bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling growth curve in Moghani sheep: comparison of non-linear mixed growth models and estimation of genetic relationship between growth curve parameters
Authors: GHAVI HOSSEIN-ZADEH N.
Published: June 2017

In order to describe the growth curves in Iranian Moghani sheep, five non-linear mixed mathematical equations (Brody, Negative exponential, Logistic, Gompertz and von Bertalanffy) were compared. After selecting the best-fitted model based on purely statistical criteria, variance components and genetic parameters for growth curve characteristics were estimated. The data set and pedigree information used in the current study were obtained from the breeding station of Moghani sheep and included 7905 weight records of 1581 lambs from birth to 400 days of age between the years 1994 and 2012 inclusive. Each model was fitted to body weight records for all lambs, males, females, single and twin lambs using the NLMIXED procedure in SAS and the parameters were estimated. Animal was considered as subject in the models. The non-linear mixed models were examined for goodness of fit using Akaike's information criterion (AIC) and residual variance. Marginal posterior distribution of genetic parameters and variance components were estimated using the Threshold Model programme. The Gibbs sampler was run for 1 000 000 rounds and the first 200 000 rounds were discarded as a burn-in period. Logistic model provided the best fit of growth curve in males, females, singles, twins and all lambs due to the lower values of AIC and residual variance compared with other models. Posterior mean estimates of direct heritabilities for asymptotic weight (A), initial animal weight (B) and maturation rate (K) parameters of Logistic model were 0·21, 0·24 and 0·29, respectively. Also, posterior mean estimates of maternal heritabilities forA,BandKwere 0·27, 0·24 and 0·19, respectively. Estimate of correlation between direct and maternal genetic effects forA,BandKparameters were −0·33, −0·69 and −0·51, respectively. Estimates of direct genetic correlation betweenA–B,A–KandB–Kwere positive and equal to 0·19, 0·07 and 0·28, respectively. Also, maternal genetic correlations betweenA–B,A–KandB–Kwere positive and equal to 0·43, 0·34 and 0·55, respectively. In general, evaluation of different growth equations used in the current study indicated the potential of the non-linear functions to fit body weight records of Moghani sheep. Also, the results of the current study showed that improvement of growth curve parameters of Moghani sheep could be possible in selection programmes. Therefore, development of an optimal selection strategy to achieve a desired shape of growth curve through changing genetically the parameters of model would be very important.
Phylogenetic relationships among European and Asian representatives of the genus Aspidogaster Baer, 1827 (Trematoda: Aspidogastrea) inferred from molecular data
Authors: Atopkin D.M. , Shedko M.B. , Sokolov S.G. , Zhokhov A.E.
Published: June 2017

In the present study, phylogenetic relationships of European and Far Eastern representatives of the genus Aspidogaster Baer, 1827 were analysed: A. conchicola Baer, 1827, A. limacoides Diesing, 1834, A. ijimai Kawamura, 1915 and A. chongqingensis Wei, Huang & Dai, 2001. Based on ITS1–5.8S–ITS2 rDNA sequence data, an obvious differentiation was seen between specimens of A. limacoides sensu stricto from the European part of Russia and A. limacoides sensu Chen et al., 2010 from China (13.7%); the latter parasites were recognized as A. chongqingensis. Aspidogaster chongqingensis was more closely related to A. ijimai than to A. limacoides s. str. Specimens of A. ijimai from the Amur River, Khanka Lake (Russian Far East) and China were grouped into a single clade with low intra specific molecular differentiation (d = 0–0.3%). Specimens of A. conchicola from the European part of Russia, the Russian Far East and China also formed a single distinct clade. Genetic differentiation between European and Chinese samples of this species was two times lower (d = 0.45%) than between Russian Far East and European or Chinese samples (d = 0.96%), suggesting a long-term separate existence of A. conchicola in the Russian Far East.
Changing understandings of local knowledge in island environments
Authors: LAUER MATTHEW
Published: June 2017

Island ecosystems have rich marine biodiversity and high levels of terrestrial endemism, but are potentially the most vulnerable to climate change and anthropogenic stressors. To effectively manage environments, scholars and conservation practitioners have increasingly turned their attention to local islander knowledge (LK) and practices. To date, much of the literature treats LK definitionally rather than examining its theoretical underpinnings. This review focuses explicitly on the concept of LK and it describes three discernible phases of research marked by conceptual shifts. Over the 20th century, LK underwent a dramatic reversal from something understood as inferior and deficient to something that is valuable and empirically sound. This shift ushered in widespread acceptance of local islander knowledge as a unique, rich corpus of information that could be tapped by Western science to enhance community-based resource management. Over the last several decades, a third phase of LK research has emerged in which a more dynamic framing has developed, emphasizing LK's hybrid and adaptive dimensions, as well as its constitutive entanglements with other social–ecological processes. This has expanded the scope of inquiry into the strategies islanders employ as they adapt to changing social and environmental milieus, and as they attempt to co-produce knowledge with scientists and conservation practitioners.
Influence of gonadotropins on ovarian follicle growth and developmentin vivoandin vitro
Authors: Filatov Maxim , Khramova Yulia , Parshina Elena , Bagaeva Tatiana , Semenova Maria
Published: June 2017

