bluuebunny/crossref_metadata_2025 huggingface dataset:
Topologically associated domains: a successful scaffold for the evolution of gene regulation in animals
Authors: Acemel Rafael D. , Maeso Ignacio , Gómez‐Skarmeta José Luis
Published: April 2017

The evolution of gene regulation is considered one of the main drivers causing the astonishing morphological diversity in the animal kingdom. Gene regulation in animals heavily depends upon cis‐regulatory elements, discrete pieces of DNA that interact with target promoters to regulate gene expression. In the last years, Chromosome Conformation Capture experiments (4C‐seq, 5C, and HiC) in several organisms have shown that the genomes of many bilaterian animals are organized in the 3D chromatin space in compartments called topologically associated domains (TADs). The appearance of the architectural protein CTCF in the bilaterian ancestor likely facilitated the origin of this chromatin 3D organization. TADs play a critical role favoring the contact of cis‐regulatory elements with their proper target promoters (that often lay within the same TAD) and preventing undesired regulatory interactions with promoters located in neighboring TADs. We propose that TAD may have had a major influence in the history of the evolution of gene regulation. They have contributed to the increment of regulatory complexity in bilaterians by allowing newly evolved cis‐regulatory elements to find target promoters in a range of hundreds of kilobases. In addition, they have conditioned the mechanisms of evolution of gene regulation. These mechanisms include the appearance, removal, or relocation of TAD borders. Such architectural changes have been able to wire or unwire promoters with different sets of cis‐regulatory elements in a single mutational event. We discuss the contribution of these architectural changes to the generation of critical genomic 3D structures required for new regulatory mechanisms associated to morphological novelties. WIREs Dev Biol 2017, 6:e265. doi: 10.1002/wdev.265

This article is categorized under:

Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms

Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics

Comparative Development and Evolution > Evolutionary Novelties
Cover Image, Volume 8, Issue 3
Authors: Woodward Lauren A. , Mabin Justin W. , Gangras Pooja , Singh Guramrit
Published: April 2017

The cover image, by Lauren A.Woodward et al., is based on Advanced Review The exon junction complex: a lifelong guardian of mRNA fate, DOI: 10.1002/wrna.1411.

image
Resource use by the dryad butterfly is scale‐dependent
Authors: Kalarus Konrad , Nowicki Piotr
Published: April 2017

The factors shaping the ways in which animals use resources are a key element of conservation biology, but ecological studies on resource use typically neglect to consider how the study's spatial scale may have affected the outcomes. We used the dryad butterfly, inhabiting xerothermic grassland and wet meadow, to test for differences in its resource use at two scales–habitat patch and landscape. Based on records of plant species composition from random points within four habitat patches and from points in 53 patches along surveyed transects, we compared the microhabitat preferences of the butterfly on the patch scale, and species occurrence and abundance patterns on the landscape scale. We distinguished four main groups of factors related to vegetation structure which affected the butterfly's resource use—factors having similar effects on both spatial scales, factors operating primarily on one of the scales considered, factors relevant only on a single spatial scale, and factors operating on both scales but with effects differing between the two habitat types. We suggest that invertebrates may respond on two spatial levels or on only one, and conclude that larger‐scale studies can meet the challenges of a sophisticated metapopulation approach and can give insight into the habitat characteristics affecting the persistence of species in landscapes. We stress the value of large‐scale studies on species’ habitat preferences when planning conservation strategies, while pointing out that small‐scale studies provide useful information about species ecology and behavior, especially if conducted in multiple habitats.
Bone health in epilepsy
Authors: Menon Bindu , Mehndiratta Man Mohan
Published: April 2017

Epilepsy is one of the most common neurological disorder usually requiring life long treatment. Long term treatment with antiepileptic drugs (AED’s) is associated with chronic side effects which includes effect on bone health

There is a growing volume of literature suggesting that chronic use of AED in patients with epilepsy significantly reduces bone mineral density (BMD) with an increased fracture risk. The causes of these associations are likely to be multifactorial. Unlike other chronic side effects, symptoms of bone loss are insidious and asymptomatic; hence they are usually not recognized, and thus untreated. Hence one needs to determine the presence of osteoporosis before the overt signs are evident to reduce fracture risk. Evaluation of bone health is mandatory for a comprehensive treatment and to provide calcium and 25-OH vitamin-D 3 supplementation if needed. The goals of epilepsy treatment are to achieve seizure freedom while minimizing adverse effects of treatment. Management goal should include a comprehensive care of the patient and this includes much more than controlling seizures.
Streaming patterns in Faraday waves
Authors: Périnet Nicolas , Gutiérrez Pablo , Urra Héctor , Mujica Nicolás , Gordillo Leonardo
Published: April 2017

