiang , Han Xiufeng , Ji Yang , Zhang Shufeng
Published: December 2015

Magnetization switching between parallel and antiparallel alignments of two magnetic layers in magnetic tunnel junctions (MTJs) is conventionally controlled either by an external magnetic field or by an electric current. Here, we report that the manipulation of magnetization switching and tunnel magnetoresistance (TMR) in perpendicularly magnetized CoFeB/MgO/CoFeB MTJs can be achieved by both temperature and voltage. At a certain range of temperature, coercivity crossover between top and bottom magnetic layers is observed in which the TMR ratio of the MTJs is almost unmeasurable. Furthermore, the temperature range can be tuned reversibly by an electric voltage. Magnetization switching driven by the voltage reveals an unconventional phenomenon such that the voltage driven coercivity changes with temperature are quite different for top and bottom CoFeB layers. A model based on thermally-assisted domain nucleation and propagation is developed to explain the frequency and temperature dependence of coercivity. The present results of controlling the magnetization switching by temperature and voltage may provide an alternative route for novel applications of MTJs based spintronic devices.
Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro
Authors: Su Zhonghao , Ye Jin , Qin Zhenxia , Ding Xianting
Published: December 2015

Madecassoside (MA), a triterpenoid saponin isolated from C. asitica, exerts various pharmacological activity including antioxidative and antinflammatory. Doxorubicin (DOX), a common chemotherapeutic drug, has been reported to induce numerous toxic side effects including renal-toxicity. We hypothesized that MA administration may decrease renal-toxicity caused by DOX. In this study, we investigated this hypothesis by introducing MA and DOX into the culture of Human Proximal Tubule Cells HK-2 and mice model. Our in vivo study demonstrated that MA (12 mg/kg), treatment for two weeks attenuated DOX-induced renal injury via protecting renal function, recovering antioxidant enzyme activity, inhibiting Bax, p-ERK1/2, NF-κB p65, iNOS expression and increasing Bcl-2 expression. Similar findings were obtained in our in vitro studies with treatment of DOX and/or MA. Further studies with application of iNOS inhibitor and ERK1/2 kinase inhibitor indicated that the inhibitory effects of MA on DOX-induced apoptosis and inflammation might be mediated by the suppression of the activation of cleaved caspase-3, ERK1/2 pathways, NF-κB p65 and NO production. These results suggest that MA is a promising protective agent for DOX-induced renal toxicity and can be a potential candidate to protect against renal toxicity in DOX-treated cancer patients.
Protective immune barrier against hepatitis B is needed in individuals born before infant HBV vaccination program in China
Authors: Yang Shigui , Yu Chengbo , Chen Ping , Deng Min , Cao Qing , Li Yiping , Ren Jingjing , Xu Kaijin , Yao Jun , Xie Tiansheng , Wang Chencheng , Cui Yuanxia , Ding Cheng , Tian Guo , Wang Bing , Zhang Xiaoyan , Ruan Bing , Li Lanjuan
Published: December 2015

The hepatitis B prevalence rate in adults is still at a high to intermediate level in China. Our purpose was to explore the incidence rate and protective immune barrier against hepatitis B in adults in China. A sample of 317961 participants was multi-screened for hepatitis B surface antigens (HBsAg) in a large-scale cohort of the National Hepatitis B Demonstration Project. A total of 5401 persons were newly-infected, representing an incidence rate of 0.81 (95% CI: 0.77–0.85) per 100 person-years after adjusted by gender and age. History of acquired immune deficiency syndrome, birth prior to 1992, coastal residence, family history of HBV and migrant worker status were significantly associated with higher incidence, while HBV vaccination and greater exercise with lower incidence. The hepatitis B surface antibody (HBsAb) positive rate was negatively correlated with the incidence rate of hepatitis B (r = −0.826). Linear fitting yielded an incidence rate of 1.23 plus 0.02 multiplied by HBsAb positive rate. The study firstly identified the HBsAg incidence rate, which was reduced to 0.1 per 100 person-years after vaccination coverage of about 64%. The protective immune barrier against hepatitis B needs to be established in individuals born prior to the advent of infant HBV vaccination.