Gonadotropins are the key regulators of ovarian follicles development. They are applied in therapeutic practice in assisted reproductive technology clinics. In the present review we discuss the basic gonadotropic hormones – recombinant human follicle-stimulating hormone, its derivatives, luteinizing hormone and gonadotropin serum of pregnant mares, their origin, and application in ovarian follicle systems inin vitroculture systems.
The Development and Evaluation of the Psychometric Properties of the Negative Beliefs about Post-Event Processing Scale
Authors: Rodriguez Hayley , Kissell Kellie , Lucas Lloyd , Fisak Brian
Published: June 2017

Background: Although negative beliefs have been found to be associated with worry symptoms and depressive rumination, negative beliefs have yet to be examined in relation to post-event processing and social anxiety symptoms. Aims: The purpose of the current study was to examine the psychometric properties of the Negative Beliefs about Post-Event Processing Questionnaire (NB-PEPQ). Method: A large, non-referred undergraduate sample completed the NB-PEPQ along with validation measures, including a measure of post-event processing and social anxiety symptoms. Results: Based on factor analysis, a single-factor model was obtained, and the NB-PEPQ was found to exhibit good validity, including positive associations with measures of post-event processing and social anxiety symptoms. Conclusions: These findings add to the literature on the metacognitive variables that may lead to the development and maintenance of post-event processing and social anxiety symptoms, and have relevant clinical applications.
The Power and Limits of Russia’s Strategic Narrative in Ukraine: The Role of Linkage
Authors: Szostek Joanna
Published: June 2017

Governments project strategic narratives about international affairs, hoping thereby to shape the perceptions and behaviour of foreign audiences. If individuals encounter incompatible narratives projected by different states, how can their acceptance of one narrative over another be explained? I suggest that support for the strategic narrative of a foreign government is more likely when there is social and communicativelinkageat the individual level, i.e., when an individual maintains personal and cultural connections to the foreign state through regular travel, media consumption, religious attendance, and conversations with friends or relatives. The role of linkage is demonstrated in Ukraine, where a “pro-Russian, anti-Western” narrative projected from Moscow has been competing against a “pro-Western, anti-Russian” narrative projected from Kyiv. Previous accounts of international persuasion have been framed in terms of a state’s resources producing advantageous “soft power.” However, I propose a shift in focus—from the resources stateshaveto what individualsdoto maintain social and communicative ties via which ideas cross borders. In a competitive discursive environment such linkage can in fact have mixed consequences for the states involved, as the Ukrainian case illustrates.
A Discussion of Aviezer Tucker's The Legacies of Totalitarianism: A Theoretical Framework
Authors: Falk Barbara J.
Published: June 2017

The concept of totalitarianism emerged between the two world wars in twentieth-century Europe to become a central concept of Cold War social science designed to highlight similarities between the Nazi and Soviet regimes and implicitly to contrast these forms of dictatorship with liberal democracy. While in the 1960s and 1970s many critics challenged the concept’s Cold War uses as an ideology of “the West,” the idea of totalitarianism and later “post-totalitarianism” played important roles in East Central Europe, where they helped dissident intellectuals, academics, and activists both to understand and to challenge Soviet-style communism. The concept of “totalitarianism” remains heavily contested. But whatever one thinks about the concept’s social scientific validity, there can be no doubt that it played a crucial role in both the scholarship of communism and the public intellectual debates about the possibilities of post-communism. Aviezer Tucker’s The Legacies of Totalitarianism: A Theoretical Framework (Cambridge 2015) addresses many of these issues, and so we have invited a range of political scientists to comment on the book and the broader theme denoted by its title.
A Discussion of Péter Krasztev and Jon Van Til’s The Hungarian Patient: Social Opposition to an Illiberal Democracy
Authors: Heller Ágnes
Published: June 2017

In the wake of the Revolutions of 1989, Hungary was long considered one of the “success stories” of post-communist transition to liberal democracy. Yet in recent years the Hungarian government, under the leadership of Prime Minister Viktor Orban, has pioneered a new conception of “illiberal democracy.” In a July 2014 speech, Orban indeed declared that “the era of liberal democracies is over.” Similar declarations can be heard in other parts of post-communist Eastern Europe. The Hungarian Patient: Social Opposition to an Illiberal Democracy, is a collection of essays by Hungarian social scientists and intellectuals reflecting on both the sources of this emergent illiberalism and the sources of opposition to it. Because it is important for American political scientists to understand the way their colleagues in other parts of the world reflect on the challenges of democracy, and because the Hungarian situation is significant for the future of Europe and the EU, we have invited a wide range of scholars to comment on the book and on its topic—the significance of the emergence of “illiberal democracy” in Hungary and in Europe.
A Discussion of Péter Krasztev and Jon Van Til’s The Hungarian Patient: Social Opposition to an Illiberal Democracy
Authors: Fodor Eva
Published: June 2017