Wave patterns in the Faraday instability have been studied for decades. Besides the rich wave dynamics observed at the interface, Faraday waves hide elusive flow patterns in the bulk – streaming patterns – which have not been studied experimentally. The streaming patterns are responsible for a net circulation in the flow, which is reminiscent of the circulation in convection cells. In this article, we analyse these streaming flows by conducting experiments in a Faraday-wave set-up using particle image velocimetry. To visualise the flows, we perform stroboscopic measurements to both generate trajectory maps and probe the streaming velocity field. We identify three types of patterns and experimentally show that identical Faraday waves can mask streaming patterns that are qualitatively very different. Next, we consider a three-dimensional model for streaming flows in quasi-inviscid fluids, whose key is the complex coupling occurring at all of the viscous boundary layers. This coupling yields modified boundary conditions in a three-dimensional Navier–Stokes formulation of the streaming flow. Numerical simulations based on this framework show reasonably good agreement, both qualitative and quantitative, with the velocity fields of our experiments. The model highlights the relevance of three-dimensional effects in the streaming patterns. Our simulations also reveal that the variety of streaming patterns is deeply linked to the boundary condition at the top interface, which may be strongly affected by the presence of contaminants.
The tribal partners of empire in Arabia: the Ottomans and the Rashidis of Najd, 1880–1918
Authors: Çiçek M. Talha
Published: April 2017

This article is about an aspect of the Ottoman-Rashidi partnership in the late Ottoman Empire that deeply influenced the order of things in Arabia and resulted in both the Ottomans and the Rashidis becoming more significant actors in regional politics. The main argument is that this partnership made a great contribution to the visibly increasing Ottoman influence in Najd (i.e., central Arabia) and the Persian Gulf in the late nineteenth and early twentieth centuries. At the same time, the Rashidi family’s alliance with the Ottoman Empire paved the way for their emergence as a regional power. Since scholarship on the late nineteenth- and early twentieth-century history of Najd and the Arab lands has tended to neglect the importance of this collaboration, the article sets out to analyze it from its inception until its end, drawing on documents from Ottoman, British, German, and Austrian archives.
Homo Diplomaticus: Mixed-Method Evidence of Variation in Strategic Rationality
Authors: Rathbun Brian C. , Kertzer Joshua D. , Paradis Mark
Published: April 2017

Psychology is traditionally used in political science to explain deviations from rationality. Lost in the debate between rationalists and their critics, however, is a sense of whether the kinds of strategic self-interested behavior predicted by these models has psychological microfoundations: what wouldhomo economicuslook like in the real world? We argue that strategic rationality varies across individuals and is characterized by a pro-self social-value orientation and a high level of epistemic motivation. Testing our argument in the context of international relations, we employ a laboratory bargaining game and integrate it with archival research on German foreign policy-making in the 1920s. We find in both contexts that even among those interested in maximizing only their own egoistic gains, those with greater epistemic motivation are better able to adapt to the strategic situation, particularly the distribution of power. Our results build a bridge between two approaches often considered to be antithetical to one another.
Rising Power on the Mind
Authors: Tingley Dustin
Published: April 2017

A prominent explanation of war claims that international conflict can result when shifts in bargaining power induce the declining power to behave aggressively today because the rising power cannot credibly commit to not behave aggressively tomorrow. This paper asks whether individuals respond to shifting power in ways assumed by these models. Rather than use abstract laboratory-based bargaining games as in other work, I use vignettes describing the United States in an international bargaining situation to explore the microfoundations of power transitions models empirically. The vignettes vary whether the individual is a member of a declining or a rising power and whether there are previous public commitments to the status quo division of territory. Subjects propose a response the United States should make and then explain their decision in their own words. I apply new methods for analyzing these open-ended responses. Consistent with predictions from the behavioral literature, I find important asymmetries in behavior across these conditions as well as substantial heterogeneities in individuals' motivations for their decisions. The results of the experiments suggest potential ways that power-transition models should be refined to have a firmer behavioral basis.
No Substitute for Experience: Presidents, Advisers, and Information in Group Decision Making
Authors: Saunders Elizabeth N.
Published: April 2017

Despite advances in the study of individuals in international relations, we still know little about how the traits and biases of individuals aggregate. Most foreign policy decisions are made in groups, usually by elites with varying degrees of experience, which can have both positive and negative psychological effects. This paper addresses the aggregation problem by exploring how the balance of foreign policy experience among leaders and advisers affects decision making in war, using a principal-agent framework that allows the relative experience of leaders and advisers to vary. A leader's experience affects decision making and, ultimately, the risks associated with conflict, through three mechanisms. First, experience influences a leader's ability to monitor advisers. Second, a leader's experience affects the credibility of delegation to experienced advisers and, in turn, the nature and extent of information gathering. Third, experience affects whether leaders are able to diversify advice, as well as their preference for policies that appear certain. I illustrate the argument using two cases that hold an unusual number of factors constant: the 1991 and 2003 Iraq Wars. George W. Bush's inexperience exacerbated the biases of his advisers, whereas his father's experience cast a long shadow over many of the same officials. Understanding the experience and biases of any one individual is insufficient—the balance of experience within a group is also important. Experience is therefore not fungible: a seasoned team cannot substitute for an experienced leader.
CEO Tournaments: A Cross-Country Analysis of Causes, Cultural Influences, and Consequences
Authors: Burns Natasha , Minnick Kristina , Starks Laura
Published: April 2017