In the wake of the Revolutions of 1989, Hungary was long considered one of the “success stories” of post-communist transition to liberal democracy. Yet in recent years the Hungarian government, under the leadership of Prime Minister Viktor Orban, has pioneered a new conception of “illiberal democracy.” In a July 2014 speech, Orban indeed declared that “the era of liberal democracies is over.” Similar declarations can be heard in other parts of post-communist Eastern Europe. The Hungarian Patient: Social Opposition to an Illiberal Democracy, is a collection of essays by Hungarian social scientists and intellectuals reflecting on both the sources of this emergent illiberalism and the sources of opposition to it. Because it is important for American political scientists to understand the way their colleagues in other parts of the world reflect on the challenges of democracy, and because the Hungarian situation is significant for the future of Europe and the EU, we have invited a wide range of scholars to comment on the book and on its topic—the significance of the emergence of “illiberal democracy” in Hungary and in Europe.
The fascist new–old order
Authors: Hofmann Reto
Published: June 2017

Contemporaries and historians alike have explained the imperialism of interwar Japan, Italy, and Germany through the paradigm of a ‘new world order’. This article critically revisits this received assumption by analysing the place of the Axis in the longer history of imperialism from the late nineteenth century to the Second World War. If we cast Axis empires – a blend of fascism and imperialism – in the larger framework constituted by the relationship between the nation and capital, it becomes clear that they were not so much the result of the peculiar national histories of Japan, Italy, and Germany, but products of larger, global forces. Through an examination of recent scholarship, this article offers a new conceptual interpretation of the link between imperialism and fascism. In so doing, it adds to our understanding of the interwar period by breaking down the neat boundaries between liberal and fascist world orders.
The imperial nexus: the Second World War and the Axis in global perspective
Authors: Hedinger Daniel
Published: June 2017

To date, the alliance between Tokyo, Berlin, and Rome has been interpreted primarily as an alliance between nation-states and has therefore been studied using bi-national approaches. However, this article argues that the strength and globality of the Axis becomes comprehensible if we understand it first and foremost as an alliance between empires. By discussing the interwar years from the viewpoint of trans-imperial cooperation and competition, we discover an imperial nexus. The history, characteristics, diversity, and consequences of this imperial nexus are shown in three parts. The first describes how the nexus helped to bring the distantly located partners together. This occurred against the backdrop of what they called proletarian imperialism, which turned out to be a kind of post-colonial imperialism. The second part analyses how the imperial nexus led others, such as Great Britain, to believe in the existence and strength of a global Axis. In this context, the anti-colonial tendencies put forth mostly by the Japanese turned out to be dangerous. The last part shows how and why the imperial Axis remained intact during the war. Considered from the standpoint of an imperial nexus, the familiar reading of the alliance as well as of the world war shifts. First, Japan and Italy play more important roles than often assumed, while the primacy of Germany is relativized. Second, the chronologies change in relation to the genesis of the Axis and thus the origins of the Second World War. These origins are more strongly associated with non-European world regions and ‘colonial peripheries’, particularly with China and Ethiopia. Third, the issue of ideological similarities and thus of fascism once again becomes a key focus. Fourth and finally, the Axis appears far more diverse and also stronger than previously understood.
When economics, strategy, and racial ideology meet: inter-Axis connections in the wartime Indian Ocean
Authors: Kowner Rotem
Published: June 2017

Japan’s relations with Germany and Italy during the Second World War were rather limited. Nevertheless, there were some regional nuances and growing cooperation as the war drew to its close. In the Indian Ocean, at least, and especially in the area around the Straits of Malacca and the Java Sea, the Japanese and German empires, and to a lesser extent the Italian empire too, did develop a rather intensive cooperation during the final two years of the war (1943–45). This cooperation encompassed several domains, such as the exchange of vital raw materials and military technology, coordinated naval activity, and even an ideological affinity that materialized in pressures to implement harsher racial policies towards Jewish communities in the region. This article examines the scope of this unique inter-Axis collaboration, the specific reasons for why which came into being in this region in particular, and the lessons we may draw from it.
Five Marks of Mission: History, Theology, Critique
Authors: Zink Jesse
Published: June 2017

In recent years the Five Marks of Mission have become the latest in a long series of mission ‘slogans’ in the Anglican Communion, but little attention has been paid to their origin or theological presuppositions. This paper traces the development of an Anglican definition of mission from the 1984 meeting of the Anglican Consultative Council, at which a four-fold definition was first put forth, to the present use of the Five Marks of Mission across many parts of the Communion. The strong influence of evangelical mission thinking on this definition is demonstrated, as is the contributions from African Anglican bishops. Anglican mission thinking has shifted from emphasizing pragmatism and coordination to providing a vision for the Communion to live into. Mission thinking has been a site of genuine cross-cultural interchange among Anglicans from diverse backgrounds.
Variability of Coefficient Alpha: An Empirical Investigation of the Scales of Psychological Wellbeing
Authors: Crouch Meghan K. , Mack Diane E. , Wilson Philip M. , Kwan Matthew Y. W.
Published: June 2017