Using a cross-country sample, we examine the chief executive officer (CEO) tournament structure (measured alternatively as the ratio and the difference of pay between the CEO and other top executives within a firm). We find the tournament structure to vary systematically with firm and country cultural characteristics. In particular, firm size and the cultural values of power distance, fair income differences, and competition are significantly associated with variations in tournament structures. We also establish support for the primary implication of tournament theory in that tournament structure tends to be positively related to firm value, even after controlling for endogeneity.
A genetic variant brain-derived neurotrophic factor (BDNF) polymorphism interacts with hostile parenting to predict error-related brain activity and thereby risk for internalizing disorders in children
Authors: Meyer Alexandria , Hajcak Greg , Hayden Elizabeth , Sheikh Haroon I. , Singh Shiva M. , Klein Daniel N.
Published: April 2017

The error-related negativity (ERN) is a negative deflection in the event-related potential occurring when individuals make mistakes, and is increased in children with internalizing psychopathology. We recently found that harsh parenting predicts a larger ERN in children, and recent work has suggested that variation in the brain-derived neurotrophic factor (BDNF) gene may moderate the impact of early life adversity. Parents and children completed measures of parenting when children were 3 years old (N= 201); 3 years later, the ERN was measured and diagnostic interviews as well as dimensional symptom measures were completed. We found that harsh parenting predicted an increased ERN only among children with a methionine allele of theBDNFgenotype, and evidence of moderated mediation: the ERN mediated the relationship between parenting and internalizing diagnosesanddimensional symptoms only if children had a methionine allele. We tested this model with externalizing disorders, and found that harsh parenting predicted externalizing outcomes, but the ERN did not mediate this association. These findings suggest that harsh parenting predicts both externalizing and internalizing outcomes in children; however, this occurs through different pathways that uniquely implicate error-related brain activity in the development of internalizing disorders.
First Impressions of a Young Turk. Introductory Remarks to the Gelenbe 2015 Symposium
Authors: Pavella Mania
Published: April 2017

These remarks constitute an introduction to this special issue and were made on 21 September 2015, at the opening of a special symposium honouring Professor Erol Gelenbe at Imperial College London, UK. Gelenbe is a Computer Scientist and Computer Engineer, who has been a Fellow of Academia Europaea since 2005. He is also a Fellow of the Royal Academy of Sciences, Arts and Letters of Belgium, as well as of the Science Academies of Hungary, Poland and Turkey, and of the National Academy of Technologies of France.
The Founding of the National Academy of Technologies of France
Authors: Castillon Pierre
Published: April 2017

This text was written for the symposium honouring Erol Gelenbe and to deliver a message from the French academy of engineering, NATF, the National Academy of Technologies of France, in the presence of six of our Fellows, including Erol as an active member. I will explain what our goals were when we created our engineering academy 15 years ago, and how our concept was and still is very different from that of an academy of sciences.
Can Europe have a Telecommunications Industry?
Authors: Bravo Alain
Published: April 2017

This paper summarises the author’s remarks during a symposium held at Imperial College, London, UK, in honour of Erol Gelenbe. It provides a perspective for the future of the Telecommunications industry in Europe.
Interventionsstudie zur Entwicklung mathematikbezogener Einstellungen frühpädagogischer Fachpersonen
Authors: Eichen Lars , Bruns Julia
Published: April 2017

Zusammenfassung. Die einjährige Fortbildung EmMa – Erzieherinnen und Erzieher machen Mathematik verfolgt das Ziel, frühpädagogische Fachpersonen in der Weiterentwicklung ihrer (fach-) didaktischen Kompetenzen im Bereich Mathematik zu unterstützen. Für den Forschungsaufbau der begleitenden Wirkungsforschung konnte ein quasi-experimentelles Prä-Post-Design mit Kontrollgruppe abgeleitet werden. Mithilfe des KomMa-Fragebogens ( Blömeke et al., 2015 ) wurden die mathematikbezogenen Einstellungen von n = 51 Fachpersonen in der Interventionsgruppe, n = 48 in der Kontrollgruppe erhoben. Die Ergebnisse der t-Tests zeigen, dass die Intervention in einem Teilbereich der Einstellungen einen erwünschten Effekt erzielt.
Low absolute peripheral blood CD4+ T-cell count predicts poor prognosis in R-CHOP-treated patients with diffuse large B-cell lymphoma
Authors: Kusano Y , Yokoyama M , Terui Y , Nishimura N , Mishima Y , Ueda K , Tsuyama N , Hirofumi Y , Takahashi A , Inoue N , Takeuchi K , Hatake K
Published: April 2017

The absolute peripheral blood lymphocyte count at diagnosis is known to be a strong prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), but it remains unclear as to which peripheral blood lymphocyte population is reflective of DLBCL prognosis. In this cohort, 355 patients with DLBCL treated with R-CHOP from 2006 to 2013 were analyzed. The low absolute CD4+ T-cell count (ACD4C) at diagnosis negatively correlated with the overall response rate and the complete response rate significantly (P<0.00001). An ACD4C<343 × 106/l had a significant negative impact on the 5-year progression-free survival and the overall survival as compared with an ACD4C⩾343 × 106/l (73.7% (95% confidence interval (CI)=66.7–79.5) versus 50.3% (95% CI=39.0–60.6), P<0.00001 and 83.3% (95% CI=77.1–88.0) versus 59.0% (95% CI=47.9–68.5), P<0.00000001, respectively). Multivariate analysis revealed that the ACD4C was an independent prognostic marker (hazard ratio=2.2 (95% CI=1.3–3.7), P<0.01). In conclusion, a low ACD4C at diagnosis served as an independent poor prognostic marker in patients with DLBCL.
Granzyme K‐deficient mice show no evidence of impaired antiviral immunity
Authors: Joeckel Lars T , Allison Cody C , Pellegrini Marc , Bird Catherina H , Bird Phillip I
Published: April 2017

The biological role of granzyme K, a serine protease of cytotoxic T lymphocytes (CTL), is controversial. It has been reported to induce perforin‐mediated cell death in vitro, but is also reported to be non‐cytotoxic and to operate in inflammatory processes. To elucidate the biological role of this protease, we have deleted the granzyme K gene in mice (mutant allele: Gzmktm1.1Pib; MGI:5636646). Gzmk −/− mice are healthy, anatomically normal, fecund and show normal hematopoietic development. Gzmk −/− mice readily recover from lymphocytic choriomeningitis virus and mouse pox Ectromelia virus infection. Ex vivo, virus‐specific granzyme K‐deficient CTL are indistinguishable from those of wild‐type mice in apoptosis induction of target cells. These data suggest that granzyme K does not play an essential role in viral immunity or cytotoxicity. Our granzyme K knockout line completes the collection of mouse models for the human granzymes, and will further our understanding of their biological roles and relationships.
The human amygdala parametrically encodes the intensity of specific facial emotions and their categorical ambiguity
Authors: Wang Shuo , Yu Rongjun , Tyszka J. Michael , Zhen Shanshan , Kovach Christopher , Sun Sai , Huang Yi , Hurlemann Rene , Ross Ian B. , Chung Jeffrey M. , Mamelak Adam N. , Adolphs Ralph , Rutishauser Ueli
Published: April 2017

The human amygdala is a key structure for processing emotional facial expressions, but it remains unclear what aspects of emotion are processed. We investigated this question with three different approaches: behavioural analysis of 3 amygdala lesion patients, neuroimaging of 19 healthy adults, and single-neuron recordings in 9 neurosurgical patients. The lesion patients showed a shift in behavioural sensitivity to fear, and amygdala BOLD responses were modulated by both fear and emotion ambiguity (the uncertainty that a facial expression is categorized as fearful or happy). We found two populations of neurons, one whose response correlated with increasing degree of fear, or happiness, and a second whose response primarily decreased as a linear function of emotion ambiguity. Together, our results indicate that the human amygdala processes both the degree of emotion in facial expressions and the categorical ambiguity of the emotion shown and that these two aspects of amygdala processing can be most clearly distinguished at the level of single neurons.
Fine structure of the topological defect cores studied for disclinations in lyotropic chromonic liquid crystals
Authors: Zhou Shuang , Shiyanovskii Sergij V. , Park Heung-Shik , Lavrentovich Oleg D.
Published: April 2017

The detailed structure of singularities of ordered field represents a fundamental problem in diverse areas of physics. At the defect cores, the deformations are so strong that the system explores states with symmetry different from that of an undistorted material. These regions are difficult to explore experimentally as their spatial extension is very small, a few molecular lengths in the condensed matter. Here we explore the cores of disclinations in the so-called chromonic nematics that extend over macroscopic length scales accessible for optical characterization. We demonstrate that the amplitudeSand the phase "Equation missing"(the director) of the order parameter vary along both the radial and azimuthal directions, in contrast to the classic models in whichSvaries only with the distance from the centre and "Equation missing"depends only on the azimuthal coordinate. This unexpected core structure is explained by a strong coupling of the phase and amplitude of the order parameter in the free energy.
Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies
Authors: Wang Hai , Tian Lin , Goldstein Amit , Liu Jun , Lo Hin-Ching , Sheng Kuanwei , Welte Thomas , Wong Stephen T.C. , Gugala Zbigniew , Stossi Fabio , Zong Chenghang , Li Zonghai , Mancini Michael A. , Zhang Xiang H.-F.
Published: April 2017

The majority of breast cancer models for drug discovery are based on orthotopic or subcutaneous tumours. Therapeutic responses of metastases, especially microscopic metastases, are likely to differ from these tumours due to distinct cancer-microenvironment crosstalk in distant organs. Here, to recapitulate such differences, we established an ex vivo bone metastasis model, termed bone-in-culture array or BICA, by fragmenting mouse bones preloaded with breast cancer cells via intra-iliac artery injection. Cancer cells in BICA maintain features of in vivo bone micrometastases regarding the microenvironmental niche, gene expression profile, metastatic growth kinetics and therapeutic responses. Through a proof-of-principle drug screening using BICA, we found that danusertib, an inhibitor of the Aurora kinase family, preferentially inhibits bone micrometastases. In contrast, certain histone methyltransferase inhibitors stimulate metastatic outgrowth of indolent cancer cells, specifically in the bone. Thus, BICA can be used to investigate mechanisms involved in bone colonization and to rapidly test drug efficacies on bone micrometastases.
Direct comparison of distinct naive pluripotent states in human embryonic stem cells
Authors: Warrier S. , Van der Jeught M. , Duggal G. , Tilleman L. , Sutherland E. , Taelman J. , Popovic M. , Lierman S. , Chuva De Sousa Lopes S. , Van Soom A. , Peelman L. , Van Nieuwerburgh F. , De Coninck D. I. M. , Menten B. , Mestdagh P. , Van de Sompele J. , Deforce D. , De Sutter P. , Heindryckx B.
Published: April 2017