Using reliability generalization analysis, the purpose of this study was to characterize the average score reliability, the variability of the score reliability estimates, and explore possible characteristics (e.g., sample size) that influence the reliability of scores across studies using the Scales of Psychological Wellbeing (PWB; Ryff, 1989 , 2014 ). Published studies were included in this investigation if they appeared in a peer-reviewed journal, used 1 or more PWB subscales, estimated coefficient alpha value(s) for the PWB subscale(s), and were written in English. Of the 924 articles generated by the search strategy, a total of 264 were included in the final sample for meta-analysis. The average value reported for coefficient alpha referencing the composite PWB Scale was 0.858, with mean coefficient alphas ranging from 0.722 for the autonomy subscale to 0.801 for the self-acceptance subscale. The 95% prediction intervals ranged from [.653, .996] for the composite PWB. The lower bound of the prediction intervals for specific subscales were >.350. Moderator analyses revealed significant differences in score reliability estimates across select sample and test characteristics. Most notably, R2 values linked with test length ranged from 40% to 71%. Concerns were identified with the use of the 3-item per PWB subscale which reinforces claims advanced by Ryff (2014) . Suggestions for researchers using the PWB are advanced which span measurement considerations and standards of reporting. Psychological researchers who calculate score reliability estimates within their own work should recognize the implications of alpha coefficient values on validity, null hypothesis significant testing, and effect sizes.
Precision medicine for hepatocelluar carcinoma using molecular pattern diagnostics: results from a preclinical pilot study
Authors: Agarwal Rahul , Cao Yuan , Hoffmeier Klaus , Krezdorn Nicolas , Jost Lukas , Meisel Alejandro Rodriguez , Jüngling Ruth , Dituri Francesco , Mancarella Serena , Rotter Björn , Winter Peter , Giannelli Gianluigi
Published: June 2017

The aim of this study was to design a road map for personalizing cancer therapy in hepatocellular carcinoma (HCC) by using molecular pattern diagnostics. As an exploratory study, we investigated molecular patterns of tissues of two tumors from individual HCC patients, which in previous experiments had shown contrasting reactions to the phase 2 transforming growth factor beta receptor 1 inhibitor galunisertib. Cancer-driving molecular patterns encompass – inter alias – altered transcription profiles and somatic mutations in coding regions differentiating tumors from their respective peritumoral tissues and from each other. Massive analysis of cDNA ends and all-exome sequencing demonstrate a highly divergent transcriptional and mutational landscape, respectively, for the two tumors, that offers potential explanations for the tumors contrasting responses to galunisertib. Molecular pattern diagnostics (MPDs) suggest alternative, individual-tumor-specific therapies, which in both cases deviate from the standard sorafenib treatment and from each other. Suggested personalized therapies use kinase inhibitors and immune-focused drugs as well as low-toxicity natural compounds identified using an advanced bioinformatics routine included in the MPD protocol. The MPD pipeline we describe here for the prediction of suitable drugs for treatment of two contrasting HCCs may serve as a blueprint for the design of therapies for various types of cancer.
Circulation of HAdV-41 with diverse genome types and recombination in acute gastroenteritis among children in Shanghai
Authors: Li Peng , Yang Lang , Guo Jiayin , Zou Wenwei , Xu Xuebin , Yang Xiaoxia , Du Xinying , Qiu Shaofu , Song Hongbin
Published: June 2017

Human adenovirus F (HAdV-F) is one of the major causative species detected in acute gastroenteritis in children worldwide. HAdV-F is composed of serotypes 40 and 41. Most studies have reported the prevalence of HAdV-41 and focused on its epidemiologic characteristics. In this study, seventeen samples were identified as HAdV-41 out of 273 fecal specimens from children with acute diarrhea in Shanghai. Five isolates were isolated and subjected to whole genome sequencing and analysis to characterize the genetic variation and evolution. Full genome analysis revealed low genetic variation (99.07–99.92% identity) among the isolates, and InDels are observed in the E2A gene and the hexon gene compared to the reference strain NIVD103. Phylogenetic analysis showed that all isolates mainly formed two genome-type clusters but with incongruence in the trees of whole genomes and individual genes. The recombination breakpoints of the five isolates were inferred by the Recombination Detection Program (RDP) and varied in the number and location of the recombination events, indicating different evolution origins. Overall, our study highlights the genetic diversity of HAdV-41 isolates circulating in Shanghai, which may have evolved from inter-strain recombination.
Effect Of Microgravity On Aromatase Expression In Sertoli Cells
Authors: Cirelli Elisa , De Domenico Emanuela , Botti Flavia , Massoud Renato , Geremia Raffaele , Grimaldi Paola
Published: June 2017

Cytochrome P450-aromatase catalyzes estrogen biosynthesis from C19 steroids. In the testis, Sertoli cells express P450-aromatase and represent the primary source of estrogen during prepuberal age. This study focused on the effect of simulated microgravity (SM) on aromatase expression in primary mouse Sertoli cells. When cultured in Rotary Cell Culture System (RCCS), Sertoli cells, formed multicellular three dimensional spheroids (3D). Biological properties were first analyzed in terms of viability, cell cycle, expression of cytoskeletal components and growth factors in comparison to Sertoli cells cultured in spheroids at unit gravity (G). SM did not affect cell viability and proliferation, nor expression of the main cytoskeleton proteins and of growth factors like Kit Ligand (KL) and glial derived neurotrophic factor (GDNF). On the other hand, SM caused a strong increase in P450 aromatase mRNA and protein expression. Interestingly, P450-aromatase was no more inducible by 8-Br-cAMP. The presence of a functional aromatase was confirmed by enrichment of 17β-estradiol released in the medium by androgen precursors. We concluded that SM causes a significant upregulation of aromatase gene expression in Sertoli cells, leading to a consequent increase in 17β-estradiol secretion. High level of 17β-estradiol in the testis could have potentially adverse effects on male fertility and testicular cancer.
Glucocorticoids ameliorate TGF-β1-mediated epithelial-to-mesenchymal transition of airway epithelium through MAPK and Snail/Slug signaling pathways
Authors: Yang Hyun-Woo , Lee Seoung-Ae , Shin Jae-Min , Park Il-Ho , Lee Heung-Man
Published: June 2017