Until recently, human embryonic stem cells (hESCs) were shown to exist in a state of primed pluripotency, while mouse embryonic stem cells (mESCs) display a naive or primed pluripotent state. Here we show the rapid conversion of in-house-derived primed hESCs on mouse embryonic feeder layer (MEF) to a naive state within 5–6 days in naive conversion media (NCM-MEF), 6–10 days in naive human stem cell media (NHSM-MEF) and 14–20 days using the reverse-toggle protocol (RT-MEF). We further observe enhanced unbiased lineage-specific differentiation potential of naive hESCs converted in NCM-MEF, however, all naive hESCs fail to differentiate towards functional cell types. RNA-seq analysis reveals a divergent role of PI3K/AKT/mTORC signalling, specifically of the mTORC2 subunit, in the different naive hESCs. Overall, we demonstrate a direct evaluation of several naive culture conditions performed in the same laboratory, thereby contributing to an unbiased, more in-depth understanding of different naive hESCs.
Transiently antigen-primed B cells return to naive-like state in absence of T-cell help
Authors: Turner Jackson S. , Marthi Matangi , Benet Zachary L. , Grigorova Irina
Published: April 2017

The perspective that naive B-cell recognition of antigen in the absence of T-cell help causes cell death or anergy is supported byin vivostudies of B cells that are continuously exposed to self-antigens. However, intravital imaging suggests that early B-cell recognition of large foreign antigens may be transient. Whether B cells are tolerized or can be recruited into humoural immune responses following such encounters is not clear. Here we show that in the presence of T-cell help, single transient antigen acquisition is sufficient to recruit B cells into the germinal centre and induce memory and plasma cell responses. In the absence of T-cell help, transiently antigen-primed B cells do not undergo apoptosisin vivo; they return to quiescence and are recruited efficiently into humoural responses upon reacquisition of antigen and T-cell help.
Clonal evolution in myelodysplastic syndromes
Authors: da Silva-Coelho Pedro , Kroeze Leonie I. , Yoshida Kenichi , Koorenhof-Scheele Theresia N. , Knops Ruth , van de Locht Louis T. , de Graaf Aniek O. , Massop Marion , Sandmann Sarah , Dugas Martin , Stevens-Kroef Marian J. , Cermak Jaroslav , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Miyano Satoru , de Witte Theo , Blijlevens Nicole M. A. , Muus Petra , Huls Gerwin , van der Reijden Bert A. , Ogawa Seishi , Jansen Joop H.
Published: April 2017

Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5–11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment. The application of disease-modifying therapy may create an evolutionary bottleneck after which more complex MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition, subclones that acquired an additional mutation associated with treatment resistance (TP53) or disease progression (NRAS, KRAS) may be detected months before clinical changes become apparent. Monitoring the genetic landscape during the disease may help to guide treatment decisions.
Effect of Unsaturated Sn Atoms on Gas-Sensing Property in Hydrogenated SnO2 Nanocrystals and Sensing Mechanism
Authors: Yuan Y. , Wang Y. , Wang M. , Liu J. , Pei C. , Liu B. , Zhao H. , Liu S. , Yang H.
Published: April 2017

Sensing reaction mechanism is crucial for enhancing the sensing performance of semiconductor-based sensing materials. Here we show a new strategy to enhancing sensing performance of SnO2 nanocrystals by increasing the density of unsaturated Sn atoms with dangling bonds at the SnO2 surface through hydrogenation. A concept of the surface unsaturated Sn atoms serving as active sites for the sensing reaction is proposed, and the sensing mechanism is described in detail at atomic and molecule level for the first time. Sensing properties of other metal oxide sensors and catalytic activity of other catalysts may be improved by using the hydrogenation strategy. The concept of the surface unsaturated metal atoms serving as active sites may be very useful for understanding the sensing and catalytic reaction mechanisms and designing advanced sensing sensors, catalysts and photoelectronic devices.
Deficiency of CCN5/WISP-2-Driven Program in breast cancer Promotes Cancer Epithelial cells to mesenchymal stem cells and Breast Cancer growth
Authors: Das Amlan , Dhar Kakali , Maity Gargi , Sarkar Sandipto , Ghosh Arnab , Haque Inamul , Dhar Gopal , Banerjee Snigdha , Banerjee Sushanta K.
Published: April 2017

Breast cancer progression and relapse is conceivably due to tumor initiating cells (TICs)/cancer stem cells. EMT (epithelial-mesenchymal-transition)-signaling regulates TICs’ turnover. However, the mechanisms associated with this episode are unclear. We show that, in triple-negative-breast cancer (TNBC) cells enriched with TICs, CCN5 significantly blocks cellular growth via apoptosis, reversing EMT-signaling and impairing mammosphere formation, thereby blocking the tumor-forming ability and invasive capacity of these cells. To corroborate these findings, we isolated tumor-initiating side populations (SP) and non-side population (NSP or main population) from MCF-7 cell line, and evaluated the impact of CCN5 on these subpopulations. CCN5 was overexpressed in the NSP but downregulated in the SP. Characteristically, NSP cells are ER-α positive and epithelial type with little tumorigenic potency, while SP cells are very similar to triple-negative ones that do not express ER-α- and Her-2 and are highly tumorigenic in xenograft models. The overexpression of CCN5 in SP results in EMT reversion, ER-α upregulation and delays in tumor growth in xenograft models. We reasoned that CCN5 distinguishes SP and NSP and could reprogram SP to NSP transition, thereby delaying tumor growth in the xenograft model. Collectively, we reveal how CCN5-signaling underlies the driving force to prevent TNBC growth and progression.
The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets
Authors: Iaconis Daniela , Monti Maria , Renda Mario , van Koppen Arianne , Tammaro Roberta , Chiaravalli Marco , Cozzolino Flora , Pignata Paola , Crina Claudia , Pucci Piero , Boletta Alessandra , Belcastro Vincenzo , Giles Rachel H. , Surace Enrico Maria , Gallo Simone , Pende Mario , Franco Brunella
Published: April 2017

Protein synthesis is traditionally associated with specific cytoplasmic compartments. We now show that OFD1, a centrosomal/basal body protein, interacts with components of the Preinitiation complex of translation (PIC) and of the eukaryotic Initiation Factor (eIF)4F complex and modulates the translation of specific mRNA targets in the kidney. We demonstrate that OFD1 cooperates with the mRNA binding protein Bicc1 to functionally control the protein synthesis machinery at the centrosome where also the PIC and eIF4F components were shown to localize in mammalian cells. Interestingly, Ofd1 and Bicc1 are both involved in renal cystogenesis and selected targets were shown to accumulate in two models of inherited renal cystic disease. Our results suggest a possible role for the centrosome as a specialized station to modulate translation for specific functions of the nearby ciliary structures and may provide functional clues for the understanding of renal cystic disease.
Diabetic Retinopathy and Clinical Parameters Favoring the Presence of Diabetic Nephropathy could Predict Renal Outcome in Patients with Diabetic Kidney Disease
Authors: Hung Chi-Chih , Lin Hugo You-Hsien , Hwang Daw-Yang , Kuo I-Ching , Chiu Yi-Wen , Lim Lee-Moay , Hwang Shang-Jyh , Chen Hung-Chun
Published: April 2017

Diabetes duration, diabetic retinopathy (DR), and a diagnostic model have been proposed as clinical parameters favoring the presence of diabetic nephropathy (DN) in biopsied patients with diabetic kidney disease. DN, compared with non-diabetic renal disease, had poorer renal outcomes. We tested whether these clinical parameters favoring DN are associated with poorer renal outcomes in non-biopsied patients. In this study, 1330 patients with type 2 diabetes and chronic kidney disease stages 1–4 were included and divided according to diabetes mellitus (DM) duration >8 years, DR, or a diagnostic model for DN. These clinical parameters favoring DN were found in 62–77% of patients and associated with higher levels of proteinuria. In a Cox survival analysis, DR and the diagnostic model favoring DN were associated with an increased risk for end-stage renal disease with adjusted hazard ratios of 1.69 (95% CI: 1.16–2.45, P = 0.006) and 1.66 (95% CI: 1.05–2.61, P = 0.029), respectively. DR was associated with an increased risk for rapid renal disease progression. DM >8 years was not associated with renal outcome. Propensity score-matched analyses also showed similar results. In conclusion, DR and the diagnostic model favoring DN were associated with poorer renal outcomes.
Sensitization of glioblastoma tumor micro-environment to chemo- and immunotherapy by Galectin-1 intranasal knock-down strategy
Authors: Van Woensel Matthias , Mathivet Thomas , Wauthoz Nathalie , Rosière Rémi , Garg Abhishek D. , Agostinis Patrizia , Mathieu Véronique , Kiss Robert , Lefranc Florence , Boon Louis , Belmans Jochen , Van Gool Stefaan W. , Gerhardt Holger , Amighi Karim , De Vleeschouwer Steven
Published: April 2017

In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells. Gal-1 knock-down reduces macrophages’ polarization switch from M1 (pro-inflammatory) to M2 (anti-inflammatory) during GBM progression. These changes are accompanied by normalization of the tumor vasculature and increased survival for tumor bearing mice. The combination of siGal-1 treatment with temozolomide or immunotherapy (dendritic cell vaccination and PD-1 blocking) displays synergistic effects, increasing the survival of tumor bearing mice. Moreover, we could confirm the role of Gal-1 on lymphocytes in GBM patients by matching the Gal-1 expression and their T cell signatures. These findings indicate that intranasal siGal-1 nanoparticle delivery could be a valuable adjuvant treatment to increase the efficiency of immune-checkpoint blockade and chemotherapy.
Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men
Authors: Foghmar Caroline , Brøns Charlotte , Pilely Katrine , Vaag Allan , Garred Peter
Published: April 2017