Chronic rhinosinusitis with nasal polyps (CRSwNP) is closely associated with tissue remodeling. Epithelial-to-mesenchymal transition (EMT), a process of tissue remodeling, can be a therapeutic target of CRSwNP. Glucocorticoids are a type of steroid hormone that is used primarily in medical therapy for patients with CRSwNP; however, their effects on EMT in the airway epithelium remain unknown. To investigate the effects of dexamethasone and fluticasone propionate, a class of glucocorticoids, on transforming growth factor-β1 (TGF-β1) -induced EMT, we used A549 cells, human primary nasal epithelial cells (hPNECs) and ex vivo organ culture of the inferior turbinate. TGF-β1 induced changes in cell morphology, suppressed the expression of E-cadherin and enhanced the expression of a-smooth muscle actin, vimentin and fibronectin in A549 cells. However, glucocorticoids inhibited EMT, migration and invasion enhancement by TGF-β1. We found that the induction of phosphorylated ERK, p38 and the activity of Snail and Slug transcription factors by TGF-β1 were suppressed by glucocorticoids. Glucocorticoids also had a similar effect in hPNECs and ex vivo organ cultures of the inferior turbinate. These findings suggest that glucocorticoids might be a useful therapy for preventing tissue remodeling by blocking the EMT initiated by TGF-β1-induced MAPK and Snail/Slug signaling pathways in CRSwNP.
Associations between radiologist-defined semantic and automatically computed radiomic features in non-small cell lung cancer
Authors: Yip Stephen S. F. , Liu Ying , Parmar Chintan , Li Qian , Liu Shichang , Qu Fangyuan , Ye Zhaoxiang , Gillies Robert J. , Aerts Hugo J. W. L.
Published: June 2017

Tumor phenotypes captured in computed tomography (CT) images can be described qualitatively and quantitatively using radiologist-defined “semantic” and computer-derived “radiomic” features, respectively. While both types of features have shown to be promising predictors of prognosis, the association between these groups of features remains unclear. We investigated the associations between semantic and radiomic features in CT images of 258 non-small cell lung adenocarcinomas. The tumor imaging phenotypes were described using 9 qualitative semantic features that were scored by radiologists, and 57 quantitative radiomic features that were automatically calculated using mathematical algorithms. Of the 9 semantic features, 3 were rated on a binary scale (cavitation, air bronchogram, and calcification) and 6 were rated on a categorical scale (texture, border definition, contour, lobulation, spiculation, and concavity). 32–41 radiomic features were associated with the binary semantic features (AUC = 0.56–0.76). The relationship between all radiomic features and the categorical semantic features ranged from weak to moderate (|Spearmen’s correlation| = 0.002–0.65). There are associations between semantic and radiomic features, however the associations were not strong despite being significant. Our results indicate that radiomic features may capture distinct tumor phenotypes that fail to be perceived by naked eye that semantic features do not describe and vice versa.
Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement
Authors: Hori Ikumi , Otomo Takanobu , Nakashima Mitsuko , Miya Fuyuki , Negishi Yutaka , Shiraishi Hideaki , Nonoda Yutaka , Magara Shinichi , Tohyama Jun , Okamoto Nobuhiko , Kumagai Takeshi , Shimoda Konomi , Yukitake Yoshiya , Kajikawa Daigo , Morio Tomohiro , Hattori Ayako , Nakagawa Motoo , Ando Naoki , Nishino Ichizo , Kato Mitsuhiro , Tsunoda Tatsuhiko , Saitsu Hirotomo , Kanemura Yonehiro , Yamasaki Mami , Kosaki Kenjiro , Matsumoto Naomichi , Yoshimori Tamotsu , Saitoh Shinji
Published: June 2017

Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Mutations in EPG5, a gene that encodes a key autophagy regulator, have been shown to cause VICIS, however, the precise pathomechanism underlying VICIS is yet to be clarified. Here, we describe detailed clinical (including brain MRI and muscle biopsy) and genetic features of nine Japanese patients with VICIS. Genetic dissection of these nine patients from seven families identified 14 causative mutations in EPG5. These included five nonsense, two frameshift, three splicing, one missense, and one multi-exon deletion mutations, and two initiation codon variants. Furthermore, cultured skin fibroblasts (SFs) from two affected patients demonstrated partial autophagic dysfunction. To investigate the function of EPG5, siRNA based EPG5 knock-down, and CRISPR/Cas9 mediated EPG5 knock-out HeLa cells were generated. EPG5-depleted cells exhibited a complete block of autophagic flux caused by defective autophagosome-lysosome fusion. Unexpectedly, endocytic degradation was normal in both VICIS SFs and EPG5 depleted cells, suggesting that EPG5 function is limited to the regulation of autophagosome-lysosome fusion.
Population-based study of effectiveness of neoadjuvant radiotherapy on survival in US rectal cancer patients according to age
Authors: Wu Leilei , Pang Shichao , Yao Qianlan , Jian Chen , Lin Ping , Feng Fangyoumin , Li Hong , Li Yixue
Published: June 2017