Insulin resistance is associated with high circulating level of complement factor C3. Animal studies suggest that improper complement activation mediates high-fat-diet-induced insulin resistance. Individuals born with low birth weight (LBW) are at increased risk of developing insulin resistance. We hypothesized that high-fat overfeeding (HFO) increase circulating C3 and induce complement activation in a birth weight differential manner. Twenty LBW and 26 normal birth weight (NBW) young men were studied using a randomised crossover design. Insulin resistance was measured after a control-diet and after 5-days HFO by a hyperinsulinemic-euglycemic-clamp. Circulating C4, C3, ficolins, mannose-binding-lectin, complement activation products C3bc, terminal complement complex (TCC) and complement activation capacity were determined using turbidimetry and ELISA. HFO induced peripheral insulin resistance in LBW individuals only, while both groups had the same degree of hepatic insulin resistance after HFO. Viewing all individuals circulating levels of C4, C3, C3bc, TCC and complement activation capacity decreased paradoxically along the development of insulin resistance after HFO (P = 0.0015, P < 0.0001, P = 0.01, P < 0.0001, P = 0.0002, P < 0.0001, P = 0.0006). Birth weight did not influence these results. This might reflect a hitherto unrecognized down-regulatory mechanism of the complement system. More human studies are needed to understand the underlying physiology and the potential consequences of these findings.
Monitoring Chemical Changes on the Surface of Kenaf Fiber during Degumming Process Using Infrared Microspectroscopy
Authors: Jiang Wei , Han Guangting , Zhang Yuanming , Liu Shaoyang , Zhou Chengfeng , Song Yan , Zhang Xiao , Xia Yanzhi
Published: April 2017

Degumming is the dominant method to obtain lignocellulosic fibers in the textile industry. Traditionally, wet chemistry methods are used to monitor the evolution of major chemical components during the degumming process. However, these methods lack the ability to provide spatial information for these heterogeneous materials. In this study, besides wet chemistry and scanning electron microscopy (SEM) analysis, a Fourier-transform infrared microspectroscopy (FTIRM) method was employed to monitor the changes in spatial distribution of the main chemical components on the kenaf surface during a steam explosion followed by chemical degum process. The results showed that hemicellulose and lignin were degummed at different rates, and the mechanisms of their degumming are different. The infrared microspectral images revealed the distribution changes of chemical components on the fiber bundle surface during the process, indicating that FTIRM is an effective tool to analyze the degumming process and improve degumming methods.
Pressure Self-focusing Effect and Novel Methods for Increasing the Maximum Pressure in Traditional and Rotational Diamond Anvil Cells
Authors: Feng Biao , Levitas Valery I.
Published: April 2017

The main principles of producing a region near the center of a sample, compressed in a diamond anvil cell (DAC), with a very high pressure gradient and, consequently, with high pressure are predicted theoretically. The revealed phenomenon of generating extremely high pressure gradient is called the pressure self-focusing effect. Initial analytical predictions utilized generalization of a simplified equilibrium equation. Then, the results are refined using our recent advanced model for elastoplastic material under high pressures in finite element method (FEM) simulations. The main points in producing the pressure self-focusing effect are to use beveled anvils and reach a very thin sample thickness at the center. We find that the superposition of torsion in a rotational DAC (RDAC) offers drastic enhancement of the pressure self-focusing effect and allows one to reach the same pressure under a much lower force and deformation of anvils.
Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution
Authors: Chung Hwa Hwa , Or Yu Zuan , Shrestha Smeeta , Loh Jia Tong , Lim Chew Leng , Ong Zoe , Woo Amanda Rui En , Su I-Hsin , Lin Valerie C. L.
Published: April 2017

Epidemiological studies have indicated increased risk for breast cancer within 10 years of childbirth. Acute inflammation during mammary involution has been suggested to promote this parity-associated breast cancer. We report here that estrogen exacerbates mammary inflammation during involution. Microarray analysis shows that estrogen induces an extensive proinflammatory gene signature in the involuting mammary tissue. This is associated with estrogen-induced neutrophil infiltration. Furthermore, estrogen induces the expression of protumoral cytokines/chemokines, COX-2 and tissue-remodeling enzymes in isolated mammary neutrophils and systemic neutrophil depletion abolished estrogen-induced expression of these genes in mammary tissue. More interestingly, neutrophil depletion diminished estrogen-induced growth of ERα-negative mammary tumor 4T1 in Balb/c mice. These findings highlight a novel aspect of estrogen action that reprograms the activity of neutrophils to create a pro-tumoral microenvironment during mammary involution. This effect on the microenvironment would conceivably aggravate its known neoplastic effect on mammary epithelial cells.
Intracellular lipid binding protein family diversity from Oyster Crassostrea gigas: genomic and structural features of invertebrate lipid transporters
Authors: de Toledo-Silva Guilherme , Razzera Guilherme , Zacchi Flavia Lucena , Wendt Nestor Cubas , Mattos Jacó Joaquim , Bainy Afonso Celso Dias
Published: April 2017