Recent cancer researches pay more attention to younger patients due to the variable treatment response among different age groups. Here we investigated the effectiveness of neoadjuvant radiation on the survival of younger and older patients in stage II/III rectal cancer. Data was obtained from Surveillance, Epidemiology, and End Results (SEER) database (n = 12801). Propensity score matching was used to balance baseline covariates according to the status of neoadjuvant radiation. Our results showed that neoadjuvant radiation had better survival benefit (Log-rank P = 3.25e-06) and improved cancer-specific 3-year (87.6%; 95% CI: 86.4–88.7% vs. 84.1%; 95% CI: 82.8–85.3%) and 5-year survival rates (78.1%; 95% CI: 76.2–80.1% vs. 77%; 95% CI: 75.3–78.8%). In older groups (>50), neoadjuvant radiation was associated with survival benefits in stage II (HR: 0.741; 95% CI: 0.599–0.916; P = 5.80e-3) and stage III (HR: 0.656; 95% CI 0.564–0.764; P = 5.26e-08). Interestingly, neoadjuvant radiation did not increase survival rate in younger patients (< = 50) both in stage II (HR: 2.014; 95% CI: 0.9032–4.490; P = 0.087) and stage III (HR: 1.168; 95% CI: 0.829–1.646; P = 0.372). Additionally, neoadjuvant radiation significantly decreased the cancer-specific mortality in older patients, but increased mortality in younger patients. Our results provided new insights on the neoadjuvant radiation in rectal cancer, especially for the younger patients.
Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain
Authors: Vandersarren Lana , Bosteels Cedric , Vanheerswynghels Manon , Moon James J. , Easton Andrew J. , Van Isterdael Gert , Janssens Sophie , Lambrecht Bart N. , van Helden Mary J.
Published: June 2017

Pneumonia virus of mice (PVM) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hRSV). While T cells are indispensable for viral clearance, they also contribute to immunopathology. To gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific T cells in C57BL/6 mice as the majority of transgenic mice are only available on this background. While PVM-specific CD8 T cell epitopes were recently described, so far no PVM-specific CD4 T cell epitopes have been identified within the C57BL/6 strain. Therefore, we set out to map H2-IAb-restricted epitopes along the PVM proteome. By means of in silico prediction and subsequent functional validation, we were able to identify a MHCII-restricted CD4 T cell epitope, corresponding to amino acids 37–47 in the PVM matrix protein (M37–47). Using this newly identified MHCII-restricted M37–47 epitope and a previously described MHCI-restricted N339–347 epitope, we generated peptide-loaded MHCII and MHCI tetramers and characterized the dynamics of virus-specific CD4 and CD8 T cell responses in vivo. The findings of this study can provide a basis for detailed investigation of T cell-mediated immune responses to PVM in a variety of genetically modified C57BL/6 mice.
Cell-specific expression of aquaporin-5 (Aqp5) in alveolar epithelium is directed by GATA6/Sp1 via histone acetylation
Authors: Flodby Per , Li Changgong , Liu Yixin , Wang Hongjun , Rieger Megan E. , Minoo Parviz , Crandall Edward D. , Ann David K. , Borok Zea , Zhou Beiyun
Published: June 2017

Epigenetic regulation of differentiation-related genes is poorly understood. We previously reported that transcription factors GATA6 and Sp1 interact with and activate the rat proximal 358-bp promoter/enhancer (p358P/E) of lung alveolar epithelial type I (AT1) cell-specific gene aquaporin-5 (Aqp5). In this study, we found that histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) increased AQP5 expression and Sp1-mediated transcription of p358P/E. HDAC3 overexpression inhibited Sp1-mediated Aqp5 activation, while HDAC3 knockdown augmented AQP5 protein expression. Knockdown of GATA6 or transcriptional co-activator/histone acetyltransferase p300 decreased AQP5 expression, while p300 overexpression enhanced p358P/E activation by GATA6 and Sp1. GATA6 overexpression, SAHA treatment or HDAC3 knockdown increased histone H3 (H3) but not histone H4 (H4) acetylation within the homologous p358P/E region of mouse Aqp5. HDAC3 binds to Sp1 and HDAC3 knockdown increased interaction of GATA6/Sp1, GATA6/p300 and Sp1/p300. These results indicate that GATA6 and HDAC3 control Aqp5 transcription via modulation of H3 acetylation/deacetylation, respectively, through competition for binding to Sp1, and suggest that p300 modulates acetylation and/or interacts with GATA6/Sp1 to regulate Aqp5 transcription. Cooperative interactions among transcription factors and histone modifications regulate Aqp5 expression during alveolar epithelial cell transdifferentiation, suggesting that HDAC inhibitors may enhance repair by promoting acquisition of AT1 cell phenotype.
Differential depression of neuronal network activity by midazolam and its main metabolite 1-hydroxymidazolam in cultured neocortical slices
Authors: Balk Monika , Hentschke Harald , Rudolph Uwe , Antkowiak Bernd , Drexler Berthold
Published: June 2017

The benzodiazepine midazolam is widely used in critical care medicine. Midazolam has a clinically active metabolite, 1-hydroxymidazolam. The contribution of 1-hydroxymidazolam to the effects of midazolam is controversial. The aim of the current study was to compare the actions of midazolam and 1-hydroxymidazolam on network activity of cortical neurons. Midazolam depressed neuronal activity at a low concentration of 5 nM. When midazolam concentration was increased, it depressed neuronal discharge rates in a biphasic manner. In comparison, 1-hydroxymidazolam did not depress the cortical network activity at low nanomolar concentrations. Higher concentrations of 1-hydroxymidazolam consistently inhibited neuronal activity. Moreover, midazolam shortened cortical up states at low, but not at high concentrations, while the opposite effect was observed with 1-hydroxymidazolam. The network depressant action of midazolam at low concentrations was absent in slices from GABAAreceptor α1(H101R)mutant mice. The α1(H101R)mutation renders α1-subunit containing GABAAreceptors insensitive towards benzodiazepines. This GABAAreceptor subtype is thought to mediate sedation. As midazolam is more potent than its metabolite 1-hydroxymidazolam, the major clinical effects are thus likely caused by midazolam itself. However, 1-hydroxymidazolam could add to the effects of midazolam, especially after the application of high doses of midazolam, and in case of impaired drug metabolism.
Inverse problem for multi-body interaction of nonlinear waves
Authors: Marruzzo Alessia , Tyagi Payal , Antenucci Fabrizio , Pagnani Andrea , Leuzzi Luca
Published: June 2017

The inverse problem is studied in multi-body systems with nonlinear dynamics representing, e.g., phase-locked wave systems, standard multimode and random lasers. Using a general model for four-body interacting complex-valued variables we test two methods based on pseudolikelihood, respectively with regularization and with decimation, to determine the coupling constants from sets of measured configurations. We test statistical inference predictions for increasing number of sampled configurations and for an externally tunable temperature-like parameter mimicing real data noise and helping minimization procedures. Analyzed models with phasors and rotors are generalizations of problems of real-valued spherical problems (e.g., density fluctuations), discrete spins (Ising and vectorial Potts) or finite number of states (standard Potts): inference methods presented here can, then, be straightforward applied to a large class of inverse problems. The high versatility of the exposed techniques also concerns the number of expected interactions: results are presented for different graph topologies, ranging from sparse to dense graphs.
Transcriptome analysis reveals similarities between human blood CD3− CD56bright cells and mouse CD127+ innate lymphoid cells
Authors: Allan David S. J. , Cerdeira Ana Sofia , Ranjan Anuisa , Kirkham Christina L. , Aguilar Oscar A. , Tanaka Miho , Childs Richard W. , Dunbar Cynthia E. , Strominger Jack L. , Kopcow Hernan D. , Carlyle James R.
Published: June 2017

For many years, human peripheral blood natural killer (NK) cells have been divided into functionally distinct CD3−CD56brightCD16−and CD3−CD56dimCD16+subsets. Recently, several groups of innate lymphoid cells (ILC), distinct from NK cells in development and function, have been defined in mouse. A signature of genes present in mouse ILC except NK cells, defined by Immunological Genome Project studies, is significantly over-represented in human CD56brightcells, by gene set enrichment analysis. Conversely, the signature genes of mouse NK cells are enriched in human CD56dimcells. Correlations are based upon large differences in expression of a few key genes. CD56brightcells show preferential expression of ILC-associatedIL7R(CD127),TNFSF10(TRAIL),KIT(CD117),IL2RA(CD25), CD27,CXCR3, DPP4(CD26),GPR183, and MHC class II transcripts and proteins. This could indicate an ontological relationship between human CD56brightcells and mouse CD127+ILC, or conserved networks of transcriptional regulation. In line with the latter hypothesis, among transcription factors known to impact ILC or NK cell development,GATA3,TCF7(TCF-1),AHR,SOX4, RUNX2, andZEB1transcript levels are higher in CD56brightcells, whileIKZF3(AIOLOS),TBX21(T-bet),NFIL3(E4BP4),ZEB2,PRDM1(BLIMP1), andRORAmRNA levels are higher in CD56dimcells.
99mTc-labeled bevacizumab for detecting atherosclerotic plaque linked to plaque neovascularization and monitoring antiangiogenic effects of atorvastatin treatment in ApoE−/− mice
Authors: Tan Hui , Zhou Jun , Yang Xiangdong , Abudupataer Mieradilijiang , Li Xiao , Hu Yan , Xiao Jie , Shi Hongcheng , Cheng Dengfeng
Published: June 2017