Intracellular lipid binding proteins (iLBPs) play a role in the transport and cellular uptake of fatty acids and gene expression regulation. The aim of this work was to characterize the iLBP gene family of the Pacific oyster Crassostrea gigas, one of the most cultivated marine bivalves in the world, using bioinformatics and molecular biology approaches. A total of 26 different iLBPs transcripts were identified in the Pacific oyster genome, including alternative splicing and gene duplication events. The oyster iLBP gene family seems to be more expanded than in other invertebrates. Furthermore, 3D structural modeling and molecular docking analysis mapped the main amino acids involved in ligand interactions, and comparisons to available protein structures from vertebrate families revealed new binding cavities. Ten different CgiLBPs were analyzed by quantitative PCR in various tissues of C. gigas, which suggested differential prevalent gene expression of CgiLBPs among tissue groups. The data indicate a wider repertoire of iLBPs in labial palps, a food-sorting tissue. The different gene transcription profiles and reported docking systems suggest that the iLBPs are a non-generalist ligand binding protein family with specific functions.
Sites of overt and covert attention define simultaneous spatial reference centers for visuomotor response
Authors: Zhou Yang , Liang Lixin , Pan Yujun , Qian Ning , Zhang Mingsha
Published: April 2017

The site of overt attention (fixation point) defines a spatial reference center that affects visuomotor response as indicated by the stimulus-response-compatibility (SRC) effect: When subjects press, e.g., a left key to report stimuli, their reaction time is shorter when stimuli appear to the left than to the right of the fixation. Covert attention to a peripheral site appears to define a similar reference center but previous studies did not control for confounding spatiotemporal factors or investigate the relationship between overt- and covert-attention-defined centers. Using an eye tracker to monitor fixation, we found an SRC effect relative to the site of covert attention induced by a flashed cue dot, and a concurrent reduction, but not elimination, of the overt-attention SRC effect. The two SRC effects jointly determined the overall motor reaction time. Since trials with different cue locations were randomly interleaved, the integration of the two reference centers must be updated online. When the cue was invalid and diminished covert attention, the covert-attention SRC effect disappeared and the overt-attention SRC effect retained full strength, excluding non-attention-based interpretations. We conclude that both covert- and overt-attention sites define visual reference centers that simultaneously contribute to motor response.
Long term stability and infectivity of herpesviruses in water
Authors: Dayaram Anisha , Franz Mathias , Schattschneider Alexander , Damiani Armando M. , Bischofberger Sebastian , Osterrieder Nikolaus , Greenwood Alex D.
Published: April 2017

For viruses to utilize environmental vectors (hard surfaces, soil, water) for transmission, physical and chemical stability is a prerequisite. There are many factors including pH, salinity, temperature, and turbidity that are known to contribute to the ability of viruses to persist in water. Equine herpesvirus type-1 (EHV-1) is a pathogenic alphaherpesvirus associated with domestic horses and wild equids. EHV-1 and recombinants of EHV-1 and EHV-9 are able to cause infections in non-equid animal species, particularly in captive settings. Many of the captive non-equid mammals are not naturally sympatric with equids and do not share enclosures, however, in many cases water sources may overlap. Similarly, in the wild, equids encounter many species at waterholes in times of seasonal drought. Therefore, we hypothesized that EHV-1 is stable in water and that water may act as a vector for EHV-1. In order to establish the conditions promoting or hindering EHV-1 longevity, infectivity and genomic stability in water; we exposed EHV-1 to varied water environments (pH, salinity, temperature, and turbidity) in controlled experiments over 21 days. The presence and infectivity of the virus was confirmed by both qPCR and cell culture experiments. Our results show that EHV-1 remains stable and infectious under many conditions in water for up to three weeks.
Sirtuins in the phylum Basidiomycota: A role in virulence in Cryptococcus neoformans
Authors: Arras Samantha D. M. , Chitty Jessica L. , Wizrah Maha S. I. , Erpf Paige E. , Schulz Benjamin L. , Tanurdzic Milos , Fraser James A.
Published: April 2017

Virulence of Cryptococcus neoformans is regulated by a range of transcription factors, and is also influenced by the acquisition of adaptive mutations during infection. Beyond the temporal regulation of virulence factor production by transcription factors and these permanent microevolutionary changes, heritable epigenetic modifications such as histone deacetylation may also play a role during infection. Here we describe the first comprehensive analysis of the sirtuin class of NAD+ dependent histone deacetylases in the phylum Basidiomycota, identifying five sirtuins encoded in the C. neoformans genome. Each sirtuin gene was deleted and a wide range of phenotypic tests performed to gain insight into the potential roles they play. Given the pleiotropic nature of sirtuins in other species, it was surprising that only two of the five deletion strains revealed mutant phenotypes in vitro. However, cryptic consequences of the loss of each sirtuin were identified through whole cell proteomics, and mouse infections revealed a role in virulence for SIR2, HST3 and HST4. The most intriguing phenotype was the repeated inability to complement mutant phenotypes through the reintroduction of the wild-type gene. These data support the model that regulation of sirtuin activity may be employed to enable a drastic alteration of the epigenetic landscape and virulence of C. neoformans.