Atherosclerotic neovascularization plays a significant role in plaque instability as it provides additional lipids and inflammatory mediators to lesions, and resulting in intraplaque hemorrhage. Vascular endothelial growth factor-A (VEGF-A) is considered the predominant proangiogenic factor in angiogenesis. Bevacizumab, a humanized monoclonal antibody, specifically binds to all VEGF-A isoforms with high affinity. Therefore, in this study, we designed 99mTc-MAG3-bevacizumab as a probe, and then investigated its usefulness as a new imaging agent for the detection of plaque neovessels, while also assessing the therapeutic effect of atorvastatin treatment. The ApoE−/− mice treated with atorvastatin were used as the treatment group, and C57BL/6 J mice were selected as the control group. 99mTc-MAG3-bevacizumab uptake was visualized on atherosclerotic lesions by non-invasive in-vivo micro-SPECT/CT and ex-vivo BSGI planar imaging. The value of P/B in each part of the aorta of ApoE−/− mice was higher than in the treatment group and the C57BL/6 J mice, which was confirmed by Oil Red O staining, CD31 staining and VEGF immunohistochemistry staining. 99mTc-MAG3-bevacizumab imaging allowed for the non-invasive diagnosis and assessment of plaque neovascularization. Furthermore, this probe may be used as a new molecular imaging agent to assess the antiangiogenic effect of atorvastatin.
Repeated evolution of camouflage in speciose desert rodents
Authors: Boratyński Zbyszek , Brito José C. , Campos João C. , Cunha José L. , Granjon Laurent , Mappes Tapio , Ndiaye Arame , Rzebik-Kowalska Barbara , Serén Nina
Published: June 2017

There are two main factors explaining variation among species and the evolution of characters along phylogeny: adaptive change, including phenotypic and genetic responses to selective pressures, and phylogenetic inertia, or the resemblance between species due to shared phylogenetic history. Phenotype-habitat colour match, a classic Darwinian example of the evolution of camouflage (crypsis), offers the opportunity to test the importance of historical versus ecological mechanisms in shaping phenotypes among phylogenetically closely related taxa. To assess it, we investigated fur (phenotypic data) and habitat (remote sensing data) colourations, along with phylogenetic information, in the species-rich Gerbillus genus. Overall, we found a strong phenotype-habitat match, once the phylogenetic signal is taken into account. We found that camouflage has been acquired and lost repeatedly in the course of the evolutionary history of Gerbillus. Our results suggest that fur colouration and its covariation with habitat is a relatively labile character in mammals, potentially responding quickly to selection. Relatively unconstrained and substantial genetic basis, as well as structural and functional independence from other fitness traits of mammalian colouration might be responsible for that observation.
Excess reciprocity distorts reputation in online social networks
Authors: Livan Giacomo , Caccioli Fabio , Aste Tomaso
Published: June 2017

The peer-to-peer (P2P) economy relies on establishing trust in distributed networked systems, where the reliability of a user is assessed through digital peer-review processes that aggregate ratings into reputation scores. Here we present evidence of a network effect which biases digital reputation, revealing that P2P networks display exceedingly high levels of reciprocity. In fact, these are much higher than those compatible with a null assumption that preserves the empirically observed level of agreement between all pairs of nodes, and rather close to the highest levels structurally compatible with the networks’ reputation landscape. This indicates that the crowdsourcing process underpinning digital reputation can be significantly distorted by the attempt of users to mutually boost reputation, or to retaliate, through the exchange of ratings. We uncover that the least active users are predominantly responsible for such reciprocity-induced bias, and that this fact can be exploited to obtain more reliable reputation estimates. Our findings are robust across different P2P platforms, including both cases where ratings are used to vote on the content produced by users and to vote on user profiles.
Family aggression in a social lizard
Authors: Botterill-James Thomas , Halliwell Ben , McKeown Simon , Sillince Jacinta , Uller Tobias , Wapstra Erik , While Geoffrey M.
Published: June 2017

The evolution of family living is underpinned by conflict and cooperation between family members. While family groups can be maintained by reducing conflict between parents and offspring, interactions between siblings may play an equally important role. Here, we compared the level of aggressive interactions between siblings to that between parents and their offspring in the family living skinkLiopholis whitii. Aggressive interactions occurred much more frequently between siblings and between fathers and offspring than between mothers and their offspring. These results suggest that ecological and social conditions that reduce conflict between siblings and between males and offspring will be fundamental in the evolutionary maintenance and diversification of family living in these lizards.
Transcriptome profiling of Cucumis metuliferus infected by Meloidogyne incognita provides new insights into putative defense regulatory network in Cucurbitaceae
Authors: Ling Jian , Mao Zhenchuan , Zhai Mingjuan , Zeng Feng , Yang Yuhong , Xie Bingyan
Published: June 2017

Root-knot nematodes (RKN) represent extensive challenges to Cucurbitaceae crops. However,Cucumis metuliferus(Cm) is known to be resistant toMeloidogyne incognita(Mi) infections. Thus, analysis of differentially expressed genes may lead to a comprehensive gene expression profiling of the incompatibleCm-Miinteraction. In this study, the time-course transcriptome ofCmagainstMiinfection was monitored using RNA-Seq. More than 170000 transcripts were examined inCmroots, and 2430 genes were subsequently identified as differentially expressed in response toMiinfection. Based on function annotation and orthologs finding, the potential mechanism of transcriptional factor, cytoskeleton, pathogen-related genes and plant hormone were assessed at the transcription level. A comparison of gene expression levels betweenMi-infectedCmand cucumber plants revealed that cytoskeleton-related genes are key regulators ofCmresistance toMi. We herein discuss the dual nature of cytoskeleton-related genes in the susceptibility and resistance of plant hosts toMi. Our observations provide novel insights into the responses ofCmtoMiat the transcriptome level. The data generated in this study may be useful for elucidating the mechanism underlying resistance to RKNs in cucurbitaceous crops.